FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Folweiler, KA
Bondi, CO
Ogunsanya, EA
LaPorte, MJ
Leary, JB
Radabaugh, HL
Monaco, CM
Kline, AE
AF Folweiler, Kaitlin A.
Bondi, Corina O.
Ogunsanya, Elizabeth A.
LaPorte, Megan J.
Leary, Jacob B.
Radabaugh, Hannah L.
Monaco, Christina M.
Kline, Anthony E.
TI Combining the Antipsychotic Drug Haloperidol and Environmental
Enrichment after Traumatic Brain Injury Is a Double-Edged Sword
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE antipsychotic drugs; behavioral outcome; controlled cortical impact;
environmental enrichment; functional recovery; learning and memory;
Morris water maze; traumatic brain injury
ID CONTROLLED CORTICAL IMPACT; WATER MAZE PERFORMANCE; RAT CEREBRAL-CORTEX;
COGNITIVE FUNCTION; ATYPICAL ANTIPSYCHOTICS; LIPID-PEROXIDATION;
WORKING-MEMORY; UNITED-STATES; IN-VIVO; RECOVERY
AB Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. Hence, the goal of this study was to determine how the two therapeutic approaches interact and influence motor and cognitive recovery. Anesthetized adult male rats received a controlled cortical impact (2.8mmtissue deformation at 4 m/sec) or sham injury and then were provided HAL (0.5 mg/kg; intraperitoneally [IP]) or vehicle (VEH; 1 mL/kg; IP) commencing 24 h after surgery and once daily for 19 days while housed in EE or standard (STD) conditions. Beam balance/walk and Morris water maze performance were assessed on post-injury days 1-5 and 14-19, respectively, followed immediately by quantification of cortical lesion volumes. The data revealed both expected and unexpected findings. It was not surprising that the TBI groups receiving EE performed significantly better than those in STD housing and that the TBI + STD + HAL group performed worse than the TBI + STD + VEH group (p < 0.05). What was surprising was that the therapeutic effects of EE were greatly reduced by concomitant administration of HAL. No differences in cortical lesion volumes were observed among the groups (p > 0.05). The potential clinical implications of these findings suggest that administering HAL to patients undergoing neurorehabilitation may be a double-edged sword because agitation must be controlled before rehabilitation can be safely initiated and executed, but its use may compromise therapeutic efficacy.
C1 [Folweiler, Kaitlin A.; Bondi, Corina O.; Ogunsanya, Elizabeth A.; LaPorte, Megan J.; Leary, Jacob B.; Radabaugh, Hannah L.; Monaco, Christina M.; Kline, Anthony E.] Univ Pittsburgh, Phys Med & Rehabil, Pittsburgh, PA USA.
[Folweiler, Kaitlin A.; Bondi, Corina O.; Ogunsanya, Elizabeth A.; LaPorte, Megan J.; Leary, Jacob B.; Radabaugh, Hannah L.; Monaco, Christina M.; Kline, Anthony E.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA USA.
[Bondi, Corina O.] Univ Pittsburgh, Neurobiol, Pittsburgh, PA USA.
[Kline, Anthony E.] Univ Pittsburgh, Crit Care Med, Pittsburgh, PA USA.
[Kline, Anthony E.] Univ Pittsburgh, Psychol, Pittsburgh, PA USA.
[Kline, Anthony E.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA.
[Kline, Anthony E.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15260 USA.
[Folweiler, Kaitlin A.] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA.
[Folweiler, Kaitlin A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Leary, Jacob B.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Monaco, Christina M.] Philadelphia Coll Osteopath Med, Philadelphia, PA USA.
RP Kline, AE (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Phys Med & Rehabil, 3471 Fifth Ave,Suite 201, Pittsburgh, PA 15213 USA.; Kline, AE (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, 3471 Fifth Ave,Suite 201, Pittsburgh, PA 15213 USA.; Kline, AE (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Psychol, 3471 Fifth Ave,Suite 201, Pittsburgh, PA 15213 USA.
EM klineae@upmc.edu
FU National Institutes of Health [R01NS060005, R01HD069620, HD069620-S1,
R01NS084967]; University of Pittsburgh Physicians / UPMC Academic
Foundation
FX This work was supported, in part, by the National Institutes of Health
grants R01NS060005, R01HD069620, HD069620-S1, R01NS084967 (AEK) and the
University of Pittsburgh Physicians / UPMC Academic Foundation (COB).
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PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JAN 15
PY 2017
VL 34
IS 2
BP 451
EP +
DI 10.1089/neu.2016.4417
PG 9
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA EH4QD
UT WOS:000391754800021
PM 26975872
ER
PT J
AU Chen, G
Shin, YW
Taylor, PA
Glen, DR
Reynolds, RC
Israel, RB
Cox, RW
AF Chen, Gang
Shin, Yong Wook
Taylor, Paul A.
Glen, Daniel R.
Reynolds, Richard C.
Israel, Robert B.
Cox, Robert W.
TI Untangling the relatedness among correlations, Part I: Nonparametric
approaches to inter-subject correlation analysis at the group level (vol
142, pg 248, 2016)
SO NEUROIMAGE
LA English
DT Correction
C1 [Chen, Gang; Taylor, Paul A.; Glen, Daniel R.; Reynolds, Richard C.; Cox, Robert W.] NIMH, Sci & Stat Comp Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Shin, Yong Wook] Univ Ulsan, Coll Med, Dept Psychiat, Asan Med Ctr, 88 Olymp Ro 43 Gil, Seoul 05535, South Korea.
[Israel, Robert B.] Univ British Columbia, Dept Math, Vancouver, BC, Canada.
RP Chen, G (reprint author), NIMH, Sci & Stat Comp Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.; Shin, YW (reprint author), Univ Ulsan, Coll Med, Dept Psychiat, Asan Med Ctr, 88 Olymp Ro 43 Gil, Seoul 05535, South Korea.
EM gangchen@mail.nih.gov; shaman_korea@mac.com
NR 5
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Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2017
VL 145
BP 130
EP 132
DI 10.1016/j.neuroimage.2016.10.021
PN A
PG 3
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA EG7QF
UT WOS:000391243200011
PM 28340982
ER
PT J
AU Steele, VR
Rao, V
Calhoun, VD
Kiehl, KA
AF Steele, Vaughn R.
Rao, Vikram
Calhoun, Vince D.
Kiehl, Kent A.
TI Machine learning of structural magnetic resonance imaging predicts
psychopathic traits in adolescent offenders
SO NEUROIMAGE
LA English
DT Article
DE Prediction; Voxel-based morphometry; SVM; Psychopathy
ID CALLOUS-UNEMOTIONAL TRAITS; BIPOLAR DISORDER; GRAY-MATTER; CONDUCT
PROBLEMS; VIOLENCE; CLASSIFICATION; SCHIZOPHRENIA; CHILDREN; REARREST;
FMRI
AB Classification models are becoming useful tools for finding patterns in neuroimaging data sets that are not observable to the naked eye. Many of these models are applied to discriminating clinical groups such as schizophrenic patients from healthy controls or from patients with bipolar disorder. A more nuanced model might be to discriminate between levels of personality traits. Here, as a proof of concept, we take an initial step toward developing prediction models to differentiate individuals based on a personality disorder: psychopathy. We included three groups of adolescent participants: incarcerated youth with elevated psychopathic traits (i.e., callous and unemotional traits and conduct disordered traits; n = 71), incarcerated youth with low psychopathic traits (n = 72), and non-incarcerated youth as healthy controls (n = 21). Support vector machine (SVM) learning models were developed to separate these groups using an out-of-sample cross-validation method on voxel-based morphometry (VBM) data. Regions of interest from the paralimbic system, identified in an independent forensic sample, were successful in differentiating youth groups. Models seeking to classify incarcerated individuals to have high or low psychopathic traits achieved 69.23% overall accuracy. As expected, accuracy increased in models differentiating healthy controls from individuals with high psychopathic traits (82.61%) and low psychopathic traits (80.65%). Here we have laid the foundation for using neural correlates of personality traits to identify group membership within and beyond psychopathy. This is only the first step, of many, toward prediction models using neural measures as a proxy for personality traits. As these methods are improved, prediction models with neural measures of personality traits could have far-reaching impact on diagnosis, treatment, and prediction of future behavior. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Steele, Vaughn R.] NIDA, Intramural Res Program, Neuroimaging Res Branch, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
[Steele, Vaughn R.; Rao, Vikram; Calhoun, Vince D.; Kiehl, Kent A.] Nonprofit Mind Res Network MRN, Albuquerque, NM USA.
[Steele, Vaughn R.; Rao, Vikram; Calhoun, Vince D.; Kiehl, Kent A.] Lovelace Biomed & Environm Res Inst LBERI, Albuquerque, NM USA.
[Steele, Vaughn R.; Kiehl, Kent A.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
[Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA.
[Calhoun, Vince D.] Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA.
[Calhoun, Vince D.; Kiehl, Kent A.] Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA.
RP Steele, VR (reprint author), NIDA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.; Kiehl, KA (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA.
EM vaughn.r.steele@gmail.com; kkiehl@mrn.org
FU National Institute of Mental Health (NIMH) [1R01MH071896]; National
Institute of Biomedical Imaging and Bioengineering (NIBIB)
[1R01EB006841]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD) [1R01HD082257]
FX This study was funded by the National Institute of Mental Health (NIMH)
grant 1R01MH071896 (K.A.K., PI), the National Institute of Biomedical
Imaging and Bioengineering (NIBIB) grant 1R01EB006841 (V.D.C., PI), and
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) grant 1R01HD082257 (K.A.K., PI). We thank Ebany
Martinez-Finley, J. Michael Maurer, and Prashanth Nyalakanti for their
contributions. We gratefully acknowledge the staff and inmates of the
New Mexico Corrections Department for without their generous
cooperation, this work could not have been completed.
NR 70
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U1 20
U2 20
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 JAN 15
PY 2017
VL 145
SI SI
BP 265
EP 273
DI 10.1016/j.neuroimage.2015.12.013
PN B
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA EG3WU
UT WOS:000390976200012
PM 26690808
ER
PT J
AU Lindquist, MA
Krishnan, A
Lopez-Sola, M
Jepma, M
Woo, CW
Koban, L
Roy, M
Atlas, LY
Schmidt, L
Chang, LJ
Losin, EAR
Eisenbarth, H
Ashar, YK
Delk, E
Wager, TD
AF Lindquist, Martin A.
Krishnan, Anjali
Lopez-Sola, Marina
Jepma, Marieke
Woo, Choong-Wan
Koban, Leonie
Roy, Mathieu
Atlas, Lauren Y.
Schmidt, Liane
Chang, Luke J.
Losin, Elizabeth A. Reynolds
Eisenbarth, Hedwig
Ashar, Yoni K.
Delk, Elizabeth
Wager, Tor D.
TI Group-regularized individual prediction: theory and application to pain
SO NEUROIMAGE
LA English
DT Article
DE Machine leaming; Statistical learning; Pain; MVPA; Empirical Bayes;
Prediction; fMRI; Mega-analysis; Meta-analysis; Shrinkage
ID VENTRAL TEMPORAL CORTEX; HUMAN BRAIN ACTIVITY; PATTERN-ANALYSIS;
FUNCTIONAL CONNECTIVITY; NEURAL REPRESENTATIONS; PHYSICAL PAIN; FMRI;
ACTIVATION; CLASSIFICATION; MEMORY
AB Multivariate pattern analysis (MVPA) has become an important tool for identifying brain representations of psychological processes and clinical outcomes using fMRI and related methods. Such methods can be used to predict or 'decode' psychological states in individual subjects. Single-subject MVPA approaches, however, are limited by the amount and quality of individual-subject data. In spite of higher spatial resolution, predictive accuracy from single-subject data often does not exceed what can be accomplished using coarser, group-level maps, because single-subject patterns are trained on limited amounts of often-noisy data. Here, we present a method that combines population-level priors, in the form of biomarker patterns developed on prior samples, with single-subject MVPA maps to improve single-subject prediction. Theoretical results and simulations motivate a weighting based on the relative variances of biomarker-based prediction based on population-level predictive maps from prior groups and individual-subject, cross-validated prediction. Empirical results predicting pain using brain activity on a trial-by-trial basis (single-trial prediction) across 6 studies (N = 180 participants) confirm the theoretical predictions. Regularization based on a population-level biomarker in this case, the Neurologic Pain Signature (NPS) improved single-subject prediction accuracy compared with idiographic maps based on the individuals' data alone. The regularization scheme that we propose, which we term group-regularized individual prediction (GRIP), can be applied broadly to within-person MVPA-based prediction. We also show how GRIP can be used to evaluate data quality and provide benchmarks for the appropriateness of population-level maps like the NPS for a given individual or study. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Lindquist, Martin A.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Krishnan, Anjali; Lopez-Sola, Marina; Jepma, Marieke; Woo, Choong-Wan; Koban, Leonie; Chang, Luke J.; Losin, Elizabeth A. Reynolds; Eisenbarth, Hedwig; Ashar, Yoni K.; Delk, Elizabeth; Wager, Tor D.] Univ Colorado Boulder, 345 UCB, Boulder, CO 80309 USA.
[Roy, Mathieu] Concordia Univ, Chicago, IL USA.
[Atlas, Lauren Y.] NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA.
[Losin, Elizabeth A. Reynolds] Univ Miami, Coral Gables, FL 33124 USA.
[Krishnan, Anjali] CUNY Brooklyn Coll, Brooklyn, NY 11210 USA.
[Schmidt, Liane] INSEAD, Fontainebleau, France.
[Schmidt, Liane] Ecole Normale Super, Cognit Neurosci Lab, Dept Cognit Sci, INSERM,U960, Paris, France.
RP Wager, TD (reprint author), Univ Colorado Boulder, Dept Psychol & Neurosci, 345 UCB, Boulder, CO 80309 USA.
EM tor.wager@colorado.edu
OI KOBAN, LEONIE/0000-0002-3121-6491
FU NIH [R01DA035484, 2R01MH076136, R01DA027794, R01 EB016061, P41 E8015909]
FX Author note: We are grateful for the funding support of NIH, which
supported this work under grants R01DA035484 (TDW), 2R01MH076136 (TDW),
R01DA027794 (TDW), R01 EB016061 (MAL) and P41 E8015909 (MAL).
NR 66
TC 2
Z9 2
U1 5
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2017
VL 145
SI SI
BP 274
EP 287
DI 10.1016/j.neuroimage.2015.10.074
PN B
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA EG3WU
UT WOS:000390976200013
PM 26592808
ER
PT J
AU Thompson, PM
Andreassen, OA
Arias-Vasquez, A
Bearden, CE
Boedhoe, PS
Brouwer, RM
Buckner, RL
Buitelaar, JK
Bulayeva, KB
Cannon, DM
Cohen, RA
Conrod, PJ
Dale, AM
Deary, IJ
Dennis, EL
de Reus, MA
Desrivieres, S
Dima, D
Donohoe, G
Fisher, SE
Fouche, JP
Francks, C
Frangou, S
Franke, B
Ganjgahi, H
Garavan, H
Glahn, DC
Grabe, HJ
Guadalupe, T
Gutman, BA
Hashimoto, R
Hibar, DP
Holland, D
Hoogman, M
Pol, HEH
Hosten, N
Jahanshad, N
Kelly, S
Kochunov, P
Kremen, WS
Lee, PH
Mackey, S
Martin, NG
Mazoyer, B
McDonald, C
Medland, SE
Morey, RA
Nichols, TE
Paus, T
Pausova, Z
Schmaal, L
Schumann, G
Shen, L
Sisodiya, SM
Smit, DJA
Smoller, JW
Stein, DJ
Stein, JL
Toro, R
Turner, JA
van den Heuvel, MP
van den Heuvel, OL
van Erp, TGM
van Rooij, D
Veltman, DJ
Walter, H
Wang, YL
Wardlaw, JM
Whelan, CD
Wright, MJ
Ye, JP
AF Thompson, Paul M.
Andreassen, Ole A.
Arias-Vasquez, Alejandro
Bearden, Carrie E.
Boedhoe, Premika S.
Brouwer, Rachel M.
Buckner, Randy L.
Buitelaar, Jan K.
Bulayeva, Kazima B.
Cannon, Dara M.
Cohen, Ronald A.
Conrod, Patricia J.
Dale, Anders M.
Deary, Ian J.
Dennis, Emily L.
de Reus, Marcel A.
Desrivieres, Sylvane
Dima, Danai
Donohoe, Gary
Fisher, Simon E.
Fouche, Jean-Paul
Francks, Clyde
Frangou, Sophia
Franke, Barbara
Ganjgahi, Habib
Garavan, Hugh
Glahn, David C.
Grabe, Hans J.
Guadalupe, Tulio
Gutman, Boris A.
Hashimoto, Ryota
Hibar, Derrek P.
Holland, Dominic
Hoogman, Martine
Pol, Hilleke E. Hulshoff
Hosten, Norbert
Jahanshad, Neda
Kelly, Sinead
Kochunov, Peter
Kremen, William S.
Lee, Phil H.
Mackey, Scott
Martin, Nicholas G.
Mazoyer, Bernard
McDonald, Colm
Medland, Sarah E.
Morey, Rajendra A.
Nichols, Thomas E.
Paus, Tomas
Pausova, Zdenka
Schmaal, Lianne
Schumann, Gunter
Shen, Li
Sisodiya, Sanjay M.
Smit, Dirk J. A.
Smoller, Jordan W.
Stein, Dan J.
Stein, Jason L.
Toro, Roberto
Turner, Jessica A.
van den Heuvel, Martijn P.
van den Heuvel, Odile L.
van Erp, Theo G. M.
van Rooij, Daan
Veltman, Dick J.
Walter, Henrik
Wang, Yalin
Wardlaw, Joanna M.
Whelan, Christopher D.
Wright, Margaret J.
Ye, Jieping
CA ENIGMA Consortium
TI ENIGMA and the individual: Predicting factors that affect the brain in
35 countries worldwide
SO NEUROIMAGE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; 22Q11.2 DELETION SYNDROME; CORTICAL
SURFACE-AREA; ALZHEIMERS-DISEASE; WHITE-MATTER; CHRONIC-SCHIZOPHRENIA;
HERITABILITY ANALYSIS; GENETIC ASSOCIATIONS; SUSCEPTIBILITY LOCI;
CANDIDATE GENES
AB In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others(1), ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Thompson, Paul M.; Dennis, Emily L.; Gutman, Boris A.; Hibar, Derrek P.; Jahanshad, Neda; Kelly, Sinead; Stein, Jason L.; Whelan, Christopher D.] Univ Southern Calif, Keck Sch Med, Mark & Mary Stevens Inst Neuroimaging & Informat, Imaging Genet Ctr, Marina Del Rey, CA 90292 USA.
[Andreassen, Ole A.] Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, N-0315 Oslo, Norway.
[Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, N-0315 Oslo, Norway.
[Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Ctr Cognit Neurosci, NL-6525 Nijmegen, Netherlands.
[Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Donders Ctr Cognit Neurosci, NL-6525 Nijmegen, Netherlands.
[Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Ctr Cognit Neurosci, NL-6525 Nijmegen, Netherlands.
[Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA.
[Boedhoe, Premika S.; van den Heuvel, Odile L.; Veltman, Dick J.] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands.
[Brouwer, Rachel M.; de Reus, Marcel A.; Pol, Hilleke E. Hulshoff; van den Heuvel, Martijn P.] UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, NL-3584 CX Utrecht, Netherlands.
[Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Buitelaar, Jan K.; Fisher, Simon E.; Francks, Clyde; Franke, Barbara; Hoogman, Martine; van Rooij, Daan] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands.
[Buitelaar, Jan K.] Harvard Univ, Dept Psychol, Ctr Brain Sci, 33 Kirkland St, Cambridge, MA 02138 USA.
[Bulayeva, Kazima B.] Russian Acad Sci, NI Vavilov Inst Gen Genet, Gubkin Str 3, Moscow 119991, Russia.
[Cannon, Dara M.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Cannon, Dara M.; McDonald, Colm] Natl Univ Ireland Galway, Coll Med Nursing & Hlth Sci, NCBES Galway Neurosci Ctr, Neuroimaging & Cognit Genom Ctr NICOG,Clin Neuroi, Galway H91 TK33, Ireland.
[Cohen, Ronald A.] Univ Florida, Inst Aging, Gainesville, FL 32611 USA.
[Conrod, Patricia J.] Univ London, Kings Coll London, Sect Addict, Dept Psychol Med & Psychiat, London, England.
[Dale, Anders M.; Holland, Dominic] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Dale, Anders M.; Holland, Dominic] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Dale, Anders M.; Holland, Dominic; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Dale, Anders M.; Holland, Dominic] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA.
[Thompson, Paul M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA.
[Thompson, Paul M.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA.
[Thompson, Paul M.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.
[Thompson, Paul M.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92093 USA.
[Deary, Ian J.; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Desrivieres, Sylvane; Schumann, Gunter] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London SE5 8AF, England.
[Dima, Danai] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England.
[Dima, Danai; Frangou, Sophia] Icahn Sch Med Mt Sinai, Dept Psychiat, Clin Neurosci Studies CNS Ctr, New York, NY 10029 USA.
[Donohoe, Gary] Natl Univ Ireland, Sch Psychol, Neuroimaging & Cognit Genom Ctr NICOG, Galway, Ireland.
[Fisher, Simon E.; Francks, Clyde; Guadalupe, Tulio] Max Planck Inst Psycholinguist, Language & Genet Dept, NL-6525 XD Nijmegen, Netherlands.
[Fouche, Jean-Paul; Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa.
[Franke, Barbara; Hoogman, Martine] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 Nijmegen, Netherlands.
[Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 Nijmegen, Netherlands.
[Ganjgahi, Habib] Univ Warwick, Dept Stat, Coventry, W Midlands, England.
[Garavan, Hugh; Mackey, Scott] Univ Vermont, Dept Psychiat, Burlington, VT 05401 USA.
[Glahn, David C.] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA.
[Glahn, David C.] Olin Neuropsychiat Res Ctr, Hartford, CT 06114 USA.
[Grabe, Hans J.] Univ Med Greifswald, Dept Psychiat, D-17489 Greifswald, Germany.
[Grabe, Hans J.] HELIOS Hosp, Dept Psychiat & Psychotherapy, D-18435 Stralsund, Germany.
[Guadalupe, Tulio] Int Max Planck Res Sch Language Sci, NL-6525 XD Nijmegen, Netherlands.
[Hashimoto, Ryota] Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Suita, Osaka, Japan.
[Hosten, Norbert] Univ Med Greifswald, Dept Radiol, D-17475 Greifswald, Germany.
[Kochunov, Peter] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Lee, Phil H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Lee, Phil H.] Harvard Med Sch, Dept Psychiat, Boston, MA USA.
[Lee, Phil H.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Mazoyer, Bernard] Univ Bordeaux, CEA, CNRS, UMR5296,Grp Imagerie Neurofonct, Bordeaux, France.
[Martin, Nicholas G.; Medland, Sarah E.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
[Morey, Rajendra A.] Duke Univ, Duke Inst Brain Sci, Durham, NC 27710 USA.
[Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England.
[Nichols, Thomas E.] Univ Warwick, WMG, Coventry CV4 7AL, W Midlands, England.
[Nichols, Thomas E.] Univ Oxford, FMRIB Ctr, Oxford OX3 9DU, England.
[Paus, Tomas] Baycrest, Rotman Res Inst, Toronto, ON, Canada.
[Paus, Tomas] Univ Toronto, Dept Psychol, Toronto, ON, Canada.
[Paus, Tomas] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Paus, Tomas] Child Mind Inst, New York, NY USA.
[Pausova, Zdenka] Univ Toronto, Hosp Sick Children, Toronto, ON, Canada.
[Pausova, Zdenka] Univ Toronto, Dept Physiol, Toronto, ON, Canada.
[Pausova, Zdenka] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada.
[Shen, Li] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, 355 W 16th St,Suite 4100, Indianapolis, IN 46202 USA.
[Shen, Li] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, 355 W 16th St,Suite 4100, Indianapolis, IN 46202 USA.
[Sisodiya, Sanjay M.] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England.
[Sisodiya, Sanjay M.] Epilepsy Soc, Gerrards Cross, Bucks, England.
[Smit, Dirk J. A.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Stein, Dan J.] MRC Res Unit Anxiety & Stress Disorders, Stellenbosch, South Africa.
[Stein, Jason L.] UCLA Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90095 USA.
[Toro, Roberto] Inst Pasteur, F-75015 Paris, France.
[Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA.
[Turner, Jessica A.] Georgia State Univ, Dept Neurosci, Atlanta, GA 30302 USA.
[Boedhoe, Premika S.; Schmaal, Lianne; van den Heuvel, Odile L.; Veltman, Dick J.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Boedhoe, Premika S.; Schmaal, Lianne; Smit, Dirk J. A.; van den Heuvel, Odile L.; Veltman, Dick J.] VU VUMC, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
[van Erp, Theo G. M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA.
[Walter, Henrik] Charite, CCM, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany.
[Wang, Yalin] Arizona State Univ, Sch Comp Informat & Decis Syst Engn, Tempe, AZ 85281 USA.
[Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh EH4 2XU, Midlothian, Scotland.
[Wardlaw, Joanna M.] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH4 2XU, Midlothian, Scotland.
[Wright, Margaret J.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
[Ye, Jieping] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Ye, Jieping] Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA.
RP Thompson, PM (reprint author), Univ Southern Calif, Keck Sch Med, Mark & Mary Stevens Inst Neuroimaging & Informat, Imaging Genet Ctr, Marina Del Rey, CA 90292 USA.; Thompson, PM (reprint author), Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA.; Thompson, PM (reprint author), Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA.; Thompson, PM (reprint author), Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.; Thompson, PM (reprint author), Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92093 USA.
RI McDonald, Colm/C-1430-2009; Franke, Barbara/D-4836-2009;
OI Franke, Barbara/0000-0003-4375-6572; Donohoe, Gary/0000-0003-3037-7426;
Wright, Margaret/0000-0001-7133-4970; Shen, Li/0000-0002-5443-0503;
Medland, Sarah/0000-0003-1382-380X
FU NIH Institutes [U54 EB 020403]; NIBIB
FX This work was supported in part by a Consortium grant (U54 EB 020403)
from the NIH Institutes contributing to the Big Data to Knowledge (BD2K)
Initiative, including the NIBIB. Funding for individual consortium
authors is listed in Hibar et al., Nature, 2015 and in other papers
cited here. This paper was collaboratively written on Google Docs by all
authors, over a period of several weeks. We thank Josh Faskowitz for
making Fig. 3, the ENIGMA "roadmap".
NR 123
TC 2
Z9 3
U1 8
U2 8
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 JAN 15
PY 2017
VL 145
SI SI
BP 389
EP 408
DI 10.1016/j.neuroimage.2015.11.057
PN B
PG 20
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA EG3WU
UT WOS:000390976200022
PM 26658930
ER
PT J
AU McCormack, VA
Menya, D
Munishi, MO
Dzamalala, C
Gasmelseed, N
Roux, ML
Assefa, M
Osano, O
Watts, M
Mwasamwaja, AO
Mmbaga, BT
Murphy, G
Abnet, CC
Dawsey, SM
Schuz, J
AF McCormack, V. A.
Menya, D.
Munishi, M. O.
Dzamalala, C.
Gasmelseed, N.
Roux, M. Leon
Assefa, M.
Osano, O.
Watts, M.
Mwasamwaja, A. O.
Mmbaga, B. T.
Murphy, G.
Abnet, C. C.
Dawsey, S. M.
Schuz, J.
TI Informing etiologic research priorities for squamous cell esophageal
cancer in Africa: A review of setting-specific exposures to known and
putative risk factors
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Review
DE Africa; esophageal cancer; risk factors
ID AROMATIC-HYDROCARBON EXPOSURE; SOUTH-AFRICA; WESTERN KENYA;
HUMAN-PAPILLOMAVIRUS; GASTRIC CANCERS; BOMET DISTRICT; HIV-INFECTION;
ORAL HYGIENE; YOUNG-PEOPLE; ADDIS-ABABA
AB Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC-affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies.
C1 [McCormack, V. A.; Roux, M. Leon; Schuz, J.] Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
[Menya, D.] Moi Univ, Sch Publ Hlth, Eldoret, Kenya.
[Munishi, M. O.; Mwasamwaja, A. O.; Mmbaga, B. T.] Kilimanjaro Clin Res Inst, Moshi, Tanzania.
[Dzamalala, C.] Univ Malawi, Coll Med, Blantyre, Malawi.
[Dzamalala, C.] Malawi Canc Registry, Blantyre, Malawi.
[Gasmelseed, N.] Univ Gezira, Natl Canc Inst, Wad Madani, Sudan.
[Gasmelseed, N.] Univ Hafr Al Batin, Fac Sci, Hafar al Batin, Saudi Arabia.
[Assefa, M.] Univ Addis Ababa, Radiotherapy Ctr, Addis Ababa, Ethiopia.
[Osano, O.] Univ Eldoret, Sch Environm Studies, Eldoret, Kenya.
[Watts, M.] British Geol Survey, Ctr Environm Geochem, Inorgan Chem, Nottingham, England.
[Mwasamwaja, A. O.; Mmbaga, B. T.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
[Murphy, G.; Abnet, C. C.; Dawsey, S. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP McCormack, VA (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM mccormackv@iarc.fr
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
FU IARC
FX Grant sponsor: IARC
NR 106
TC 0
Z9 0
U1 8
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JAN 15
PY 2017
VL 140
IS 2
BP 259
EP 271
DI 10.1002/ijc.30292
PG 13
WC Oncology
SC Oncology
GA EG0EI
UT WOS:000390703600001
PM 27466161
ER
PT J
AU Elliott, EG
Trinh, P
Ma, XM
Leaderer, BP
Ward, MH
Deziel, NC
AF Elliott, Elise G.
Trinh, Pauline
Ma, Xiaomei
Leaderer, Brian P.
Ward, Mary H.
Deziel, Nicole C.
TI Unconventional oil and gas development and risk of childhood leukemia:
Assessing the evidence
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Air pollution; Carcinogens; Hydraulic fracturing; Shale; Wastewater;
Water contamination
ID BARNETT SHALE REGION; ACUTE LYMPHOBLASTIC-LEUKEMIA; HYDRAULIC FRACTURING
FLUIDS; AIR-POLLUTANT EMISSIONS; SENTINEL HEALTH EVENTS; DRINKING-WATER
WELLS; TAKE-HOME EXPOSURE; NATURAL-GAS; MARCELLUS SHALE; METHANE
EMISSIONS
AB The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into the relationship between UO&G development and risk of cancer in general and childhood leukemia in particular. (C) 2016 The Authors. Published by Elsevier B.V.
C1 [Elliott, Elise G.; Trinh, Pauline; Ma, Xiaomei; Leaderer, Brian P.; Deziel, Nicole C.] Yale Univ, Yale Sch Publ Hlth, 60 Coll St, New Haven, CT 06520 USA.
[Ward, Mary H.] NCI, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
RP Deziel, NC (reprint author), Yale Sch Publ Hlth, 60 Coll St, New Haven, CT 06520 USA.
EM nicole.deziel@yale.edu
NR 125
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U1 27
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
EI 1879-1026
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD JAN 15
PY 2017
VL 576
BP 138
EP 147
DI 10.1016/j.scitotenv.2016.10.072
PG 10
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA EG3SJ
UT WOS:000390964700013
PM 27783932
ER
PT J
AU Mendola, P
Sundaram, R
Louis, GMB
Sun, LP
Wallace, ME
Smarr, MM
Sherman, S
Zhu, YY
Ying, Q
Liu, DP
AF Mendola, Pauline
Sundaram, Rajeshwari
Louis, Germaine M. Buck
Sun, Liping
Wallace, Maeve E.
Smarr, Melissa M.
Sherman, Seth
Zhu, Yeyi
Ying, Qi
Liu, Danping
TI Proximity to major roadways and prospectively-measured time-to-pregnancy
and infertility
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Infertility; Time-to-pregnancy; Major roadways; Traffic
ID AIR-POLLUTION; RESIDENTIAL PROXIMITY; PROSPECTIVE COHORT; SEMEN QUALITY;
TRAFFIC NOISE; HUMAN SPERM; EXPOSURE; FERTILITY; IMPACT; MORTALITY
AB We aimed to study the potential impact of proximity to major roadways on time-to-pregnancy and infertility in couples attempting pregnancy in the Longitudinal Investigation of Fertility and Environment (LIFE) study (20052009), a population-based, prospective cohort study. Couples attempting pregnancy (n = 500) were enrolled and followed prospectively until pregnancy or 12 months of trying and 393 couples (78%) had complete data and full follow-up. Time-to-pregnancy was based on a standard protocol using fertility monitors, tracking estrone-3-glucuonide and luteinizing hormone, and pregnancy test kits to detect human chorionic gonadotropin (hCG). The fecundability odds ratio (FOR) and 95% confidence interval (CI) were estimated using proportional odds models. Infertility was defined as 12 months of trying to conceive without an hCG pregnancy and the relative risk (RR) and 95% CI were estimated with log-binomial regression. Final models were adjusted for age, parity, study site, and salivary alpha-amylase, a stress marker. Infertile couples (53/393; 14%) tended to live closer to major roadways on average than fertile couples (689 m vs. 843 m, respectively) but the difference was not statistically significant. The likelihood of pregnancy was increased 3% for every 200 m further away the couples residence was from a major roadway (FOR = 1.03; CI = 1.01-1.06). Infertility also appeared elevated at moderate distances compared to 1000 m or greater, but estimates lacked precision. Our findings suggest that proximity to major roadways may be related to reductions in fecundity. Prospective data from larger populations is warranted to corroborate these findings. Published by Elsevier B.V.
C1 [Mendola, Pauline; Sundaram, Rajeshwari; Louis, Germaine M. Buck; Wallace, Maeve E.; Smarr, Melissa M.; Zhu, Yeyi; Liu, Danping] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6710B Rockledge Dr,Room 3119,MSC 7004, Bethesda, MD 20892 USA.
[Sun, Liping] Glotech Inc, 1801 Res Blvd 605, Rockville, MD 20850 USA.
[Sherman, Seth] Emmes Corp, 401 N Washington St 700, Rockville, MD 20850 USA.
[Ying, Qi] Texas A&M Univ, 401 Joe Routt Blvd, College Stn, TX 77843 USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6710B Rockledge Dr,Room 3119,MSC 7004, Bethesda, MD 20892 USA.
EM pauline.mendola@nih.gov
OI Sherman, Seth/0000-0003-3667-9898; Mendola, Pauline/0000-0001-5330-2844;
Sundaram, Rajeshwari/0000-0002-6918-5002
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institutes of Child Health and Human Development (LIFE study)
[N01-HD-3-3355, N01-HD-#-3356, N01-HD-3-3358]; Air Quality and
Reproductive Health Study [HHSN275200800002I, HHSN27500008]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institutes of Child Health and Human
Development (LIFE study contract nos. #N01-HD-3-3355, N01-HD-#-3356,
N0I-HD-3-3358 and the Air Quality and Reproductive Health Study Contract
No. HHSN275200800002I, Task Order No. HHSN27500008). All manuscripts
undergo institute clearance but the funding source is not responsible
for study design; collection, analysis and interpretation of data;
writing of the report, or the decision to submit the manuscript.
NR 36
TC 0
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U1 2
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
EI 1879-1026
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD JAN 15
PY 2017
VL 576
BP 172
EP 177
DI 10.1016/j.scitotenv.2016.10.038
PG 6
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA EG3SJ
UT WOS:000390964700016
PM 27783935
ER
PT J
AU Taylor, SF
Bhati, MT
Dubin, MJ
Hawkins, JM
Lisanby, SH
Morales, O
Reti, IM
Sampson, S
Short, EB
Spino, C
Watcharotone, K
Wright, J
AF Taylor, Stephan F.
Bhati, Mahendra T.
Dubin, Marc J.
Hawkins, John M.
Lisanby, Sarah H.
Morales, Oscar
Reti, Irving M.
Sampson, Shirlene
Short, E. Baron
Spino, Catherine
Watcharotone, Kuanwong
Wright, Jesse
TI A naturalistic, multi-site study of repetitive transcranial magnetic
stimulation therapy for depression
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Dorsolateral prefrontal cortex; Neuromodulation; Registry; Brain
ID TREATING MAJOR DEPRESSION; TREATMENT-RESISTANT DEPRESSION; RANDOMIZED
CONTROLLED-TRIAL; BRAIN-STIMULATION; METAANALYSIS; DISORDER; EFFICACY;
RISK; RTMS; SAFETY
AB Background: Repetitive transcranial magnetic stimulation (rTMS) was approved in 2008 in the United States, and there are relatively few studies describing its use in regular clinical practice since approval. Methods: From April 2011 to October 2014, ten sites within the National Network of Depression Centers (NNDC) provided data on 62 evaluable patients with a depressive episode. Treatment was determined naturalistically. Response was assessed by the Quick Inventory of Depressive Symptoms, Self-Report (QIDSSR) as the primary outcome, and the Patient Health Questionnaire-9 (PHQ-9) and the clinician-rated Clinical Global Impression (CGI) as secondary depression measures.
Results: Enrolled patients exhibited significant treatment resistance, with 70.2% reporting more than 4 prior depressive episodes. Most patients received treatment with standard parameters (10 Hz over the left dorsolateral prefrontal cortex), although 22.6% of the patients received 1 or 5 Hz stimulation at some point. Over 6 weeks of treatment, response and remission rates were 29.4% and 5.9%, respectively, for the QIDS-SR; 39.2% and 15.7%, respectively, for the PHQ-9; and 50.9% and 17.9%, respectively, for the CGI. Moderator analyses revealed no effect of prior depressive episodes, history of ECT or gender, although early life stress predicted a better response to rTMS therapy.
Limitations: The study was an open-label, registry trial, with relatively coarse clinical data, reflecting practice only in academic, depression-specialty centers. Because of the relatively small size and heterogeneity of the sample, type 2 errors are possible and positive findings are in need of replication.
Conclusion: rTMS demonstrates effectiveness in clinical practice within the NNDC, although remission rates appear slightly lower in comparison with other recent naturalistic studies.
C1 [Taylor, Stephan F.; Spino, Catherine; Watcharotone, Kuanwong] Univ Michigan, Ann Arbor, MI 48109 USA.
[Bhati, Mahendra T.] Univ Penn, Philadelphia, PA 19104 USA.
[Dubin, Marc J.] Weill Cornell Med Coll, New York, NY USA.
[Hawkins, John M.] Univ Cincinnati, Linder Ctr, Cincinnati, OH USA.
[Lisanby, Sarah H.] Duke Univ, Durham, NC USA.
[Lisanby, Sarah H.] NIMH, Bethesda, MD 20892 USA.
[Morales, Oscar] Harvard Univ, McLean Hosp, Cambridge, MA 02138 USA.
[Reti, Irving M.] Johns Hopkins Univ, Baltimore, MD USA.
[Sampson, Shirlene] Mayo Clin, Rochester, MN USA.
[Short, E. Baron] Med Univ South Carolina, Charleston, SC 29425 USA.
[Wright, Jesse] Univ Louisville, Louisville, KY 40292 USA.
RP Taylor, SF (reprint author), Dept Psychiat, Rachel Upjohn Bldg,4250 Plymouth Rd, Ann Arbor, MI 48109 USA.
EM sftaylor@umich.edu
FU National Network of Depression Centers; University of Michigan
Department of Psychiatry; Michigan Institute for Clinical and Health
Research [UL1TR000433]
FX This research was supported by The National Network of Depression
Centers, The University of Michigan Department of Psychiatry and The
Michigan Institute for Clinical and Health Research (UL1TR000433).
NR 36
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U1 12
U2 12
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 JAN 15
PY 2017
VL 208
BP 284
EP 290
DI 10.1016/j.jad.2016.08.049
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA EG0OR
UT WOS:000390732600042
PM 27794252
ER
PT J
AU Bernert, RA
Luckenbaugh, DA
Duncan, WC
Iwata, NG
Ballard, ED
Zarate, CA
AF Bernert, Rebecca A.
Luckenbaugh, David A.
Duncan, Wallace C.
Iwata, Naomi G.
Ballard, Elizabeth D.
Zarate, Carlos A.
TI Sleep architecture parameters as a putative biomarker of suicidal
ideation in treatment-resistant depression
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Sleep architecture; Suicide risk; Depression; Bipolar disorder;
Treatment-resistance
ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; BIPOLAR
DISORDER; METABOLIC SYNDROME; MENTAL-DISORDERS; INSOMNIA; RISK;
HOPELESSNESS; METAANALYSIS; DISTURBANCE
AB Background: Disturbed sleep may confer risk for suicidal behaviors. Polysomnographic (PSG) sleep parameters have not been systematically evaluated in association with suicidal ideation (SI) among individuals with treatment-resistant depression (TRD).
Methods: This secondary data analysis included 54 TRD individuals (N=30 with major depressive disorder (MDD) and N=24 with bipolar depression (BD)). PSG sleep parameters included Sleep Efficiency (SE), Total Sleep Time (TST), Wakefulness After Sleep Onset (WASO), REM percent/latency, and non-REM (NREM) Sleep Stages 1-4. The Hamilton Depression Rating Scale (HAM-D) was used to group participants according to presence or absence of SI. Sleep abnormalities were hypothesized among those with current SI. ANOVA analyses were conducted before (Model 1) and after adjusting for depression (Model 2) and diagnostic variables (Model 3).
Results: Significant differences in PSG parameters were observed in Model 1; those with SI had less NREM Stage 4 sleep (p <.05). After adjusting for central covariates, Models 2 and 3 revealed significantly less NREM Stage 4 sleep, lower SE (P <.05), and higher WASO (P <.05) among those with SI. BD participants with SI also had less NREM Stage 4 and more NREM Stage 1 sleep.
Limitations: 1) a predominantly white sample; 2) exclusion of imminent suicide risk; 3) concomitant mood stabilizer use among BD patients; and 4) single-item SI assessment.
Conclusions: Independent of depression severity, SI was associated with less NREM Stage 4 sleep, and higher nocturnal wakefulness across diagnostic groups. Sleep may warrant further investigation in the pathogenesis of suicide risk, particularly in TRD, where risk may be heightened.
C1 [Bernert, Rebecca A.; Iwata, Naomi G.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Suicide Prevent Res Lab, Stanford, CA 94305 USA.
[Luckenbaugh, David A.; Duncan, Wallace C.; Ballard, Elizabeth D.; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Bernert, RA (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Suicide Prevent Res Lab, Stanford, CA 94305 USA.
EM rbernert@stanford.edu
NR 72
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Z9 0
U1 10
U2 10
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 JAN 15
PY 2017
VL 208
BP 309
EP 315
DI 10.1016/j.jad.2016.08.050
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA EG0OR
UT WOS:000390732600045
PM 27810712
ER
PT J
AU Pennybaker, SJ
Niciu, MJ
Luckenbaugh, DA
Zarate, CA
AF Pennybaker, Steven J.
Niciu, Mark J.
Luckenbaugh, David A.
Zarate, Carlos A., Jr.
TI Symptomatology and predictors of antidepressant efficacy in extended
responders to a single ketamine infusion
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Major depressive disorder; Bipolar depression; Treatment-resistant
depression; Ketamine; NMDA receptor antagonist; Antidepressant;
Glutamatergic modulator
ID MAJOR DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; TREATMENT-RESISTANT
DEPRESSION; STAR-ASTERISK-D; ADD-ON TRIAL; BIPOLAR DEPRESSION; ALCOHOL
DEPENDENCE; FAMILY-HISTORY; DOUBLE-BLIND; RECEPTOR ANTAGONISTS
AB Background: Antidepressant response to a single subanesthetic dose infusion of the glutamatergic modulator ketamine is transient in most depressed patients; however, a minority continue to experience an extended response. This study examined depressive symptoms and potential clinical predictors of extended response to ketamine in subjects with mood disorders.
Methods: Subjects were diagnosed with either major depressive disorder (MDD) or bipolar depression. All subjects were treatment-resistant and experiencing a major depressive episode of at least moderate severity. MDD subjects were unmedicated and those with bipolar depression were receiving therapeutic-dose lithium or valproate. All subjects received a single 0.5 mg/kg ketamine infusion. Data were collected pre-infusion (baseline) and at days one, 14, and 28 post-infusion.
Results: Twelve of 93 (12.9%) participants continued to meet response criteria (50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score) at two weeks. All depressive symptoms assessed by the MADRS were improved at two weeks in ketamine responders except for sleep duration/depth. A positive family history of alcohol use disorder in a first-degree relative (FHP) and greater dissociation during the infusion were associated with better antidepressant response at two weeks. Improved measures of apparent sadness, reported sadness, inability to feel, and difficulty concentrating at day 1 correlated most strongly with antidepressant effects at two weeks.
Limitations: Post-hoc design, small sample size, diagnostic heterogeneity.
Conclusions: Static (FHP) and dynamic (improved depressive symptoms) factors may be clinically useful in predicting whether a patient will have an extended response to ketamine.
C1 [Pennybaker, Steven J.; Niciu, Mark J.; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Bldg 10 CRC,10 Ctr Dr, Bethesda, MD 20892 USA.
[Pennybaker, Steven J.] Johns Hopkins Univ, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA.
RP Zarate, CA (reprint author), NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Bldg 10 CRC,10 Ctr Dr, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU Intramural Research Program at the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH) [00088699, 04-M-0222];
Brain and Behavior Research Foundation (NARSAD); Brain & Behavior Mood
Disorders Research Award; NIH
FX This work was supported by the Intramural Research Program at the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH; NCT#00088699, protocol 04-M-0222, substudies 2-4), by a
Brain and Behavior Research Foundation (NARSAD) Independent Investigator
to Dr. Zarate, and by a Brain & Behavior Mood Disorders Research Award
to Dr. Zarate. The 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 by generous
contributions to the Foundation for the NIH from the Doris Duke
Charitable Foundation, The American Association for Dental Research, The
Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as
well as other private donors.These funding sources had no further role
in study design; in the collection, analysis, or interpretation of data;
in the writing of the report; or in the decision to submit the paper for
publication.
NR 60
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Z9 0
U1 31
U2 31
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 JAN 15
PY 2017
VL 208
BP 560
EP 566
DI 10.1016/j.jad.2016.10.026
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA EG0OR
UT WOS:000390732600080
PM 27839782
ER
PT J
AU Grabowski, JM
Gulia-Nuss, M
Kuhn, RJ
Hill, CA
AF Grabowski, Jeffrey M.
Gulia-Nuss, Monika
Kuhn, Richard J.
Hill, Catherine A.
TI RNAi reveals proteins for metabolism and protein processing associated
with Langat virus infection in Ixodes scapularis (black-legged tick)
ISE6 cells
SO PARASITES & VECTORS
LA English
DT Article
DE Ixodes scapularis; Tick-borne disease; Flavivirus; Langat; ISE6; RNAi;
Functional studies; Metabolism; Protein-processing
ID HEPATITIS-C-VIRUS; DENGUE VIRUS; FLAVIVIRUS INFECTION; BORNE FLAVIVIRUS;
LYME-DISEASE; FUMARYLACETOACETATE HYDROLASE; CRYSTAL-STRUCTURE;
OXIDATIVE STRESS; WEST-NILE; INHIBITION
AB Background: Tick-borne flaviviruses (TBFs) cause thousands of human cases of encephalitis worldwide each year, with some TBF infections progressing to hemorrhagic fever. TBFs are of medical and veterinary importance and strategies to reduce flavivirus transmission by the tick vector may have significant application. Analyses of the proteome of ISE6 cells derived from the black legged tick, Ixodes scapularis infected with the TBF, Langat virus (LGTV), have provided insights into proteins and cellular processes involved with LGTV infection.
Methods: RNA interference (RNAi)-induced knockdown of transcripts was used to investigate the role of ten tick proteins in the LGTV infection cycle in ISE6 cells. LGTV-infected cells were separately transfected with dsRNA corresponding to each gene of interest and the effect on LGTV genome replication and release of infectious virus was assessed by RT-qPCR and plaque assays, respectively.
Results: RNAi-induced knockdown of transcripts for two enzymes that likely function in amino acid, carbohydrate, lipid, terpenoid/polykeytide and vitamin metabolism, and a transcript for one protein of unknown function were associated with decreased replication of the LGTV genome and release of infectious virus from cells. The knockdown of transcripts for five enzymes predicted to function in metabolism, a protein likely associated with folding, sorting and degradation, and a protein of unknown function was associated with a decrease only in the amount of infectious LGTV released from cells.
Conclusions: These data suggest tick proteins potentially associated with metabolism and protein processing may be involved in LGTV infection of ISE6 cells. Our study provides information to begin to elucidate the function of these proteins and identify targets for the development of new interventions aimed at controlling the transmission of TBFs.
C1 [Grabowski, Jeffrey M.; Gulia-Nuss, Monika; Hill, Catherine A.] Purdue Univ, Coll Agr, Dept Entomol, 901 W State St, W Lafayette, IN 47907 USA.
[Grabowski, Jeffrey M.; Kuhn, Richard J.] Purdue Univ, Markey Ctr Struct Biol, Dept Biol Sci, Coll Sci, 915 W State St, W Lafayette, IN 47907 USA.
[Kuhn, Richard J.; Hill, Catherine A.] Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.
[Grabowski, Jeffrey M.] NIAID, NIH, Rocky Mt Labs, Lab Virol,Biol Vector Borne Viruses Sect, 903 S 4th St, Hamilton, MT 59840 USA.
[Gulia-Nuss, Monika] Univ Nevada, Dept Biochem & Mol Biol, Coll Agr Biotechnol & Nat Resources, 1664 N Virginia St, Reno, NV 89503 USA.
RP Hill, CA (reprint author), Purdue Univ, Coll Agr, Dept Entomol, 901 W State St, W Lafayette, IN 47907 USA.; Hill, CA (reprint author), Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.
EM hillca@purdue.edu
FU NSF Graduate Research Fellowship [DGE-1333468]; Indiana Clinical and
Translational Science Institute Pre-doctoral Training Program
[NIH/NCATS-ICTSI TL1 TR000162]; Entomological Society of America,
Monsanto Research Grant
FX JMG was supported by an NSF Graduate Research Fellowship (Program
DGE-1333468) and the Indiana Clinical and Translational Science
Institute Pre-doctoral Training Program (NIH/NCATS-ICTSI TL1 TR000162).
Research funds provided by the Entomological Society of America,
Monsanto Research Grant Award to JMG are gratefully acknowledged. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 63
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U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD JAN 13
PY 2017
VL 10
AR 24
DI 10.1186/s13071-016-1944-0
PG 14
WC Parasitology
SC Parasitology
GA EN9MR
UT WOS:000396324800001
PM 28086865
ER
PT J
AU Esser, L
Zhou, F
Pluchino, KM
Shiloach, J
Ma, JC
Tang, W
Gutierrez, C
Zhang, A
Shukla, S
Madigan, JP
Zhou, TQ
Kwong, PD
Ambudkar, SV
Gottesman, MM
Xia, D
AF Esser, Lothar
Zhou, Fei
Pluchino, Kristen M.
Shiloach, Joseph
Ma, Jichun
Tang, Wai-kwan
Gutierrez, Camilo
Zhang, Alex
Shukla, Suneet
Madigan, James P.
Zhou, Tongqing
Kwong, Peter D.
Ambudkar, Suresh V.
Gottesman, Michael M.
Xia, Di
TI Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric
ATP Binding and the Mechanism of Polyspecificity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ABC TRANSPORTER; DRUG-BINDING; CRYSTAL-STRUCTURE; CATALYTIC CYCLE;
NUCLEOTIDE; RESISTANCE; SITES; FLEXIBILITY; HYDROLYSIS; STATE
AB P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancer; it plays important roles in determining the pharmacokinetics of many drugs. Understanding the structural basis of P-gp, substrate polyspecificity has been hampered by its intrinsic flexibility, which is facilitated by a 75-residue linker that connects the two halves of P-gp. Here we constructed a mutant murine P-gp with a shortened linker to facilitate structural determination. Despite dramatic reduction in rhodamine 123 and calcein-AM transport, the linker-shortened mutant P-gp possesses basal ATPase activity and binds ATP only in its N-terminal nucleotide-binding domain. Nine independently determined structures of wild type, the linker mutant, and a methylated P-gp at up to 3.3 angstrom resolution display significant movements of individual transmembrane domain helices, which correlated with the opening and closing motion of the two halves of P-gp. The open-and-close motion alters the surface topology of P-gp within the drug-binding pocket, providing a mechanistic explanation for the polyspecificity of P-gp in substrate interactions.
C1 [Esser, Lothar; Zhou, Fei; Pluchino, Kristen M.; Ma, Jichun; Tang, Wai-kwan; Gutierrez, Camilo; Zhang, Alex; Shukla, Suneet; Madigan, James P.; Ambudkar, Suresh V.; Gottesman, Michael M.; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 2122C,37 Convent Dr, Bethesda, MD 20892 USA.
[Shiloach, Joseph] NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA.
[Zhou, Tongqing; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Xia, D (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2122C,37 Convent Dr, Bethesda, MD 20892 USA.
EM xiad@mail.nih.gov
FU Intramural Research Program of the NCI, Center for Cancer Research,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the NCI,
Center for Cancer Research, National Institutes of Health. The authors
declare that they have no conflicts of interest with the contents of
this article. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Institutes of Health.
NR 61
TC 0
Z9 0
U1 7
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 13
PY 2017
VL 292
IS 2
BP 446
EP +
DI 10.1074/jbc.M116.755884
PG 28
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EI2KN
UT WOS:000392316100004
PM 27864369
ER
PT J
AU Beg, I
Minton, AP
Islam, A
Hassan, MI
Ahmad, F
AF Beg, Ilyas
Minton, Allen P.
Islam, Asimul
Hassan, Md. Imtaiyaz
Ahmad, Faizan
TI The pH Dependence of Saccharides' Influence on Thermal Denaturation of
Two Model Proteins Supports an Excluded Volume Model for Stabilization
Generalized to Allow for Intramolecular Electrostatic Interactions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GUANIDINE-HYDROCHLORIDE; TREHALOSE SYNTHESIS; ORGANIC OSMOLYTES;
CHARGE-DENSITY; IN-VITRO; STABILITY; THERMOTOLERANCE; POLYELECTROLYTE;
ACQUISITION; EQUILIBRIA
AB The reversible thermal denaturation of apo alpha-lactalbumin (alpha-LA) and lysozyme was measured in the absence and presence of multiple concentrations of each of seven saccharides (glucose, galactose, fructose, sucrose, trehalose, raffinose, and stachyose) at multiple pH values. It was observed that with increasing pH, the absolute stability of alpha-LA decreased, whereas the stabilizing effect per mole of all saccharides increased, and that the absolute stability of lysozyme increased, whereas the stabilizing effect per mole of all saccharides decreased. All of the data may be accounted for quantitatively by straightforward electrostatic generalization of a previously introduced coarse-grained model for stabilization of proteins by sugars.
C1 [Beg, Ilyas; Islam, Asimul; Hassan, Md. Imtaiyaz; Ahmad, Faizan] Jamia Millia Islamia, Ctr Interdisciplinary Res Basic Sci, New Delhi 110025, India.
[Minton, Allen P.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Ahmad, F (reprint author), Jamia Millia Islamia, Ctr Interdisciplinary Res Basic Sci, New Delhi 110025, India.; Minton, AP (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov; fahmad@jmi.ac.in
OI Minton, Allen/0000-0001-8459-1247
FU Council of Scientific and Industrial Research, India [37(1603)/13/EMRII,
37(1604)/13/EMRII)]; National Institutes of Health Intramural Research
Program of the NIDDK
FX This work was supported by Council of Scientific and Industrial
Research, India, Research Grants 37(1603)/13/EMRII and
37(1604)/13/EMRII) (to F. A. and A. I.) and the National Institutes of
Health Intramural Research Program of the NIDDK (to A. P. M). The
authors declare that they have no conflicts of interest with the
contents of this article. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 35
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 13
PY 2017
VL 292
IS 2
BP 505
EP +
DI 10.1074/jbc.M116.757302
PG 27
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EI2KN
UT WOS:000392316100008
PM 27909048
ER
PT J
AU Bullock, A
Burrows, NR
Narva, AS
Sheff, K
Hora, I
Lekiachvili, A
Cain, H
Espey, D
AF Bullock, Ann
Burrows, Nilka Rios
Narva, Andrew S.
Sheff, Karen
Hora, Israel
Lekiachvili, Akaki
Cain, Hannah
Espey, David
TI Vital Signs: Decrease in Incidence of Diabetes-Related End-Stage Renal
Disease among American Indians/Alaska Natives - United States, 1996-2013
SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
LA English
DT Article
ID KIDNEY-DISEASE; NEPHROPATHY; MELLITUS; OUTCOMES; CARE
AB Background: American Indians and Alaska Natives (AI/AN) have the highest diabetes prevalence among any racial/ethnic group in the United States. Among AI/AN, diabetes accounts for 69% of new cases of end-stage renal disease (ESRD), defined as kidney failure treated with dialysis or transplantation. During 1982-1996, diabetes-related ESRD (ESRD-D) in AI/AN increased substantially and disproportionately compared with other racial/ethnic groups.
Methods: Data from the U.S. Renal Data System, the Indian Health Service (IHS), the National Health Interview Survey, and the U.S. Census were used to calculate ESRD-D incidence rates by race/ethnicity among U.S. adults aged =18 years during 1996-2013 and in the diabetic population during 2006-2013. Rates were age-adjusted based on the 2000 U.S. standard population. IHS clinical data from the Diabetes Cares and Outcomes Audit were analyzed for diabetes management measures in AI/AN.
Results: Among AI/AN adults, age-adjusted ESRD-D rates per 100,000 population decreased 54%, from 57.3 in 1996 to 26.5 in 2013. Although rates for adults in other racial/ethnic groups also decreased during this period, AI/AN had the steepest decline. Among AI/AN with diabetes, ESRD-D incidence decreased during 2006-2013 and, by 2013, was the same as that for whites. Measures related to the assessment and treatment of ESRD-D risk factors also showed more improvement during this period in AI/AN than in the general population.
Conclusion and Implications for Public Health Practice: Despite well-documented health and socioeconomic disparities among AI/AN, ESRD-D incidence rates among this population have decreased substantially since 1996. This decline followed implementation by the IHS of public health and population management approaches to diabetes accompanied by improvements in clinical care beginning in the mid-1980s. These approaches might be a useful model for diabetes management in other health care systems, especially those serving populations at high risk.
C1 [Bullock, Ann; Sheff, Karen] Indian Hlth Serv, Div Diabet Treatment & Prevent, Rockville, MD USA.
[Burrows, Nilka Rios; Hora, Israel] CDC, Div Diabet Translat, Atlanta, GA 30333 USA.
[Narva, Andrew S.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Lekiachvili, Akaki; Espey, David] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Cain, Hannah] CDC, Off State Tribal Local & Terr Support, Atlanta, GA 30333 USA.
RP Burrows, NR (reprint author), CDC, Div Diabet Translat, Atlanta, GA 30333 USA.
EM NRios@cdc.gov
NR 19
TC 0
Z9 0
U1 3
U2 3
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 0149-2195
EI 1545-861X
J9 MMWR-MORBID MORTAL W
JI MMWR-Morb. Mortal. Wkly. Rep.
PD JAN 13
PY 2017
VL 66
IS 1
BP 26
EP 32
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EI2YO
UT WOS:000392356300006
PM 28081061
ER
PT J
AU Chung, YW
Ahmad, F
Tang, Y
Hockman, SC
Kee, HJ
Berger, K
Guirguis, E
Choi, YH
Schimel, DM
Aponte, AM
Park, S
Degerman, E
Manganiello, VC
AF Chung, Youn Wook
Ahmad, Faiyaz
Tang, Yan
Hockman, Steven C.
Kee, Hyun Jung
Berger, Karin
Guirguis, Emilia
Choi, Young Hun
Schimel, Dan M.
Aponte, Angel M.
Park, Sunhee
Degerman, Eva
Manganiello, Vincent C.
TI White to beige conversion in PDE3B KO adipose tissue through activation
of AMPK signaling and mitochondrial function
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DEPENDENT PROTEIN-KINASE; FATTY-ACID OXIDATION; BROWN ADIPOCYTE
DIFFERENTIATION; ENERGY HOMEOSTASIS; TRANSCRIPTIONAL CONTROL; ADAPTIVE
THERMOGENESIS; INSULIN-RESISTANCE; 3T3-L1 ADIPOCYTES; METABOLIC-CONTROL;
TUMOR-SUPPRESSOR
AB Understanding mechanisms by which a population of beige adipocytes is increased in white adipose tissue (WAT) reflects a potential strategy in the fight against obesity and diabetes. Cyclic adenosine monophosphate (cAMP) is very important in the development of the beige phenotype and activation of its thermogenic program. To study effects of cyclic nucleotides on energy homeostatic mechanisms, mice were generated by targeted inactivation of cyclic nucleotide phosphodiesterase 3b (Pde3b) gene, which encodes PDE3B, an enzyme that catalyzes hydrolysis of cAMP and cGMP and is highly expressed in tissues that regulate energy homeostasis, including adipose tissue, liver, and pancreas. In epididymal white adipose tissue (eWAT) of PDE3B KO mice on a SvJ129 background, cAMP/protein kinase A (PKA) and AMP-activated protein kinase (AMPK) signaling pathways are activated, resulting in "browning" phenotype, with a smaller increases in body weight under high-fat diet, smaller fat deposits, increased beta-oxidation of fatty acids (FAO) and oxygen consumption. Results reported here suggest that PDE3B and/or its downstream signaling partners might be important regulators of energy metabolism in adipose tissue, and potential therapeutic targets for treating obesity, diabetes and their associated metabolic disorders.
C1 [Chung, Youn Wook; Ahmad, Faiyaz; Tang, Yan; Hockman, Steven C.; Guirguis, Emilia; Choi, Young Hun; Park, Sunhee; Manganiello, Vincent C.] NHLBI, CPB, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Chung, Youn Wook] Yonsei Univ, Coll Med, Severance Integrat Res Inst Cerebral & Cardiovasc, Seoul 03722, South Korea.
[Kee, Hyun Jung] Yonsei Univ, Dept Surg, Coll Med, Seoul 03722, South Korea.
[Berger, Karin; Degerman, Eva] Lund Univ, Dept Expt Med Sci, Ctr Diabet, S-22184 Lund, Sweden.
[Schimel, Dan M.] NIH, NIH MRI Res Facil, Bldg 10, Bethesda, MD 20892 USA.
[Aponte, Angel M.] NHLBI, Prote Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Chung, YW (reprint author), NHLBI, CPB, NIH, Bldg 10, Bethesda, MD 20892 USA.; Chung, YW (reprint author), Yonsei Univ, Coll Med, Severance Integrat Res Inst Cerebral & Cardiovasc, Seoul 03722, South Korea.
EM chungyw@yuhs.ac
FU Intramural Research Programs (NIH/NHLBI); Intramural Research Programs
(NIDDK); Basic Science Research Program through the National Research
Foundation of Korea (NRF); Ministry of Education
[NRF-2015R1D1A1A01057981]; Swedish Diabetes Society; Albert Pahlsson
Foundation [DIA 2014-031, DIA 2014-2832]
FX We thank Dr. Bruce M. Spiegelman for providing PGC-1 alpha adenovirus,
which was used to infect H4IIE hepatoma cells to produce PGC-1 alpha
protein. We also acknowledge the NIDDK Mouse Metabolism Core for
indirect calorimetry data. This work was supported in part by the
Intramural Research Programs (NIH/NHLBI and NIDDK). Y.W.C. was supported
by the Basic Science Research Program through the National Research
Foundation of Korea (NRF), funded by the Ministry of Education
(NRF-2015R1D1A1A01057981). K.B. and E.D. were supported by the Swedish
Diabetes Society and the Albert Pahlsson Foundation, DIA 2014-031 and
DIA 2014-2832, respectively. Dr. Manganiello died prior to completion of
the manuscript. Joel Moss, a long-time colleague, assisted with review
of the data and completion of the manuscript.
NR 102
TC 0
Z9 0
U1 6
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 13
PY 2017
VL 7
AR 40445
DI 10.1038/srep40445
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EI0NZ
UT WOS:000392172500001
PM 28084425
ER
PT J
AU Ghitza, UE
AF Ghitza, Udi E.
TI Commentary: Addictions Neuroclinical Assessment: A Neuroscience-Based
Framework for Addictive Disorders
SO FRONTIERS IN PSYCHIATRY
LA English
DT Editorial Material
DE addiction; addictive disorders; addiction treatment; drug abuse; drug
abuse treatment; personalized medicine; precision medicine; substance
abuse
ID RDOC
C1 [Ghitza, Udi E.] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
RP Ghitza, UE (reprint author), NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
EM ghitzau@nida.nih.gov
FU Center for the Clinical Trials Network, NIDA
FX UG is a Health Scientist Administrator, Program Official, at the Center
for the Clinical Trials Network, NIDA, which is the funding agency for
the National Drug Abuse Treatment Clinical Trials Network. This
commentary was supported through UG's duties as a Health Scientist
Administrator.
NR 10
TC 0
Z9 0
U1 6
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-0640
J9 FRONT PSYCHIATRY
JI Front. Psychiatry
PD JAN 13
PY 2017
VL 8
AR 2
DI 10.3389/fpsyt.2017.00002
PG 3
WC Psychiatry
SC Psychiatry
GA EH5JO
UT WOS:000391809400001
PM 28133452
ER
PT J
AU Barrett, AJ
AF Barrett, Austin John
TI Transplant biomarkers ready for the clinic?
SO BLOOD
LA English
DT Editorial Material
ID VERSUS-HOST-DISEASE; T-CELLS; GVHD; ST2
C1 [Barrett, Austin John] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
U1 3
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 JAN 12
PY 2017
VL 129
IS 2
BP 137
EP 139
DI 10.1182/blood-2016-11-751842
PG 5
WC Hematology
SC Hematology
GA EO2LO
UT WOS:000396528200004
PM 28082289
ER
PT J
AU Iwamura, C
Bouladoux, N
Belkaid, Y
Sher, A
Jankovic, D
AF Iwamura, Chiaki
Bouladoux, Nicolas
Belkaid, Yasmine
Sher, Alan
Jankovic, Dragana
TI Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates
murine hematopoiesis
SO BLOOD
LA English
DT Article
ID GUT MICROBIOTA; STEM-CELLS; BACTERIAL-INFECTION; IMMUNE-SYSTEM;
PEPTIDOGLYCAN; DISEASE
AB The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characterized. We observed that stimulation with NOD1 or NOD2 ligand had no effect on the survival/ proliferation of hematopoietic precursors. Nonetheless, NOD1, but not NOD2, ligand induced expression of multiple hematopoietic cytokines (interleukin-7 [IL-7], Flt3L, stem cell factor [SCF], ThPO, and IL-6) from bone marrow mesenchymal stromal cells (MSCs) in vitro. Moreover, in vivo administration of NOD1 ligand to germ-free mice restored the numbers of hematopoietic stem cells and precursors in bone marrow as well as serum concentrations of IL-7, Flt3L, SCF, and ThPO to the levels displayed by specific pathogen-free control animals. Based on these findings, we propose that NOD1 signaling in MSCs serves as an important pathway underlying the requirement for microbiota in the maintenance of steady-state hematopoiesis. This function is distinct from that triggered by lipopolysaccharide in both its broad effects on multiple progenitors and specific targeting of MSCs as cytokine producing intermediates.
C1 [Iwamura, Chiaki; Sher, Alan; Jankovic, Dragana] NIAID, Immunobiol Sect, Parasit Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bouladoux, Nicolas; Belkaid, Yasmine] NIAID, Microbiome Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bouladoux, Nicolas; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Jankovic, D (reprint author), BG33 RM 1W10A3,33 North Dr, Bethesda, MD 20814 USA.
EM djankovic@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Uehara Memorial
Foundation
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and by a fellowship from the Uehara Memorial
Foundation (C.I.).
NR 22
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JAN 12
PY 2017
VL 129
IS 2
BP 171
EP 176
DI 10.1182/blood-2016-06-723742
PG 6
WC Hematology
SC Hematology
GA EO2LO
UT WOS:000396528200013
PM 27799160
ER
PT J
AU Kim, J
Bowlby, R
Mungall, AJ
Robertson, AG
Odze, RD
Cherniack, AD
Shih, J
Pedamallu, CS
Cibulskis, C
Dunford, A
Meier, SR
Kim, J
Raphael, BJ
Wu, HT
Wong, AM
Willis, JE
Bass, AJ
Derks, S
Garman, K
McCall, SJ
Wiznerowicz, M
Pantazi, A
Parfenov, M
Thorsson, V
Shmulevich, I
Dhankani, V
Miller, M
Sakai, R
Wang, K
Schultz, N
Shen, R
Arora, A
Weinhold, N
Sanchez-Vega, F
Kelsen, DP
Zhang, J
Felau, I
Demchok, J
Rabkin, CS
Camargo, MC
Zenklusen, JC
Bowen, J
Leraas, K
Lichtenberg, TM
Curtis, C
Seoane, JA
Ojesina, AI
Beer, DG
Gulley, ML
Pennathur, A
Luketich, JD
Zhou, ZR
Weisenberger, DJ
Akbani, R
Lee, JS
Liu, W
Mills, GB
Zhang, W
Reid, BJ
Hinoue, T
Laird, PW
Shen, H
Piazuelo, MB
Schneider, BG
McLellan, M
Taylor-Weiner, A
Cibulskis, C
Lawrence, M
Cibulskis, K
Stewart, C
Getz, G
Lander, E
Gabriel, SB
Ding, L
McLellan, MD
Miller, CA
Appelbaum, EL
Cordes, MG
Fronick, CC
Fulton, LA
Mardis, ER
Wilson, RK
Schmidt, HK
Fulton, RS
Ally, A
Balasundaram, M
Bowlby, R
Carlsen, R
Chuah, E
Dhalla, N
Holt, RA
Jones, SJM
Kasaian, K
Brooks, D
Li, HI
Ma, Y
Marra, MA
Mayo, M
Moore, RA
Mungall, AJ
Mungall, KL
Robertson, AG
Schein, JE
Sipahimalani, P
Tam, A
Thiessen, N
Wong, T
Cherniack, AD
Shih, J
Pedamallu, CS
Beroukhim, R
Bullman, S
Cibulskis, C
Murray, BA
Saksena, G
Schumacher, SE
Gabriel, S
Meyerson, M
Hadjipanayis, A
Kucherlapati, R
Pantazi, A
Parfenov, M
Ren, X
Park, PJ
Lee, S
Kucherlapati, M
Yang, LX
Baylin, SB
Hoadley, KA
Weisenberger, DJ
Bootwalla, MS
Lai, PH
Van den Berg, DJ
Berrios, M
Holbrook, A
Akbani, R
Hwang, JE
Jang, HJ
Liu, WB
Weinstein, JN
Lee, JS
Lu, YL
Sohn, BH
Mills, G
Seth, S
Protopopov, A
Bristow, CA
Mahadeshwar, HS
Tang, JB
Song, XZ
Zhang, JH
Laird, PW
Hinoue, T
Shen, H
Cho, J
Defrietas, T
Frazer, S
Gehlenborg, N
Heiman, DI
Lawrence, MS
Lin, P
Meier, SR
Noble, MS
Voet, D
Zhang, HL
Kim, J
Polak, P
Saksena, G
Chin, L
Getz, G
Wong, AM
Raphael, BJ
Wu, HT
Lee, S
Park, PJ
Yang, LX
Thorsson, V
Bernard, B
Iype, L
Miller, M
Reynolds, SM
Shmulevich, I
Dhankani, V
Abeshouse, A
Arora, A
Armenia, J
Kundra, R
Ladanyi, M
Kjong-Van Lehmann
Gao, J
Sander, C
Schultz, N
Sanchez-Vega, F
Shen, RL
Weinhold, N
Chakravarty, D
Zhang, HX
Radenbaugh, A
Hegde, A
Akbani, R
Liu, WB
Weinstein, JN
Chin, L
Bristow, CA
Lu, YL
Penny, R
Crain, D
Gardner, J
Curley, E
Mallery, D
Morris, S
Paulauskis, J
Shelton, T
Shelton, C
Bowen, J
Frick, J
Gastier-Foster, JM
Gerken, M
Leraas, KM
Lichtenberg, TM
Ramirez, NC
Wise, L
Zmuda, E
Tarvin, K
Saller, C
Park, YS
Button, M
Carvalho, AL
Reis, RM
Matsushita, MM
Lucchesi, F
de Oliveira, AT
Le, X
Paklina, O
Setdikova, G
Lee, JH
Bennett, J
Iacocca, M
Huelsenbeck-Dill, L
Potapova, CO
Voronina, O
Liu, O
Fulidou, V
Cates, C
Sharp, A
Behera, M
Force, S
Khuri, F
Owonikoko, T
Pickens, A
Ramalingam, S
Sica, G
Dinjens, W
van Nistelrooij, A
Wijnhoven, B
Sandusky, G
Stepa, S
Crain, D
Paulauskis, J
Penny, R
Gardner, J
Mallery, D
Morris, S
Shelton, T
Shelton, C
Curley, E
Juhl, IH
Zornig, C
Kwon, SY
Kelsen, D
Kim, GHK
Bartlett, J
Parfitt, J
Chetty, R
Darling, G
Knox, J
Wong, R
El-Zimaity, H
Liu, G
Boussioutas, A
Park, DY
Kemp, R
Carlotti, CG
Tirapelli, DPD
Saggioro, FP
Sankarankutty, AK
Noushmehr, H
dos Santos, JS
Trevisan, FA
Eschbacher, J
Eschbacher, J
Dubina, M
Mozgovoy, E
Carey, F
Chalmers, S
Forgie, I
Godwin, A
Reilly, C
Madan, R
Naima, Z
Ferrer-Torres, D
Vinco, M
Dhir, R
Luketich, J
Pennathur, A
Ajani, JA
McCall, SJ
Janjigian, Y
Kelsen, D
Ladanyi, M
Tang, L
Camargo, MC
Ajani, JA
Cheong, JH
Chudamani, S
Liu, J
Lolla, L
Naresh, R
Pihl, T
Sun, Q
Wan, YH
Wu, Y
Demchok, JA
Felau, I
Ferguson, ML
Shaw, KRM
Sheth, M
Tarnuzzer, R
Wang, ZN
Yang, LM
Zenklusen, JC
Hutter, CM
Sofia, HJ
Zhang, JS
AF Kim, Jihun
Bowlby, Reanne
Mungall, Andrew J.
Robertson, A. Gordon
Odze, Robert D.
Cherniack, Andrew D.
Shih, Juliann
Pedamallu, Chandra Sekhar
Cibulskis, Carrie
Dunford, Andrew
Meier, Samuel R.
Kim, Jaegil
Raphael, Benjamin J.
Wu, Hsin-Ta
Wong, Alexandra M.
Willis, Joseph E.
Bass, Adam J.
Derks, Sarah
Garman, Katherine
McCall, Shannon J.
Wiznerowicz, Maciej
Pantazi, Angeliki
Parfenov, Michael
Thorsson, Vesteinn
Shmulevich, Ilya
Dhankani, Varsha
Miller, Michael
Sakai, Ryo
Wang, Kenneth
Schultz, Nikolaus
Shen, Ronglai
Arora, Arshi
Weinhold, Nils
Sanchez-Vega, Francisco
Kelsen, David P.
Zhang, Julia
Felau, Ina
Demchok, John
Rabkin, Charles S.
Camargo, M. Constanza
Zenklusen, Jean Claude
Bowen, Jay
Leraas, Kristen
Lichtenberg, Tara M.
Curtis, Christina
Seoane, Jose A.
Ojesina, Akinyemi I.
Beer, David G.
Gulley, Margaret L.
Pennathur, Arjun
Luketich, James D.
Zhou, Zhongren
Weisenberger, Daniel J.
Akbani, Rehan
Lee, Ju-Seog
Liu, Wenbin
Mills, Gordon B.
Zhang, Wei
Reid, Brian J.
Hinoue, Toshinori
Laird, Peter W.
Shen, Hui
Piazuelo, M. Blanca
Schneider, Barbara G.
McLellan, Michael
Taylor-Weiner, Amaro
Cibulskis, Carrie
Lawrence, Michael
Cibulskis, Kristian
Stewart, Chip
Getz, Gad
Lander, Eric
Gabriel, Stacey B.
Ding, Li
McLellan, Michael D.
Miller, Christopher A.
Appelbaum, Elizabeth L.
Cordes, Matthew G.
Fronick, Catrina C.
Fulton, Lucinda A.
Mardis, Elaine R.
Wilson, Richard K.
Schmidt, Heather K.
Fulton, Robert S.
Ally, Adrian
Balasundaram, Miruna
Bowlby, Reanne
Carlsen, Rebecca
Chuah, Eric
Dhalla, Noreen
Holt, Robert A.
Jones, Steven J. M.
Kasaian, Katayoon
Brooks, Denise
Li, Haiyan I.
Ma, Yussanne
Marra, Marco A.
Mayo, Michael
Moore, Richard A.
Mungall, Andrew J.
Mungall, Karen L.
Robertson, A. Gordon
Schein, Jacqueline E.
Sipahimalani, Payal
Tam, Angela
Thiessen, Nina
Wong, Tina
Cherniack, Andrew D.
Shih, Juliann
Pedamallu, Chandra Sekhar
Beroukhim, Rameen
Bullman, Susan
Cibulskis, Carrie
Murray, Bradley A.
Saksena, Gordon
Schumacher, Steven E.
Gabriel, Stacey
Meyerson, Matthew
Hadjipanayis, Angela
Kucherlapati, Raju
Pantazi, Angeliki
Parfenov, Michael
Ren, Xiaojia
Park, Peter J.
Lee, Semin
Kucherlapati, Melanie
Yang, Lixing
Baylin, Stephen B.
Hoadley, Katherine A.
Weisenberger, Daniel J.
Bootwalla, Moiz S.
Lai, Phillip H.
Van den Berg, David J.
Berrios, Mario
Holbrook, Andrea
Akbani, Rehan
Hwang, Jun-Eul
Jang, Hee-Jin
Liu, Wenbin
Weinstein, John N.
Lee, Ju-Seog
Lu, Yiling
Sohn, Bo Hwa
Mills, Gordon
Seth, Sahil
Protopopov, Alexei
Bristow, Christopher A.
Mahadeshwar, Harshad S.
Tang, Jiabin
Song, Xingzhi
Zhang, Jianhua
Laird, Peter W.
Hinoue, Toshinori
Shen, Hui
Cho, Juok
Defrietas, Timothy
Frazer, Scott
Gehlenborg, Nils
Heiman, David I.
Lawrence, Michael S.
Lin, Pei
Meier, Samuel R.
Noble, Michael S.
Doug Voet
Zhang, Hailei
Kim, Jaegil
Polak, Paz
Saksena, Gordon
Chin, Lynda
Getz, Gad
Wong, Alexandra M.
Raphael, Benjamin J.
Wu, Hsin-Ta
Lee, Semin
Park, Peter J.
Yang, Lixing
Thorsson, Vesteinn
Bernard, Brady
Iype, Lisa
Miller, Michael
Reynolds, Sheila M.
Shmulevich, Ilya
Dhankani, Varsha
Abeshouse, Adam
Arora, Arshi
Armenia, Joshua
Kundra, Ritika
Ladanyi, Marc
Kjong-Van Lehmann
Gao, Jianjiong
Sander, Chris
Schultz, Nikolaus
Sanchez-Vega, Francisco
Shen, Ronglai
Weinhold, Nils
Chakravarty, Debyani
Zhang, Hongxin
Radenbaugh, Amie
Hegde, Apruva
Akbani, Rehan
Liu, Wenbin
Weinstein, John N.
Chin, Lynda
Bristow, Christopher A.
Lu, Yiling
Penny, Robert
Crain, Daniel
Gardner, Johanna
Curley, Erin
Mallery, David
Morris, Scott
Paulauskis, Joseph
Shelton, Troy
Shelton, Candace
Bowen, Jay
Frick, Jessica
Gastier-Foster, Julie M.
Gerken, Mark
Leraas, Kristen M.
Lichtenberg, Tara M.
Ramirez, Nilsa C.
Wise, Lisa
Zmuda, Erik
Tarvin, Katherine
Saller, Charles
Park, Young Soo
Button, Michael
Carvalho, Andre L.
Reis, Rui Manuel
Matsushita, Marcus Medeiros
Lucchesi, Fabiano
de Oliveira, Antonio Talvane
Le, Xuan
Paklina, Oxana
Setdikova, Galiya
Lee, Jae-Hyuck
Bennett, Joseph
Iacocca, Mary
Huelsenbeck-Dill, Lori
Potapova, Cureline Olga
Voronina, Olga
Liu, Ouida
Fulidou, Victoria
Cates, Crystal
Sharp, Alexis
Behera, Madhusmitara
Force, Seth
Khuri, Fadio
Owonikoko, Taofeek
Pickens, Allan
Ramalingam, Suresh
Sica, Gabriel
Dinjens, Winand
van Nistelrooij, Anna
Wijnhoven, Bas
Sandusky, George
Stepa, Serghei
Crain, Daniel
Paulauskis, Joseph
Penny, Robert
Gardner, Johanna
Mallery, David
Morris, Scott
Shelton, Troy
Shelton, Candace
Curley, Erin
Juhl, Invidumed Hartmut
Zornig, Carsten
Kwon, Sun Young
Kelsen, David
Kim, Goyang Hark Kyun
Bartlett, John
Parfitt, Jeremy
Chetty, Runjan
Darling, Gail
Knox, Jennifer
Wong, Rebecca
El-Zimaity, Haila
Liu, Geoffrey
Boussioutas, Alex
Park, Do Young
Kemp, Rafael
Carlotti, Carlos Gilberto, Jr.
da Cunha Tirapelli, Daniela Pretti
Saggioro, Fabiano Pinto
Sankarankutty, Ajith Kumar
Noushmehr, Houtan
dos Santos, Jose Sebastiao
Trevisan, Felipe Amstalden
Eschbacher, Jennifer
Eschbacher, Jennifer
Dubina, Michael
Mozgovoy, Eugene
Carey, Frank
Chalmers, Sally
Forgie, Ian
Godwin, Andrew
Reilly, Colleen
Madan, Rashna
Naima, Zaid
Ferrer-Torres, Daysha
Rathmell, W. Kimryn
Dhir, Rajiv
Luketich, James
Pennathur, Arjun
Ajani, Jaffer A.
McCall, Shannon J.
Janjigian, Yelena
Kelsen, David
Ladanyi, Marc
Tang, Laura
Camargo, M. Constanza
Ajani, Jaffer A.
Cheong, Jae-Ho
Chudamani, Sudha
Liu, Jai
Lolla, Laxmi
Naresh, Rashi
Pihl, Todd
Sun, Qiang
Wan, Yunhu
Wu, Ye
Demchok, John A.
Felau, Ina
Ferguson, Martin L.
Shaw, Kenna R. Mills
sheth, Margi
Tarnuzzer, Roy
Wang, Zhining
Yang, Liming
Zenklusen, Jean Claude
Hutter, Carolyn M.
Sofia, Heidi J.
Zhang, Jiashan
CA Canc Genome Atlas Res Network
TI Integrated genomic characterization of oesophageal carcinoma
SO NATURE
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; HUMAN CANCER; ESOPHAGOGASTRIC JUNCTION;
STRUCTURAL VARIATIONS; LINEAGE-SURVIVAL; SEQUENCING DATA;
ADENOCARCINOMA; GENES; LUNG; IDENTIFICATION
AB Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.
C1 [Kim, Jihun; Park, Young Soo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 05505, South Korea.
[Ally, Adrian; Balasundaram, Miruna; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert A.; Jones, Steven J. M.; Kasaian, Katayoon; Brooks, Denise; Li, Haiyan I.; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Karen L.; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
[Odze, Robert D.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Odze, Robert D.; Meyerson, Matthew] Harvard Med Sch, Dept Pathol, Boston, MA 02215 USA.
[Cherniack, Andrew D.; Pedamallu, Chandra Sekhar; Dunford, Andrew; Taylor-Weiner, Amaro; Lawrence, Michael; Cibulskis, Kristian; Stewart, Chip; Lander, Eric; Gabriel, Stacey B.; Cherniack, Andrew D.; Pedamallu, Chandra Sekhar; Beroukhim, Rameen; Bullman, Susan; Murray, Bradley A.; Schumacher, Steven E.; Gabriel, Stacey; Cho, Juok; Defrietas, Timothy; Frazer, Scott; Gehlenborg, Nils; Heiman, David I.; Lawrence, Michael S.; Lin, Pei; Noble, Michael S.; Doug Voet; Zhang, Hailei; Polak, Paz] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
[Pedamallu, Chandra Sekhar; Bass, Adam J.; Derks, Sarah; Cherniack, Andrew D.; Beroukhim, Rameen; Bullman, Susan; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Raphael, Benjamin J.; Wu, Hsin-Ta; Wong, Alexandra M.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
[Raphael, Benjamin J.; Wu, Hsin-Ta; Wong, Alexandra M.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA.
[Willis, Joseph E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
[Willis, Joseph E.] Case Med Ctr, Dept Pathol, Cleveland, OH 44106 USA.
[Bass, Adam J.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Derks, Sarah] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands.
[Garman, Katherine; Cates, Crystal; Sharp, Alexis] Duke Univ, Dept Pathol, Durham, NC 27710 USA.
[Wiznerowicz, Maciej] Int Inst Mol Oncol, PL-60203 Poznan, Poland.
[Wiznerowicz, Maciej] Greater Poland Canc Ctr, PL-61866 Poznan, Poland.
[Wiznerowicz, Maciej] Poznan Univ Med Sci, PL-61866 Poznan, Poland.
[Hadjipanayis, Angela; Kucherlapati, Raju; Ren, Xiaojia; Kucherlapati, Melanie] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
[Ren, Xiaojia; Protopopov, Alexei] KEW Grp Inc, Cambridge, MA 02139 USA.
[Thorsson, Vesteinn; Bernard, Brady; Iype, Lisa; Reynolds, Sheila M.] Inst Syst Biol, Seattle, WA 98109 USA.
[Sakai, Ryo] Katholieke Univ Leuven, Dept Elect Engn ESAT STADIUS, Leuven, Belgium.
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[Wang, Kenneth] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA.
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[Kelsen, David P.; Janjigian, Yelena] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Zhang, Julia; Demchok, John; Demchok, John A.; Ferguson, Martin L.; Shaw, Kenna R. Mills; sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zhang, Jiashan] NCI, Bethesda, MD 20892 USA.
[Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Leraas, Kristen; Frick, Jessica; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
[Curtis, Christina; Seoane, Jose A.] Stanford Univ, Sch Med, Div Oncol, Dept Med, Stanford, CA 94305 USA.
[Curtis, Christina; Seoane, Jose A.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Ojesina, Akinyemi I.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA.
[Ojesina, Akinyemi I.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Beer, David G.; Ferrer-Torres, Daysha] Univ Michigan, Ctr Comprehens Canc, Dept Thorac Surg, Ann Arbor, MI 48109 USA.
[Gulley, Margaret L.] Univ North Carolina Chapel Hill, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Luketich, James D.; Luketich, James] Univ Pittsburgh, Med Ctr, Sch Med, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA.
[Zhou, Zhongren] Univ Rochester, Dept Pathol & Lab Med, Rochester, NY 14642 USA.
[Weisenberger, Daniel J.] Univ Southern Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
[Liu, Wenbin; Weinstein, John N.; Hegde, Apruva] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Lee, Ju-Seog; Mills, Gordon B.; Mills, Gordon] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Reid, Brian J.] Fred Hutchinson Canc Res Ctr, North Seattle, WA 98109 USA.
[Hinoue, Toshinori] Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA.
[Piazuelo, M. Blanca; Schneider, Barbara G.] Vanderbilt Univ, Med Ctr, Div Gastroenterol, Dept Med, Nashville, TN 37232 USA.
[McLellan, Michael; Ding, Li; McLellan, Michael D.; Miller, Christopher A.; Appelbaum, Elizabeth L.; Cordes, Matthew G.; Fronick, Catrina C.; Fulton, Lucinda A.; Mardis, Elaine R.; Wilson, Richard K.; Schmidt, Heather K.; Fulton, Robert S.] Washington Univ, McDonnell Genome Inst, St Louis, MO 63108 USA.
[Taylor-Weiner, Amaro; Lee, Semin; Gehlenborg, Nils] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA.
[Polak, Paz] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
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[Beroukhim, Rameen] Harvard Med Sch, Dept Med, Boston, MA 02215 USA.
[Schumacher, Steven E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Hadjipanayis, Angela; Kucherlapati, Raju; Kucherlapati, Melanie] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.
[Baylin, Stephen B.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Biol Div, Baltimore, MD 21231 USA.
[Hoadley, Katherine A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA.
[Bootwalla, Moiz S.; Lai, Phillip H.; Berrios, Mario; Holbrook, Andrea] USC, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Van den Berg, David J.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hwang, Jun-Eul; Jang, Hee-Jin; Lee, Ju-Seog; Sohn, Bo Hwa] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Inst Personalized Canc Treatment, Houston, TX 77030 USA.
[Hwang, Jun-Eul] Chonnam Natl Univ, Sch Med, Dept Hematooncol, Kwangju, South Korea.
[Seth, Sahil; Protopopov, Alexei; Mahadeshwar, Harshad S.; Tang, Jiabin; Song, Xingzhi; Zhang, Jianhua] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77054 USA.
[Weinstein, John N.; Le, Xuan; Tang, Laura] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Radenbaugh, Amie] Univ Calif Santa Cruz, Genom Inst, Santa Cruz, CA 95064 USA.
[Gardner, Johanna; Morris, Scott; Paulauskis, Joseph; Shelton, Troy] Int Genom Consortium, Phoenix, AZ 85004 USA.
[Tarvin, Katherine; Saller, Charles] Analyt Biol Serv Inc, Wilmington, DE 19801 USA.
[Button, Michael] Asterand Biosci, Detroit, MI 48202 USA.
[Carvalho, Andre L.; Reis, Rui Manuel] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil.
[Reis, Rui Manuel] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal.
[Matsushita, Marcus Medeiros] Barretos Canc Hosp, Dept Pathol, Sao Paulo, Brazil.
[Lucchesi, Fabiano] Barretos Canc Hosp, Dept Radiol, Sao Paulo, Brazil.
[de Oliveira, Antonio Talvane] Barretos Canc Hosp, Dept Surg, Sao Paulo, Brazil.
[Le, Xuan] BioreclamationIVT, Dept Res Pathol, Chestertown, MD 21620 USA.
[Paklina, Oxana; Setdikova, Galiya] Botkin Municipal Clin, Moscow 125284, Russia.
[Lee, Jae-Hyuck] Chonnam Natl Univ, Sch Med, Dept Pathol, Hwasun, South Korea.
[Bennett, Joseph; Iacocca, Mary; Huelsenbeck-Dill, Lori] Christiana Care Hlth Syst, Helen F Graham Canc Ctr & Res Inst, Newark, DE 19713 USA.
[Potapova, Cureline Olga; Voronina, Olga; Liu, Ouida; Fulidou, Victoria] Cureline Inc, San Francisco, CA 94080 USA.
[Behera, Madhusmitara; Force, Seth; Khuri, Fadio; Owonikoko, Taofeek; Pickens, Allan; Ramalingam, Suresh; Sica, Gabriel] Emory Univ, Atlanta, GA 30322 USA.
[Behera, Madhusmitara; Force, Seth; Khuri, Fadio; Owonikoko, Taofeek; Pickens, Allan; Ramalingam, Suresh; Sica, Gabriel] Winship Canc Inst, Atlanta, GA 30322 USA.
[Dinjens, Winand] Univ Med Ctr, Erasmus MC Canc Inst, Dept Pathol, NL-3000 CA Rotterdam, Netherlands.
[van Nistelrooij, Anna; Wijnhoven, Bas] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Surg, NL-3000 CA Rotterdam, Netherlands.
[van Nistelrooij, Anna] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Pathol, NL-3000 CA Rotterdam, Netherlands.
[Sandusky, George] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA.
[Stepa, Serghei] Inst Oncol Moldova, Kishinev, Moldova.
[Juhl, Invidumed Hartmut] Indivumed GmbH, D-20251 Hamburg, Germany.
[Zornig, Carsten] Israelit Krankenhaus Hamburg, D-22297 Hamburg, Germany.
[Kwon, Sun Young] Keimyung Univ, Sch Med, Dept Pathol, Daegu, South Korea.
[Kim, Goyang Hark Kyun] Natl Canc Ctr, Ctr Gastr Canc, Goyang, South Korea.
[Bartlett, John] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada.
[Parfitt, Jeremy] London Hlth Sci Ctr, Ontario Tumour Bank, London, ON N6A 5A5, Canada.
[Chetty, Runjan; Darling, Gail; Knox, Jennifer; Wong, Rebecca; El-Zimaity, Haila; Liu, Geoffrey] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
[Boussioutas, Alex] Univ Melbourne, Sir Peter MacCallum Canc Dept Oncol, Melbourne, Vic 3002, Australia.
[Park, Do Young] Pusan Natl Univ, Sch Med, Dept Pathol, Pusan, South Korea.
[Kemp, Rafael; Carlotti, Carlos Gilberto, Jr.; da Cunha Tirapelli, Daniela Pretti; Sankarankutty, Ajith Kumar; dos Santos, Jose Sebastiao; Trevisan, Felipe Amstalden] Univ Sao Paulo, Ribeirao Preto Med School FMRP, Dept Surg & Anat, BR-14049900 Sao Paulo, Brazil.
[Saggioro, Fabiano Pinto] Univ Sao Paulo, Ribeirao Preto Med School FMRP, Dept Pathol, BR-14049900 Sao Paulo, Brazil.
[Noushmehr, Houtan] Univ Sao Paulo, Ribeirao Preto Med School FMRP, Dept Genet, BR-14049900 Sao Paulo, Brazil.
[Eschbacher, Jennifer] St Josephs Hosp, Dept Pathol, Phoenix, AZ 85013 USA.
[Dubina, Michael; Mozgovoy, Eugene] St Petersburg Acad Univ, RAS, St Petersburg 194021, Russia.
[Carey, Frank; Chalmers, Sally; Forgie, Ian] Univ Dundee, Ninewells Hosp & Med Sch, Tayside Tissue Bank, Dundee DD1 9SY, Scotland.
[Godwin, Andrew; Reilly, Colleen; Madan, Rashna; Naima, Zaid] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA.
[Ferrer-Torres, Daysha] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Rathmell, W. Kimryn] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA.
[Dhir, Rajiv] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
[Ajani, Jaffer A.] Univ Texas MD Anderson Canc Ctr, Dept GI Med Oncol, Houston, TX 77030 USA.
[Cheong, Jae-Ho] Yonsei Univ, Coll Med, Dept Surg, Seoul 120752, South Korea.
[Chudamani, Sudha; Liu, Jai; Lolla, Laxmi; Wu, Ye] Leidos Biomed, Rockville, MD 20850 USA.
[Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu] CSRA Inc, Falls Church, VA 22042 USA.
[Hutter, Carolyn M.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Bass, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Bass, AJ (reprint author), Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.; Thorsson, V (reprint author), Inst Syst Biol, Seattle, WA 98109 USA.
EM adam_bass@dfci.harvard.edu; Vesteinn.Thorsson@systemsbiology.org
RI Carlotti, Carlos/C-1608-2012;
OI Carlotti, Carlos/0000-0002-7055-0564; Reis, Rui/0000-0002-9639-7940
FU Intramural Research Program; 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 patients who contributed to this study, to K.
Hoadley and R. Kucherlapati for scientific editing, and to J. Zhang and
I. Felau for administrative support. This work was supported by the
Intramural Research Program and 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.
NR 58
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 12
PY 2017
VL 541
IS 7636
BP 169
EP +
DI 10.1038/nature20805
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EN6PI
UT WOS:000396125500030
ER
PT J
AU Qiang, W
Yau, WM
Lu, JX
Collinge, J
Tycko, R
AF Qiang, Wei
Yau, Wai-Ming
Lu, Jun-Xia
Collinge, John
Tycko, Robert
TI Structural variation in amyloid-beta fibrils from Alzheimer's disease
clinical subtypes
SO NATURE
LA English
DT Article
ID ATOMIC-RESOLUTION STRUCTURE; PRION STRAINS; POLYMORPHISM; MODEL; MICE
AB Aggregation of amyloid-beta peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer's disease. Fibrils formed in vitro by 40- and 42-residue amyloid-beta peptides (A beta 40 and A beta 42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions(1-12). Recent experiments(1,13-16) suggest that variations in amyloid-beta fibril structure in vivo may correlate with variations in Alzheimer's disease phenotype, in analogy to distinct prion strains that are associated with different clinical and pathological phenotypes(17-19). Here we investigate correlations between structural variation and Alzheimer's disease phenotype using solid-state nuclear magnetic resonance (ssNMR) measurements on A beta 40 and A beta 42 fibrils prepared by seeded growth from extracts of Alzheimer's disease brain cortex. We compared two atypical Alzheimer's disease clinical subtypes-the rapidly progressive form (r-AD) and the posterior cortical atrophy variant (PCA-AD)-with a typical prolonged-duration form (t-AD). On the basis of ssNMR data from 37 cortical tissue samples from 18 individuals, we find that a single A beta 40 fibril structure is most abundant in samples from patients with t-AD and PCA-AD, whereas A beta 40 fibrils from r-AD samples exhibit a significantly greater proportion of additional structures. Data for A beta 42 fibrils indicate structural heterogeneity in most samples from all patient categories, with at least two prevalent structures. These results demonstrate the existence of a specific predominant A beta 40 fibril structure in t-AD and PCA-AD, suggest that r-AD may relate to additional fibril structures and indicate that there is a qualitative difference between A beta 40 and A beta 42 aggregates in the brain tissue of patients with Alzheimer's disease.
C1 [Qiang, Wei; Yau, Wai-Ming; Lu, Jun-Xia; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Collinge, John] UCL Inst Neurol, MRC Prion Unit, London WC1N 3BG, England.
[Collinge, John] UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England.
[Qiang, Wei] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
[Lu, Jun-Xia] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China.
RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.; Collinge, J (reprint author), UCL Inst Neurol, MRC Prion Unit, London WC1N 3BG, England.; Collinge, J (reprint author), UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England.
EM jc@prion.ucl.ac.uk; robertty@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
US National Institutes of Health; UK Medical Research Council; National
Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre;
Reta Lila Weston Trust for Medical Research; Progressive Supranuclear
Palsy [Europe] Association; Medical Research Council
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases of the
US National Institutes of Health, by the UK Medical Research Council and
by the National Institute of Health Research (NIHR) UCLH/UCL Biomedical
Research Centre. We are grateful for the assistance of S. Mead, O.
Avwenagha, and J. Wadsworth at the MRC Prion Unit in selection and
processing of tissue samples. We thank UK neurologists for referral of
rapidly progressive dementias to the NHS National Prion Clinic, National
Hospital for Neurology and Neurosurgery (NHNN), University College
London Hospitals NHS Foundation Trust (UCLH). We thank the Queen Square
Brain Bank for Neurological Disorders (supported by the Reta Lila Weston
Trust for Medical Research, the Progressive Supranuclear Palsy [Europe]
Association and the Medical Research Council) at the UCL Institute of
Neurology, for provision of the human brain tissue samples. We thank all
patients and their families for consent to use tissues in research.
NR 30
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 12
PY 2017
VL 541
IS 7636
BP 217
EP +
DI 10.1038/nature20814
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EN6PI
UT WOS:000396125500041
PM 28052060
ER
PT J
AU Stagno, JR
Liu, Y
Bhandari, YR
Conrad, CE
Panja, S
Swain, M
Fan, L
Nelson, G
Li, C
Wendel, DR
White, TA
Coe, JD
Wiedorn, MO
Knoska, J
Oberthuer, D
Tuckey, RA
Yu, P
Dyba, M
Tarasov, SG
Weierstall, U
Grant, TD
Schwieters, CD
Zhang, J
Ferre-D'Amare, AR
Fromme, P
Draper, DE
Liang, M
Hunter, MS
Boutet, S
Tan, K
Zuo, X
Ji, X
Barty, A
Zatsepin, NA
Chapman, HN
Spence, JCH
Woodson, SA
Wang, YX
AF Stagno, J. R.
Liu, Y.
Bhandari, Y. R.
Conrad, C. E.
Panja, S.
Swain, M.
Fan, L.
Nelson, G.
Li, C.
Wendel, D. R.
White, T. A.
Coe, J. D.
Wiedorn, M. O.
Knoska, J.
Oberthuer, D.
Tuckey, R. A.
Yu, P.
Dyba, M.
Tarasov, S. G.
Weierstall, U.
Grant, T. D.
Schwieters, C. D.
Zhang, J.
Ferre-D'Amare, A. R.
Fromme, P.
Draper, D. E.
Liang, M.
Hunter, M. S.
Boutet, S.
Tan, K.
Zuo, X.
Ji, X.
Barty, A.
Zatsepin, N. A.
Chapman, H. N.
Spence, J. C. H.
Woodson, S. A.
Wang, Y. -X.
TI Structures of riboswitch RNA reaction states by mix-and-inject XFEL
serial crystallography
SO NATURE
LA English
DT Article
ID X-RAY-DIFFRACTION; PHOTOACTIVE YELLOW PROTEIN; STANDARD ATOMIC VOLUMES;
FEMTOSECOND CRYSTALLOGRAPHY; BINDING RIBOSWITCHES; MOLECULAR-STRUCTURE;
ADENINE RIBOSWITCH; GENETIC-CONTROL; SCATTERING DATA; LIGAND
AB Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform(1-3). A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time(4). Here we use femtosecond X-ray free electron laser (XFEL) pulses(5,6) to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro-and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.
C1 [Stagno, J. R.; Liu, Y.; Bhandari, Y. R.; Swain, M.; Wendel, D. R.; Tuckey, R. A.; Yu, P.; Dyba, M.; Tarasov, S. G.; Wang, Y. -X.] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Conrad, C. E.; Coe, J. D.; Fromme, P.] Arizona State Univ, Dept Biochem, Tempe, AZ 85287 USA.
[Conrad, C. E.; Coe, J. D.; Weierstall, U.; Fromme, P.; Zatsepin, N. A.; Spence, J. C. H.] Arizona State Univ, Biodesign Inst, Ctr Appl Struct Discovery, Tempe, AZ 85287 USA.
[Panja, S.; Woodson, S. A.] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA.
[Fan, L.] NCI, Small Angle Xray Scattering Core Facil, Ctr Canc Res, Frederick, MD 21702 USA.
[Nelson, G.; Li, C.; Weierstall, U.; Zatsepin, N. A.; Spence, J. C. H.] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA.
[White, T. A.; Wiedorn, M. O.; Knoska, J.; Oberthuer, D.; Barty, A.; Chapman, H. N.] Deutsch Elektronen Synchrotron DESY, Ctr Free Electron Laser Sci, Notkestr 85, D-22607 Hamburg, Germany.
[Wiedorn, M. O.; Knoska, J.; Chapman, H. N.] Univ Hamburg, Dept Phys, Luruper Chaussee 149, D-22607 Hamburg, Germany.
[Grant, T. D.] Hauptmann Woodward Med Res Inst, Buffalo, NY 14203 USA.
[Schwieters, C. D.] NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Zhang, J.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Ferre-D'Amare, A. R.] NHLBI, Lab RNA Biophys & Cellular Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Draper, D. E.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA.
[Liang, M.; Hunter, M. S.; Boutet, S.] SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
[Tan, K.] Argonne Natl Lab, Adv Photon Source, Struct Biol Ctr, Biosci Div, Argonne, IL 60439 USA.
[Zuo, X.] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA.
[Ji, X.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Wang, YX (reprint author), NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM wangyunx@mail.nih.gov
FU LCLS Ultrafast Science Instruments (LUSI) project - US Department of
Energy, Office of Basic Energy Sciences; US Department of Energy, Office
of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]; NSF-STC
"BioXFEL" [NSF-1231306]; NIH Intramural Research Program of NCI; NIH
Intramural Research Program of CIT; NIH Intramural Research Program of
NHLBI; NIH Intramural Research Program of US Department of Energy,
Office of Biological and Environmental Research [DE-AC02-06CH11357];
European Research Council [ERC-2013-SyG 609920]; BMBF [05K16GU1]
FX Portions of this research were carried out at the Linac Coherent Light
Source, a National User Facility operated by Stanford University on
behalf of the US Department of Energy, Office of Basic Energy Sciences.
The CXI instrument was funded by the LCLS Ultrafast Science Instruments
(LUSI) project funded by the US Department of Energy, Office of Basic
Energy Sciences. Use of the Linac Coherent Light Source (LCLS), SLAC
National Accelerator Laboratory, is supported by the US Department of
Energy, Office of Science, Office of Basic Energy Sciences under
Contract No. DE-AC02-76SF00515. We thank J. Strathern and M. Dunne for
their support and S. Wakatsuki for discussions. This work is supported
in part by the NSF-STC "BioXFEL" (NSF-1231306), the NIH Intramural
Research Programs of NCI, CIT, NHLBI, and the US Department of Energy,
Office of Biological and Environmental Research under Contract
DE-AC02-06CH11357, the European Research Council, "Frontiers in
Attosecond X-ray Science: Imaging and Spectroscopy (AXSIS)",
ERC-2013-SyG 609920, and the BMBF through project 05K16GU1.
NR 55
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U1 4
U2 4
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 JAN 12
PY 2017
VL 541
IS 7636
BP 242
EP +
DI 10.1038/nature20599
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EN6PI
UT WOS:000396125500046
PM 27841871
ER
PT J
AU Zhang, Q
Lenardo, MJ
Baltimore, D
AF Zhang, Qian
Lenardo, Michael J.
Baltimore, David
TI 30 Years of NF-kappa B: A Blossoming of Relevance to Human Pathobiology
SO CELL
LA English
DT Review
ID HERPES-SIMPLEX ENCEPHALITIS; HYPOHIDROTIC ECTODERMAL DYSPLASIA; COMMON
VARIABLE IMMUNODEFICIENCY; PYOGENIC BACTERIAL-INFECTIONS; BETA-BINDING
PROTEIN; DEFICIENT MICE; LYMPHOCYTE-ACTIVATION; ANTIGEN-RECEPTOR;
IMMUNE-SYSTEM; FRONTOMETAPHYSEAL DYSPLASIA
AB NF-kappa B was discovered 30 years ago as a rapidly inducible transcription factor. Since that time, it has been found to have a broad role in gene induction in diverse cellular responses, particularly throughout the immune system. Here, we summarize elaborate regulatory pathways involving this transcription factor and use recent discoveries in human genetic diseases to place specific proteins within their relevant medical and biological contexts.
C1 [Zhang, Qian] Sidra Med & Res Ctr, Dept Translat Med, Doha, Qatar.
[Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lenardo, Michael J.] NIAID, NIAID Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Baltimore, David] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
RP Lenardo, MJ (reprint author), NIAID, Mol Dev Immune Syst Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Lenardo, MJ (reprint author), NIAID, NIAID Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
FU Intramural Research Program of the NIAID; Intramural Research Program of
the NIH
FX We apologize to the many hundreds of colleagues over the past 30 years
whose work has created this rich tapestry of science but could not be
cited due to space limitations. We thank Sankar Ghosh for critically
reading the manuscript. This work was supported by the Intramural
Research Program of the NIAID, NIH.
NR 138
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U2 1
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 JAN 12
PY 2017
VL 168
IS 1-2
BP 37
EP 57
DI 10.1016/j.cell.2016.12.012
PG 21
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EN8JM
UT WOS:000396246700010
PM 28086098
ER
PT J
AU Tenente, IM
Hayes, MN
Ignatius, MS
McCarthy, K
Yohe, M
Sindiri, S
Gryder, B
Oliveira, ML
Ramakrishnan, A
Tang, Q
Chen, EY
Nielsen, GP
Khan, J
Langenau, DM
AF Tenente, Ines M.
Hayes, Madeline N.
Ignatius, Myron S.
McCarthy, Karin
Yohe, Marielle
Sindiri, Sivasish
Gryder, Berkley
Oliveira, Mariana L.
Ramakrishnan, Ashwin
Tang, Qin
Chen, Eleanor Y.
Nielsen, G. Petur
Khan, Javed
Langenau, David M.
TI Myogenic regulatory transcription factors regulate growth in
rhabdomyosarcoma
SO ELIFE
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDRENS ONCOLOGY GROUP; ACUTE
MYELOID-LEUKEMIA; GENOME-WIDE BINDING; SKELETAL-MUSCLE; EMBRYONAL
RHABDOMYOSARCOMA; TRANSGENIC ZEBRAFISH; CELL TRANSPLANTATION;
SELF-RENEWAL; SATELLITE CELL
AB Rhabdomyosarcoma (RMS) is a pediatric malignacy of muscle with myogenic regulatory transcription factors MYOD and MYF5 being expressed in this disease. Consensus in the field has been that expression of these factors likely reflects the target cell of transformation rather than being required for continued tumor growth. Here, we used a transgenic zebrafish model to show that Myf5 is sufficient to confer tumor-propagating potential to RMS cells and caused tumors to initiate earlier and have higher penetrance. Analysis of human RMS revealed that MYF5 and MYOD are mutually-exclusively expressed and each is required for sustained tumor growth. ChIP-seq and mechanistic studies in human RMS uncovered that MYF5 and MYOD bind common DNA regulatory elements to alter transcription of genes that regulate muscle development and cell cycle progression. Our data support unappreciated and dominant oncogenic roles for MYF5 and MYOD convergence on common transcriptional targets to regulate human RMS growth.
C1 [Tenente, Ines M.; Hayes, Madeline N.; Ignatius, Myron S.; McCarthy, Karin; Oliveira, Mariana L.; Ramakrishnan, Ashwin; Tang, Qin; Langenau, David M.] Massachusetts Gen Hosp, Mol Pathol Canc Ctr & Regenerat Med, Boston, MA 02114 USA.
[Tenente, Ines M.; Hayes, Madeline N.; Ignatius, Myron S.; McCarthy, Karin; Oliveira, Mariana L.; Ramakrishnan, Ashwin; Tang, Qin; Langenau, David M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Tenente, Ines M.] Univ Porto, Abel Salazar Biomed Sci Inst, GABBA Program, Oporto, Portugal.
[Ignatius, Myron S.] Greehey Childrens Canc Res Inst, Mol Med, San Antonio, TX USA.
[Yohe, Marielle; Sindiri, Sivasish; Gryder, Berkley; Khan, Javed] NCI, Adv Technol Ctr, Pediat Oncol Branch, Oncogen Sec, Gaithersburg, MD USA.
[Oliveira, Mariana L.] Univ Lisbon, Fac Med, Inst Mol Med, Lisbon, Portugal.
[Chen, Eleanor Y.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Langenau, DM (reprint author), Massachusetts Gen Hosp, Mol Pathol Canc Ctr & Regenerat Med, Boston, MA 02114 USA.; Langenau, DM (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
EM dlangenau@mgh.harvard.edu
RI Khan, Javed/P-9157-2014
OI Khan, Javed/0000-0002-5858-0488
FU National Institutes of Health [R01CA154923, U54CA168512]; Fundacao para
a Ciencia e a Tecnologia; China Scholarship Council; Alex's Lemonade
Stand Foundation for Childhood Cancer; Saint Baldrick's Foundation; NIH
Office of the Director [R24OD016761]
FX National Institutes of Health Ines M Tenente; Fundacao para a Ciencia e
a Tecnologia Myron S Ignatius David M Langenau; China Scholarship
Council Qin Tang; Alex's Lemonade Stand Foundation for Childhood Cancer
David M Langena; Saint Baldrick's Foundation David M Langenau; National
Institutes of Health R01CA154923 David M Langenau; National Institutes
of Health U54CA168512 David M Langenau; NIH Office of the Director
R24OD016761 David M Langenau; The funders had no role in study design,
data collection and interpretation, or the decision to submit the work
for publication.
NR 80
TC 0
Z9 0
U1 3
U2 3
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD JAN 12
PY 2017
VL 6
AR e19214
DI 10.7554/eLife.19214
PG 24
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EJ7RN
UT WOS:000393420000001
ER
PT J
AU Pardo, LM
Li, WQ
Hwang, SJ
Verkouteren, JAC
Hofman, A
Uitterlinden, AG
Kraft, P
Turman, C
Han, JL
Cho, E
Murabito, JM
Levy, D
Qureshi, AA
Nijsten, T
AF Pardo, Luba M.
Li, Wen-Qing
Hwang, Shih-Jen
Verkouteren, Joris A. C.
Hofman, Albert
Uitterlinden, Andre G.
Kraft, Peter
Turman, Constance
Han, Jiali
Cho, Eunyoung
Murabito, Joanne M.
Levy, Daniel
Qureshi, Abrar A.
Nijsten, Tamar
TI Genome-Wide Association Studies of Multiple Keratinocyte Cancers
SO PLOS ONE
LA English
DT Article
ID BASAL-CELL CARCINOMA; NONMELANOMA SKIN CANCERS; PIGMENTATION TRAITS;
METAANALYSIS; RISK; NETHERLANDS; DESIGN; HEART; LOCI; GENE
AB There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [ NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value <= 5.5x10(-6)) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value <= 5.5x10(-6)) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10(-7)). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10(-4)). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene.
C1 [Pardo, Luba M.; Verkouteren, Joris A. C.; Nijsten, Tamar] Erasmus MC Canc Inst, Dept Dermatol, Rotterdam, Netherlands.
[Li, Wen-Qing; Cho, Eunyoung; Qureshi, Abrar A.] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA.
[Li, Wen-Qing; Cho, Eunyoung; Qureshi, Abrar A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.
[Hwang, Shih-Jen; Murabito, Joanne M.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hwang, Shih-Jen; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA.
[Hofman, Albert] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Uitterlinden, Andre G.] Erasmus MC Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Kraft, Peter; Turman, Constance] Harvard Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
[Kraft, Peter; Han, Jiali; Cho, Eunyoung; Qureshi, Abrar A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Kraft, Peter; Han, Jiali; Cho, Eunyoung; Qureshi, Abrar A.] Harvard Med Sch, Boston, MA USA.
[Han, Jiali] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Bloomington, IN 47405 USA.
[Han, Jiali] Indiana Univ, Melvin & Bren Simon Canc Ctr, Bloomington, IN 47405 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02215 USA.
RP Nijsten, T (reprint author), Erasmus MC Canc Inst, Dept Dermatol, Rotterdam, Netherlands.; Qureshi, AA (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA.; Qureshi, AA (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.; Qureshi, AA (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.; Qureshi, AA (reprint author), Harvard Med Sch, Boston, MA USA.
EM abrar_qureshi@brown.edu; t.nijsten@erasmusmc.nl
FU Vidi Grant of ZonMw [91711315]; Erasmus Medical Center; Research
Institute for Diseases in the Elderly; Netherlands Genomics Initiative
(NGI); Netherlands Organisation for Scientific Research (NOW);
Netherlands Organization for the Health Research and Development
(ZonMw); Ministry of Education, Culture and Science; Ministry for
Health, Welfare and Sports; European Commission (DG XII); Municipality
of Rotterdam; National Institutes of Health [N01-HC-25195]; Division of
Intramural Research, National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD; NIH [UM1 CA186107, P01 CA87969, R01
CA49449, UM1 CA176726, R01 CA67262, UM1 CA167552, CA122838, CA055075,
CA100264, CA093459]; Erasmus University, Rotterdam
FX The study is funded by a Vidi Grant of ZonMw (nr. 91711315). The
Rotterdam Study is supported by Erasmus Medical Center and Erasmus
University, Rotterdam; the Research Institute for Diseases in the
Elderly; The Netherlands Genomics Initiative (NGI); The Netherlands
Organisation for Scientific Research (NOW); The Netherlands Organization
for the Health Research and Development (ZonMw); 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 funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript. The
Framingham Heart Study is funded by National Institutes of Health
contract N01-HC-25195. The analytical component of this project was
funded by the Division of Intramural Research, National Heart, Lung, and
Blood Institute, National Institutes of Health, Bethesda, MD. The study
was also supported by NIH grants UM1 CA186107, P01 CA87969, R01 CA49449,
UM1 CA176726, R01 CA67262, UM1 CA167552, CA122838, CA055075, CA100264,
and CA093459.
NR 33
TC 0
Z9 0
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 12
PY 2017
VL 12
IS 1
AR e0169873
DI 10.1371/journal.pone.0169873
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH7JQ
UT WOS:000391949500095
PM 28081215
ER
PT J
AU Kuboki, R
Sugase-Miyamoto, Y
Matsumoto, N
Richmond, BJ
Shidara, M
AF Kuboki, Ryosuke
Sugase-Miyamoto, Yasuko
Matsumoto, Narihisa
Richmond, Barry J.
Shidara, Munetaka
TI Information Accumulation over Time in Monkey Inferior Temporal Cortex
Neurons Explains Pattern Recognition Reaction Time under Visual Noise
SO FRONTIERS IN INTEGRATIVE NEUROSCIENCE
LA English
DT Article
DE inferior temporal cortex; information theory; pattern recognition;
visual noise; behavioral latency; rhesus monkey
ID TWO-DIMENSIONAL PATTERNS; INFEROTEMPORAL CORTEX; OBJECT RECOGNITION;
SINGLE UNITS; PROGRESS; VISION; DISCRIMINATION; CATEGORIZATION;
RESPONSES; POSITION
AB We recognize objects even when they are partially degraded by visual noise. We studied the relation between the amount of visual noise (5, 10, 15, 20, or 25%) degrading 8 black-and-white stimuli and stimulus identification in 2 monkeys performing a sequential delayed match-to-sample task. We measured the accuracy and speed with which matching stimuli were identified. The performance decreased slightly (errors increased) as the amount of visual noise increased for both monkeys. The performance remained above 80% correct, even with 25% noise. However, the reaction times markedly increased as the noise increased, indicating that the monkeys took progressively longer to decide what the correct response would be as the amount of visual noise increased, showing that the monkeys trade time to maintain accuracy. Thus, as time unfolds the monkeys act as if they are accumulating the information and/or testing hypotheses about whether the test stimulus is likely to be a match for the sample being held in short-term memory. We recorded responses from 13 single neurons in area TE of the 2 monkeys. We found that stimulus-selective information in the neuronal responses began accumulating when the match stimulus appeared. We found that the greater the amount of noise obscuring the test stimulus, the more slowly stimulus-related information by the 13 neurons accumulated. The noise induced slowing was about the same for both behavior and information. These data are consistent with the hypothesis that area TE neuron population carries information about stimulus identity that accumulates over time in such a manner that it progressively overcomes the signal degradation imposed by adding visual noise.
C1 [Kuboki, Ryosuke; Shidara, Munetaka] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki, Japan.
[Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa] Natl Inst Adv Ind Sci & Technol, Human Informat Res Inst, Tsukuba, Ibaraki, Japan.
[Richmond, Barry J.] NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA.
[Shidara, Munetaka] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan.
RP Shidara, M (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki, Japan.; Shidara, M (reprint author), Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan.
EM mshidara@md.tsukuba.ac.jp
FU IRP/NIMH/USA; MEXT/JSPS KAKENHI [23650105, JP16H01684]; New Energy and
Industrial Technology Development Organization (NEDO)
FX We would like to thank Dr. Zheng Liu for data recording. This work was
supported by IRP/NIMH/USA and MEXT/JSPS KAKENHI Grant Number 23650105,
JP16H01684, and the New Energy and Industrial Technology Development
Organization (NEDO).
NR 34
TC 0
Z9 0
U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
EI 1662-5145
J9 FRONT INTEGR NEUROSC
JI Front. Integr. Neurosci.
PD JAN 12
PY 2017
VL 10
AR 43
DI 10.3389/fnint.2016.00043
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA EH6GM
UT WOS:000391870900001
ER
PT J
AU Hudson, KL
Collins, FS
AF Hudson, Kathy L.
Collins, Francis S.
TI The 21st Century Cures Act - A View from the NIH
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Hudson, Kathy L.; Collins, Francis S.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Hudson, KL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 3
TC 1
Z9 1
U1 2
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 12
PY 2017
VL 376
IS 2
BP 111
EP 113
DI 10.1056/NEJMp1615745
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA EI0XI
UT WOS:000392198400005
PM 27959585
ER
PT J
AU Powers, SW
Coffey, CS
Chamberlin, LA
Ecklund, DJ
Klingner, EA
Yankey, JW
Korbee, LL
Porter, LL
Hershey, AD
AF Powers, Scott W.
Coffey, Christopher S.
Chamberlin, Leigh A.
Ecklund, Dixie J.
Klingner, Elizabeth A.
Yankey, Jon W.
Korbee, Leslie L.
Porter, Linda L.
Hershey, Andrew D.
CA CHAMP Investigators
TI Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PHARMACOLOGICAL-TREATMENT; ADOLESCENT MIGRAINE; PREVENTION CHAMP;
CHILDHOOD; CHILDREN; HEADACHE; PREVALENCE; DISABILITY; EFFICACY; AGE
AB BACKGROUND
Which, medication, if any, to use to prevent the headache of pediatric migraine has not been established.
METHODS
We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2: 2: 1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment.
RESULTS
A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P = 0.26; topiramate vs. placebo, P = 0.48; amitriptyline vs. topiramate, P = 0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt.
CONCLUSIONS
There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281).
C1 [Powers, Scott W.; Hershey, Andrew D.] Univ Cincinnati, Dept Pediat, Coll Med, Cincinnati, OH 45221 USA.
[Powers, Scott W.; Chamberlin, Leigh A.] Cincinnati Childrens Hosp Med Ctr, Div Behav Med & Clin Psychol, Cincinnati, OH 45229 USA.
[Korbee, Leslie L.] Cincinnati Childrens Hosp Med Ctr, Off Clin & Translat Res, Cincinnati, OH 45229 USA.
[Hershey, Andrew D.] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH 45229 USA.
[Coffey, Christopher S.; Ecklund, Dixie J.; Klingner, Elizabeth A.; Yankey, Jon W.] Univ Iowa, Dept Biostat, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA.
[Porter, Linda L.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Powers, SW (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 7039, Cincinnati, OH 45229 USA.
EM scott.powers@cchmc.org
FU National Institutes of Health
FX Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov
number, NCT01581281).
NR 25
TC 6
Z9 6
U1 15
U2 15
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 JAN 12
PY 2017
VL 376
IS 2
BP 115
EP 124
DI 10.1056/NEJMoa1610384
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA EI0XI
UT WOS:000392198400006
PM 27788026
ER
PT J
AU Hao, M
Bryant, SH
Wang, YL
AF Hao, Ming
Bryant, Stephen H.
Wang, Yanli
TI Predicting drug-target interactionsby dual-network integrated logistic
matrix factorization
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DATABASE; IDENTIFICATION; INFORMATION
AB In this work, we propose a dual-network integrated logistic matrix factorization (DNILMF) algorithm to predict potential drug-target interactions (DTI). The prediction procedure consists of four steps: (1) inferring new drug/target profiles and constructing profile kernel matrix; (2) diffusing drug profile kernel matrix with drug structure kernel matrix; (3) diffusing target profile kernel matrix with target sequence kernel matrix; and (4) building DNILMF model and smoothing new drug/target predictions based on their neighbors. We compare our algorithm with the state-of-the-art method based on the benchmark dataset. Results indicate that the DNILMF algorithm outperforms the previously reported approaches in terms of AUPR (area under precision-recall curve) and AUC (area under curve of receiver operating characteristic) based on the 5 trials of 10-fold cross-validation. We conclude that the performance improvement depends on not only the proposed objective function, but also the used nonlinear diffusion technique which is important but under studied in the DTI prediction field. In addition, we also compile a new DTI dataset for increasing the diversity of currently available benchmark datasets. The top prediction results for the new dataset are confirmed by experimental studies or supported by other computational research.
C1 [Hao, Ming; Bryant, Stephen H.; Wang, Yanli] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov
FU Intramural Research Program of the NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
NIH, National Library of Medicine.
NR 38
TC 0
Z9 0
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 12
PY 2017
VL 7
AR 40376
DI 10.1038/srep40376
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH3KI
UT WOS:000391670100001
PM 28079135
ER
PT J
AU Li, Y
Wang, HB
Wang, K
Hu, QL
Yao, Q
Shen, YQ
Yu, GC
Tang, GP
AF Li, Yang
Wang, Hebin
Wang, Kai
Hu, Qinglian
Yao, Qi
Shen, Youqing
Yu, Guocan
Tang, Guping
TI Targeted Co-delivery of PTX and TR3 siRNA by PTP Peptide Modified
Dendrimer for the Treatment of Pancreatic Cancer
SO SMALL
LA English
DT Article
ID SYSTEMICALLY ADMINISTERED SIRNA; MESOPOROUS SILICA NANOPARTICLES;
POLYMER HYBRID NANOPARTICLES; NEGATIVE BREAST-CANCER; COMBINATION
THERAPY; ANTICANCER DRUG; DOXORUBICIN; MICELLES; CELLS; PACLITAXEL
C1 [Li, Yang; Wang, Hebin; Wang, Kai; Yao, Qi; Tang, Guping] Zhejiang Univ, Dept Chem, Inst Chem Biol & Pharmaceut Chem, Hangzhou 310028, Zhejiang, Peoples R China.
[Wang, Hebin] Tarim Univ, Coll Life Sci, Alar 843300, Peoples R China.
[Hu, Qinglian] Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310032, Zhejiang, Peoples R China.
[Shen, Youqing] Zhejiang Univ, Ctr Bionanoengn, Hangzhou 310027, Zhejiang, Peoples R China.
[Shen, Youqing] Zhejiang Univ, Dept Chem & Biol Engn, State Key Lab Chem Engn, Hangzhou 310027, Zhejiang, Peoples R China.
[Yu, Guocan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Tang, GP (reprint author), Zhejiang Univ, Dept Chem, Inst Chem Biol & Pharmaceut Chem, Hangzhou 310028, Zhejiang, Peoples R China.; Yu, GC (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM guocan.yu@nih.gov; tangguping@zju.edu.cn
FU National Basic Research Program of China [2014CB931900]
FX Y.L. and H.W. contributed equally to this work. This research was funded
by the National Basic Research Program of China (Grant No.
2014CB931900). Animal care and handling procedures were in agreement
with the guidelines evaluated and approved by the ethics committee of
Zhejiang University. Study protocols involving animals were approved by
the Zhejiang University Animal Care and Use Committee.
NR 48
TC 0
Z9 0
U1 9
U2 9
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1613-6810
EI 1613-6829
J9 SMALL
JI Small
PD JAN 11
PY 2017
VL 13
IS 2
AR UNSP 1602697
DI 10.1002/smll.201602697
PG 9
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA EO2ZM
UT WOS:000396564600016
ER
PT J
AU De Ravin, SS
Li, LH
Wu, XL
Choi, U
Allen, C
Koontz, S
Lee, J
Theobald-Whiting, N
Chu, J
Garofalo, M
Sweeney, C
Kardava, L
Moir, S
Viley, A
Natarajan, P
Su, L
Kuhns, D
Zarember, KA
Peshwa, MV
Malech, HL
AF De Ravin, Suk See
Li, Linhong
Wu, Xiaolin
Choi, Uimook
Allen, Cornell
Koontz, Sherry
Lee, Janet
Theobald-Whiting, Narda
Chu, Jessica
Garofalo, Mary
Sweeney, Colin
Kardava, Lela
Moir, Susan
Viley, Angelia
Natarajan, Pachai
Su, Ling
Kuhns, Douglas
Zarember, Kol A.
Peshwa, Madhusudan V.
Malech, Harry L.
TI CRISPR-Cas9 gene repair of hematopoietic stem cells from patients with
X-linked chronic granulomatous disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; B-CELLS; THERAPY; EXPRESSION;
NUCLEASES; MUTATION; IMMUNITY
AB Gene repair of CD34(+) hematopoietic stem and progenitor cells (HSPCs) may avoid problems associated with gene therapy, such as vector-related mutagenesis and dysregulated transgene expression. We used CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 (CRISPR-associated 9) to repair a mutation in the CYBB gene of CD34(+) HSPCs from patients with the immunodeficiency disorder X-linked chronic granulomatous disease (X-CGD). Sequence-confirmed repair of >20% of HSPCs from X-CGD patients restored the function of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and superoxide radical production in myeloid cells differentiated from these progenitor cells in vitro. Transplant of gene-repaired X-CGD HSPCs into NOD (nonobese diabetic) SCID (severe combined immunodeficient) gamma c(-/-) mice resulted in efficient engraftment and production of functional mature human myeloid and lymphoid cells for up to 5 months. Whole-exome sequencing detected no indels outside of the CYBB gene after gene correction. CRISPR-mediated gene editing of HSPCs may be applicable to other CGD mutations and other monogenic disorders of the hematopoietic system.
C1 [De Ravin, Suk See; Choi, Uimook; Koontz, Sherry; Lee, Janet; Theobald-Whiting, Narda; Chu, Jessica; Garofalo, Mary; Sweeney, Colin; Kuhns, Douglas; Zarember, Kol A.; Malech, Harry L.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Li, Linhong; Allen, Cornell; Viley, Angelia; Natarajan, Pachai; Peshwa, Madhusudan V.] MaxCyte Inc, Gaithersburg, MD 20878 USA.
[Wu, Xiaolin; Su, Ling] Leidos Biomed Res Inc, Canc Res Technol Program, Frederick, MD 21701 USA.
[Kardava, Lela; Moir, Susan] NIAID, Lab Immunoregulat, NIH, Bethesda, MD USA.
RP De Ravin, SS; Malech, HL (reprint author), NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA.
EM sderavin@niaid.nih.gov; hmalech@nih.gov
FU Intramural Research Program of NIAID, NIH [Z01-A1-00644, Z01-A1-00988];
Maryland Stem Cell Research Fund [2015-MSCRFP-1752]
FX This research was supported by the Intramural Research Program of NIAID,
NIH (Intramural project numbers Z01-A1-00644 and Z01-A1-00988) and the
Maryland Stem Cell Research Fund (#2015-MSCRFP-1752).
NR 31
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U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JAN 11
PY 2017
VL 9
IS 372
AR eaah3480
DI 10.1126/scitranslmed.aah3480
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA EL2JK
UT WOS:000394445700006
ER
PT J
AU Gonzalez-Suarez, AD
Nash, AI
Garcia-Olivares, J
Torres-Salazar, D
AF Gonzalez-Suarez, Aneysis D.
Nash, Abigail I.
Garcia-Olivares, Jennie
Torres-Salazar, Delany
TI Emerging Evidence for a Direct Link between EAAT-Associated Anion
Channels and Neurological Disorders
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
ID GLUTAMATE TRANSPORTER EAAT1; CHLORIDE CHANNEL; EPISODIC ATAXIA;
MUTATION; ASTROCYTES
C1 [Gonzalez-Suarez, Aneysis D.] Yale Univ, Sch Med, Interdept Neurosci Program, New Haven, CT 06510 USA.
[Nash, Abigail I.; Garcia-Olivares, Jennie; Torres-Salazar, Delany] NIMH, NIH, Bethesda, MD 20892 USA.
RP Torres-Salazar, D (reprint author), NIMH, Lab Mol & Cellular Neurobiol, NIH, 35 Convent Dr,Room 3A-207, Bethesda, MD 20892 USA.
EM delany.torressalazar@nih.gov
OI Torres-Salazar, Delany/0000-0002-6789-9810
NR 21
TC 0
Z9 0
U1 0
U2 0
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 JAN 11
PY 2017
VL 37
IS 2
BP 241
EP 243
DI 10.1523/JNEUROSCI.2947-16.2017
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA EJ9CZ
UT WOS:000393525500003
PM 28077704
ER
PT J
AU Hoest, C
Seidman, JC
Lee, G
Platts-Mills, JA
Ali, A
Olortegui, MP
Bessong, P
Chandyo, R
Babji, S
Mohan, VR
Mondal, D
Mahfuz, M
Mduma, ER
Nyathi, E
Abreu, C
Miller, MA
Pan, W
Mason, CJ
Knobler, SL
AF Hoest, Christel
Seidman, Jessica C.
Lee, Gwenyth
Platts-Mills, James A.
Ali, Asad
Paredes Olortegui, Maribel
Bessong, Pascal
Chandyo, Ram
Babji, Sudhir
Mohan, Venkata Raghava
Mondal, Dinesh
Mahfuz, Mustafa
Mduma, Estomih R.
Nyathi, Emanuel
Abreu, Claudia
Miller, Mark A.
Pan, William
Mason, Carl J.
Knobler, Stacey L.
CA MAL-ED Network Investigators
TI Vaccine coverage and adherence to EPI schedules in eight resource poor
settings in the MAL-ED cohort study
SO VACCINE
LA English
DT Article
DE Public health; Vaccine coverage; Vaccine timing; EPI; Socioeconomic
factors; Measles
ID IMMUNIZATION COVERAGE; ENTERIC INFECTIONS; BIRTH COHORT; SOUTH-AFRICA;
RISK-FACTORS; TIMELINESS; POLIO; SITE; MALNUTRITION; NETWORK
AB Background: Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings.
Methods: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered.
Results: Coverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guerin coverage was high across all sites, 87-100%, whereas measles vaccination rates ranged widely, 73-100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific.
Conclusions: Our findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.
C1 [Hoest, Christel; Seidman, Jessica C.; Miller, Mark A.; Knobler, Stacey L.] Natl Inst Hlth, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies Fogarty, 16 Ctr Dr,Bldg 16,Room 202, Bethesda, MD 20892 USA.
[Lee, Gwenyth] Johns Hopkins Univ, Dept Int Hlth, Baltimore, MD 21205 USA.
[Platts-Mills, James A.] Univ Virginia, Div Infect Dis & Int Hlth, POB 801340,345 Crispell Dr,Carter Harrison Bldg, Charlottesville, VA 22908 USA.
[Ali, Asad] Aga Khan Univ, Dept Pediat & Child Hlth, Stadium Rd, Karachi, Pakistan.
[Paredes Olortegui, Maribel] Asociac Benef Proyectos Informat Sauld Med & Agr, Ramirez Hurtado 622, Iquitos, Peru.
[Bessong, Pascal] Univ Venda, HIV AIDS & Global Hlth Res Programme, ZA-0950 Thohoyandou, South Africa.
[Chandyo, Ram] Tribhuvan Univ, Inst Med, Dept Child Hlth, Kathmandu, Nepal.
[Chandyo, Ram] Univ Bergen, Ctr Int Hlth, POB 7800, N-5020 Bergen, Norway.
[Babji, Sudhir; Mohan, Venkata Raghava] Christian Med Coll & Hosp, Dept Community Hlth, Dept Gastrointestinal Sci, Vellore 632004, Tamil Nadu, India.
[Mondal, Dinesh; Mahfuz, Mustafa] Int Ctr Diarrhoeal Dis Res, Nutr & Clin Serv Div, 68 Shaheed Tajuddin Ahmed Sarani, Dhaka 1212, Bangladesh.
[Mduma, Estomih R.] Haydom Lutheran Hosp, POB 9041, Haydom, Manyara Region, Tanzania.
[Abreu, Claudia; MAL-ED Network Investigators] Univ Fed Ceara, Fac Med, Inst Biomed, Dept Fisiol & Farmacol, Rua Coronel Nunes Melo 1315,CP 3229, BR-60430270 Fortaleza, Ceara, Brazil.
[Pan, William] Duke Univ, Dept Environm Sci & Policy, Durham, NC USA.
[Pan, William] Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
[Mason, Carl J.] Armed Forces Res Inst Med Sci, Bangkok, Thailand.
RP Hoest, C (reprint author), Natl Inst Hlth, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies Fogarty, 16 Ctr Dr,Bldg 16,Room 202, Bethesda, MD 20892 USA.
EM christel.host@nih.gov
OI Ali, Syed Asad/0000-0001-5274-7665
FU Bill & Melinda Gates Foundation; Foundation for the NIH; National
Institutes of Health, Fogarty International Center
FX The Etiology, Risk Factors and Interactions of Enteric Infections and
Malnutrition and the Consequences for Child Health and Development
Project (MAL-ED) is carried out as a collaborative project supported by
the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the
National Institutes of Health, Fogarty International Center.
NR 32
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 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JAN 11
PY 2017
VL 35
IS 3
BP 443
EP 451
DI 10.1016/j.vaccine.2016.11.075
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA EJ2AK
UT WOS:000393011900006
PM 27998640
ER
PT J
AU Kim, S
Kahn, P
Robinson, AB
Lang, B
Shulman, A
Oberle, EJ
Schikler, K
Curran, ML
Barillas-Arias, L
Spencer, CH
Rider, LG
Huber, AM
AF Kim, Susan
Kahn, Philip
Robinson, Angela B.
Lang, Bianca
Shulman, Andrew
Oberle, Edward. J.
Schikler, Kenneth
Curran, Megan Lea
Barillas-Arias, Lilliana
Spencer, Charles H.
Rider, Lisa G.
Huber, Adam M.
TI Childhood Arthritis and Rheumatology Research Alliance consensus
clinical treatment plans for juvenile dermatomyositis with skin
predominant disease
SO Pediatric Rheumatology
LA English
DT Article
DE Dermatomyositis; Childhood Type; Therapeutics; Child; Adolescent;
Amyopathic
ID CUTANEOUS ASSESSMENT-TOOL; IDIOPATHIC INFLAMMATORY MYOPATHIES;
AMYOPATHIC DERMATOMYOSITIS; SINE MYOSITIS; CORE SET; RELIABILITY;
VALIDATION; ADULT; HYPERTENSION; INVOLVEMENT
AB Background: Juvenile dermatomyositis (JDM) is the most common form of the idiopathic inflammatory myopathies in children. A subset of children have the rash of JDM without significant weakness, and the optimal treatments for these children are unknown. The goal of this study was to describe the development of consensus clinical treatment plans (CTPs) for children with JDM who have active skin rashes, without significant muscle involvement, referred to as skin predominant JDM in this manuscript.
Methods: The Children's Arthritis and Rheumatology Research Alliance (CARRA) is a North American consortium of pediatric rheumatology health care providers. CARRA members collaborated to determine consensus on typical treatments for JDM patients with skin findings without significant weakness, to develop CTPs for this subgroup of patients. We used a combination of Delphi surveys and nominal group consensus meetings to develop these CTPs.
Results: Consensus was reached on patient characteristics and outcome assessment, and CTPs were developed and finalized for patients with skin predominant JDM. Treatment option A included hydroxychloroquine alone, Treatment option B included hydroxychloroquine and methotrexate, and Treatment option C included hydroxychloroquine, methotrexate and corticosteroids.
Conclusions: Three CTPs were developed for use in children with skin predominant JDM, which reflect typical treatment approaches. These are not considered to be specific recommendations or standard of care. Using the CARRA network and prospective data collection, we will be able to apply statistical methods in the future to allow comparisons of JDM patients following these consensus treatment plans.
C1 [Kim, Susan] Univ Calif San Francisco, Benioff Childrens Hosp, Div Pediat Rheumatol, 550 16th St, San Francisco, CA 94143 USA.
[Kahn, Philip] NYU, Langone Med Ctr, Div Pediat Rheumatol, 550 First Ave, New York, NY USA.
[Robinson, Angela B.] Rainbow Babies & Childrens Hosp, Pediat Rheumatol, 11100 Euclid Ave MS6008B, Cleveland, OH USA.
[Lang, Bianca; Huber, Adam M.] IWK Hlth Ctr, Dept Pediat, 5980 Univ Ave, Halifax, NS, Canada.
[Lang, Bianca; Huber, Adam M.] Dalhousie Univ, 5980 Univ Ave, Halifax, NS, Canada.
[Shulman, Andrew] Childrens Hosp Orange Cty, Pediat Rheumatol, 1201 W La Veta Ave, Irvine, CA USA.
[Oberle, Edward. J.; Spencer, Charles H.] Nationwide Childrens Hosp, Res Inst, Dept Pediat, 700 Childrens Dr, Columbus, OH USA.
[Schikler, Kenneth] Univ Louisville, Div Adolescent Med, Dept Pediat, Sch Med, 571 South Floyd St, Louisville, KY USA.
[Schikler, Kenneth] Univ Louisville, Div Pediat Rheumatol, Dept Pediat, Sch Med, 571 South Floyd St, Louisville, KY USA.
[Curran, Megan Lea] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA.
[Curran, Megan Lea] Ann & Robert H Lurie Childrens Hosp Chicago, Div Rheumatol, 225 E Chicago Ave, Chicago, IL 60611 USA.
[Barillas-Arias, Lilliana] Albany Med Ctr, Dept Pediat, Rheumatol, 43 New Scotland Ave, Albany, NY USA.
[Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, Clin Res Branch, NIH, 10 Ctr Dr, Bethesda, MD USA.
RP Kim, S (reprint author), Univ Calif San Francisco, Benioff Childrens Hosp, Div Pediat Rheumatol, 550 16th St, San Francisco, CA 94143 USA.
EM Susan.kim@ucsf.edu
FU Arthritis Foundation; NIAMS; Duke Clinical Research Institute; WASIE
Foundation; CureJM; National Institutes of Health, National Institute of
Environmental Health Sciences
FX CARRA is supported in part by grants from the Arthritis Foundation,
NIAMS, Duke Clinical Research Institute, the WASIE Foundation, and
CureJM. Dr. Rider is supported in part by the intramural research
program of the National Institutes of Health, National Institute of
Environmental Health Sciences. We thank Dr. Alison Ehrlich for critical
reading of the manuscript. We also would like to thank our PeDRA
collaborators and Dermatology Colleagues who helped to review and
distribute the survey, including Dr. Shielagh Maguiness, Dr. Ruth Ann
Vleugels, Dr. Jennifer Huang, Dr. Yvonne Chiu, Dr. Michele Ramien, Dr.
Jerome Coulombe, MD, Dr. Regina-Celeste Ahmad, Dr. Lisa M. Arkin and Dr.
Reagan Hunt. Mitali Dave is acknowledged for her insights and
contribution as a parent of a child with JDM to our CTP development, as
well as Dr. Fatma Dedeoglu, Dr. Andrew Eichenfield, Dr. Donald
Goldsmith, Dr. Peri Pepmueller, Dr. Kathryn Phillippi, Dr. Kara Schmidt,
Dr. Rosie Scuccimarri and Dr. Amy Woodward were active participants in
the development of this CTP.
NR 38
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1546-0096
J9 PEDIATR RHEUMATOL
JI Pediatr. Rheumatol.
PD JAN 11
PY 2017
VL 15
AR 1
DI 10.1186/s12969-016-0134-0
PG 8
WC Pediatrics; Rheumatology
SC Pediatrics; Rheumatology
GA EJ1TL
UT WOS:000392993000001
PM 28077146
ER
PT J
AU Pashakhanloo, F
Herzka, DA
Mori, S
Zviman, M
Halperin, H
Gai, N
Bluemke, DA
Trayanova, NA
McVeigh, ER
AF Pashakhanloo, Farhad
Herzka, Daniel A.
Mori, Susumu
Zviman, Muz
Halperin, Henry
Gai, Neville
Bluemke, David A.
Trayanova, Natalia A.
McVeigh, Elliot R.
TI Submillimeter diffusion tensor imaging and late gadolinium enhancement
cardiovascular magnetic resonance of chronic myocardial infarction
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Myocardial infarction; Fiber structure; Microstructural remodeling;
Diffusion tensor imaging; Late gadolinium enhancement
ID HEART-DISEASE; CARDIAC ELECTROPHYSIOLOGY; HISTOLOGICAL VALIDATION; FIBER
ARCHITECTURE; BORDER ZONE; MRI; ORIENTATION; MODELS; RECONSTRUCTION;
ANISOTROPY
AB Background: Knowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and post-infarction electromechanical functioning of the heart. Accurate imaging of infarct microstructure necessitates imaging techniques that produce high image spatial resolution and high signal-to-noise ratio (SNR). The aim of this study is to provide detailed reconstruction of 3D chronic infarcts in order to characterize the infarct microstructural remodeling in porcine and human hearts.
Methods: We employed a customized diffusion tensor imaging (DTI) technique in conjunction with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) on a 3T clinical scanner to image, at submillimeter resolution, myofiber orientation and scar structure in eight chronically infarcted porcine hearts ex vivo. Systematic quantification of local microstructure was performed and the chronic infarct remodeling was characterized at different levels of wall thickness and scar transmurality. Further, a human heart with myocardial infarction was imaged using the same DTI sequence.
Results: The SNR of non-diffusion-weighted images was > 100 in the infarcted and control hearts. Mean diffusivity and fractional anisotropy (FA) demonstrated a 43% increase, and a 35% decrease respectively, inside the scar tissue. Despite this, the majority of the scar showed anisotropic structure with FA higher than an isotropic liquid. The analysis revealed that the primary eigenvector orientation at the infarcted wall on average followed the pattern of original fiber orientation (imbrication angle mean: 1.96 +/- 11.03 degrees vs. 0.84 +/- 1.47 degrees, p = 0.61, and inclination angle range: 111.0 +/- 10.7 degrees vs. 112.5 +/- 6.8 degrees, p = 0.61, infarcted/control wall), but at a higher transmural gradient of inclination angle that increased with scar transmurality (r = 0.36) and the inverse of wall thickness (r = 0.59). Further, the infarcted wall exhibited a significant increase in both the proportion of left-handed epicardial eigenvectors, and in the angle incoherency. The infarcted human heart demonstrated preservation of primary eigenvector orientation at the thinned region of infarct, consistent with the findings in the porcine hearts.
Conclusions: The application of high-resolution DTI and LGE-CMR revealed the detailed organization of anisotropic infarct structure at a chronic state. This information enhances our understanding of chronic post-infarction remodeling in large animal and human hearts.
C1 [Pashakhanloo, Farhad; Herzka, Daniel A.; Trayanova, Natalia A.; McVeigh, Elliot R.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
[Mori, Susumu] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Zviman, Muz; Halperin, Henry; McVeigh, Elliot R.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA.
[Gai, Neville; Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[McVeigh, Elliot R.] Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr MC0412, San Diego, CA 92093 USA.
[McVeigh, Elliot R.] Univ Calif San Diego, Dept Med, 9500 Gilman Dr MC0412, San Diego, CA 92093 USA.
[McVeigh, Elliot R.] Univ Calif San Diego, Dept Radiol, 9500 Gilman Dr MC0412, San Diego, CA 92093 USA.
RP McVeigh, ER (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.; McVeigh, ER (reprint author), Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA.; McVeigh, ER (reprint author), Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr MC0412, San Diego, CA 92093 USA.; McVeigh, ER (reprint author), Univ Calif San Diego, Dept Med, 9500 Gilman Dr MC0412, San Diego, CA 92093 USA.; McVeigh, ER (reprint author), Univ Calif San Diego, Dept Radiol, 9500 Gilman Dr MC0412, San Diego, CA 92093 USA.
EM emcveigh@ucsd.edu
FU National Institutes of Health (NIH) [DP1HL123271]; NIH intramural
research program
FX The authors acknowledge support by the National Institutes of Health
(NIH) Pioneer Award (DP1HL123271) to NT, and the NIH intramural research
program.
NR 45
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U1 2
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 JAN 11
PY 2017
VL 19
AR 9
DI 10.1186/s12968-016-0317-3
PG 14
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA EI7IC
UT WOS:000392670000001
PM 28122618
ER
PT J
AU Monroe, A
Nakigozi, G
Ddaaki, W
Bazaale, JM
Gray, RH
Wawer, MJ
Reynolds, SJ
Kennedy, CE
Chang, LW
AF Monroe, April
Nakigozi, Gertrude
Ddaaki, William
Bazaale, Jeremiah Mulamba
Gray, Ronald H.
Wawer, Maria J.
Reynolds, Steven J.
Kennedy, Caitlin E.
Chang, Larry W.
TI Qualitative insights into implementation, processes, and outcomes of a
randomized trial on peer support and HIV care engagement in Rakai,
Uganda
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE HIV; Pre-ART; Peer support; Randomized controlled trial; Qualitative
research; Linkage; Uganda; Mixed methods research; Implementation
science
ID BEHAVIORAL SKILLS MODEL; ANTIRETROVIRAL THERAPY; RETENTION;
TRANSMISSION; PREVENTION; INITIATION; ADHERENCE; SETTINGS; LINKAGE
AB Background: People living with human immunodeficiency virus (HIV) who have not yet initiated antiretroviral therapy (ART) can benefit from being engaged in care and utilizing preventive interventions. Community-based peer support may be an effective approach to promote these important HIV services.
Methods: After conducting a randomized trial of the impact of peer support on pre-ART outcomes, we conducted a qualitative evaluation to better understand trial implementation, processes, and results. Overall, 75 participants, including trial participants (clients), peer supporters, and clinic staff, participated in 41 in-depth interviews and 6 focus group discussions. A situated Information Motivation, and Behavioral skills model of behavior change was used to develop semi-structured interview and focus group guides. Transcripts were coded and thematically synthesized.
Results: We found that participant narratives were generally consistent with the theoretical model, indicating that peer support improved information, motivation, and behavioral skills, leading to increased engagement in pre-ART care. Clients described how peer supporters reinforced health messages and helped them better understand complicated health information. Peer supporters also helped clients navigate the health system, develop support networks, and identify strategies for remembering medication and clinic appointments. Some peer supporters adopted roles beyond visiting patients, serving as a bridge between the client and his or her family, community, and health system. Qualitative results demonstrated plausible processes by which peer support improved client engagement in care, cotrimoxazole use, and safe water vessel use. Challenges identified included insufficient messaging surrounding ART initiation, lack of care continuity after ART initiation, rare breaches in confidentiality, and structural challenges.
Conclusions: The evaluation found largely positive perceptions of the peer intervention across stakeholders and provided valuable information to inform uptake and scalability of the intervention. Study findings also suggest several areas for improvement for future implementation of pre-ART peer support programs.
C1 [Monroe, April; Kennedy, Caitlin E.; Chang, Larry W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
[Nakigozi, Gertrude; Ddaaki, William; Bazaale, Jeremiah Mulamba] Rakai Hlth Sci Program, Rakai, Uganda.
[Gray, Ronald H.; Wawer, Maria J.; Chang, Larry W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Immunoregulat Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Reynolds, Steven J.; Chang, Larry W.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
RP Chang, LW (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.; Chang, LW (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.; Chang, LW (reprint author), Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
EM lchang8@jhmi.edu
FU National Institute of Mental Health, National Institutes of Health
[K23MH086338]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institute of Health; Johns
Hopkins University Center for AIDS Research [P30AI094189]
FX This study was supported by The National Institute of Mental Health,
National Institutes of Health (K23MH086338), the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institute of Health, and the Johns Hopkins University Center
for AIDS Research (P30AI094189).
NR 24
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD JAN 10
PY 2017
VL 17
AR 54
DI 10.1186/s12879-016-2156-0
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA EP4IV
UT WOS:000397345100005
PM 28068935
ER
PT J
AU Soreq, L
Rose, J
Soreq, E
Hardy, J
Trabzuni, D
Cookson, MR
Smith, C
Ryten, M
Patani, R
Ule, J
AF Soreq, Lilach
Rose, Jamie
Soreq, Eyal
Hardy, John
Trabzuni, Daniah
Cookson, Mark R.
Smith, Colin
Ryten, Mina
Patani, Rickie
Ule, Jernej
CA UK Brain Expression Consortium
North Amer Brain Expression Consor
TI Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark
of Human Brain Aging
SO CELL REPORTS
LA English
DT Article
ID ALZHEIMERS-DISEASE; GENE-EXPRESSION; TRANSGENIC MICE; CEREBRAL-CORTEX;
WHITE-MATTER; OLIGODENDROCYTES; MICROGLIA; NEURONS; CELLS;
NEURODEGENERATION
AB Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region-and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte-and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia-and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.
C1 [Soreq, Lilach; Hardy, John; Trabzuni, Daniah; Ryten, Mina; Patani, Rickie; Ule, Jernej] UCL, Inst Neurol, London WC1N 3BG, England.
[Soreq, Lilach; Patani, Rickie; Ule, Jernej] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England.
[Rose, Jamie; Smith, Colin] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh Brain Bank, MRC,Acad Neuropathol, Edinburgh EH16 4SB, Midlothian, Scotland.
[Soreq, Eyal] Imperial Coll, Div Brain Sci, Computat Cognit & Clin NeuroImaging Lab, London SW7 2AZ, England.
[Hardy, John; Patani, Rickie] UCL ION, Reta Lila Weston Inst Neurol Studies, 1 Wakefield St, London WC1N 1PJ, England.
[Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 12713, Saudi Arabia.
[Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Patani, Rickie] Univ Edinburgh, Euan MacDonald Ctr MND, Edinburgh EH8 9YL, Midlothian, Scotland.
[Ryten, Mina] Kings Coll London, Guys Hosp, Dept Med & Mol Genet, London SE1 9RT, England.
[Patani, Rickie] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England.
RP Patani, R; Ule, J (reprint author), UCL, Inst Neurol, London WC1N 3BG, England.; Patani, R; Ule, J (reprint author), Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England.; Patani, R (reprint author), UCL ION, Reta Lila Weston Inst Neurol Studies, 1 Wakefield St, London WC1N 1PJ, England.; Patani, R (reprint author), Univ Edinburgh, Euan MacDonald Ctr MND, Edinburgh EH8 9YL, Midlothian, Scotland.; Patani, R (reprint author), Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England.
EM rickie.patani@ucl.ac.uk; j.ule@ucl.ac.uk
FU European Research Council [617837]; Marie Curie Intra European
Fellowship [330430]; Alzheimer's Society [172065, 534121]; Francis Crick
Institute; Cancer Research UK [FC001002]; UK Medical Research Council
[FC001002]; Wellcome Trust [FC001002]; UK Medical Research Council (MRC)
through the MRC Sudden Death Brain Bank; Intramural Research Program of
the US National Institute on Aging, NIH, Department of Health and Human
Services [ZO1 AG000947]; King Faisal Specialist Hospital and Research
Centre, Saudi Arabia; US National Institute of Neurological Disorders
and Stroke [U24 NS072026]; National Institute on Aging [P30 AG19610];
Arizona Department of Health Services [211002]; Arizona Biomedical
Research Commission [4001, 0011, 05-901, 1001]; Michael J. Fox
Foundation for Parkinson's Research; Intramural Research Program of the
NIH, National Institute on Aging; [G0901254]; [G0802462]
FX This work was supported by the European Research Council
(617837-Translate) to J.U.; the Marie Curie Intra European Fellowship
(330430-PRANA), and the Alzheimer's Society for Junior Investigator
award (award 172065, project 534121) to L.S.; the Francis Crick
Institute, which receives its core funding from Cancer Research UK
(FC001002), the UK Medical Research Council (FC001002); the Wellcome
Trust (FC001002); the UK Medical Research Council (MRC) through the MRC
Sudden Death Brain Bank to C.S.; a project grant (G0901254) to J.H.and a
training fellowship (G0802462) to M.R.; and in part by the Intramural
Research Program of the US National Institute on Aging, NIH, Department
of Health and Human Services (project ZO1 AG000947). R.P. is a Wellcome
Trust Intermediate Clinical Fellow (101149/Z/13/A) and an Anne Rowling
Fellow in Regenerative Neurology. D.T.was supported by the King Faisal
Specialist Hospital and Research Centre, Saudi Arabia. We are grateful
to the Banner Sun Health Research Institute Brain and Body Donation
Program of Sun City, Arizona, for the provision of human biospecimens.
The Brain and Body Donation Program is supported by the US National
Institute of Neurological Disorders and Stroke (U24 NS072026 to the
National Brain and Tissue Resource for Parkinson's Disease and Related
Disorders), the National Institute on Aging (P30 AG19610 to the Arizona
Alzheimer's Disease Core Center), the Arizona Department of Health
Services (contract 211002 to the Arizona Alzheimer's Research Center),
the Arizona Biomedical Research Commission (contracts 4001, 0011,
05-901, and 1001 to the Arizona Parkinson's Disease Consortium), and the
Michael J.Fox Foundation for Parkinson's Research. This research was
supported in part by the Intramural Research Program of the NIH,
National Institute on Aging.
NR 44
TC 1
Z9 1
U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JAN 10
PY 2017
VL 18
IS 2
BP 557
EP 570
DI 10.1016/j.celrep.2016.12.011
PG 14
WC Cell Biology
SC Cell Biology
GA EO1OQ
UT WOS:000396468200023
PM 28076797
ER
PT J
AU McGarry, A
McDermott, M
Kieburtz, K
de Blieck, EA
Beal, F
Marder, K
Ross, C
Shoulson, I
Gilbert, P
Mallonee, WM
Guttman, M
Wojcieszek, J
Kumar, R
LeDoux, MS
Jenkins, M
Rosas, HD
Nance, M
Biglan, K
Como, P
Dubinsky, RM
Shannon, KM
O'Suilleabhain, P
Chou, K
Walker, F
Martin, W
Wheelock, VL
McCusker, E
Jankovic, J
Singer, C
Sanchez-Ramos, J
Scott, B
Suchowersky, O
Factor, SA
Higgins, DS
Molho, E
Revilla, F
Caviness, JN
Friedman, JH
Perlmutter, JS
Feigin, A
Anderson, K
Rodriguez, R
McFarland, NR
Margolis, RL
Farbman, ES
Raymond, LA
Suski, V
Kostyk, S
Colcher, A
Seeberger, L
Epping, E
Esmail, S
Diaz, N
Fung, WLA
Diamond, A
Frank, S
Hanna, P
Hermanowicz, N
Dure, LS
Cudkowicz, M
AF McGarry, Andrew
McDermott, Michael
Kieburtz, Karl
de Blieck, Elisabeth A.
Beal, Flint
Marder, Karen
Ross, Christopher
Shoulson, Ira
Gilbert, Peter
Mallonee, William M.
Guttman, Mark
Wojcieszek, Joanne
Kumar, Rajeev
LeDoux, Mark S.
Jenkins, Mary
Rosas, H. Diana
Nance, Martha
Biglan, Kevin
Como, Peter
Dubinsky, Richard M.
Shannon, Kathleen M.
O'Suilleabhain, Padraig
Chou, Kelvin
Walker, Francis
Martin, Wayne
Wheelock, Vicki L.
McCusker, Elizabeth
Jankovic, Joseph
Singer, Carlos
Sanchez-Ramos, Juan
Scott, Burton
Suchowersky, Oksana
Factor, Stewart A.
Higgins, Donald S., Jr.
Molho, Eric
Revilla, Fredy
Caviness, John N.
Friedman, Joseph H.
Perlmutter, Joel S.
Feigin, Andrew
Anderson, Karen
Rodriguez, Ramon
McFarland, Nikolaus R.
Margolis, Russell L.
Farbman, Eric S.
Raymond, Lynn A.
Suski, Valerie
Kostyk, Sandra
Colcher, Amy
Seeberger, Lauren
Epping, Eric
Esmail, Sherali
Diaz, Nancy
Fung, Wai Lun Alan
Diamond, Alan
Frank, Samuel
Hanna, Philip
Hermanowicz, Neal
Dure, Leon S.
Cudkowicz, Merit
CA Huntington Study Grp 2CARE
TI A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in
Huntington disease
SO NEUROLOGY
LA English
DT Article
ID TRANSGENIC MOUSE MODEL; ENERGY-METABOLISM; CLINICAL-TRIALS; IN-VIVO;
Q(10); CREATINE; IMPAIRMENT; REMACEMIDE; DEFECTS; MICE
AB Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD.
Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach.
Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study.
Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD.
ClinicalTrials.gov identifier: NCT00608881.
Classification of evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD. Neurology (R) 2017;88:152-159
C1 [McGarry, Andrew] Rowan Univ, Cooper Univ Healthcare, Camden, NJ 08102 USA.
[McDermott, Michael; Kieburtz, Karl; de Blieck, Elisabeth A.; Biglan, Kevin; Como, Peter] Univ Rochester, Rochester, NY 14627 USA.
[Beal, Flint] Weill Cornell Med Ctr, New York, NY USA.
[Marder, Karen] Columbia Presbyterian Med Ctr, New York, NY 10032 USA.
[Ross, Christopher] Johns Hopkins Med Ctr, Baltimore, MD USA.
[Shoulson, Ira; Anderson, Karen] Georgetown Univ, Washington, DC USA.
[Gilbert, Peter] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Mallonee, William M.] Hereditary Neurol Dis Ctr, Wichita, KS USA.
[Guttman, Mark] Ctr Movement Disorders, Toronto, ON, Canada.
[Wojcieszek, Joanne] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Kumar, Rajeev] Colorado Neurol Inst, Englewood, CO USA.
[LeDoux, Mark S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Jenkins, Mary] London Hlth Sci Ctr, London, ON, Canada.
[Rosas, H. Diana] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nance, Martha] Struthers Parkinsons Ctr, Minneapolis, MN USA.
[Dubinsky, Richard M.] Univ Kansas Med Ctr, Kansas City, KS USA.
[Shannon, Kathleen M.] Rush Univ Med Ctr, Chicago, IL USA.
[O'Suilleabhain, Padraig] Univ Texas Southwestern Med Ctr, Dallas, TX USA.
[Chou, Kelvin] Univ Michigan, Ann Arbor, MI 48109 USA.
[Walker, Francis] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Martin, Wayne] Univ Alberta, Edmonton, AB, Canada.
[Wheelock, Vicki L.] Univ Calif Davis, Sacramento, CA 95817 USA.
[McCusker, Elizabeth] Westmead Hosp, Westmead, NSW, Australia.
[Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA.
[Singer, Carlos] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA.
[Sanchez-Ramos, Juan] Univ S Florida, Tampa, FL USA.
[Scott, Burton] Duke Univ, Durham, NC USA.
[Suchowersky, Oksana] Univ Calgary, Calgary, AB T2N 1N4, Canada.
[Factor, Stewart A.] Emory Univ, Sch Med, Atlanta, GA USA.
[Higgins, Donald S., Jr.; Molho, Eric] Albany Med Coll, Albany, NY 12208 USA.
[Revilla, Fredy] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Caviness, John N.] Mayo Clin Arizona, Scottsdale, AZ USA.
[Friedman, Joseph H.] Butler Hosp, Providence, RI 02906 USA.
[Perlmutter, Joel S.] Washington Univ, St Louis, MO USA.
[Feigin, Andrew] Feinstein Inst Med Res, Manhasset, NY USA.
[Rodriguez, Ramon; McFarland, Nikolaus R.] Univ Florida, Gainesville, FL USA.
[Margolis, Russell L.] Johns Hopkins Univ, Baltimore, MD USA.
[Farbman, Eric S.] Univ Nevada, Sch Med, Reno, NV 89557 USA.
[Raymond, Lynn A.] Univ British Columbia, Vancouver, BC, Canada.
[Suski, Valerie] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Kostyk, Sandra] Ohio State Univ, Columbus, OH 43210 USA.
[Colcher, Amy] Cooper Univ Hlth Syst, Camden, NJ USA.
[Seeberger, Lauren] Idaho Elks Rehabil Hosp, Boise, ID USA.
[Epping, Eric] Univ Iowa, Iowa City, IA USA.
[Esmail, Sherali] North York Gen Hosp 1, Toronto, ON, Canada.
[Diaz, Nancy] St Lukes Hosp, Allentown, PA USA.
[Fung, Wai Lun Alan] Univ Toronto, North York Gen Hosp 2, Toronto, ON M5S 1A1, Canada.
[Diamond, Alan] Washington Reg Med Ctr, Fayetteville, AR USA.
[Frank, Samuel] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Hanna, Philip] NJ Neurosci Inst, Edison, NJ USA.
[Hermanowicz, Neal] Univ Calif Irvine, Irvine, CA 92717 USA.
[Dure, Leon S.] Univ Alabama Birmingham, Birmingham, AL USA.
[Cudkowicz, Merit] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
RP McGarry, A (reprint author), Rowan Univ, Cooper Univ Healthcare, Camden, NJ 08102 USA.
EM mcgarry-andrew@cooperhealth.edu
RI Raymond, Lynn/A-6664-2010
OI Raymond, Lynn/0000-0002-8610-1042
FU National Institute of Neurological Disorders and Stroke [NS052592,
NS052619]
FX Study funded by National Institute of Neurological Disorders and Stroke
(grants NS052592 and NS052619).
NR 34
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JAN 10
PY 2017
VL 88
IS 2
BP 152
EP 159
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA EO2YH
UT WOS:000396561500011
PM 27913695
ER
PT J
AU Cnaan, A
Shinnar, S
Arya, R
Adamson, PC
Clark, PO
Dlugos, D
Hirtz, DG
Masur, D
Glauser, TA
AF Cnaan, Avital
Shinnar, Shlomo
Arya, Ravindra
Adamson, Peter C.
Clark, Peggy O.
Dlugos, Dennis
Hirtz, Deborah G.
Masur, David
Glauser, Tracy A.
CA Childhood Absence Epilepsy Study
TI Second monotherapy in childhood absence epilepsy
SO NEUROLOGY
LA English
DT Article
ID CENSORED SURVIVAL-DATA; TONIC-CLONIC SEIZURES; INITIAL MONOTHERAPY;
ANTIEPILEPTIC DRUG; ONSET EPILEPSY; VALPROIC ACID; OUTCOMES;
CARBAMAZEPINE; ETHOSUXIMIDE; LAMOTRIGINE
AB Objective: To determine optimal second monotherapy for children with childhood absence epilepsy (CAE) experiencing initial treatment failure.
Methods: Children with CAE experiencing treatment failure during the double-blind phase of a randomized controlled trial comparing ethosuximide, valproic acid, and lamotrigine were randomized to open-label second monotherapy with one of the 2 other study therapies. Primary study outcome was freedom from failure proportion at week 16-20 and month 12 visits after randomization. Secondary study outcome was percentage of participants experiencing attentional dysfunction at these visits.
Results: A total of 208 children were enrolled, randomized, and received second therapy. At both week 16-20 visit and month 12 visit, ethosuximide's (63%, 57%) and valproic acid's (65%, 49%) freedom from failure proportions were similar to each other and higher than lamotrigine's (45%, 36%, p = 0.051 and p = 0.062). At both time points, ethosuximide and valproic acid had superior seizure control compared to lamotrigine (p < 0.0001). At both the week 16-20 and month 12 visits, attentional dysfunction was numerically more common with valproic acid than with ethosuximide or lamotrigine. For each medication, second monotherapy freedom from failure proportions demonstrated noninferiority to initial monotherapy freedom from failure proportions.
Conclusions: As second monotherapy, ethosuximide and valproic acid, demonstrated higher freedom from failure proportions and greater efficacy than lamotrigine; valproic acid was associated with more attentional dysfunction. Ethosuximide is the optimal second monotherapy for children with CAE not responding to initial therapy with other medications.
C1 [Cnaan, Avital] Childrens Natl Hlth Syst, Washington, DC USA.
[Shinnar, Shlomo; Masur, David] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA.
[Arya, Ravindra; Clark, Peggy O.; Glauser, Tracy A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Arya, Ravindra; Clark, Peggy O.; Glauser, Tracy A.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA.
[Adamson, Peter C.; Dlugos, Dennis] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Adamson, Peter C.; Dlugos, Dennis] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hirtz, Deborah G.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Cnaan, A (reprint author), Childrens Natl Hlth Syst, Washington, DC USA.
EM acnaan@trinds.com
FU NIH [U01-NS045911, U01-NS045803]
FX Supported by NIH (U01-NS045911 and U01-NS045803).
NR 25
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JAN 10
PY 2017
VL 88
IS 2
BP 182
EP 190
DI 10.1212/WNL.0000000000003480
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA EO2YH
UT WOS:000396561500016
PM 27986874
ER
PT J
AU Liu, S
Zhang, F
Shugart, YY
Yang, L
Li, X
Liu, Z
Sun, N
Yang, C
Guo, X
Shi, J
Wang, L
Cheng, L
Zhang, K
Yang, T
Xu, Y
AF Liu, S.
Zhang, F.
Shugart, Y. Y.
Yang, L.
Li, X.
Liu, Z.
Sun, N.
Yang, C.
Guo, X.
Shi, J.
Wang, L.
Cheng, L.
Zhang, K.
Yang, T.
Xu, Y.
TI The early growth response protein 1-miR-30a-5p-neurogenic
differentiation factor 1 axis as a novel biomarker for schizophrenia
diagnosis and treatment monitoring
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID POTENTIAL PERIPHERAL MARKER; PREFRONTAL CORTEX; GENE-EXPRESSION;
MICROARRAY ANALYSIS; MICRORNA EXPRESSION; EARLY INTERVENTION;
MONONUCLEAR-CELLS; TEMPORAL CORTEX; HUMAN-DISEASE; C-ELEGANS
AB To date, diagnosis of schizophrenia is still based on clinical interviews and careful observations, which is subjective and variable, and can lead to misdiagnosis and/or delay in diagnosis. As early intervention in schizophrenia is important in improving outcomes, objective tests that can be used for schizophrenia diagnosis or treatment monitoring are thus in great need. MicroRNAs (miRNAs) negatively regulate target gene expression and their biogenesis is tightly controlled by various factors including transcription factors (TFs). Dysregulation of miRNAs in brain tissue and peripheral blood mononuclear cells (PBMNCs) from patients with schizophrenia has been well documented, but analysis of the sensitivity and specificity for potential diagnostic utility of these alternations is limited. In this study, we explored the TF-miRNA-30-target gene axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring. Using bioinformatics analysis, we retrieved all TFs that control the biogenesis of miRNA 30 members as well as all target genes that are regulated by miRNA-30 members. Further, reverse transcription-quantitative PCR analysis revealed that the early growth response protein 1 (EGR1) and miR-30a-5p were remarkably downregulated, whereas neurogenic differentiation factor 1 (NEUROD1) was significantly upregulated in PBMNCs from patients in acute psychotic state. Antipsychotics treatment resulted in the elevation of EGR1 and miR-30a-5p but the reduction of NEUROD1. Receiver operating characteristic analysis showed that the EGR1-miR-30a-5p-NEUROD1 axis possessed significantly greater diagnostic value than miR-30a-5p alone. Our data suggest the EGR1-miR-30a-5p-NEUROD1 axis might serve as a promising biomarker for diagnosis and treatment monitoring for those patients in acute psychotic state.
C1 [Liu, S.; Li, X.; Liu, Z.; Sun, N.; Yang, C.; Guo, X.; Shi, J.; Wang, L.; Cheng, L.; Zhang, K.; Xu, Y.] Shanxi Med Univ, Hosp 1, Dept Psychiat, Taiyuan, Peoples R China.
[Zhang, F.] Wuxi Mental Hlth Ctr, Wuxi, Peoples R China.
[Shugart, Y. Y.] NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Yang, L.; Yang, T.] Shanxi Med Univ, Dept Biochem & Mol Biol, Taiyuan 030001, Peoples R China.
[Guo, X.; Shi, J.; Wang, L.; Cheng, L.; Zhang, K.; Xu, Y.] Shanxi Med Univ, Clin Med Coll 1, Taiyuan, Peoples R China.
RP Yang, T (reprint author), Shanxi Med Univ, Dept Biochem & Mol Biol, Taiyuan 030001, Peoples R China.; Xu, Y (reprint author), Shanxi Med Univ, Clin Med Coll 1, Hosp 1, Dept Psychiat, Taiyuan 030001, Peoples R China.
EM yangtao056cn@126.com; xuyongshanxi@sina.com
FU National Natural Science Foundation of China [81271482, 81471364,
81571319]; Program for New Century Excellent Talents [NCET-121036];
Construction Plan for Shanxi Science & Technology Infrastructure
Platforms [2015091002-0102]; Natural Science Foundation of Shanxi
[201601D021150]; Doctoral Fund of Shanxi Medical University [03201314];
Intramural Research Program of National Institute of Mental Health,
National Institutes of Health [MH002929-04]
FX We sincerely thank all the subjects for their support and participation
in this study. We are indebted to staff at the blood lab who helped
collect blood samples. This work was supported by the National Natural
Science Foundation of China (81271482, 81471364 and 81571319); the
Program for New Century Excellent Talents (NCET-121036); the
Construction Plan for Shanxi Science & Technology Infrastructure
Platforms (2015091002-0102); Natural Science Foundation of Shanxi
(201601D021150); and the Doctoral Fund of Shanxi Medical University
(03201314). Shugart was supported by the Intramural Research Program of
National Institute of Mental Health, National Institutes of Health
(MH002929-04).
NR 47
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JAN 10
PY 2017
VL 7
AR e998
DI 10.1038/tp.2016.268
PG 7
WC Psychiatry
SC Psychiatry
GA EO1IA
UT WOS:000396450700006
PM 28072411
ER
PT J
AU McEvoy, JW
Martin, SS
Dardari, ZA
Miedema, MD
Sandfort, V
Yeboah, J
Budoff, MJ
Goff, DC
Psaty, BM
Post, WS
Nasir, K
Blumenthal, RS
Blaha, MJ
AF McEvoy, John W.
Martin, Seth S.
Dardari, Zeina A.
Miedema, Michael D.
Sandfort, Veit
Yeboah, Joseph
Budoff, Matthew J.
Goff, David C., Jr.
Psaty, Bruce M.
Post, Wendy S.
Nasir, Khurram
Blumenthal, Roger S.
Blaha, Michael J.
TI Coronary Artery Calcium to Guide a Personalized Risk-Based Approach to
Initiation and Intensification of Antihypertensive Therapy
SO CIRCULATION
LA English
DT Article
DE antihypertensive therapy; cardiovascular disease risk; coronary artery
calcium; systolic blood pressure
ID BLOOD-PRESSURE; CARDIOVASCULAR RISK; RANDOMIZED-TRIALS; HEART-DISEASE;
ATHEROSCLEROSIS; INDIVIDUALS; HYPERTENSION; METAANALYSIS; POPULATION;
PREVENTION
AB BACKGROUND: The use of atherosclerotic cardiovascular disease (ASCVD) risk to personalize systolic blood pressure (SBP) treatment goals is a topic of increasing interest. Therefore, we studied whether coronary artery calcium (CAC) can further guide the allocation of anti-hypertensive treatment intensity.
METHODS: We included 3733 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with SBP between 120 and 179 mm Hg. Within subgroups categorized by both SBP (120-139 mm Hg, 140-159 mm Hg, and 160-179 mm Hg) and estimated 10-year ASCVD risk (using the American College of Cardiology/American Heart Assocation pooled-cohort equations), we compared multivariable-adjusted hazard ratios for the composite outcome of incident ASCVD or heart failure after further stratifying by CAC (0, 1-100, or >100). We estimated 10-year number-needed-to-treat for an intensive SBP goal of 120 mm Hg by applying the treatment benefit recorded in meta-analyses to event rates within CAC strata.
RESULTS: The mean age was 65 years, and 642 composite events took place over a median of 10.2 years. In persons with SBP <160 mm Hg, CAC stratified risk for events. For example, among those with an ASCVD risk of <15% and who had an SBP of either 120 to 139 mm Hg or 140 to 159 mm Hg, respectively, we found increasing hazard ratios for events with CAC 1 to 100 (1.7 [95% confidence interval, 1.0-2.6] or 2.0 [1.1-3.8]) and CAC >100 (3.0 [1.8-5.0] or 5.7 [2.9-11.0]), all relative to CAC= 0. There appeared to be no statistical association between CAC and events when SBP was 160 to 179 mm Hg, irrespective of ASCVD risk level. Estimated 10-year number-needed-to-treat for a SBP goal of 120mmHg varied substantially according to CAC levels when predicted ASCVD risk <15% and SBP <160mmHg (eg, 10-year number-needed-to-treat of 99 for CAC= 0 and 24 for CAC>100, when SBP 120-139mm Hg). However, few participants with ASCVD risk <5% had elevated CAC. Furthermore, 10-year number-needed-to-treat estimates were consistently low and varied less among CAC strata when SBP was 160 to 179 mm Hg or when ASCVD risk was >= 15% at any SBP level.
CONCLUSIONS: Combined CAC imaging and assessment of global ASCVD risk has the potential to guide personalized SBP goals (eg, choosing a traditional goal of 140 or a more intensive goal of 120 mm Hg), particularly among adults with an estimated ASCVD risk of 5% to 15% and prehypertension or mild hypertension.
C1 [McEvoy, John W.; Martin, Seth S.; Dardari, Zeina A.; Post, Wendy S.; Nasir, Khurram; Blumenthal, Roger S.; Blaha, Michael J.] Johns Hopkins Univ, Sch Med, Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA.
[Miedema, Michael D.] Minneapolis Heart Inst, Minneapolis, MN USA.
[Miedema, Michael D.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA.
[Sandfort, Veit] NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
[Yeboah, Joseph] Wake Forest Baptist Hlth, Heart & Vasc Ctr Excellence, Winston Salem, NC USA.
[Budoff, Matthew J.] Harbor UCLA, Los Angeles Biomed Res Inst, Torrance, CA USA.
[Goff, David C., Jr.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Nasir, Khurram] Baptist Hlth South Florida, Ctr Healthcare Adv & Outcomes, South Miami, FL USA.
[Nasir, Khurram] Baptist Hlth South Florida, Miami Cardiac & Vasc Inst, South Miami, FL USA.
RP McEvoy, JW (reprint author), Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Blalock 524C,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jmcevoy1@jhmi.edu
FU National Heart, Lung, and Blood Institute [HHS-N268201500003I,
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-TR-001079]
FX This research was supported by contracts HHS-N268201500003I,
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
grants UL1-TR-000040 and UL1-TR-001079 from the National Center for
Research Resources.
NR 34
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 10
PY 2017
VL 135
IS 2
BP 153
EP +
DI 10.1161/CIRCULATIONAHA.116.025471
PG 30
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA EI2AW
UT WOS:000392289500012
PM 27881560
ER
PT J
AU Bruno, RD
Fleming, JM
George, AL
Boulanger, CA
Schedin, P
Smith, GH
AF Bruno, Robert D.
Fleming, Jodie M.
George, Andrea L.
Boulanger, Corinne A.
Schedin, Pepper
Smith, Gilbert H.
TI Mammary extracellular matrix directs differentiation of testicular and
embryonic stem cells to form functional mammary glands in vivo
SO SCIENTIFIC REPORTS
LA English
DT Article
ID BREAST-CANCER; EPITHELIAL PROGENITOR; MICROENVIRONMENT; PREGNANCY;
EXPRESSION; PHENOTYPE; BEHAVIOR; CULTURE; GENES; FATE
AB Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo.
C1 [Bruno, Robert D.] Old Dominion Univ, Coll Hlth Sci, Sch Med Diagnost & Translat Sci, Norfolk, VA 23529 USA.
[Fleming, Jodie M.] North Carolina Cent Univ, Dept Biol & Biomed Sci, Durham, NC 27707 USA.
[George, Andrea L.; Boulanger, Corinne A.; Smith, Gilbert H.] NCI, Mammary Stem Cell Biol Sect, Basic Res Lab, CCR,NIH, Bethesda, MD 20892 USA.
[Schedin, Pepper] Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
RP Smith, GH (reprint author), NCI, Mammary Stem Cell Biol Sect, Basic Res Lab, CCR,NIH, Bethesda, MD 20892 USA.
EM smithg@mail.nih.gov
FU NCI NIH HHS [R01 CA169175]
NR 35
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 10
PY 2017
VL 7
AR 40196
DI 10.1038/srep40196
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EI1LF
UT WOS:000392238100001
PM 28071703
ER
PT J
AU Siersbaek, M
Varticovski, L
Yang, ST
Baek, S
Nielsen, R
Mandrup, S
Hager, GL
Chung, JH
Grontved, L
AF Siersbaek, Majken
Varticovski, Lyuba
Yang, Shutong
Baek, Songjoon
Nielsen, Ronni
Mandrup, Susanne
Hager, Gordon L.
Chung, Jay H.
Grontved, Lars
TI High fat diet-induced changes of mouse hepatic transcription and
enhancer activity can be reversed by subsequent weight loss
SO SCIENTIFIC REPORTS
LA English
DT Article
ID REACTOME PATHWAY KNOWLEDGEBASE; CONTAINING 2 GENE; LIVER-DISEASE;
CHROMATIN ACCESSIBILITY; DEFICIENCY PROTECTS; INDUCED OBESITY; C57BL/6J
MICE; EXPRESSION PROFILES; HUMAN GENOME; RNA-SEQ
AB Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers. After return to the same body weight as chow fed control mice, the fasting insulin, glucose, and hepatic triglyceride levels were fully restored to normal levels. Moreover, HFD-regulated H3K27Ac and mRNA levels returned to similar levels as control mice. These data demonstrates that the transcription regulatory landscape in the liver induced by HFD is highly dynamic and can be reversed by weight loss. This provides hope for efficient treatment of early obesity-associated changes to hepatic complications by simple weight loss intervention without persistent reprograming of the liver transcriptome.
C1 [Siersbaek, Majken; Nielsen, Ronni; Mandrup, Susanne; Grontved, Lars] Univ Southern Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark.
[Varticovski, Lyuba; Baek, Songjoon; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yang, Shutong; Chung, Jay H.] NHLBI, Lab Obes & Aging Res, Genet & Dev Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Grontved, L (reprint author), Univ Southern Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark.
EM larsgr@bmb.sdu.dk
OI Grontved, Lars/0000-0002-6735-8483
FU Danish Independent Research Council; VILLUM Foundation
FX This study was supported by a research grant to LG from the Danish
Independent Research Council. Furthermore, the work was supported by the
VILLUM Foundation to the VILLUM Center for Bioanalytical Sciences at
University of Southern Denmark.
NR 60
TC 0
Z9 0
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 10
PY 2017
VL 7
AR 40220
DI 10.1038/srep40220
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EI1LV
UT WOS:000392239800001
PM 28071704
ER
PT J
AU Dogan, RI
Kim, S
Chatr-Aryamontri, A
Chang, CS
Oughtred, R
Rust, J
Wilbur, WJ
Comeau, DC
Dolinski, K
Tyers, M
AF Dogan, Rezarta Islamaj
Kim, Sun
Chatr-aryamontri, Andrew
Chang, Christie S.
Oughtred, Rose
Rust, Jennifer
Wilbur, W. John
Comeau, Donald C.
Dolinski, Kara
Tyers, Mike
TI The BioC-BioGRID corpus: full text articles annotated for curation of
protein-protein and genetic interactions
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID BIOLOGY; CHALLENGE; COMMUNITY
AB A great deal of information on the molecular genetics and biochemistry of model organisms has been reported in the scientific literature. However, this data is typically described in free text form and is not readily amenable to computational analyses. To this end, the BioGRID database systematically curates the biomedical literature for genetic and protein interaction data. This data is provided in a standardized computationally tractable format and includes structured annotation of experimental evidence. BioGRID curation necessarily involves substantial human effort by expert curators who must read each publication to extract the relevant information. Computational text-mining methods offer the potential to augment and accelerate manual curation. To facilitate the development of practical text-mining strategies, a new challenge was organized in BioCreative V for the BioC task, the collaborative Biocurator Assistant Task. This was a noncompetitive, cooperative task in which the participants worked together to build BioCcompatible modules into an integrated pipeline to assist BioGRID curators. As an integral part of this task, a test collection of full text articles was developed that contained both biological entity annotations (gene/protein and organism/species) and molecular interaction annotations (protein-protein and genetic interactions (PPIs and GIs)). This collection, which we call the BioC-BioGRID corpus, was annotated by four BioGRID curators over three rounds of annotation and contains 120 full text articles curated in a dataset representing two major model organisms, namely budding yeast and human. The BioC-BioGRID corpus contains annotations for 6409 mentions of genes and their Entrez Gene IDs, 186 mentions of organism names and their NCBI Taxonomy IDs, 1867 mentions of PPIs and 701 annotations of PPI experimental evidence statements, 856 mentions of GIs and 399 annotations of GI evidence statements. The purpose, characteristics and possible future uses of the BioC-BioGRID corpus are detailed in this report.
C1 [Dogan, Rezarta Islamaj; Kim, Sun; Wilbur, W. John; Comeau, Donald C.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Chatr-aryamontri, Andrew; Tyers, Mike] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
[Chang, Christie S.; Oughtred, Rose; Rust, Jennifer; Dolinski, Kara] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
[Tyers, Mike] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
RP Dogan, RI (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM Rezarta.Islamaj@nih.gov
FU NIH, National Library of Medicine; National Institutes of Health
[R01OD010929, R24OD011194]
FX Intramural Research Program of the NIH, National Library of Medicine to
R.I.D., S.K., W.J.W. and D.C.C.; National Institutes of Health
R01OD010929 to M.T. and K.D., National Institutes of Health R24OD011194
to K.D. and M.T.
NR 24
TC 0
Z9 0
U1 6
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD JAN 10
PY 2017
AR baw147
DI 10.1093/database/baw147
PG 11
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA EH0ZQ
UT WOS:000391493500001
ER
PT J
AU El Kennani, S
Adrait, A
Shaytan, AK
Khochbin, S
Bruley, C
Panchenko, AR
Landsman, D
Pflieger, D
Govin, J
AF El Kennani, Sara
Adrait, Annie
Shaytan, Alexey K.
Khochbin, Saadi
Bruley, Christophe
Panchenko, Anna R.
Landsman, David
Pflieger, Delphine
Govin, Jerome
TI MS_HistoneDB, a manually curated resource for proteomic analysis of
human and mouse histones
SO EPIGENETICS & CHROMATIN
LA English
DT Article
DE Histone; Histone variants; Chromatin; Mass spectrometry; Proteomics
ID DOWN MASS-SPECTROMETRY; INACTIVE X-CHROMOSOME; CENP-A; MESSENGER-RNA;
MAMMALIAN SPERMIOGENESIS; H1-LIKE PROTEIN; GENE-EXPRESSION;
CHROMATIN-STRUCTURE; SEQUENCE-ANALYSIS; VARIANT H2A.BBD
AB Background: Histones and histone variants are essential components of the nuclear chromatin. While mass spectrometry has opened a large window to their characterization and functional studies, their identification from proteomic data remains challenging. Indeed, the current interpretation of mass spectrometry data relies on public databases which are either not exhaustive (Swiss-Prot) or contain many redundant entries (UniProtKB or NCBI). Currently, no protein database is ideally suited for the analysis of histones and the complex array of mammalian histone variants.
Results: We propose two proteomics-oriented manually curated databases for mouse and human histone variants. We manually curated >1700 gene, transcript and protein entries to produce a non-redundant list of 83 mouse and 85 human histones. These entries were annotated in accordance with the current nomenclature and unified with the "HistoneDB2.0 with Variants" database. This resource is provided in a format that can be directly read by programs used for mass spectrometry data interpretation. In addition, it was used to interpret mass spectrometry data acquired on histones extracted from mouse testis. Several histone variants, which had so far only been inferred by homology or detected at the RNA level, were detected by mass spectrometry, confirming the existence of their protein form.
Conclusions: Mouse and human histone entries were collected from different databases and subsequently curated to produce a non-redundant protein-centric resource, MS_HistoneDB. It is dedicated to the proteomic study of histones in mouse and human and will hopefully facilitate the identification and functional study of histone variants.
C1 [El Kennani, Sara; Adrait, Annie; Bruley, Christophe; Pflieger, Delphine; Govin, Jerome] Univ Grenoble Alpes, INSERM, CEA, BIG,FR,CNRS,BGE 3425,U1038, Grenoble, France.
[Shaytan, Alexey K.; Panchenko, Anna R.; Landsman, David] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Khochbin, Saadi] Univ Grenoble Alpes, Inst Adv Biosci, INSERM, CNRS,UMR 5309,U1209, Grenoble, France.
RP Pflieger, D; Govin, J (reprint author), Univ Grenoble Alpes, INSERM, CEA, BIG,FR,CNRS,BGE 3425,U1038, Grenoble, France.
EM Delphine.Pflieger@cea.fr; Jerome.Govin@inserm.fr
RI Shaytan, Alexey/D-7306-2012;
OI Shaytan, Alexey/0000-0003-0312-938X; Govin, Jerome/0000-0001-5511-6965
FU Fond d'Intervention of the University Grenoble Alpes; Agence Nationale
de la Recherche [ANR-11-PDOC-0011]; European Union FP7 Marie Curie
Action "Career Integration Grant" [304003]; French National Research
Agency [ANR-10-INBS-08]; Intramural Research Program of the National
Library of Medicine, National Institutes of Health
FX This work was supported by the Fond d'Intervention of the University
Grenoble Alpes (to JG), the Agence Nationale de la Recherche
(ANR-11-PDOC-0011 to JG), and the European Union FP7 Marie Curie Action
"Career Integration Grant" (304003 to JG). This study also received
financial support from the French National Research Agency
ANR-10-INBS-08 ProFI, Proteomics French Infrastructure. This research
was supported by the Intramural Research Program of the National Library
of Medicine, National Institutes of Health.
NR 131
TC 0
Z9 0
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8935
J9 EPIGENET CHROMATIN
JI Epigenetics Chromatin
PD JAN 10
PY 2017
VL 10
AR 2
DI 10.1186/s13072-016-0109-x
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA EH1HE
UT WOS:000391513800001
PM 28096900
ER
PT J
AU Volkow, ND
Compton, WM
Wargo, EM
AF Volkow, Nora D.
Compton, Wilson M.
Wargo, Eric M.
TI The Risks of Marijuana Use During Pregnancy
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Volkow, Nora D.; Compton, Wilson M.; Wargo, Eric M.] NIDA, NIH, Bethesda, MD 20892 USA.
RP Wargo, EM (reprint author), NIDA, Off Sci Policy & Commun, Sci Policy Branch, 6001 Execut Blvd,Room 5235, Bethesda, MD 20892 USA.
EM wargoem@nida.nih.gov
NR 6
TC 0
Z9 0
U1 11
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 10
PY 2017
VL 317
IS 2
BP 129
EP 130
DI 10.1001/jama.2016.18612
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA EH5PV
UT WOS:000391826200009
PM 27992628
ER
PT J
AU Mills, JL
AF Mills, James L.
TI Strategies for Preventing Folate-Related Neural Tube Defects
Supplements, Fortified Foods, or Both?
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID FOLIC-ACID FORTIFICATION; UNITED-STATES; TRENDS; EUROPE
C1 [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Epidemiol Branch, 6710B Bldg,Room 3117, Bethesda, MD 20892 USA.
RP Mills, JL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Epidemiol Branch, 6710B Bldg,Room 3117, Bethesda, MD 20892 USA.
EM jamesmills@nih.gov
FU Intramural Research Program, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
FX This research was supported by the Intramural Research Program, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 15
TC 0
Z9 0
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 10
PY 2017
VL 317
IS 2
BP 144
EP 145
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA EH5PV
UT WOS:000391826200016
PM 28097344
ER
PT J
AU Forouzanfar, MH
Liu, P
Roth, GA
Ng, M
Biryukov, S
Marczak, L
Alexander, L
Estep, K
Abate, KH
Akinyemiju, TF
Ali, R
Alvis-Guzman, N
Azzopardi, P
Banerjee, A
Barnighausen, T
Basu, A
Bekele, T
Bennett, DA
Biadgilign, S
Catala-Lopez, F
Feigin, VL
Fernandes, JC
Fischer, F
Gebru, AA
Gona, P
Gupta, R
Hankey, GJ
Jonas, JB
Judd, SE
Khang, YH
Khosravi, A
Kim, YJ
Kimokoti, RW
Kokubo, Y
Kolte, D
Lopez, A
Lotufo, PA
Malekzadeh, R
Melaku, YA
Mensah, GA
Misganaw, A
Mokdad, AH
Moran, AE
Nawaz, H
Neal, B
Ngalesoni, FN
Ohkubo, T
Pourmalek, F
Rafay, A
Rai, RK
Rojas-Rueda, D
Sampson, UK
Santos, IS
Sawhney, M
Schutte, AE
Sepanlou, SG
Shifa, GT
Shiue, I
Tedla, BA
Thrift, AG
Tonelli, M
Truelsen, T
Tsilimparis, N
Ukwaja, KN
Uthman, OA
Vasankari, T
Venketasubramanian, N
Vlassov, VV
Vos, T
Westerman, R
Yan, LJL
Yano, Y
Yonemoto, N
Zaki, MES
Murray, CJL
AF Forouzanfar, Mohammad H.
Liu, Patrick
Roth, Gregory A.
Ng, Marie
Biryukov, Stan
Marczak, Laurie
Alexander, Lily
Estep, Kara
Abate, Kalkidan Hassen
Akinyemiju, Tomi F.
Ali, Raghib
Alvis-Guzman, Nelson
Azzopardi, Peter
Banerjee, Amitava
Baernighausen, Till
Basu, Arindam
Bekele, Tolesa
Bennett, Derrick A.
Biadgilign, Sibhatu
Catala-Lopez, Ferran
Feigin, Valery L.
Fernandes, Joao C.
Fischer, Florian
Gebru, Alemseged Aregay
Gona, Philimon
Gupta, Rajeev
Hankey, Graeme J.
Jonas, Jost B.
Judd, Suzanne E.
Khang, Young-Ho
Khosravi, Ardeshir
Kim, Yun Jin
Kimokoti, Ruth W.
Kokubo, Yoshihiro
Kolte, Dhaval
Lopez, Alan
Lotufo, Paulo A.
Malekzadeh, Reza
Melaku, Yohannes Adama
Mensah, George A.
Misganaw, Awoke
Mokdad, Ali H.
Moran, Andrew E.
Nawaz, Haseeb
Neal, Bruce
Ngalesoni, Frida Namnyak
Ohkubo, Takayoshi
Pourmalek, Farshad
Rafay, Anwar
Rai, Rajesh Kumar
Rojas-Rueda, David
Sampson, Uchechukwu K.
Santos, Itamar S.
Sawhney, Monika
Schutte, Aletta E.
Sepanlou, Sadaf G.
Shifa, Girma Temam
Shiue, Ivy
Tedla, Bemnet Amare
Thrift, Amanda G.
Tonelli, Marcello
Truelsen, Thomas
Tsilimparis, Nikolaos
Ukwaja, Kingsley Nnanna
Uthman, Olalekan A.
Vasankari, Tommi
Venketasubramanian, Narayanaswamy
Vlassov, Vasiliy Victorovich
Vos, Theo
Westerman, Ronny
Yan, Lijing L.
Yano, Yuichiro
Yonemoto, Naohiro
Zaki, Maysaa El Sayed
Murray, Christopher J. L.
TI Global Burden of Hypertension and Systolic Blood Pressure of at Least
110 to 115 mm Hg, 1990-2015
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ARTERIAL
STIFFNESS; KIDNEY-DISEASE; AGE; METAANALYSIS; MORTALITY; PROGRESSION;
PREVALENCE
AB IMPORTANCE Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions.
OBJECTIVE To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015.
DESIGN A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis.
MAIN OUTCOMES AND MEASURES Mean SBP level, cause-specific deaths, and health burden related to SBP (>110-115mmHg and also >= 140 mm Hg) by age, sex, country, and year.
RESULTS Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20526 (95% UI, 20283-20746) per 100000. The estimated annual death rate per 100000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deathswere caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg.
CONCLUSIONS AND RELEVANCE In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (>= 110-115 and >= 140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher. Copyright 2016 American Medical Association. All rights reserved.
C1 [Forouzanfar, Mohammad H.; Liu, Patrick; Roth, Gregory A.; Ng, Marie; Biryukov, Stan; Marczak, Laurie; Alexander, Lily; Estep, Kara; Misganaw, Awoke; Mokdad, Ali H.; Vos, Theo; Murray, Christopher J. L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Abate, Kalkidan Hassen] Jimma Univ, Jimma, Ethiopia.
[Akinyemiju, Tomi F.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
[Ali, Raghib; Bennett, Derrick A.] Univ Oxford, Oxford, England.
[Alvis-Guzman, Nelson] Univ Cartagena, Cartagena Indias, Colombia.
[Azzopardi, Peter] Ctr Adolescent Hlth, Parkville, Vic, Australia.
[Azzopardi, Peter] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
[Banerjee, Amitava] UCL, Farr Inst Hlth Informat Res, London, England.
[Baernighausen, Till] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Baernighausen, Till] Wellcome Trust Africa Ctr Hlth & Populat Studies, Mtubatuba, Kwazulu Natal, South Africa.
[Basu, Arindam] Univ Canterbury, Sch Hlth Sci, Christchurch, New Zealand.
[Bekele, Tolesa] Madawalabu Univ, Bale Goba, Ethiopia.
[Catala-Lopez, Ferran] Univ Valencia, INCLIVA Hlth Res Inst, Valencia, Spain.
[Catala-Lopez, Ferran] CIBERSAM, Dept Med, Valencia, Spain.
[Catala-Lopez, Ferran] Ottawa Hosp Res Inst, Program Epidemiol, Ottawa, ON, Canada.
[Feigin, Valery L.] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
[Fernandes, Joao C.] Univ Coimbra, Fac Med, IBILI Inst Biomed Imaging & Life Sci, Pharmacol & Expt Therapeut, Coimbra, Portugal.
[Fischer, Florian] Univ Bielefeld, Bielefeld, Germany.
[Gebru, Alemseged Aregay] Mekelle Univ, Kilte Awlaelo I Hlth & Demog Surveillance Syst, Mekelle, Ethiopia.
[Gona, Philimon] Univ Massachusetts, Boston, MA 02125 USA.
[Gupta, Rajeev] Eternal Heart Care Ctr, Res Inst, Jaipur, Rajasthan, India.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia.
[Hankey, Graeme J.] Harry Perkins Inst Med Res, Nedlands, WA, Australia.
[Hankey, Graeme J.] Western Australian Neurosci Res Inst, Nedlands, WA, Australia.
[Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
[Judd, Suzanne E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Khang, Young-Ho] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Khosravi, Ardeshir] Iranian Minist Hlth & Med Educ, Tehran, Iran.
[Kim, Yun Jin] Southern Univ Coll, Johor Baharu, Malaysia.
[Kimokoti, Ruth W.] Simmons Coll, Boston, MA USA.
[Kokubo, Yoshihiro] Natl Cerebral & Cardiovasc Ctr, Dept Prevent Cardiol, Suita, Osaka, Japan.
[Kolte, Dhaval] Brown Univ, Rhode Isl Hosp, Providence, RI 02912 USA.
[Lopez, Alan] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, QLD, Australia.
[Lotufo, Paulo A.] Univ Sao Paulo, Sao Paulo, Brazil.
[Malekzadeh, Reza; Sepanlou, Sadaf G.] Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.
[Melaku, Yohannes Adama] Mekelle Univ, Sch Publ Hlth, Mekelle, Ethiopia.
[Melaku, Yohannes Adama] Univ Adelaide, Sch Med, Adelaide, SA, Australia.
[Mensah, George A.] NHLBI, NIH, Ctr Translat Res & Implementat Sci, Bethesda, MD 20892 USA.
[Moran, Andrew E.] Columbia Univ, New York, NY USA.
[Nawaz, Haseeb] Southern Illinois Univ, Springfield, IL USA.
[Neal, Bruce] George Inst Global Hlth, Sydney, NSW, Australia.
[Neal, Bruce] Univ Sydney, Sydney, NSW, Australia.
[Neal, Bruce] Royal Prince Alfred Hosp, Sydney, NSW, Australia.
[Neal, Bruce] Imperial Coll London, London, England.
[Ngalesoni, Frida Namnyak] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania.
[Ohkubo, Takayoshi] Teikyo Univ, Sch Med, Tokyo, Japan.
[Pourmalek, Farshad] Univ British Columbia, Vancouver, BC, Canada.
[Rafay, Anwar] Contech Sch Publ Hlth, Lahore, Punjab, Pakistan.
[Rai, Rajesh Kumar] Soc Hlth & Demog Surveillance, Suri, India.
[Rojas-Rueda, David] ISGlobal, Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Sampson, Uchechukwu K.] NHLBI, NIH, Bethesda, MD USA.
[Santos, Itamar S.] Univ Sao Paulo, Dept Internal Med, Sao Paulo, Brazil.
[Sawhney, Monika] Marshall Univ, Huntington, WV USA.
[Schutte, Aletta E.] North West Univ, HART, South African Med Res Council, Potchefstroom, South Africa.
[Shifa, Girma Temam] Arba Minch Univ, Arba Minch, SNNPR, Ethiopia.
[Shifa, Girma Temam] Univ Addis Ababa, Addis Ababa, Ethiopia.
[Shiue, Ivy] Northumbria Univ, Fac Hlth & Life Sci, Newcastle Upon Tyne, Tyne & Wear, England.
[Shiue, Ivy] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
[Tedla, Bemnet Amare] Univ Gondar, Gondar, Ethiopia.
[Tedla, Bemnet Amare] James Cook Univ, Cairns, Queensland, Australia.
[Thrift, Amanda G.] Monash Univ, Sch Clin Sci Monash Hlth, Melbourne, Vic, Australia.
[Tonelli, Marcello] Univ Calgary, Calgary, AB, Canada.
[Truelsen, Thomas] Univ Copenhagen, Dept Neurol, Copenhagen, Denmark.
[Tsilimparis, Nikolaos] Univ Heart Ctr Hamburg, Hamburg, Germany.
[Ukwaja, Kingsley Nnanna] Fed Teaching Hosp, Dept Internal Med, Abakaliki, Nigeria.
[Uthman, Olalekan A.] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England.
[Vasankari, Tommi] UKK Inst Hlth Promot Res, Tampere, Finland.
[Venketasubramanian, Narayanaswamy] Raffles Hosp, Raffles Neurosci Ctr, Singapore, Singapore.
[Vlassov, Vasiliy Victorovich] Natl Res Univ, Higher Sch Econ, Moscow, Russia.
[Westerman, Ronny] Fed Inst Populat Res, Wiesbaden, Germany.
[Westerman, Ronny] German Natl Cohort Consortium, Heidelberg, Germany.
[Yan, Lijing L.] Duke Kunshan Univ, Global Hlth Res Ctr, Kunshan, Peoples R China.
[Yano, Yuichiro] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Yonemoto, Naohiro] Natl Ctr Neurol & Psychiat, Kodaira, Tokyo, Japan.
[Zaki, Maysaa El Sayed] Mansoura Fac Med, Mansoura, Egypt.
RP Murray, CJL (reprint author), Inst Hlth Metr & Evaluat, 2301 Fifth Ave,Ste 600, Seattle, WA 98121 USA.
EM cjlm@uw.edu
RI Tonelli, Marcello/B-3028-2009; Lotufo, Paulo/A-9843-2008; Hankey, Graeme
/H-4968-2014;
OI Lotufo, Paulo/0000-0002-4856-8450; Hankey, Graeme /0000-0002-6044-7328;
Catala-Lopez, Ferran/0000-0002-3833-9312
FU Bill and Melinda Gates Foundation
FX This research was supported by funding from the Bill and Melinda Gates
Foundation.
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PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 10
PY 2017
VL 317
IS 2
BP 165
EP 182
DI 10.1001/jama.2016.19043
PG 18
WC Medicine, General & Internal
SC General & Internal Medicine
GA EH5PV
UT WOS:000391826200019
PM 28097354
ER
PT J
AU Compton, WM
Han, B
Hughes, A
Jones, CM
Blanco, C
AF Compton, Wilson M.
Han, Beth
Hughes, Arthur
Jones, Christopher M.
Blanco, Carlos
TI Use of Marijuana for Medical Purposes Among Adults in the United States
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Compton, Wilson M.; Blanco, Carlos] Natl Inst Drug Abuse, 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA.
[Han, Beth; Hughes, Arthur] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
[Jones, Christopher M.] US Dept HHS, Off Assistant Secretary Planning & Evaluat, Washington, DC 20201 USA.
RP Compton, WM (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA.
EM wcompton@nida.nih.gov
FU Substance Abuse and Mental Health Services Administration; National
Institute on Drug Abuse of the National Institutes of Health; Office of
the Assistant Secretary for Planning and Evaluation of the US Department
of Health and Human Services
FX The National Survey on Drug Use and Health was supported by contracts
from the Substance Abuse and Mental Health Services Administration. This
study was jointly sponsored by the National Institute on Drug Abuse of
the National Institutes of Health, the Substance Abuse and Mental Health
Services Administration, and the Office of the Assistant Secretary for
Planning and Evaluation of the US Department of Health and Human
Services.
NR 4
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PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 10
PY 2017
VL 317
IS 2
BP 209
EP 211
DI 10.1001/jama.2016.18900
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA EH5PV
UT WOS:000391826200024
PM 27992636
ER
PT J
AU Wallace, BD
Berman, Z
Mueller, GA
Lin, YF
Chang, T
Andres, SN
Wojtaszek, JL
DeRose, EF
Appel, CD
London, RE
Yan, S
Williams, RS
AF Wallace, Bret D.
Berman, Zachary
Mueller, Geoffrey A.
Lin, Yunfeng
Chang, Timothy
Andres, Sara N.
Wojtaszek, Jessica L.
DeRose, Eugene F.
Appel, C. Denise
London, Robert E.
Yan, Shan
Williams, R. Scott
TI APE2 Zf-GRF facilitates 3 '-5 ' resection of DNA damage following
oxidative stress
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE oxidative stress; APE2; Zf-GRF; crystallography; Xenopus laevis
ID CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; ABASIC ENDONUCLEASE;
GENOME INTEGRITY; EXONUCLEASE-III; REPAIR PATHWAYS; PROTEIN MIMICRY;
ZINC-FINGERS; YEAST APN2; COMPLEX
AB The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3'-5' nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high homology with DDR proteins Topoisomerase 3 alpha(TOP3 alpha) and NEIL3 (Nei-like DNA glycosylase 3), as well as transcription and RNA regulatory proteins, such as TTF2 (transcription termination factor 2), TFIIS, and RPB9. Biochemical and NMR results establish the nucleic acid-binding activity of the Zf-GRF domain. Moreover, an APE2 Zf-GRF X-ray structure and small-angle X-ray scattering analyses show that the Zf-GRF fold is typified by a crescent-shaped ssDNA binding claw that is flexibly appended to an APE2 endonuclease/ exonuclease/phosphatase (EEP) catalytic core. Structure-guided Zf-GRF mutations impact APE2 DNA binding and 3'-5' exonuclease processing, and also prevent efficient APE2-dependent RPA recruitment to damaged chromatin and activation of the ATR-Chk1 DDR pathway in response to oxidative stress in Xenopus egg extracts. Collectively, our data unveil the APE2 Zf-GRF domain as a nucleic acid interaction module in the regulation of a key single-strand break resection function of APE2, and also reveal topologic similarity of the Zf-GRF to the zinc ribbon domains of TFIIS and RPB9.
C1 [Wallace, Bret D.; Mueller, Geoffrey A.; Chang, Timothy; Andres, Sara N.; Wojtaszek, Jessica L.; DeRose, Eugene F.; Appel, C. Denise; London, Robert E.; Williams, R. Scott] NIEHS, Genome Integr & Struct Biol Lab, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Berman, Zachary; Lin, Yunfeng; Yan, Shan] Univ N Carolina, Dept Biol Sci, Charlotte, NC 28223 USA.
RP Williams, RS (reprint author), NIEHS, Genome Integr & Struct Biol Lab, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Yan, S (reprint author), Univ N Carolina, Dept Biol Sci, Charlotte, NC 28223 USA.
EM shan.yan@uncc.edu; williamsrs@niehs.nih.gov
FU University of North Carolina at Charlotte; National Institute of General
Medical Sciences of the National Institutes of Health (NIH) [R15
GM101571, R15 GM114713]; DOE's Office of Biological and Environmental
Research; NIH Project MINOS [R01 GM105404]; DOE, Office of Science,
Office of Basic Energy Sciences [W-31-109-Eng-38]; NIH Intramural
Program; NIEHS [1Z01ES102765, 1Z01ES050111]
FX We thank Drs. Matthew Michael, Karlene Cimprich, and Howard Lindsay for
reagents; Jason Williams of the National Institute of Environmental
Health Sciences (NIEHS) protein microcharacterization core for mass
spectrometry analysis, and Lars Pedersen of the NIEHS X-ray
crystallography core for help with X- ray data collection. We also thank
Drs. Robin Stanley and Jun Zhang for comments on the manuscript. This
study was supported in part by funds provided by University of North
Carolina at Charlotte and the National Institute of General Medical
Sciences of the National Institutes of Health (NIH; Grants R15 GM101571
and R15 GM114713) to S.Y. The SAXS experiments were conducted at the
Advanced Light Source, a national user facility operated by Lawrence
Berkeley National Laboratory on behalf of the Department of Energy
(DOE), Office of Basic Energy Sciences, through the Integrated
Diffraction Analysis Technologies program, supported by the DOE's Office
of Biological and Environmental Research. Additional support came from
the NIH Project MINOS (Grant R01 GM105404). X-ray crystallographic data
were collected at Southeast Regional Collaborative Access Team beamline
22-ID at the Advanced Photon Source, Argonne National Laboratory. Use of
the Advanced Photon Source was supported by the DOE, Office of Science,
Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38.
This research was also supported by the NIH Intramural Program and the
NIEHS (Grants 1Z01ES102765, to R.S.W., and 1Z01ES050111, to R.E.L.).
NR 56
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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 JAN 10
PY 2017
VL 114
IS 2
BP 304
EP 309
DI 10.1073/pnas.1610011114
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH0FR
UT WOS:000391439300043
PM 28028224
ER
PT J
AU Garten, M
Mosgaard, LD
Bornschlogl, T
Dieudonne, S
Bassereau, P
Toombes, GES
AF Garten, Matthias
Mosgaard, Lars D.
Bornschloegl, Thomas
Dieudonne, Stephane
Bassereau, Patricia
Toombes, Gilman E. S.
TI Whole-GUV patch-clamping
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE giant unilamellar vesicle; patch clamp; electrophysiology; biomimetic
system; lipid-glass interaction
ID GIANT UNILAMELLAR VESICLES; LIPID-BILAYER; MECHANOSENSITIVE CHANNELS;
XENOPUS OOCYTES; CHAIN-LENGTH; K+ CHANNELS; MEMBRANE; ACTIVATION;
MICROSCOPY; CELLS
AB Studying how the membrane modulates ion channel and transporter activity is challenging because cells actively regulate membrane properties, whereas existing in vitro systems have limitations, such as residual solvent and unphysiologically high membrane tension. Cell-sized giant unilamellar vesicles (GUVs) would be ideal for in vitro electrophysiology, but efforts to measure the membrane current of intact GUVs have been unsuccessful. In this work, two challenges for obtaining the "whole-GUV" patch-clamp configuration were identified and resolved. First, unless the patch pipette and GUV pressures are precisely matched in the GUV-attached configuration, breaking the patch membrane also ruptures the GUV. Second, GUVs shrink irreversibly because the membrane/glass adhesion creating the high-resistance seal (> 1 G Omega) continuously pulls membrane into the pipette. In contrast, for cell-derived giant plasma membrane vesicles (GPMVs), breaking the patch membrane allows the GPMV contents to passivate the pipette surface, thereby dynamically blocking membrane spreading in the whole-GMPV mode. To mimic this dynamic passivation mechanism, beta-casein was encapsulated into GUVs, yielding a stable, high-resistance, whole-GUV configuration for a range of membrane compositions. Specific membrane capacitance measurements confirmed that the membranes were truly solvent-free and that membrane tension could be controlled over a physiological range. Finally, the potential for ion transport studies was tested using the model ion channel, gramicidin, and voltage-clamp fluorometry measurements were performed with a voltage-dependent fluorophore/ quencher pair. Whole-GUV patch-clamping allows ion transport and other voltage-dependent processes to be studied while controlling membrane composition, tension, and shape.
C1 [Garten, Matthias; Bornschloegl, Thomas; Bassereau, Patricia] PSL Res Univ, CNRS, Inst Curie, Lab Phys Chim Curie,UMR 168, F-75005 Paris, France.
[Garten, Matthias; Bornschloegl, Thomas; Bassereau, Patricia] Univ Paris 06, Sorbonne Univ, F-75005 Paris, France.
[Garten, Matthias] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Integrat Biophys, NIH, Bethesda, MD 20892 USA.
[Mosgaard, Lars D.] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
[Dieudonne, Stephane] Inst Biol Ecole Normale Super, INSERM U1024, F-75005 Paris, France.
[Dieudonne, Stephane; Toombes, Gilman E. S.] CNRS, UMR 8197, F-75005 Paris, France.
[Toombes, Gilman E. S.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Toombes, GES (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM gilman.toombes@nih.gov
OI Garten, Matthias/0000-0002-8660-1039
FU Agence Nationale de la Recherche [BLAN-0057-01]; European Commission
(NoE SoftComp); Universite Pierre et Marie Curie (Dynamique des Systemes
Complexes) [FED21]; Intramural Research Program of the NIH; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Neurological Disorders and Stroke;
Institut Curie International PhD Fellowship; Marie Curie International
Incoming Fellowship; Universite Pierre et Marie Curie
FX We thank Jacques Prost, Sophie Aimon, John Manzi, Johnathan Bradley,
Loic Auvrey, Rumiana Dimova, and Jan Behrends for helpful discussions
and suggestions. P.B. belongs to the CNRS consortium CellTiss. This work
was supported by the Agence Nationale de la Recherche (Grant
BLAN-0057-01), the European Commission (NoE SoftComp), the Universite
Pierre et Marie Curie (FED21, Dynamique des Systemes Complexes), the
Intramural Research Program of the NIH, the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, and the
National Institute of Neurological Disorders and Stroke. M.G.
acknowledges support from the Institut Curie International PhD
Fellowship, and G.E.S.T. was supported by a Marie Curie International
Incoming Fellowship and the Universite Pierre et Marie Curie.
NR 52
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 10
PY 2017
VL 114
IS 2
BP 328
EP 333
DI 10.1073/pnas.1609142114
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH0FR
UT WOS:000391439300047
PM 28003462
ER
PT J
AU Linsley, JW
Hsu, IU
Groom, L
Yarotskyy, V
Lavorato, M
Horstick, EJ
Linsley, D
Wang, WJ
Franzini-Armstrong, C
Dirksen, RT
Kuwada, JY
AF Linsley, Jeremy W.
Hsu, I-Uen
Groom, Linda
Yarotskyy, Viktor
Lavorato, Manuela
Horstick, Eric J.
Linsley, Drew
Wang, Wenjia
Franzini-Armstrong, Clara
Dirksen, Robert T.
Kuwada, John Y.
TI Congenital myopathy results from misregulation of a muscle Ca2+ channel
by mutant Stac3
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE zebrafish; skeletal muscle; excitation-contraction coupling;
dihydropyridine receptor; Native American myopathy
ID II-III-LOOP; MALIGNANT HYPERTHERMIA SUSCEPTIBILITY;
DIHYDROPYRIDINE-RECEPTOR ARRAYS; SKELETAL-MUSCLE; RYANODINE RECEPTOR;
SARCOPLASMIC-RETICULUM; RELEASE CHANNEL; CALCIUM-RELEASE; MUTATION;
ZEBRAFISH
AB Skeletalmuscle contractions are initiated by an increase in Ca2+ released during excitation-contraction (EC) coupling, and defects in EC coupling are associated with human myopathies. EC coupling requires communication between voltage-sensing dihydropyridine receptors (DHPRs) in transverse tubule membrane and Ca2+ release channel ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum (SR). Stac3 protein (SH3 and cysteine-rich domain 3) is an essential component of the EC coupling apparatus and a mutation in human STAC3 causes the debilitating Native Americanmyopathy (NAM), but the nature of how Stac3 acts on the DHPR and/or RyR1 is unknown. Using electron microscopy, electrophysiology, and dynamic imaging of zebrafish muscle fibers, we find significantly reduced DHPR levels, functionality, and stability in stac3 mutants. Furthermore, stac3(NAM) myofibers exhibited increased caffeine-induced Ca2+ release across a wide range of concentrations in the absence of altered caffeine sensitivity as well as increased Ca2+ in internal stores, which is consistent with increased SR luminal Ca2+. These findings define critical roles for Stac3 in EC coupling and human disease.
C1 [Linsley, Jeremy W.; Kuwada, John Y.] Univ Michigan, Cell & Mol Biol Program, Ann Arbor, MI 48109 USA.
[Linsley, Jeremy W.; Hsu, I-Uen; Horstick, Eric J.; Wang, Wenjia; Kuwada, John Y.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.
[Groom, Linda; Yarotskyy, Viktor; Dirksen, Robert T.] Univ Rochester, Med Ctr, Dept Pharmacol & Physiol, Rochester, NY 14642 USA.
[Lavorato, Manuela; Franzini-Armstrong, Clara] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
[Horstick, Eric J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, Bethesda, MD 20892 USA.
[Linsley, Drew] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA.
RP Kuwada, JY (reprint author), Univ Michigan, Cell & Mol Biol Program, Ann Arbor, MI 48109 USA.; Kuwada, JY (reprint author), Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.; Dirksen, RT (reprint author), Univ Rochester, Med Ctr, Dept Pharmacol & Physiol, Rochester, NY 14642 USA.; Franzini-Armstrong, C (reprint author), Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
EM armstroc@mail.med.upenn.edu; robert_dirksen@urmc.rochester.edu;
kuwada@umich.edu
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) of the National Institutes of Health [R01-AR-063056]; Rackham
Merit Fellowship (University of Michigan); NIGMS [T32 GM007315]; NIAMS
[AR059646, AR053349, AR060831, 2P01 AR 052354-06A1]
FX We thank Alex Migda, Matthew Lacey, Sean Lowe, Hoaxing Xu, and Richard
Hume for technical assistance and discussions. Research was supported by
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) of the National Institutes of Health Grant
R01-AR-063056 (to J.Y.K.); Grants NIAMS AR059646 and AR053349 (to
R.T.D.); Grant NIAMS AR060831 (to V.Y.); and Grant NIAMS 2P01 AR
052354-06A1, PI: P. D. Allen (to C.F.-A.). J.W.L. was supported in part
by a Rackham Merit Fellowship (University of Michigan) and NIGMS (Grant
T32 GM007315).
NR 43
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 10
PY 2017
VL 114
IS 2
BP E228
EP E236
DI 10.1073/pnas.1619238114
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH0FR
UT WOS:000391439300015
PM 28003463
ER
PT J
AU Clarke, GM
Rockett, K
Kivinen, K
Hubbart, C
Jeffreys, AE
Rowlands, K
Jallow, M
Conway, DJ
Bojang, KA
Pinder, M
Usen, S
Sisay-Joof, F
Sirugo, G
Toure, O
Thera, MA
Konate, S
Sissoko, S
Niangaly, A
Poudiougou, B
Mangano, VD
Bougouma, EC
Sirima, SB
Modioano, D
Amenga-Etego, LN
Ghansah, A
Koram, KA
Wilson, MD
Enimil, A
Evans, J
Amodu, OK
Olaniyan, S
Apinjoh, T
Mugri, R
Ndi, A
Ndila, CM
Uyoga, S
Macharia, A
Peshu, N
Williams, TN
Manjurano, A
Sepulveda, N
Clark, TG
Riley, E
Drakeley, C
Reyburn, H
Nyirongo, V
Kachala, D
Molyneux, M
Dunstan, SJ
Phu, NH
Quyen, NN
Thai, CQ
Hien, TT
Manning, L
Laman, M
Siba, P
Karunajeewa, H
Allen, S
Allen, A
Davis, TME
Michon, P
Mueller, I
Molloy, SF
Campino, S
Kerasidou, A
Cornelius, VJ
Hart, L
Shah, SS
Band, G
Spencer, CCA
Agbenyega, T
Achidi, E
Doumbo, OK
Farrar, J
Marsh, K
Taylor, T
Kwaitkowski, DP
AF Clarke, Geraldine M.
Rockett, Kirk
Kivinen, Katja
Hubbart, Christina
Jeffreys, Anna E.
Rowlands, Kate
Jallow, Muminatou
Conway, David J.
Bojang, Kalifa A.
Pinder, Margaret
Usen, Stanley
Sisay-Joof, Fatoumatta
Sirugo, Giorgio
Toure, Ousmane
Thera, Mahamadou A.
Konate, Salimata
Sissoko, Sibiry
Niangaly, Amadou
Poudiougou, Belco
Mangano, Valentina D.
Bougouma, Edith C.
Sirima, Sodiomon B.
Modioano, David
Amenga-Etego, Lucas N.
Ghansah, Anita
Koram, Kwadwo A.
Wilson, Michael D.
Enimil, Anthony
Evans, Jennifer
Amodu, Olukemi K.
Olaniyan, Subulade
Apinjoh, Tobias
Mugri, Regina
Ndi, Andre
Ndila, Carolyne M.
Uyoga, Sophie
Macharia, Alexander
Peshu, Norbert
Williams, Thomas N.
Manjurano, Alphaxard
Sepulveda, Nuno
Clark, Taane G.
Riley, Eleanor
Drakeley, Chris
Reyburn, Hugh
Nyirongo, Vysaul
Kachala, David
Molyneux, Malcolm
Dunstan, Sarah J.
Nguyen Hoan Phu
Nguyen Ngoc Quyen
Cao Quang Thai
Tran Tinh Hien
Manning, Laurens
Laman, Moses
Siba, Peter
Karunajeewa, Harin
Allen, Steve
Allen, Angela
Davis, Timothy M. E.
Michon, Pascal
Mueller, Ivo
Molloy, SIle F.
Campino, Susan
Kerasidou, Angeliki
Cornelius, Victoria J.
Hart, Lee
Shah, Shivang S.
Band, Gavin
Spencer, Chris C. A.
Agbenyega, Tsiri
Achidi, Eric
Doumbo, Ogobara K.
Farrar, Jeremy
Marsh, Kevin
Taylor, Terrie
Kwaitkowski, Dominic P.
CA MalariaGEn Consortium
TI Characterisation of the opposing effects of G6PD deficiency on cerebral
malaria and severe malarial anaemia
SO ELIFE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM TRANSMISSION; SEX-LINKED LOCUS; NATURAL-SELECTION;
WEST-AFRICA; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY;
DEHYDROGENASE-DEFICIENCY; LINKAGE DISEQUILIBRIUM; HETEROZYGOTE
ADVANTAGE; 2 AREAS; CHILDREN
AB Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individuals level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.
C1 [Clarke, Geraldine M.; Rockett, Kirk; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Molloy, SIle F.; Kerasidou, Angeliki; Cornelius, Victoria J.; Hart, Lee; Shah, Shivang S.; Band, Gavin; Spencer, Chris C. A.; Kwaitkowski, Dominic P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Clarke, Geraldine M.; Rockett, Kirk; Cornelius, Victoria J.; Band, Gavin; Kwaitkowski, Dominic P.] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford, England.
[Rockett, Kirk; Kivinen, Katja; Campino, Susan; Kwaitkowski, Dominic P.; MalariaGEn Consortium] Wellcome Trust Sanger Inst, Cambridge, England.
[Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio] Med Res Council Gambia, Fajara, Gambia.
[Jallow, Muminatou] Edward Small Teaching Hosp, Independence Dr, Banjul, Gambia.
[Conway, David J.; Clark, Taane G.] London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, London, England.
[Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali.
[Mangano, Valentina D.; Modioano, David] Univ Roma La Sapienza, Rome, Italy.
[Bougouma, Edith C.; Sirima, Sodiomon B.] CNRFP, Ouagadougou, Burkina Faso.
[Amenga-Etego, Lucas N.] Navrongo Hlth Res Ctr, Navrongo, Ghana.
[Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.] Univ Ghana, Noguchi Mem Inst Med Res, Accra, Ghana.
[Enimil, Anthony; Agbenyega, Tsiri] Komfo Anoyke Teaching Hosp, Kumasi, Ghana.
[Evans, Jennifer] Bernhard Nocht Inst Trop Med, Dept Mol Med, Hamburg, Germany.
[Evans, Jennifer] Kumasi Ctr Collaborat Res, Kumasi, Ghana.
[Amodu, Olukemi K.; Olaniyan, Subulade] Univ Ibadan, Ibadan, Nigeria.
[Apinjoh, Tobias] Univ Buea, Dept Biochem & Mol Biol, Buea, Cameroon.
[Mugri, Regina; Ndi, Andre; Achidi, Eric] Univ Buea, Dept Med Lab Sci, Buea, Cameroon.
[Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Marsh, Kevin] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya.
[Williams, Thomas N.] Imperial Coll, Fac Med, Dept Med, London, England.
[Manjurano, Alphaxard; Drakeley, Chris; Reyburn, Hugh] Kilimanjaro Christian Med Coll, Joint Malaria Programme, Moshi, Tanzania.
[Manjurano, Alphaxard; Sepulveda, Nuno; Clark, Taane G.; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England.
[Nyirongo, Vysaul; Molyneux, Malcolm] Univ Malawi, Malawi Liverpool Wellcome Trust Clin Res Programm, Blantyre, Malawi.
[Kachala, David; Nguyen Hoan Phu; Nguyen Ngoc Quyen; Cao Quang Thai; Tran Tinh Hien; Farrar, Jeremy] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam.
[Molyneux, Malcolm] Univ Liverpool Liverpool Sch Trop Med, Pembroke Pl, Liverpool, Merseyside, England.
[Dunstan, Sarah J.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia.
[Nguyen Hoan Phu; Cao Quang Thai; Tran Tinh Hien] Hosp Trop Dis, Ho Chi Minh City, Vietnam.
[Tran Tinh Hien; Manning, Laurens; Laman, Moses; Siba, Peter; Michon, Pascal; Mueller, Ivo] Papua New Guinea Inst Med Res, Goroka, Papua N Guinea.
[Karunajeewa, Harin; Davis, Timothy M. E.] Univ Western Australia, Perth, WA, Australia.
[Allen, Steve] Swansea Univ, Swansea, W Glam, Wales.
[Allen, Angela] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
[Michon, Pascal] Divine Word Univ, Fac Med & Hlth Sci, Madang, Papua N Guinea.
[Mueller, Ivo] Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia.
[Mueller, Ivo] Barcelona Ctr Int Hlth Res, Barcelona, Spain.
[Kerasidou, Angeliki] Univ Oxford, Ethox Ctr, Nuffield Dept Populat Hlth, Oxford, England.
[Shah, Shivang S.] NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Agbenyega, Tsiri] Kwame Nkrumah Univ Sci & Technol, Kumasi, Ghana.
[Farrar, Jeremy] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
[Taylor, Terrie] Univ Malawi, Blantyre Malaria Project, Coll Med, Blantyre, Malawi.
RP Clarke, GM; Rockett, K; Kwaitkowski, DP (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.; Clarke, GM; Rockett, K; Kwaitkowski, DP (reprint author), Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford, England.; Rockett, K; Kwaitkowski, DP (reprint author), Wellcome Trust Sanger Inst, Cambridge, England.
EM gclarke@well.ox.ac.uk; krockett@well.ox.ac.uk; dominic@well.ox.ac.uk
RI Manning, Laurens/H-5360-2014;
OI Manning, Laurens/0000-0003-4334-5351; Kwiatkowski,
Dominic/0000-0002-5023-0176
FU Wellcome Trust [090770/Z/09/Z, 097364/Z/11/Z, 076934/Z/05/Z,
091758/Z/10/Z, 084538, 089276/Z/09/Z, 077383/Z/05/Z, 090532/Z/09/Z,
077012/Z/05/Z, 087285, 096527]; Foundation for the National Institutes
of Health [566]; European Commission [LSHP-CT-2004-503578,
SANTE/2004/078-607]; National Institute of Allergy and Infectious
Diseases; European and Developing Countries Clinical Trials Partnership;
National Health and Medical Research Council; Fogarty International
Center; Seventh Framework Programme [242095]; Royal Australasian College
of Physicians; Medical Research Council [G9901439, G0600718, G0600230,
G19/9]
FX Wellcome Trust 090770/Z/09/Z Geraldine M Clarke Kirk Rockett Katja
Kivinen Christina Hubbart Anna EJeffreys Kate Rowlands Sile F Molloy
Angeliki Kerasidou Victoria JCornelius Lee Hart Gavin Band Chris CA
Spencer Dominic P Kwiatkowski; Foundation for the National Institutes of
Health Billand Melinda Gates Foundation Grand Challenges in Global
Health 566 Geraldine M Clarke Kirk Rockett Katja Kivinen Christina
Hubbart Anna E Jeffreys Kate Rowlands Muminatou Jallow David J Conway
Kalifa A Bojang Margaret Pinder Stanley Usen Fatoumatta Sisay-Joof
Giorgio Sirugo Ousmane Toure Mahamadou A Thera Salimata Konate Sibiry
Sissoko Amadou Niangaly Belco Poudiougou Valentina D Mangano Edith C
Bougouma Sodiomon BSirima David Modiano Lucas N Amenga-Etego Anita
Ghansah Kwadwo A Koram Michael D Wilson Anthony Enimil Jennifer Evans
Olukemi K Amodu Subulade Olaniyan Tobias Apinjoh Regina Mugri Andre Ndi
Carolyne M Ndila Sophie Uyoga Alexander Macharia Norbert Peshu Thomas N
Williams Alphaxard Manjurano Nuno Sepulveda Taane G Clark Eleanor Riley
Chris Drakeley Hugh Reyburn Vysaul Nyirongo David Kachala Malcolm
Molyneux Sarah J Dunstan Nguyen Hoan Phu Nguyen Ngoc Quyen Cao Quang
Thai Tran Tinh Hien Laurens Manning Moses Laman Peter Siba Harin
Karunajeewa Steve Allen Angela Allen Timothy ME Davis Pascal Michon Ivo
Mueller Sile F Molloy Susana Campino Angeliki Kerasidou Victoria J
Cornelius Lee Hart Shivang S Shah Gavin Band Chris CA Spencer Tsiri
Agbenyega Eric Achidi Ogobara K Doumbo Jeremy Farrar Kevin Marsh Terrie
Taylor Dominic P Kwiatkowski; Wellcome Trust 097364/Z/11/Z (Spencer)
Chris CA Spencer; European Commission LSHP-CT-2004-503578 (Nigeria)
Olukemi K Amodu Subulade Olaniyan; National Institute of Allergy and
Infectious Diseases Ousmane Toure Mahamadou A Thera Salimata Konate
Sibiry Sissoko Amadou Niangaly Belco Poudiougou; European Commission
Europaid: SANTE/2004/078-607 Alphaxard Manjurano Nuno Sepulveda Taane G
Clark EleanorRiley Chris Drakeley Hugh Reyburn Timothy ME Davis;
European and Developing Countries Clinical Trials Partnership Eric
Achidi; National Health and Medical Research Council Laurens Manning
Timothy ME Davis; Fogarty International Center Moses Laman; Seventh
Framework Programme 242095 Thomas N Williams Eric Achidi; Wellcome Trust
076934/Z/05/Z and 091758/Z/10/Z Sophie Uyoga Alexander Macharia Thomas N
Williams; Wellcome Trust 084538 Carolyne M Ndila; Wellcome Trust KEMRI
Core Support Carolyne M Ndila Sophie Uyoga Alexander Macharia Norbert
Peshu Thomas N Williams Kevin Marsh; Wellcome Trust WT Major Overseas
Program in Vietnam 089276/Z/09/Z David Kachala Nguyen Hoan Phu Nguyen
Ngoc Quyen Cao Quang Thai Tran Tinh Hien Jeremy Farrar; Royal
Australasian College of Physicians Laurens Manning; Wellcome Trust
MalariaGEN Project 077383/Z/05/Z Geraldine M Clarke Kirk Rockett
Christina Hubbart Anna E Jeffreys Kate Rowlands Muminatou Jallow David J
Conway Kalifa A Bojang Margaret Pinder Stanley Usen Fatoumatta
Sisay-Joof Giorgio Sirugo Ousmane Toure Mahamadou A Thera Salimata
Konate Sibiry Sissoko Amadou Niangaly Belco Poudiougou Valentina D
Mangano Edith C Bougouma Sodiomon BSirima David Modiano Lucas N
Amenga-Etego Anita Ghansah Kwadwo A Koram Michael DWilson Anthony Enimil
Jennifer Evans Olukemi K Amodu Subulade Olaniyan Tobias Apinjoh Regina
Mugri Andre Ndi Carolyne M Ndila Sophie Uyoga Alexander Macharia Norbert
Peshu Thomas N Williams Alphaxard Manjurano Nuno Sepulveda Taane G Clark
Eleanor Riley Chris Drakeley Hugh Reyburn Vysaul Nyirongo David Kachala
Malcolm Molyneux Sarah J Dunstan Nguyen Hoan Phu Nguyen Ngoc Quyen Cao
Quang Thai Tran Tinh Hien Laurens Manning Moses Laman Peter Siba Harin
Karunajeewa Steve Allen Angela Allen Timothy ME Davis Pascal Michon Ivo
Mueller Sile F Molloy Susana Campino Angeliki Kerasidou Victoria J
Cornelius Lee Hart Shivang S Shah Gavin Band Chris CA Spencer Tsiri
Agbenyega Eric Achidi Ogobara K Doumbo Jeremy Farrar Kevin Marsh Terrie
Taylor Dominic P Kwiatkowsk; Wellcome Trust WT Centre for Human Genetic
Core 090532/Z/09/Z Geraldine M Clarke Kirk Rockett Christina Hubbart
Anna E Jeffreys Kate Rowlands Sile F Molloy Angeliki Kerasidou Victoria
J Cornelius Lee Hart Shivang S Shah Gavin Band Chris CA Spencer Dominic
P Kwiatkowski; Wellcome Trust WT SangerInstitute Core 077012/Z/05/Z
Katja Kivinen Susana Campino Dominic P Kwiatkowski; Wellcome Trust
087285;096527 Angeliki Kerasidou; Medical Research Council Tanzania
Joint Collaboration G9901439 Alphaxard Manjurano Nuno Sepulveda Taane G
Clark Eleanor Riley Chris Drakeley Hugh Reyburn Timothy ME Davis;
Medical Research Council G0600718; G0600230 Kirk Rockett Dominic P
Kwiatkowsk; Medical Research Council G19/9 Dominic P Kwiatkowski
NR 66
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U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD JAN 9
PY 2017
VL 6
AR e15085
DI 10.7554/eLIFE.15085
PG 30
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EJ7FS
UT WOS:000393387700001
ER
PT J
AU Lederman, RJ
Greenbaum, AB
Rogers, T
Khan, JM
Fusari, M
Chen, MY
AF Lederman, Robert J.
Greenbaum, Adam B.
Rogers, Toby
Khan, Jaffar M.
Fusari, Melissa
Chen, Marcus Y.
TI Anatomic Suitability for Transcaval Access Based on Computed Tomography
SO JACC-CARDIOVASCULAR INTERVENTIONS
LA English
DT Review
DE aorto-caval; caval-aortic; computed tomography; structural heart
disease; transcatheter aortic valve replacement; transcatheter
electrosurgery; transcaval
ID AORTIC ACCESS
AB Transcaval access has been used successfully for over 200 transcatheter aortic valve replacements, large-bore percutaneous left ventricular assist devices, and thoracic endovascular aortic aneurysm repairs. This review teaches how to plan transcaval access and closure based on computed tomography. The main planning goals are to: 1) identify calcium-free crossing targets in the abdominal aorta along with optimal fluoroscopic projection angles and level with respect to lumbar vertebrae; 2) identify obstacles such as interposed bowel or pedunculated aortic atheroma; 3) plan covered stent bailout; and 4) identify jeopardized vascular branches such as renal arteries that might be obstructed by bailout covered stents if employed. The aorta and inferior vena cava are segmented (sculpted) using an image reconstruction workstation and crossing targets are highlighted. Important measurements such as aortic lumen diameter and target distance from renal arteries, aortoiliac bifurcation, and right femoral vein puncture site are reported to assist the operator. The proposed classification for transcaval feasibility has been revised, making some previously unfavorable candidates now feasible or favorable based on procedural success to date. Transcaval access allows percutaneous introduction of large devices into the aorta despite small or diseased iliofemoral arteries. By following these simplified procedures, both operators and imaging specialists can easily prepare comprehensive treatment plans. (C) 2017 by the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.
C1 [Lederman, Robert J.; Rogers, Toby; Khan, Jaffar M.; Chen, Marcus Y.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
[Greenbaum, Adam B.] Henry Ford Hlth Syst, Div Cardiol, Ctr Struct Heart Dis, Detroit, MI USA.
[Fusari, Melissa] Edwards Lifesci, Irvine, CA USA.
EM lederman@nih.gov
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute, National Institutes of Health [Z01-HL006040]
FX From the Cardiovascular and Pulmonary Branch, Division of Intramural
Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland;
Center for Structural Heart Disease, Division of Cardiology, Henry Ford
Health System, Detroit, Michigan; and Edwards Lifesciences, Irvine,
California. The study was supported by the Division of Intramural
Research, National Heart, Lung, and Blood Institute, National Institutes
of Health, Z01-HL006040. Drs. Lederman, Rogers, and Greenbaum are listed
as inventors on patent applications, assigned to their employers,
related to transcaval access and closure. Dr. Greenbaum has served as a
physician proctor for Edwards Lifesciences, Medtronic, and St. Jude
Medical. Mr. Khan has reported that he has no relationships relevant to
the contents of this paper to disclose. Dr. Fusari is a full-time
employee of and surgeon proctor for Edwards Lifesciences. Dr. Chen is
the National Heart, Lung, and Blood Institute core lab director for
transcaval access.
NR 4
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-8798
EI 1876-7605
J9 JACC-CARDIOVASC INTE
JI JACC-Cardiovasc. Interv.
PD JAN 9
PY 2017
VL 10
IS 1
BP 1
EP 10
DI 10.1016/j.jcin.2016.09.002
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EI6RP
UT WOS:000392624100003
PM 28057275
ER
PT J
AU Veschi, V
Liu, ZH
Voss, TC
Ozbun, L
Gryder, B
Yan, CH
Hu, Y
Ma, AQ
Jin, J
Mazur, SJ
Lam, N
Souza, BK
Giannini, G
Hager, GL
Arrowsmith, CH
Khan, J
Appella, E
Thiele, CJ
AF Veschi, Veronica
Liu, Zhihui
Voss, Ty C.
Ozbun, Laurent
Gryder, Berkley
Yan, Chunhua
Hu, Ying
Ma, Anqi
Jin, Jian
Mazur, Sharlyn J.
Lam, Norris
Souza, Barbara K.
Giannini, Giuseppe
Hager, Gordon L.
Arrowsmith, Cheryl H.
Khan, Javed
Appella, Ettore
Thiele, Carol J.
TI Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a
Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma
SO CANCER CELL
LA English
DT Article
ID PR-SET7 HISTONE METHYLTRANSFERASE; CELL-CYCLE; SUPPRESSOR GENES;
EXPRESSION; TUMORS; DIFFERENTIATION; METHYLATION; MOLECULE; CANCER;
DISCOVERY
AB Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4(K20me1) methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53(K382me1) leading to activation of the p53 canonical pathway. In pre-clinical xenograft NB models, genetic or pharmacological (UNC0379) SETD8 inhibition conferred a significant survival advantage, providing evidence for SETD8 as a therapeutic target in NB.
C1 [Veschi, Veronica; Liu, Zhihui; Lam, Norris; Souza, Barbara K.; Thiele, Carol J.] NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,CRC, 1-3940,10 Ctr Dr MSC 1105, Bethesda, MD 20892 USA.
[Voss, Ty C.; Ozbun, Laurent] NCI, High Throughput Imaging Facil, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gryder, Berkley; Khan, Javed] NCI, Oncogen Sect, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Yan, Chunhua; Hu, Ying] NCI, Ctr Biomed Informat & Informat Technol, Ctr Canc Res, Rockville, MD 20850 USA.
[Ma, Anqi; Jin, Jian] Icahn Sch Med Mt Sinai, Dept Struct & Chem Biol, Oncol Sci Pharmacol & Syst Therapeut, New York, NY 10029 USA.
[Arrowsmith, Cheryl H.] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
[Mazur, Sharlyn J.; Appella, Ettore] NCI, Chem Immunol Sect, Cell Biol Lab, Bethesda, MD 20892 USA.
[Hager, Gordon L.] NIH, Lab Receptor Biol & Gene Express, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Giannini, Giuseppe] Univ Roma La Sapienza, Dept Mol Med, Fdn Cenci Bolognetti, Ist Pasteur, I-00161 Rome, Italy.
RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,CRC, 1-3940,10 Ctr Dr MSC 1105, Bethesda, MD 20892 USA.
EM ct47a@nih.gov
RI Khan, Javed/P-9157-2014;
OI Khan, Javed/0000-0002-5858-0488; Veschi, Veronica/0000-0002-6379-7366
FU St. Baldrick's Foundation; AbbVie; Bayer Pharma AG; Boehringer
Ingelheim; Canada Foundation for Innovation; Eshelman Institute for
Innovation; Genome Canada through the Ontario Genomics Institute;
Innovative Medicines Initiative (EU/EFPIA) [115766]; Janssen; Merck;
Novartis Pharma AG; Ontario Ministry of Economic Development and
Innovation; Pfizer; Sao Paulo Research Foundation-FAPESP; Takeda;
Wellcome Trust; AIRC [IG17734]; MIUR PRIN; Center for Cancer Research,
NCI, as part of the Intramural Research Program, NIH
FX We are grateful to Drs. G. Pegoraro (High-Throughput Imaging Facility,
CCR) and D. Wei (Urologic Oncology Branch, CCR) for technical
assistance, to Dr. N. Caplen for her critical review, and to Drs. M.
Aladjem and D. Banerjee for insightful discussions. Studies on the
epigenetic siRNA screen were funded by a grant from the St. Baldrick's
Foundation to C.J.T. and Z.L. SGC is a registered charity (1097737) that
receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim,
Canada Foundation for Innovation, Eshelman Institute for Innovation,
Genome Canada through the Ontario Genomics Institute, the Innovative
Medicines Initiative (EU/EFPIA) (ULTRA-DD grant no. 115766), Janssen,
Merck, Novartis Pharma AG, the Ontario Ministry of Economic Development
and Innovation, Pfizer, Sao Paulo Research Foundation-FAPESP, Takeda,
and the Wellcome Trust. G.G. was funded by AIRC IG17734; MIUR PRIN 2015.
This work is supported by the Center for Cancer Research, NCI, as part
of the Intramural Research Program, NIH.
NR 46
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Z9 0
U1 6
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD JAN 9
PY 2017
VL 31
IS 1
BP 50
EP 63
DI 10.1016/j.ccell.2016.12.002
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EH6RJ
UT WOS:000391901300006
PM 28073004
ER
PT J
AU Hayashi, T
Lombaert, IMA
Hauser, BR
Patel, VN
Hoffman, MP
AF Hayashi, Toru
Lombaert, Isabelle M. A.
Hauser, Belinda R.
Patel, Vaishali N.
Hoffman, Matthew P.
TI Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates
Epithelial Progenitor Expansion during Organogenesis
SO DEVELOPMENTAL CELL
LA English
DT Article
ID GLAND BRANCHING MORPHOGENESIS; EXTRACELLULAR VESICLES; CELLS; CANCER;
INFORMATION; MECHANISMS; MEMBRANE; RELEASE; MIRNAS
AB Epithelial-mesenchymal interactions involve fundamental communication between tissues during organogenesis and are primarily regulated by growth factors and extracellular matrix. It is unclear whether RNA-containing exosomes are mobile genetic signals regulating epithelial-mesenchymal interactions. Here we identify that exosomes loaded with mesenchyme-specific mature microRNA contribute mobile genetic signals from mesenchyme to epithelium. The mature mesenchymal miR-133b-3p, loaded into exosomes, was transported from mesenchyme to the salivary epithelium, which did not express primary miR-133b-3p. Knockdown of miR-133b-3p in culture decreased endbud morphogenesis, reduced proliferation of epithelial KIT+ progenitors, and increased expression of a target gene, Disco-interacting protein 2 homolog B (Dip2b). DIP2B, which is involved in DNA methylation, was localized with 5-methylcytosine in the prophase nucleus of a subset of KIT+ progenitors during mitosis. In summary, exosomal transport of miR-133b-3p from mesenchyme to epithelium decreases DIP2B, which may function as an epigenetic regulator of genes responsible for KIT+ progenitor expansion during organogenesis.
C1 [Hayashi, Toru; Lombaert, Isabelle M. A.; Hauser, Belinda R.; Patel, Vaishali N.; Hoffman, Matthew P.] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Sect, NIH, Bethesda, MD 20892 USA.
[Hayashi, Toru] Asahi Univ, Sch Dent, Dept Pharmacol, 1851 Hozumi, Mizuho, Gifu 5010296, Japan.
[Lombaert, Isabelle M. A.] Univ Michigan, Sch Dent, Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[Lombaert, Isabelle M. A.] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA.
RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Sect, NIH, Bethesda, MD 20892 USA.
EM mhoffman@mail.nih.gov
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research at the NIH; JSPS [JP15K11060, JP15K20370];
Sumitomo Foundation
FX The authors would like to thank the NIDCR Combined Technical Research
Core for FACS analysis, Daniel Martin for bioinformatics analysis, Kelly
Ten Hagen for critical reading of the manuscript, and Masanori Kashimata
at Asahi University for technical support. This research was supported
by the Intramural Research Program of the National Institute of Dental
and Craniofacial Research at the NIH and by JSPS KAKENHI grants
JP15K11060 and JP15K20370, and by a grant for Basic Science Research
Projects from The Sumitomo Foundation.
NR 40
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD JAN 9
PY 2017
VL 40
IS 1
BP 95
EP 103
DI 10.1016/j.devcel.2016.12.001
PG 9
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA EH6RA
UT WOS:000391900400011
PM 28041903
ER
PT J
AU Caglayan, M
Horton, JK
Dai, DP
Stefanick, DF
Wilson, SH
AF Caglayan, Melike
Horton, Julie K.
Dai, Da-Peng
Stefanick, Donna F.
Wilson, Samuel H.
TI Oxidized nucleotide insertion by pol beta confounds ligation during base
excision repair
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DNA-POLYMERASE-BETA; OXIDATIVE STRESS; APRATAXIN DEFICIENCY;
HYDROGEN-PEROXIDE; MAMMALIAN-CELLS; NUCLEIC-ACIDS; STRAND BREAK;
ACTIVE-SITE; LIGASE I; DAMAGE
AB Oxidative stress in cells can lead to accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized purine nucleotides can be inserted into DNA during replication and repair. The main pathway for correcting oxidized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase beta (pol beta) provides gap filling and tailoring functions. Here we report that the DNA ligation step of BER is compromised after pol beta insertion of oxidized purine nucleotides into the BER intermediate in vitro. These results suggest the possibility that BER mediated toxic strand breaks are produced in cells under oxidative stress conditions. We observe enhanced cytotoxicity in oxidizing-agent treated pol beta expressing mouse fibroblasts, suggesting formation of DNA strand breaks under these treatment conditions. Increased cytotoxicity following MTH1 knockout or treatment with MTH1 inhibitor suggests the oxidation of precursor nucleotides.
C1 [Caglayan, Melike; Horton, Julie K.; Dai, Da-Peng; Stefanick, Donna F.; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES050158, Z01 ES050159]
FX We thank Rajendra Prasad, David Shock, Akira Sassa, Nadezhda Dyrkheeva,
Alan Tomkinson (Univ. of New Mexico) and Stephen Lloyd (OHSU) for gifts
of purified proteins used in this study. We thank Carl Bortner for his
advice with Flow Cytometry and Natalie Gassman for helpful discussion.
This work was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (Project numbers Z01
ES050158 and Z01 ES050159).
NR 58
TC 0
Z9 0
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN 9
PY 2017
VL 8
AR 14045
DI 10.1038/ncomms14045
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG9GA
UT WOS:000391365700001
PM 28067232
ER
PT J
AU Lin, HH
Yin, XY
Xie, ZJ
Lunetta, KL
Lubitz, SA
Larson, MG
Ko, D
Magnani, JW
Mendelson, MM
Liu, CY
McManus, DD
Levy, D
Ellinor, PT
Benjamin, EJ
AF Lin, Honghuang
Yin, Xiaoyan
Xie, Zhijun
Lunetta, Kathryn L.
Lubitz, Steven A.
Larson, Martin G.
Ko, Darae
Magnani, Jared W.
Mendelson, Michael M.
Liu, Chunyu
McManus, David D.
Levy, Daniel
Ellinor, Patrick T.
Benjamin, Emelia J.
TI Methylome-wide Association Study of Atrial Fibrillation in Framingham
Heart Study
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; DNA METHYLATION; RISK-FACTORS; ALCOHOL-CONSUMPTION;
GENE-EXPRESSION; FOLLOW-UP; PROTEIN; PREVALENCE; MORTALITY; DISEASE
AB Atrial fibrillation (AF) is the most common cardiac arrhythmia, but little is known about the molecular mechanisms associated with AF arrhythmogenesis. DNA methylation is an important epigenetic mechanism that regulates gene expression and downstream biological processes. We hypothesize that DNA methylation might play an important role in the susceptibility to develop AF. A total of 2,639 participants from the Offspring Cohort of Framingham Heart Study were enrolled in the current study. These participants included 183 participants with prevalent AF and 220 with incident AF during up to 9 years follow up. Genome-wide methylation was profiled using the Illumina Infinium HumanMethylation450 BeadChip on blood-derived DNA collected during the eighth examination cycle (2005-2008). Two CpG sites were significantly associated with prevalent AF, and five CpGs were associated with incident AF after correction for multiple testing (FDR < 0.05). Fourteen previously reported genome-wide significant AF-related SNP were each associated with at least one CpG site; the most significant association was rs6490029 at the CUX2 locus and cg10833066 (P = 9.5 x 10(-279)). In summary, we performed genome-wide methylation profiling in a community-based cohort and identified seven methylation signatures associated with AF. Our study suggests that DNA methylation might play an important role in AF arrhythmogenesis.
C1 [Lin, Honghuang; Yin, Xiaoyan; Lunetta, Kathryn L.; Larson, Martin G.; Liu, Chunyu; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham, MA 01702 USA.
[Lin, Honghuang; Yin, Xiaoyan; Lunetta, Kathryn L.; Larson, Martin G.; Liu, Chunyu; Levy, Daniel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA.
[Lin, Honghuang; Xie, Zhijun] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA.
[Xie, Zhijun] Zhejiang Chinese Med Univ, TCM Clin Basis Inst, Hangzhou, Zhejiang, Peoples R China.
[Lunetta, Kathryn L.; Liu, Chunyu] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Magnani, Jared W.] Univ Pittsburgh, Dept Med, UPMC Heart & Vasc Inst, Div Cardiol, Pittsburgh, PA USA.
[Ko, Darae; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Mendelson, Michael M.; Liu, Chunyu; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
[Mendelson, Michael M.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Med & Quantitat Hlth Sci, Worcester, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Lin, HH (reprint author), NHLBI, Framingham, MA 01702 USA.; Lin, HH (reprint author), Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA.; Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA.
EM hhlin@bu.edu
OI Mendelson, Michael/0000-0001-7590-3958
FU National Institutes of Health [N01-HC-25195, HHSN268 201500001I,
K24HL105780]; Division of Intramural Research, National Heart, Lung, and
Blood Institute, National Institutes of Health; NIH [2RO1HL092577,
1R01HL128914, K23HL114724]; American Heart Association [13EIA14220013];
Fondation Leducq [14CVD01]; Doris Duke Charitable Foundation [2014105,
2015084]; Tommy Kaplan Fund, Department of Cardiology, Boston Children's
Hospital
FX The Framingham Heart Study is funded by National Institutes of Health
contract N01-HC-25195; HHSN268 201500001I. The laboratory work for this
investigation was funded by the Division of Intramural Research,
National Heart, Lung, and Blood Institute, National Institutes of
Health, and by a Director's Challenge Award, National Institutes of
Health (DL, PI). This project also was supported by NIH grants to Drs.
Ellinor, Benjamin, and Lunetta (2RO1HL092577) and Benjamin and Ellinor
(1R01HL128914). Dr. Ellinor is supported by grants from the National
Institutes of Health (K24HL105780), an Established Investigator Award
from the American Heart Association (13EIA14220013) and by support from
the Fondation Leducq (14CVD01). Dr. Lubitz is supported by NIH grants
K23HL114724. This work was supported by Grant 2014105 and Grant 2015084
from the Doris Duke Charitable Foundation. Dr. Mendelson is partly
supported by a family foundation award from the Tommy Kaplan Fund,
Department of Cardiology, Boston Children's Hospital. The views
expressed in this manuscript are those of the authors and do not
necessarily represent the views of the National Heart, Lung, and Blood
Institute; the National Institutes of Health; or the U.S. Department of
Health and Human Services.
NR 54
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U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 9
PY 2017
VL 7
AR 40377
DI 10.1038/srep40377
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG9IR
UT WOS:000391372800001
PM 28067321
ER
PT J
AU Thomason, ME
Scheinost, D
Manning, JH
Grove, LE
Hect, J
Marshall, N
Hernandez-Andrade, E
Berman, S
Pappas, A
Yeo, L
Hassan, SS
Constable, RT
Ment, LR
Romero, R
AF Thomason, Moriah E.
Scheinost, Dustin
Manning, Janessa H.
Grove, Lauren E.
Hect, Jasmine
Marshall, Narcis
Hernandez-Andrade, Edgar
Berman, Susan
Pappas, Athina
Yeo, Lami
Hassan, Sonia S.
Constable, R. Todd
Ment, Laura R.
Romero, Roberto
TI Weak functional connectivity in the human fetal brain prior to preterm
birth
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; RESTING-STATE NETWORKS; WHITE-MATTER LESIONS;
FRAGILE-X-SYNDROME; INTRINSIC CONNECTIVITY; HEMODYNAMIC-RESPONSES;
NEURAL CONNECTIVITY; COGNITIVE FUNCTION; WILLIAMS-SYNDROME
AB It has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero.
C1 [Thomason, Moriah E.; Manning, Janessa H.; Grove, Lauren E.; Hect, Jasmine; Marshall, Narcis] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.
[Thomason, Moriah E.; Pappas, Athina] Wayne State Univ, Dept Pediat, Sch Med, Detroit, MI 48202 USA.
[Thomason, Moriah E.; Manning, Janessa H.; Grove, Lauren E.; Marshall, Narcis; Hernandez-Andrade, Edgar; Pappas, Athina; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Thomason, Moriah E.; Manning, Janessa H.; Grove, Lauren E.; Marshall, Narcis; Hernandez-Andrade, Edgar; Pappas, Athina; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Thomason, Moriah E.] Univ Michigan, Survey Res Ctr, Inst Social Res, Ann Arbor, MI 48104 USA.
[Scheinost, Dustin; Constable, R. Todd] Yale Sch Med, Dept Radiol & Biomed Imaging, New Haven, CT 06520 USA.
[Hernandez-Andrade, Edgar; Berman, Susan; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA.
[Constable, R. Todd] Yale Sch Med, Dept Neurosurg, New Haven, CT 06520 USA.
[Ment, Laura R.] Yale Sch Med, Dept Pediat, New Haven, CT 06520 USA.
[Ment, Laura R.] Yale Sch Med, Dept Neurol, New Haven, CT 06520 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med, Detroit, MI 48202 USA.
[Romero, Roberto] Univ Michigan, Sch Med, Dept Obstet & Gynecol, Ann Arbor, MI 48104 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48825 USA.
RP Thomason, ME (reprint author), Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.; Thomason, ME (reprint author), Wayne State Univ, Dept Pediat, Sch Med, Detroit, MI 48202 USA.; Thomason, ME (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.; Thomason, ME (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.; Thomason, ME (reprint author), Univ Michigan, Survey Res Ctr, Inst Social Res, Ann Arbor, MI 48104 USA.
EM moriaht@gmail.com
FU National Institutes of Health [MH110793, ES026022]; NARSAD; NIH [HHSN
275201300006 C]
FX This project was supported by awards to M.E.T. from the National
Institutes of Health, MH110793 and ES026022, and by a NARSAD Young
Investigator Award. This project was also supported in part by NIH
contract HHSN 275201300006 C. The authors thank Pavan Jella, Saige
Rutherford, Sophia Neuenfeldt, and Ki-Jana Malone for their assistance
in acquiring the scan data; Farrah Elrahal, Jamie Pierce, Jordan Boeve,
Gillian Grace Spitzley, Sydney Rooks, and Joi Webb for their assistance
in participant recruitment, screening, and conducting behavioral
testing; and Tarek Bazzi, Alison Li, Kassem Soufan, and Baldish Oberoi
for their help with data processing. The authors also thank participant
families who generously shared their time.
NR 88
TC 1
Z9 1
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 9
PY 2017
VL 7
AR 39286
DI 10.1038/srep39286
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG9MQ
UT WOS:000391383500001
PM 28067865
ER
PT J
AU Wu, C
Xu, G
Tsai, SYA
Freed, WJ
Lee, CT
AF Wu, Chun
Xu, Gang
Tsai, Shang-Yi A.
Freed, William J.
Lee, Chun-Ting
TI Transcriptional profiles of type 2 diabetes in human skeletal muscle
reveal insulin resistance, metabolic defects, apoptosis, and molecular
signatures of immune activation in response to infections
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Transcriptome; Type 2 diabetes; Insulin resistance; Metabolic defects;
Immune activation
ID GENES; INFLAMMATION; MELLITUS; PACKAGE; RISK
AB Skeletal muscle insulin resistance is considered to be the primary defect involved in type 2 diabetes mellitus (T2DM). Despite transcriptome studies in limited T2DM human subjects suggesting an association of T2DM with impaired oxidative phosphorylation in muscle, its molecular pathogenesis remains largely unknown. To identify dysregulated genes and gene networks that are associated with T2DM in human skeletal muscle, we examined expression patterns of 56,318 transcribed genes on 92 T2DM cases and 184 gender-, age- and race-matched non-diabetic controls from the Genotype-Tissue Expression (GTEx) database. RNA-Sequencing data suggest that diabetic skeletal muscle is characterized by decreased expression of genes that are related to insulin resistance (1RS2, MTOR, SLC2A4, and PPARA), carbohydrate, energy, and amino acid metabolism pathways (NDUFSI, NDUFA10, NDUFB4, NDUFB5, NDUFA5, NDUFB10, SDHB, SDHC, ATP5H, ATP5A, and ATP5J). Up-regulated genes in T2DM are mainly enriched in apoptosis pathways (TP53, GADD45A, TNFRSF10B, TP53A1P1, and PMAIP1), and notably include immune-related pathways suggestive of a response to various infectious diseases (C2, CFB, C4A, C4B, C1S, C1R, C3, HLA-DRA, HLA-DMA, HLA-DOA, and HLA-DPB1). These results confirm the essential regulation of impaired insulin signaling and oxidative phosphorylation in the muscle of T2DM patients, and provide novel molecular insights into the pathophysiological mechanisms of T2DM. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Wu, Chun] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, 1951 NW 7th Ave,Suite 240, Miami, FL 33136 USA.
[Xu, Gang] Univ Miami, Miller Sch Med, Div Biostat, Dept Publ Hlth Sci, Miami, FL 33136 USA.
[Tsai, Shang-Yi A.; Freed, William J.] NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21244 USA.
[Freed, William J.] Lebanon Valley Coll, Dept Biol, Annville, PA 17003 USA.
[Lee, Chun-Ting] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
EM c.wu6@med.miami.edu; Chun-Ting.Lee@fda.hhs.gov
OI Wu, Chun/0000-0003-2858-8064
NR 24
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JAN 8
PY 2017
VL 482
IS 2
BP 282
EP 288
DI 10.1016/j.bbrc.2016.11.055
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA EI7PJ
UT WOS:000392690100015
PM 27847319
ER
PT J
AU Taylor, LJ
Strebel, K
AF Taylor, Louis J.
Strebel, Klaus
TI Pyviko: an automated Python tool to design gene knockouts in complex
viruses with overlapping genes
SO BMC MICROBIOLOGY
LA English
DT Software Review
DE Virus; Knockout virus; Mutation; Overprinting; Bioinformatics; Cloning;
Viral mutant; Knockout; Pyviko
AB Background: Gene knockouts are a common tool used to study gene function in various organisms. However, designing gene knockouts is complicated in viruses, which frequently contain sequences that code for multiple overlapping genes. Designing mutants that can be traced by the creation of new or elimination of existing restriction sites further compounds the difficulty in experimental design of knockouts of overlapping genes. While software is available to rapidly identify restriction sites in a given nucleotide sequence, no existing software addresses experimental design of mutations involving multiple overlapping amino acid sequences in generating gene knockouts.
Results: Pyviko performed well on a test set of over 240,000 gene pairs collected from viral genomes deposited in the National Center for Biotechnology Information Nucleotide database, identifying a point mutation which added a premature stop codon within the first 20 codons of the target gene in 93.2% of all tested gene-overprinted gene pairs. This shows that Pyviko can be used successfully in a wide variety of contexts to facilitate the molecular cloning and study of viral overprinted genes.
Conclusions: Pyviko is an extensible and intuitive Python tool for designing knockouts of overlapping genes. Freely available as both a Python package and a web-based interface (http://louiejtaylor.github.io/pyViKO/), Pyviko simplifies the experimental design of gene knockouts in complex viruses with overlapping genes.
C1 [Taylor, Louis J.; Strebel, Klaus] NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Taylor, Louis J.] Univ Penn, Perelman Sch Med, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA.
RP Taylor, LJ (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Taylor, LJ (reprint author), Univ Penn, Perelman Sch Med, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA.
EM louist@upenn.edu
OI Taylor, Louis/0000-0002-6993-5838
FU Intramural Research Program of the NIH, NIAID [1 Z01 AI000669]; NIH
Post-baccalaureate Fellowship
FX This work was supported by the Intramural Research Program of the NIH,
NIAID (KS: 1 Z01 AI000669) and by an NIH Post-baccalaureate Fellowship
(LJT).
NR 23
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD JAN 7
PY 2017
VL 17
AR 12
DI 10.1186/s12866-016-0920-3
PG 6
WC Microbiology
SC Microbiology
GA EH6OG
UT WOS:000391892000004
PM 28061810
ER
PT J
AU Kodati, S
Palmore, TN
Spellman, FA
Cunningham, D
Weistrop, B
Sen, HN
AF Kodati, Shilpa
Palmore, Tara N.
Spellman, Frank A.
Cunningham, Denise
Weistrop, Benjamin
Sen, H. Nida
TI Bilateral posterior uveitis associated with Zika virus infection
SO LANCET
LA English
DT Editorial Material
C1 [Kodati, Shilpa; Cunningham, Denise; Sen, H. Nida] NEI, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Spellman, Frank A.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Spellman, Frank A.] Retina Grp Washington, Washington, DC USA.
[Weistrop, Benjamin] New York Med Coll, Valhalla, NY 10595 USA.
RP Sen, HN (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
NR 5
TC 0
Z9 0
U1 8
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JAN 7
PY 2017
VL 389
IS 10064
BP 125
EP 126
DI 10.1016/S0140-6736(16)32518-1
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG7VH
UT WOS:000391264000044
PM 27939402
ER
PT J
AU Symons, R
Cork, TE
Sahbaee, P
Fuld, MK
Kappler, S
Folio, LR
Bluemke, DA
Pourmorteza, A
AF Symons, Rolf
Cork, Tyler E.
Sahbaee, Pooyan
Fuld, Matthew K.
Kappler, Steffen
Folio, Les R.
Bluemke, David A.
Pourmorteza, Amir
TI Low-dose lung cancer screening with photon-counting CT: a feasibility
study
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE computed tomography; photon-counting CT; lung imaging; lung cancer
screening; ground-glass nodule; emphysema; low-contrast detectability
ID COMPUTED-TOMOGRAPHY; CHEST CT; DETECTOR; NODULES; SYSTEM; MODEL
AB To evaluate the feasibility of using a whole-body photon-counting detector (PCD) CT scanner for low-dose lung cancer screening compared to a conventional energy integrating detector (EID) system.
Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp). EID and PCD images were compared for quantitative Hounsfield unit (HU) accuracy, noise levels, and contrast-to-noise ratios (CNR) for detection of ground-glass nodules (GGN) and emphysema.
The PCD HU accuracy was better than EID for water at all scan parameters. PCD HU stability for lung, GGN and emphysema regions were superior to EID and PCD attenuation values were more reproducible than EID for all scan parameters (all P < 0.01), while HUs for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P < 0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2 +/- 0.3 HU versus 15.8 +/- 0.2 HU, P = 0.03; 16.1 +/- 0.3 HU versus 18.0 +/- 0.4 HU, P = 0.003; and 16.1 +/- 0.3 HU versus 17.9 +/- 0.3 HU, P = 0.001, respectively), resulting in superior CNR for evaluation of GGNs and emphysema at 100 and 80 kVp.
PCD provided better HU stability for lung, ground-glass, and emphysema-equivalent foams at lower radiation dose settings with better reproducibility than EID. Additionally, PCD showed up to 10% less noise, and 11% higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.
C1 [Symons, Rolf; Cork, Tyler E.; Folio, Les R.; Bluemke, David A.; Pourmorteza, Amir] NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Sahbaee, Pooyan; Fuld, Matthew K.] Siemens Med Solut, Malvern, PA USA.
[Kappler, Steffen] Siemens Healthcare GmbH, Forchheim, Germany.
RP Pourmorteza, A (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM amir.pourmorteza@nih.gov
FU NIH intramural research program [ZIACL090019, ZIAEB000072]; Siemens
Medical Systems (Forchheim, Germany)
FX This study was supported by the NIH intramural research program
(ZIACL090019; ZIAEB000072), and in part by a collaborative research
agreement with Siemens Medical Systems (Forchheim, Germany). Authors who
are not employees of or consultants for Siemens had control of inclusion
of any data and information that might present a conflict of interest
for the authors who are employed by Siemens.
NR 28
TC 0
Z9 0
U1 1
U2 1
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JAN 7
PY 2017
VL 62
IS 1
BP 202
EP 213
DI 10.1088/1361-6560/62/1/202
PG 12
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA EH1ZT
UT WOS:000391567700004
PM 27991453
ER
PT J
AU Lee, S
Chowell, G
AF Lee, Sunmi
Chowell, Gerardo
TI Exploring optimal control strategies in seasonally varying flu-like
epidemics
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Influenza transmission dynamics; Seasonally varying transmission rate;
Optimal control theory; Vaccination and treatment strategies
ID PANDEMIC INFLUENZA; DRUG-USE; TRANSMISSION; IMPACT
AB The impact of optimal control strategies in the context of seasonally varying infectious disease transmission remains a wide open research area. We investigate optimal control strategies for flu-like epidemics using an SIR (susceptible-infectious-recovered) type epidemic model where the transmission rate varies seasonally Specifically, we explore optimal control strategies using time-dependent treatment and vaccination as control functions alone or in combination. Optimal strategies and associated epidemic outcomes are contrasted for epidemics with constant and seasonal transmission rates. Our results show that the epidemic outcomes assessed in terms of the timing and size of seasonal epidemics subject to optimal control strategies are highly sensitive to various parameters including R-0, the timing of the introduction of the initial number of infectious individuals into the population, the time at which interventions start, and the strength of the seasonal forcing that modulates the time-dependent transmission rate. Findings highlight the difficult challenge in predicting short-term epidemic impact in the context of seasonally varying infectious disease transmission with some interventions scenarios exhibiting larger epidemic size compared to scenarios without control interventions.
C1 [Lee, Sunmi] Kyung Hee Univ, Dept Appl Math, Yongin, South Korea.
[Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Lee, S (reprint author), Kyung Hee Univ, Dept Appl Math, Yongin, South Korea.
EM sunmilee@khu.ac.kr
FU National Research Foundation of Korea (NRF) - Korean government (MSIP)
[20152194]
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korean government (MSIP) (No. 20152194). The
authors would like to thank the anonymous reviewers for their valuable
comments and suggestions to improve our manuscript.
NR 35
TC 0
Z9 0
U1 7
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
EI 1095-8541
J9 J THEOR BIOL
JI J. Theor. Biol.
PD JAN 7
PY 2017
VL 412
BP 36
EP 47
DI 10.1016/j.jtbi.2016.09.023
PG 12
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA EG5KA
UT WOS:000391081500005
PM 27693366
ER
PT J
AU Togias, A
Cooper, SF
Acebal, ML
Assa'ad, A
Baker, JR
Beck, LA
Block, J
Byrd-Bredbenner, C
Chan, ES
Eichenfield, LF
Fleischer, DM
Fuchs, GJ
Furuta, GT
Greenhawt, MJ
Gupta, RS
Habich, M
Jones, SM
Keaton, K
Muraro, A
Plaut, M
Rosenwasser, LJ
Rotrosen, D
Sampson, HA
Schneider, LC
Sicherer, SH
Sidbury, R
Spergel, J
Stukus, DR
Venter, C
Boyce, JA
AF Togias, Alkis
Cooper, Susan F.
Acebal, Maria L.
Assa'ad, Amal
Baker, James R.
Beck, Lisa A.
Block, Julie
Byrd-Bredbenner, Carol
Chan, Edmond S.
Eichenfield, Lawrence F.
Fleischer, David M.
Fuchs, George J., III
Furuta, Glenn T.
Greenhawt, Matthew J.
Gupta, Ruchi S.
Habich, Michele
Jones, Stacie M.
Keaton, Kari
Muraro, Antonella
Plaut, Marshall
Rosenwasser, Lanny J.
Rotrosen, Daniel
Sampson, Hugh A.
Schneider, Lynda C.
Sicherer, Scott H.
Sidbury, Robert
Spergel, Jonathan
Stukus, David R.
Venter, Carina
Boyce, Joshua A.
TI Addendum guidelines for the prevention of peanut allergy in the United
States: report of the National Institute of Allergy and Infectious
Diseases-sponsored expert panel
SO ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Food; Peanut; Allergy; Prevention; Guidelines
ID FOOD ALLERGY; NUTRITIONAL INTERVENTIONS; ANAPHYLACTIC REACTIONS; GRADING
QUALITY; PREVALENCE; INFANTS; CONSUMPTION; RECOMMENDATIONS; FEASIBILITY;
FATALITIES
AB Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.
Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.
Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.
Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
C1 [Togias, Alkis; Cooper, Susan F.; Plaut, Marshall; Rotrosen, Daniel] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Acebal, Maria L.] Board Directors, Food Allergy Res & Educ, Mclean, VA USA.
[Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH USA.
[Baker, James R.] Food Allergy Res & Educ, Mclean, VA USA.
[Baker, James R.] Univ Michigan Hlth Syst, Div Allergy & Clin Immunol, Ann Arbor, MI USA.
[Beck, Lisa A.] Univ Rochester, Med Ctr, Dept Dermatol, Rochester, NY 14627 USA.
[Block, Julie] Natl Eczema Assoc, San Rafael, CA USA.
[Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, Fredericton, NB, Canada.
[Chan, Edmond S.] Univ British Columbia, BC Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Vancouver, BC, Canada.
[Eichenfield, Lawrence F.] Univ Calif San Diego, Sch Med, Rady Childrens Hosp, Dept Dermatol, San Diego, CA 92103 USA.
[Eichenfield, Lawrence F.] Univ Calif San Diego, Sch Med, Rady Childrens Hosp, Dept Pediat, San Diego, CA 92103 USA.
[Fleischer, David M.; Greenhawt, Matthew J.] Univ Colorado Denver, Sch Med, Sect Allergy & Immunol, Dept Pediat,Childrens Hosp Colorado, Aurora, CO USA.
[Fuchs, George J., III] Univ Kentucky, Coll Med, Div Gastroenterol Hepatol & Nutr, Dept Pediat,Coll Med,Kentucky Childrens Hosp, Lexington, KY USA.
[Furuta, Glenn T.] Childrens Hosp Colorado, Digest Hlth Inst, Aurora, CO USA.
[Gupta, Ruchi S.] Northwestern Univ, Div Acad Gen Pediat & Primary Care, Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat,Feinberg Sch Med, Chicago, IL 60611 USA.
[Habich, Michele] Cent DuPage Hosp, Northwestern Med, Winfield, IL USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA.
[Keaton, Kari] Metro DC Food Allergy Support Grp, Rockville, MD USA.
[Muraro, Antonella] Padua Univ Hosp, Dept Women & Child Hlth, Food Allergy Referral Ctr, Padua, Italy.
[Rosenwasser, Lanny J.] Univ Missouri, Sch Med, Kansas City, MO 64110 USA.
[Sampson, Hugh A.] Harvard Med Sch, Dept Pediat, Div Allergy & Immunol, Boston, MA USA.
[Schneider, Lynda C.] Icahn Sch Med Mt Sinai, Div Pediat Allergy & Immunol, New York, NY 10029 USA.
[Sicherer, Scott H.] Boston Childrens Hosp, Div Allergy & Immunol, Boston, MA USA.
[Sidbury, Robert] Univ Washington, Sch Med, Dept Pediat, Div Dermatol,Seattle Childrens Hosp, Seattle, WA 98195 USA.
[Spergel, Jonathan] Univ Penn, Div Allergy & Immunol, Dept Pediat, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Stukus, David R.] Ohio State Univ, Dept Pediat, Sect Allergy & Immunol, Nationwide Childrens Hosp,Coll Med, Columbus, OH 43210 USA.
[Venter, Carina] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Pediat, Boston, MA USA.
RP Cooper, SF (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM coopersu@niaid.nih.gov
FU DBV Technologies; Aimmune; Stanford Foundation; TEVA Pharmaceuticals;
GlaxoSmithKline; National Institutes of Health (NIH); Astellas; Food
Allergy Research & Education (FARE); ACAAI; Pfizer; Sanofi; Mead
Johnson; Nestle; Monsanto Company; Nestle Nutrition Institute; Aimmune
Therapeutics; Agency for Healthcare Research and Quality
[1K08HS024599-01]; Reach MD; Thermo Fisher Scientific; California
Society for Allergy and Immunology; Allergy and Asthma Network; New
England Society for Allergy; UCLA/Harbor Heiner Lectureship; Medscape;
Western Michigan School of Medicine; Canadian Society of Allergy and
Clinical Immunology; Pennsylvania Society for Allergy and Immunology;
NIH; FARE; Mylan LLC; Grand Rounds; NIH/NIAID; Aimmune Technologies;
National Peanut Board; Kansas City Allergy Society; Mercy Children's
Hospital; Riley Children's Hospital; Southwester Medical
School-Children's Medical Center; European Academy of Allergy & Clinical
Immunology; New York Allergy Asthma Society; University of Iowa Paul M.
Seebohm Lectureship in Allergy; Iowa Society of Allergy, Asthma, and
Immunology; Meda; Menarini; NIAID; Immune Tolerance Network; HAL
Allergy; Epidermolysis Bullosa Research Partnership; Taiwanese
Dermatological Society; Dartmouth College; Florida Allergy Society
FX A. Assa'ad received travel support from the American College of Allergy,
Asthma & Immunology (ACAAI); was an elected member of the Board of
Directors for the American Academy of Allergy, Asthma, & Immunology
(AAAAI) from March 2012 to March 2016; has consultant arrangements with
Aimmune; is employed by Cincinnati Children's Hospital Medical Center;
has received grants from DBV Technologies, Aimmune, Stanford Foundation,
TEVA Pharmaceuticals, GlaxoSmithKline, the National Institutes of Health
(NIH), Astellas, and Food Allergy Research & Education (FARE); and has
received payment for lectures from the ACAAI. C. Byrd-Bredbenner and
G.J. Fuchs III have received travel support from the NIH/National
Institute of Allergy and Infectious Disease (NIAID). E.S. Chan has
received travel support from the NIAID, has received grants from DBV
Technologies, and has received payment for lectures from Pfizer, Sanofi,
Mead Johnson, and Nestle. D.M. Fleischer has received travel support
from the NIAID; is a board member for the National Peanut Board, the
FAACT Medical Advisory Board, and the FARE Medical Advisory Board; has
consultant arrangements with Adamis Pharmaceuticals Corporation, INSYS
Therapeutics, DBV Technologies, Aimmune Therapeutics, Intrommune
Therapeutics, and Kaleo Pharma; is employed by University Physicians;
has received grants from Monsanto Company, Nestle Nutrition Institute,
DBV Technologies, and Aimmune Therapeutics; has received payment for
lectures from Nestle Nutrition Institute; and has received royalties
from UpToDate. M.J. Greenhawt has received a grant from the Agency for
Healthcare Research and Quality (1K08HS024599-01, Career Development
Award); has received travel support from the NIAID and the Joint
Taskforce on Allergy Practice Parameters; has a board membership with
the National Peanut Board; has consultant arrangements with Adamis
Pharmaceuticals, the Canadian Transportation Agency, Nutricia,
Nestle/Gerber, Aimmune, Kaleo Pharmaceutical, and Monsanto; is an
Associate Editor for the Annals of Allergy, Asthma, and Immunology; has
received payment for lectures from the ACAAI, Reach MD, Thermo Fisher
Scientific, the California Society for Allergy and Immunology, the
Allergy and Asthma Network, the New England Society for Allergy,
UCLA/Harbor Heiner Lectureship, Medscape, the Western Michigan School of
Medicine, the Canadian Society of Allergy and Clinical Immunology, and
the Pennsylvania Society for Allergy and Immunology. R.S. Gupta has
consultant arrangements with BEFORE Brands and DBV Technologies; has
received grants from the NIH, FARE, and Mylan LLC; has received payment
for lectures from Grand Rounds; and has received royalties from
Createspace Independent Publishing Platform. S.M. Jones is on the
Research Advisory Board for FARE; is on the Scientific Advisory Board
for Aimmune; has consultant arrangements with Stallergenes; has received
grants from the NIH/NIAID (Consortium of Food Allergy Research and
Immune Tolerance Network-IMPACT Trial), FARE, Aimmune Technologies, DBV
Technologies, and the National Peanut Board; has received payment for
lectures from the Kansas City Allergy Society, Mercy Children's
Hospital, Riley Children's Hospital, Southwester Medical
School-Children's Medical Center, the European Academy of Allergy &
Clinical Immunology, the New York Allergy & Asthma Society, the
University of Iowa Paul M. Seebohm Lectureship in Allergy, and the Iowa
Society of Allergy, Asthma, and Immunology. A.; Muraro has consultant
arrangements with Meda, Novartis, and Menarini; is employed by Padua
University Hospital; and has received payment for lectures from Meda and
Menarini. L.J. Rosenwasser is a board member for the World Allergy
Organization. H.A. Sampson has consultant arrangements with Allertein
Therapeutics, Genentech/Roche, Sanofi, Stallergenes, Danone, and Merck;
is employed part time as Chief Scientific Officer for DBV Technologies;
has received grants from the NIAID and the Immune Tolerance Network; has
received royalties from UpToDate and Elsevier; has been offered stock
options in DBV Technologies; and is chairman of PhARF Award Selection
Committee for Thermo Fisher. L.C. Schneider is on the Medical Advisory
Board for FARE, has received a grant from DBV Technologies, and has
received stock/stock options in Antera Therapeutics. S.H. Sicherer has
received grants from the NIAID, FARE, and HAL Allergy; has received
royalties from UpToDate; and is serving as Associate Editor for the
Journal of Allergy and Clinical Immunology: In Practice. R. Sidbury has
received travel support from the NIH and the Hawaii Dermatology Seminar,
has consultant arrangements with Anacor, has provided expert witness
testimony on behalf of Roche in Accutane-inflammatory bowel disease
cases, has received a grant from Epidermolysis Bullosa Research
Partnership, has received payment for lectures from the Taiwanese
Dermatological Society, and has received royalties from UpToDate. J.
Spergel has consultant arrangements with DBV Technologies and Danone;
has received grants from DBV Technologies, Aimmune Therapeutics, and the
NIH; has received payment for lectures for Dartmouth College, the ACAAI,
and the Florida Allergy Society; and has received stock/stock options in
DBV Technologies. D.R. Stukus has received payment for lectures from the
ACAAI. C. Venter has consultant arrangements with Danone and Nestle, has
received payment for lectures from Mead Johnson, and has received travel
support from Thermo Fisher. The rest of the authors declare that they
have no relevant competing interests.
NR 28
TC 1
Z9 1
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1710-1484
EI 1710-1492
J9 ALLERGY ASTHMA CL IM
JI Allerg Asthma Clin. Immunol.
PD JAN 6
PY 2017
VL 13
AR 1
DI 10.1186/s13223-016-0175-4
PG 20
WC Allergy; Immunology
SC Allergy; Immunology
GA EL6CZ
UT WOS:000394709300001
ER
PT J
AU Togias, A
Cooper, SF
Acebal, ML
Assa'ad, A
Baker, JR
Beck, LA
Block, J
Byrd-Bredbenner, C
Chan, ES
Eichenfield, LF
Fleischer, DM
Fuchs, GJ
Furuta, GT
Greenhawt, MJ
Gupta, RS
Habich, M
Jones, SM
Keaton, K
Muraro, A
Plaut, M
Rosenwasser, LJ
Rotrosen, D
Sampson, HA
Schneider, LC
Sicherer, SH
Sidbury, R
Spergel, J
Stukus, DR
Venter, C
Boyce, JA
AF Togias, Alkis
Cooper, Susan F.
Acebal, Maria L.
Assa'ad, Amal
Baker, James R., Jr.
Beck, Lisa A.
Block, Julie
Byrd-Bredbenner, Carol
Chan, Edmond S.
Eichenfield, Lawrence F.
Fleischer, David M.
Fuchs, George J., III
Furuta, Glenn T.
Greenhawt, Matthew J.
Gupta, Ruchi S.
Habich, Michele
Jones, Stacie M.
Keaton, Kari
Muraro, Antonella
Plaut, Marshall
Rosenwasser, Lanny J.
Rotrosen, Daniel
Sampson, Hugh A.
Schneider, Lynda C.
Sicherer, Scott H.
Sidbury, Robert
Spergel, Jonathan
Stukus, David R.
Venter, Carina
Boyce, Joshua A.
TI Addendum guidelines for the prevention of peanut allergy in the United
States: Report of the National Institute of Allergy and Infectious
Diseases-sponsored expert panel
SO WORLD ALLERGY ORGANIZATION JOURNAL
LA English
DT Article
DE Food; Peanut; Allergy; Prevention; Guidelines
ID FOOD ALLERGY; NUTRITIONAL INTERVENTIONS; ANAPHYLACTIC REACTIONS; GRADING
QUALITY; PREVALENCE; INFANTS; CONSUMPTION; RECOMMENDATIONS; FEASIBILITY;
FATALITIES
AB Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.
Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.
Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.
Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
C1 [Togias, Alkis; Cooper, Susan F.; Plaut, Marshall; Rotrosen, Daniel] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Acebal, Maria L.; Baker, James R., Jr.] Food Allergy Res & Educ, Mclean, VA USA.
[Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH USA.
[Baker, James R., Jr.] Univ Michigan Hlth Syst, Div Allergy & Clin Immunol, Ann Arbor, MI USA.
[Beck, Lisa A.] Univ Rochester, Med Ctr, Dept Dermatol, New York, NY USA.
[Block, Julie] Natl Eczema Assoc, San Rafael, CA USA.
[Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, Fredericton, NB, Canada.
[Chan, Edmond S.] Univ British Columbia, Div Allergy & Immunol, Dept Pediat, BC Childrens Hosp, Vancouver, BC, Canada.
[Eichenfield, Lawrence F.] Univ Calif San Diego, Sch Med, Dept Pediat, Rady Childrens Hosp, San Diego, CA 92103 USA.
[Eichenfield, Lawrence F.] Univ Calif San Diego, Sch Med, Dept Pediat, Rady Childrens Hosp, San Diego, CA 92103 USA.
[Fleischer, David M.; Greenhawt, Matthew J.] Univ Colorado Denver, Sch Med, Childrens Hosp Colorado, Sect Allergy & Immunol,Dept Pediat, Aurora, CO USA.
[Fuchs, George J., III] Univ Kentucky, Coll Med, Dept Pediat, Div Gastroenterol Hepatol & Nutr,Kentucky Childre, Lexington, KY USA.
[Furuta, Glenn T.] Childrens Hosp Colorado, Digest Hlth Inst, Aurora, CO USA.
[Furuta, Glenn T.] Univ Colorado Denver, Sch Med, Sect Pediat Gastroenterol, Aurora, CO USA.
[Gupta, Ruchi S.] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Div Acad Gen Pediat & Primary Care, Chicago, IL 60611 USA.
[Gupta, Ruchi S.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Habich, Michele] Cent DuPage Hosp, Northwestern Med, Winfield, IL USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA.
[Keaton, Kari] Metro DC Food Allergy Support Grp, Rockville, MD USA.
[Muraro, Antonella] Padua Univ Hosp, Dept Women & Child Hlth, Food Allergy Referral Ctr, Padua, Italy.
[Rosenwasser, Lanny J.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA.
[Sampson, Hugh A.] Harvard Med Sch, Dept Pediat, Div Allergy & Immunol, Boston, MA USA.
[Sicherer, Scott H.] Icahn Sch Med Mt Sinai, Div Pediat Allergy & Immunol, New York, NY 10029 USA.
[Schneider, Lynda C.] Boston Childrens Hosp, Div Allergy & Immunol, Boston, MA USA.
[Sidbury, Robert] Univ Washington, Sch Med, Dept Pediat, Div Dermatol,Seattle Childrens Hosp, Seattle, WA 98195 USA.
[Spergel, Jonathan] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Allergy & Immunol,Perelman Sch Med, Philadelphia, PA 19104 USA.
[Stukus, David R.] Ohio State Univ, Coll Med, Dept Pediat, Sect Allergy & Immunol,Nationwide Childrens Hosp, Columbus, OH 43210 USA.
[Venter, Carina] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Pediat, Boston, MA USA.
RP Cooper, SF (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM coopersu@niaid.nih.gov
NR 28
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1939-4551
J9 WORLD ALLERGY ORGAN
JI World Allergy Organ. J.
PD JAN 6
PY 2017
VL 10
AR 1
DI 10.1186/s40413-016-0137-9
PG 18
WC Allergy
SC Allergy
GA EO4UU
UT WOS:000396690600001
ER
PT J
AU Van de Velde, LA
Subramanian, C
Smith, AM
Barron, L
Qualls, JE
Neale, G
Alfonso-Pecchio, A
Jackowski, S
Rock, CO
Wynn, TA
Murray, PJ
AF Van de Velde, Lee-Ann
Subramanian, Chitra
Smith, Amber M.
Barron, Luke
Qualls, Joseph E.
Neale, Geoffrey
Alfonso-Pecchio, Adolfo
Jackowski, Suzanne
Rock, Charles O.
Wynn, Thomas A.
Murray, Peter J.
TI T Cells Encountering Myeloid Cells Programmed for Amino Acid-dependent
Immunosuppression Use Rictor/mTORC2 Protein for Proliferative Checkpoint
Decisions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NITRIC-OXIDE-SYNTHASE; L-ARGININE METABOLISM; DENDRITIC CELLS;
ACTIVATION; MACROPHAGES; MTOR; INTERLEUKIN-2; SCHISTOSOMIASIS;
DIFFERENTIATION; AVAILABILITY
AB Modulation of T cell proliferation and function by immunoregulatory myeloid cells are an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage-T cell co-culture system, we show that macrophage arginase-1 is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by L-arginine elimination rather than metabolite generation. Tracking how T cells adjust their metabolism when deprived of arginine revealed the significance of macrophage-mediated arginine deprivation to T cells. We found mTORC1 activity was unaffected in the initial G1 block. After 2 days of arginine deprivation, mTORC1 activity declined paralleling a selective down-regulation of SREBP target gene expression, whereas mRNAs involved in glycolysis, gluconeogenesis, and T cell activation were unaffected. Cell cycle arrest was reversible at any point by exogenous arginine, suggesting starved T cells remain poised awaiting nutrients. Arginine deprivation-induced cell cycle arrest was mediated in part by Rictor/mTORC2, providing evidence that this nutrient recognition pathway is a central component of how T cells measure environmental arginine.
C1 [Van de Velde, Lee-Ann; Subramanian, Chitra; Smith, Amber M.; Qualls, Joseph E.; Alfonso-Pecchio, Adolfo; Jackowski, Suzanne; Rock, Charles O.; Murray, Peter J.] St Jude Childrens Res Hosp, Dept Infect Dis, Mail Stop 320,262 Danny Thomas Pl, Memphis, TN 38105 USA.
[Van de Velde, Lee-Ann; Smith, Amber M.; Qualls, Joseph E.; Murray, Peter J.] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Neale, Geoffrey] St Jude Childrens Res Hosp, Dept Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Barron, Luke; Wynn, Thomas A.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Qualls, Joseph E.] Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA.
RP Murray, PJ (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, Mail Stop 320,262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM peter.murray@stjude.org
FU National Institutes of Health [AI062921, CA138064]; Cancer Center Core
Grant [P30 CA21765]; American Lebanese Syrian Associated Charities;
National Institutes of Health Intramural Program
FX This work was supported by National Institutes of Health Grants AI062921
(to P. J. M.) and CA138064 (to J. E. Q.), Cancer Center Core Grant P30
CA21765, the American Lebanese Syrian Associated Charities, and the
National Institutes of Health Intramural Program. The authors declare
that they have no conflicts of interest with the contents of this
article. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
NR 60
TC 2
Z9 2
U1 3
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 6
PY 2017
VL 292
IS 1
BP 15
EP 30
DI 10.1074/jbc.M116.766238
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EH2DQ
UT WOS:000391578000002
PM 27903651
ER
PT J
AU Hamo, CE
Klem, I
Rao, SV
Songco, V
Najjar, S
Lakatta, EG
Raman, SV
Harrington, RA
Heitner, JF
AF Hamo, Carine E.
Klem, Igor
Rao, Sunil V.
Songco, Vincent
Najjar, Samer
Lakatta, Edward G.
Raman, Subha V.
Harrington, Robert A.
Heitner, John F.
TI The Systematic Evaluation of Identifying the Infarct Related Artery
Utilizing Cardiac Magnetic Resonance in Patients Presenting with
ST-Elevation Myocardial Infarction
SO PLOS ONE
LA English
DT Article
ID PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED CONTROLLED-TRIAL;
MULTIVESSEL DISEASE; REVASCULARIZATION; CONTRAST; ERYTHROPOIETIN;
VISUALIZATION; METAANALYSIS; ANGIOPLASTY; GUIDELINES
AB Background
Identification of the infarct-related artery (IRA) in patients with STEMI using coronary angiography (CA) is often based on the ECG and can be challenging in patients with severe multi-vessel disease. The current study aimed to determine how often percutaneous intervention (PCI) is performed in a coronary artery different from the artery supplying the territory of acute infarction on cardiac magnetic resonance imaging (CMR).
Methods
We evaluated 113 patients from the Reduction of infarct Expansion and Ventricular remodeling with Erythropoetin After Large myocardial infarction (REVEAL) trial, who underwent CMR within 4+2 days of revascularization. Blinded reviewers interpreted CA to determine the IRA and CMR to determine the location of infarction on a 17-segment model. In patients with multiple infarcts on CMR, acuity was determined with T2-weighted imaging and/or evidence of microvascular obstruction.
Results
A total of 5 (4%) patients were found to have a mismatch between the IRA identified on CMR and CA. In 4/5 cases, there were multiple infarcts noted on CMR. Thirteen patients (11.5%) had multiple infarcts in separate territories on CMR with 4 patients (3.5%) having multiple acute infarcts and 9 patients (8%) having both acute and chronic infarcts.
Conclusions
In this select population of patients, the identification of the IRA by CA was incorrect in 4% of patients presenting with STEMI. Four patients with a mismatch had an acute infarction in more than one coronary artery territory on CMR. The role of CMR in patients presenting with STEMI with multi-vessel disease on CA deserves further investigation.
C1 [Hamo, Carine E.] Stony Brook Univ Hosp, Dept Med, Stony Brook, NY USA.
[Klem, Igor; Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA.
[Songco, Vincent; Heitner, John F.] New York Methodist Hosp, Div Cardiol, Brooklyn, NY 11215 USA.
[Najjar, Samer] MedStar Hlth Res Inst, Washington, DC USA.
[Najjar, Samer; Lakatta, Edward G.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Raman, Subha V.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA.
[Harrington, Robert A.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA.
RP Heitner, JF (reprint author), New York Methodist Hosp, Div Cardiol, Brooklyn, NY 11215 USA.
EM jfh9003@nyp.org
FU Intramural Research Program of the National Institute on Aging, the
National Institutes of Health, Bethesda, MD, USA
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, the National Institutes of Health,
Bethesda, MD, USA. Clinical Trial Registration-URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00378352.
NR 27
TC 0
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U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 6
PY 2017
VL 12
IS 1
AR e0619108
DI 10.1371/journal.pone.0169108
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH3AX
UT WOS:000391641500054
PM 28060863
ER
PT J
AU Johns, LE
Ferguson, KK
McElrath, TF
Mukherjee, B
Seely, EW
Meeker, JD
AF Johns, Lauren E.
Ferguson, Kelly K.
McElrath, Thomas F.
Mukherjee, Bhramar
Seely, Ellen W.
Meeker, John D.
TI Longitudinal Profiles of Thyroid Hormone Parameters in Pregnancy and
Associations with Preterm Birth
SO PLOS ONE
LA English
DT Article
ID POPULATION-BASED COHORT; SUBCLINICAL HYPOTHYROIDISM; INFLAMMATORY
CYTOKINES; FUNCTION TESTS; 1ST TRIMESTER; DELIVERY; RISK; OUTCOMES;
DYSFUNCTION; GESTATION
AB Introduction
Overt thyroid disease in pregnancy is associated with numerous maternal and neonatal complications including preterm birth. Less is known about the contribution of trimester-specific subclinical alterations in individual thyroid hormones, especially in late gestation, on the risk of preterm birth. Herein, we examined the associations between subclinical changes in maternal thyroid hormone concentrations (TSH, total T3, free and total T4), measured at multiple time points in pregnancy, and the odds of preterm birth in pregnant women without clinical thyroid disease.
Participants and Methods
Data were obtained from pregnant women participating in a nested case-control study of preterm birth within on ongoing birth cohort study at Brigham and Women's Hospital in Boston, MA (N = 439; 116 cases and 323 controls). We measured thyroid hormones in plasma collected at up to four time points in pregnancy (median = 10, 18, 26, and 35 weeks). We used multivariate logistic regression models stratified by study visit of sample collection to examine associations. To reveal potential biological pathways, we also explored these relationships by obstetric presentation of preterm birth (e.g., spontaneous preterm delivery) that have been previously hypothesized to share common underlying mechanisms.
Results
In samples collected at median 10 and 26 weeks of gestation, we found inverse associations between FT4 and the odds of overall preterm birth (odds ratio [OR] = 0.57, 95% confidence interval (CI) = 0.33, 1.00; and OR = 0.53, 95% CI = 0.34, 0.84, respectively). Positive associations were detected for total T3 at these same time points (OR = 2.52, 95% CI = 1.20, 5.31; and OR = 3.40, 95% CI = 1.56, 7.40, respectively). These effect estimates were stronger for spontaneous preterm birth.
Conclusions
Our results suggest that subclinical alterations in individual maternal thyroid hormones may influence the risk of preterm birth, and the strength of these associations vary by gestational age.
C1 [Johns, Lauren E.; Ferguson, Kelly K.; Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Ferguson, Kelly K.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[McElrath, Thomas F.] Harvard Med Sch, Brigham & Womens Hosp, Div Maternal & Fetal Med, Boston, MA USA.
[Mukherjee, Bhramar] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Seely, Ellen W.] Harvard Med Sch, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA.
RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
EM meekerj@umich.edu
OI Ferguson, Kelly/0000-0001-8467-3250
FU Abbott Diagnostics; National Institute of Environmental Health Sciences,
National Institutes of Health [R01ES018872, P42ES017198, P01E5022844,
P30ES017885, T32ES007062]; Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences
FX Subject recruitment and sample collection was originally funded by
Abbott Diagnostics. Funding was also provided by the National Institute
of Environmental Health Sciences, National Institutes of Health (grants
R01ES018872, P42ES017198, P01E5022844, P30ES017885, and T32ES007062).
Funding support for KKF was provided by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 61
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U1 8
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 6
PY 2017
VL 12
IS 1
AR e0169542
DI 10.1371/journal.pone.0169542
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH3AX
UT WOS:000391641500107
PM 28060899
ER
PT J
AU Kelly, K
Balk, SP
AF Kelly, Kathleen
Balk, Steven P.
TI Reprogramming to resist
SO SCIENCE
LA English
DT Editorial Material
ID NEUROENDOCRINE PROSTATE-CANCER
C1 [Kelly, Kathleen] NCI, Lab Genitourinary Canc Pathogenesis, Ctr Canc Res, Bethesda, MD 20892 USA.
[Balk, Steven P.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Balk, Steven P.] Beth Israel Deaconess Med Ctr, Ctr Canc, Boston, MA 02215 USA.
[Balk, Steven P.] Harvard Med Sch, Boston, MA 02215 USA.
RP Kelly, K (reprint author), NCI, Lab Genitourinary Canc Pathogenesis, Ctr Canc Res, Bethesda, MD 20892 USA.
EM kellyka@mail.nih.gov
NR 13
TC 0
Z9 0
U1 3
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JAN 6
PY 2017
VL 355
IS 6320
BP 29
EP 30
DI 10.1126/science.aam5355
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH4KK
UT WOS:000391739900034
PM 28059730
ER
PT J
AU Passos, DO
Li, M
Yang, RB
Rebensburg, SV
Ghirlando, R
Jeon, Y
Shkriabai, N
Kvaratskhelia, M
Craigie, R
Lyumkis, D
AF Passos, Dario Oliveira
Li, Min
Yang, Renbin
Rebensburg, Stephanie V.
Ghirlando, Rodolfo
Jeon, Youngmin
Shkriabai, Nikoloz
Kvaratskhelia, Mamuka
Craigie, Robert
Lyumkis, Dmitry
TI Cryo-EM structures and atomic model of the HIV-1 strand transfer complex
intasome
SO SCIENCE
LA English
DT Article
ID DNA-BINDING; CRYSTAL-STRUCTURE; INTEGRASE STRUCTURE; CATALYTIC DOMAIN;
GENETIC ANALYSES; TARGET; PROTEIN; INHIBITION; MECHANISM; RESIDUES
AB Like all retroviruses, HIV-1 irreversibly inserts a viral DNA (vDNA) copy of its RNA genome into host target DNA (tDNA). The intasome, a higher-order nucleoprotein complex composed of viral integrase (IN) and the ends of linear vDNA, mediates integration. Productive integration into host chromatin results in the formation of the strand transfer complex (STC) containing catalytically joined vDNA and tDNA. HIV-1 intasomes have been refractory to high-resolution structural studies. We used a soluble IN fusion protein to facilitate structural studies, through which we present a high-resolution cryo-electron microscopy (cryo-EM) structure of the core tetrameric HIV-1 STC and a higher-order form that adopts carboxyl-terminal domain rearrangements. The distinct STC structures highlight how HIV-1 can use the common retroviral intasome core architecture to accommodate different IN domain modules for assembly.
C1 [Passos, Dario Oliveira; Jeon, Youngmin; Lyumkis, Dmitry] Salk Inst Biol Studies, Genet Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA.
[Passos, Dario Oliveira; Jeon, Youngmin; Lyumkis, Dmitry] Salk Inst Biol Studies, Helmsley Ctr Genom Med, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA.
[Li, Min; Yang, Renbin; Ghirlando, Rodolfo; Craigie, Robert] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
[Rebensburg, Stephanie V.; Shkriabai, Nikoloz; Kvaratskhelia, Mamuka] Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA.
[Rebensburg, Stephanie V.; Shkriabai, Nikoloz; Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA.
RP Lyumkis, D (reprint author), Salk Inst Biol Studies, Genet Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA.; Lyumkis, D (reprint author), Salk Inst Biol Studies, Helmsley Ctr Genom Med, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM dlyumkis@salk.edu
FU NIH [P50 GM103368, R01 AI062520, P41 GM103331]; Leona M. and Harry B.
Helmsley Charitable Trust [2012-PG-MED002]; National Institute of
Diabetes and Digestive Diseases of the NIH; Intramural AIDS Targeted
Antiviral Program of the Office of the Director of the NIH
FX D.L. acknowledges support from NIH grant P50 GM103368 and the Leona M.
and Harry B. Helmsley Charitable Trust grant 2012-PG-MED002. R.C. is
supported by the Intramural Program of the National Institute of
Diabetes and Digestive Diseases of the NIH and by the Intramural AIDS
Targeted Antiviral Program of the Office of the Director of the NIH.
These studies were also partly supported by NIH grant R01 AI062520 to
M.K. Molecular graphics and analyses were performed with the University
of California, San Francisco, Chimera package (supported by NIH grant
P41 GM103331). We thank B. Anderson and J.-C. Ducom for help with EM
data collection and network infrastructure, F. Dwyer for computational
support, G. Lander and M. Herzik for help with ensemble refinements, and
A. Engelman and M. Gellert for critical review of the manuscript. The
data presented in this manuscript are tabulated in the main paper and in
the supplementary materials. The EM maps of STC and STCIBD
are deposited into the Electron Microscopy Data Bank under accession
codes EMD-8481 and EMD-8483, respectively. The STC model is deposited
into the Protein Data Bank under ID 5U1C. The STC model ensemble and the
composite model of the higher-order STCIBD oligomers are
available upon request.
NR 35
TC 2
Z9 2
U1 8
U2 8
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JAN 6
PY 2017
VL 355
IS 6320
BP 89
EP 92
DI 10.1126/science.aah5163
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH4KK
UT WOS:000391739900049
PM 28059769
ER
PT J
AU Pardo, CA
Farmer, CA
Thurm, A
Shebl, FM
Ilieva, J
Kalra, S
Swedo, S
AF Pardo, Carlos A.
Farmer, Cristan A.
Thurm, Audrey
Shebl, Fatma M.
Ilieva, Jorjetta
Kalra, Simran
Swedo, Susan
TI Serum and cerebrospinal fluid immune mediators in children with autistic
disorder: a longitudinal study
SO MOLECULAR AUTISM
LA English
DT Article
DE Autism; Immune; CSF; Chemokine; Cytokine; Growth factor
ID EPIDERMAL-GROWTH-FACTOR; SPECTRUM DISORDER; CYTOKINE LEVELS; SOLUBLE
CD40; MOUSE MODEL; BRAIN; INFLAMMATION; NEUROINFLAMMATION; DISEASE;
INTERLEUKIN-15
AB Background: The causes of autism likely involve genetic and environmental factors that influence neurobiological changes and the neurological and behavioral features of the disorder. Immune factors and inflammation are hypothesized pathogenic influences, but have not been examined longitudinally.
Methods: In a cohort of 104 participants with autism, we performed an assessment of immune mediators such as cytokines, chemokines, or growth factors in serum and cerebrospinal fluid (n = 67) to determine potential influences of such mediators in autism.
Results: As compared with 54 typically developing controls, we found no evidence of differences in the blood profile of immune mediators supportive of active systemic inflammation mechanisms in participants with autism. Some modulators of immune function (e.g., EGF and soluble CD40 ligand) were increased in the autism group; however, no evidence of group differences in traditional markers of active inflammation (e.g., IL-6, TNFa, IL-1 beta) were observed in the serum. Further, within-subject stability (measured by estimated intraclass correlations) of most analytes was low, indicating that a single measurement is not a reliable prospective indicator of concentration for most analytes. Additionally, in participants with autism, there was little correspondence between the blood and CSF profiles of cytokines, chemokines, and growth factors, suggesting that peripheral markers may not optimally reflect the immune status of the central nervous system. Although the relatively high fraction of intrathecal production of selected chemokines involved in monocyte/microglia function may suggest a possible relationship with the homeostatic role of microglia, control data are needed for further interpretation of its relevance in autism.
Conclusions: These longitudinal observations fail to provide support for the hypothesized role of disturbances in the expression of circulating cytokines and chemokines as an indicator of systemic inflammation in autism. ClinicalTrials. gov, NCT00298246.
C1 [Pardo, Carlos A.; Ilieva, Jorjetta] Johns Hopkins Univ Sch Med, 627 Pathology Bld 6000 North Wolfe St, Baltimore, MD 21287 USA.
[Farmer, Cristan A.; Thurm, Audrey; Kalra, Simran; Swedo, Susan] Natl Inst Mental Hlth, Pediatr & Dev Neurosci, Bethesda, MD USA.
[Shebl, Fatma M.] Yale Univ, Yale Sch Publ Hlth, New Haven, CT USA.
RP Pardo, CA (reprint author), Johns Hopkins Univ Sch Med, 627 Pathology Bld 6000 North Wolfe St, Baltimore, MD 21287 USA.
EM cpardov1@jhmi.edu
FU National Institute of Mental Health of the National Institutes of Health
[ZIA MH002914]; Bart McLean Fund for Neuroimmunology Research; Johns
Hopkins Project Restore
FX This work was supported by the Intramural Research Program (ZIA
MH002914) of the National Institute of Mental Health of the National
Institutes of Health, and the Pardo lab is supported by the Bart McLean
Fund for Neuroimmunology Research and Johns Hopkins Project Restore.
NR 76
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2040-2392
J9 MOL AUTISM
JI Mol. Autism
PD JAN 5
PY 2017
VL 8
DI 10.1186/s13229-016-0115-7
PG 14
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA EP0RH
UT WOS:000397093900001
ER
PT J
AU Nickerson, ML
Witte, N
Im, KM
Turan, S
Owens, C
Misner, K
Tsang, SX
Cai, Z
Wu, S
Dean, M
Costello, JC
Theodorescu, D
AF Nickerson, M. L.
Witte, N.
Im, K. M.
Turan, S.
Owens, C.
Misner, K.
Tsang, S. X.
Cai, Z.
Wu, S.
Dean, M.
Costello, J. C.
Theodorescu, D.
TI Molecular analysis of urothelial cancer cell lines for modeling tumor
biology and drug response
SO ONCOGENE
LA English
DT Article
ID INVASIVE BLADDER-CANCER; WHOLE-GENOME; IMPACT ANALYSIS; ANNOTATION;
IDENTIFICATION; VISUALIZATION; SENSITIVITY; RESOURCE; GENES;
CHEMOSENSITIVITY
AB The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (Ml) primary tumors, highlighting a major mechanism(s) contributing to cancer associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study the pharmacogenomics of BCa.
C1 [Nickerson, M. L.; Turan, S.; Misner, K.; Dean, M.] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
[Witte, N.; Costello, J. C.] Univ Colorado, Computat Biosci Program, Aurora, CO USA.
[Im, K. M.] Data Sci Genom LLC, Ellicott City, MD USA.
[Owens, C.; Theodorescu, D.] Univ Colorado, Dept Surg Urol, Aurora, CO USA.
[Tsang, S. X.] BGI Shenzhen, Shenzhen, Peoples R China.
[Cai, Z.; Wu, S.] Shenzhen Second Peoples Hosp, Shenzhen, Peoples R China.
[Costello, J. C.; Theodorescu, D.] Univ Colorado, Dept Pharmacol, Anschutz Med Campus,12801 E 17th Ave, Aurora, CO 80045 USA.
[Costello, J. C.; Theodorescu, D.] Univ Colorado, Ctr Comprehens Canc, Anschutz Med Campus,13001 E 17th Pl,F-434, Aurora, CO 80045 USA.
RP Costello, JC (reprint author), Univ Colorado, Dept Pharmacol, Anschutz Med Campus,12801 E 17th Ave, Aurora, CO 80045 USA.; Theodorescu, D (reprint author), Univ Colorado, Ctr Comprehens Canc, Anschutz Med Campus,13001 E 17th Pl,F-434, Aurora, CO 80045 USA.
EM james.costello@ucdenver.edu; dan.theodorescu@ucdenver.edu
FU NIH [CA143971, CA075115]; Intramural Research Program of the NIH;
National Cancer Institute, Center for Cancer Research; National Library
of Medicine T15 training grant [LM009451]; Shenzhen municipal science
and technology project [CXZZ20140826163906370]
FX We would like to thank Dr Neeraj Agarwal for providing the TERT
experimental data. This work was in part supported by NIH grants
CA143971 and CA075115 for DT; Intramural Research Program of the NIH,
the National Cancer Institute, Center for Cancer Research for MLN and
MD; National Library of Medicine T15 training grant LM009451 for NW;
Shenzhen municipal science and technology project CXZZ20140826163906370
for SW.
NR 56
TC 1
Z9 1
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JAN 5
PY 2017
VL 36
IS 1
BP 35
EP 46
DI 10.1038/onc.2016.172
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA EK6XJ
UT WOS:000394069100004
PM 27270441
ER
PT J
AU Liu, Z
Lam, N
Wang, E
Virden, RA
Pawel, B
Attiyeh, EF
Maris, JM
Thiele, CJ
AF Liu, Z.
Lam, N.
Wang, E.
Virden, R. A.
Pawel, B.
Attiyeh, E. F.
Maris, J. M.
Thiele, C. J.
TI Identification of CASZ1 NES reveals potential mechanisms for loss of
CASZ1 tumor suppressor activity in neuroblastoma
SO ONCOGENE
LA English
DT Article
ID NUCLEAR EXPORT SIGNALS; TRANSCRIPTION FACTOR; P53 TETRAMERIZATION;
GENE-EXPRESSION; CRM1 INHIBITOR; DNA-DAMAGE; IN-VIVO; PROTEIN;
LOCALIZATION; PHOSPHORYLATION
AB As a transcription factor, localization to the nucleus and the recruitment of cofactors to regulate gene transcription is essential. Nuclear localization and nucleosome remodeling and histone deacetylase (NuRD) complex binding are required for the zinc-finger transcription factor CASZ1 to function as a neuroblastoma (NB) tumor suppressor. However, the critical amino acids (AAs) that are required for CASZ1 interaction with NuRD complex and the regulation of CASZ1 subcellular localization have not been characterized. Through alanine scanning, immunofluorescence cell staining and co-immunoprecipitation, we define a critical region at the CASZ1 N terminus (AAs 23-40) that mediates the CASZ1b nuclear localization and NuRD interaction. Furthermore, we identified a nuclear export signal (NES) at the N terminus (AAs 176-192) that contributes to CASZ1 nuclear-cytoplasmic shuttling in a chromosomal maintenance 1 -dependent manner. An analysis of CASZ1 protein expression in a primary NB tissue microarray shows that high nuclear CASZ1 staining is detected in tumor samples from NB patients with good prognosis. In contrast, cytoplasmic-restricted CASZ1 staining or low nuclear CASZ1 staining is found in tumor samples from patients with poor prognosis. These findings provide insight into mechanisms by which CASZ1 regulates transcription, and suggests that regulation of CASZ1 subcellular localization may impact its function in normal development and pathologic conditions such as NB tumorigenesis.
C1 [Liu, Z.; Lam, N.; Wang, E.; Virden, R. A.; Thiele, C. J.] NCI, Pediat Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 1W-3940,MSC 1105, Bethesda, MD 20892 USA.
[Pawel, B.; Attiyeh, E. F.; Maris, J. M.] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Thiele, CJ (reprint author), NCI, Pediat Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 1W-3940,MSC 1105, Bethesda, MD 20892 USA.
EM thielec@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research
FX We thank Dr Gregory Wray from the Institute for Genome Sciences and
Policy, Duke University for generously providing the tyrosine
hydroxylase promoter-pGL4.1-luc (TH-Luc) construct; Nisha Pawer and
Neeraj Prasad of the POB, NCI for making the CASZ1b and mutant-EGFP
constructs. We appreciate the insightful discussions with Drs Dinah
Singer and David Levens of the CCR, NCI on this study. This work was
supported by the Intramural Research Program of the NIH, National Cancer
Institute and Center for Cancer Research.
NR 52
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U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JAN 5
PY 2017
VL 36
IS 1
BP 97
EP 109
DI 10.1038/onc.2016.179
PG 13
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA EK6XJ
UT WOS:000394069100009
PM 27270431
ER
PT J
AU van Rooij, FJA
Qayyum, R
Smith, AV
Zhou, Y
Trompet, S
Tanaka, T
Keller, MF
Chang, LC
Schmidt, H
Yang, ML
Chen, MH
Hayes, J
Johnson, AD
Yanek, LR
Mueller, C
Lange, L
Floyd, JS
Ghanbari, M
Zonderman, AB
Jukema, JW
Hofman, A
van Duijn, CM
Desch, KC
Saba, Y
Ozel, AB
Snively, BM
Wu, JY
Schmidt, R
Fornage, M
Klein, RJ
Fox, CS
Matsuda, K
Kamatani, N
Wild, PS
Stott, DJ
Ford, I
Slagboom, PE
Yang, J
Chu, AY
Lambert, AJ
Uitterlinden, AG
Franco, OH
Hofer, E
Ginsburg, D
Hu, B
Keating, B
Schick, UM
Brody, JA
Li, JZ
Chen, Z
Zeller, T
Guralnik, JM
Chasman, DI
Peters, LL
Kubo, M
Becker, DM
Li, J
Eiriksdottir, G
Rotter, JI
Levy, D
Grossmann, V
Patel, KV
Chen, CH
Ridker, PM
Tang, H
Launer, LJ
Rice, KM
Li-Gao, R
Ferrucci, L
Evans, MK
Choudhuri, A
Trompouki, E
Abraham, BJ
Yang, S
Takahashi, A
Kamatani, Y
Kooperberg, C
Harris, TB
Jee, SH
Coresh, J
Tsai, FJ
Longo, DL
Chen, YT
Felix, JF
Yang, Q
Psaty, BM
Boerwinkle, E
Becker, LC
Mook-Kanamori, DO
Wilson, JG
Gudnason, V
O'Donnell, CJ
Dehghan, A
Cupples, LA
Nalls, MA
Morris, AP
Okada, Y
Reiner, AP
Zon, LI
Ganesh, SK
AF van Rooij, Frank J. A.
Qayyum, Rehan
Smith, Albert V.
Zhou, Yi
Trompet, Stella
Tanaka, Toshiko
Keller, Margaux F.
Chang, Li-Ching
Schmidt, Helena
Yang, Min-Lee
Chen, Ming-Huei
Hayes, James
Johnson, Andrew D.
Yanek, Lisa R.
Mueller, Christian
Lange, Leslie
Floyd, James S.
Ghanbari, Mohsen
Zonderman, Alan B.
Jukema, J. Wouter
Hofman, Albert
van Duijn, Cornelia M.
Desch, Karl C.
Saba, Yasaman
Ozel, Ayse B.
Snively, Beverly M.
Wu, Jer-Yuarn
Schmidt, Reinhold
Fornage, Myriam
Klein, Robert J.
Fox, Caroline S.
Matsuda, Koichi
Kamatani, Naoyuki
Wild, Philipp S.
Stott, David J.
Ford, Ian
Slagboom, P. Eline
Yang, Jaden
Chu, Audrey Y.
Lambert, Amy J.
Uitterlinden, Andre G.
Franco, Oscar H.
Hofer, Edith
Ginsburg, David
Hu, Bella
Keating, Brendan
Schick, Ursula M.
Brody, Jennifer A.
Li, Jun Z.
Chen, Zhao
Zeller, Tanja
Guralnik, Jack M.
Chasman, Daniel I.
Peters, Luanne L.
Kubo, Michiaki
Becker, Diane M.
Li, Jin
Eiriksdottir, Gudny
Rotter, Jerome I.
Levy, Daniel
Grossmann, Vera
Patel, Kushang V.
Chen, Chien-Hsiun
Ridker, Paul M.
Tang, Hua
Launer, Lenore J.
Rice, Kenneth M.
Li-Gao, Ruifang
Ferrucci, Luigi
Evans, Michelle K.
Choudhuri, Avik
Trompouki, Eirini
Abraham, Brian J.
Yang, Song
Takahashi, Atsushi
Kamatani, Yoichiro
Kooperberg, Charles
Harris, Tamara B.
Jee, Sun Ha
Coresh, Josef
Tsai, Fuu-Jen
Longo, Dan L.
Chen, Yuan-Tsong
Felix, Janine F.
Yang, Qiong
Psaty, Bruce M.
Boerwinkle, Eric
Becker, Lewis C.
Mook-Kanamori, Dennis O.
Wilson, James G.
Gudnason, Vilmundur
O'Donnell, Christopher J.
Dehghan, Abbas
Cupples, L. Adrienne
Nalls, Michael A.
Morris, Andrew P.
Okada, Yukinori
Reiner, Alexander P.
Zon, Leonard I.
Ganesh, Santhi K.
CA BioBank Japan Project
TI Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci
Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID RED-BLOOD-CELL; TRANSETHNIC METAANALYSIS; AFRICAN-AMERICANS; STEM-CELLS;
ASSOCIATION; PROTEIN; HEMOGLOBIN; LINKAGE; DIFFERENTIATION; MICROARRAY
AB Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.
C1 [van Rooij, Frank J. A.; Ghanbari, Mohsen; Hofman, Albert; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Franco, Oscar H.; Felix, Janine F.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Qayyum, Rehan; Yanek, Lisa R.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, GeneSTAR Res Program, Baltimore, MD 21287 USA.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Smith, Albert V.; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, IS-210 Kopavogur, Iceland.
[Zhou, Yi; Hu, Bella; Choudhuri, Avik; Yang, Song; Zon, Leonard I.] Harvard Univ, Harvard Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Zhou, Yi; Hu, Bella; Choudhuri, Avik; Trompouki, Eirini; Yang, Song; Zon, Leonard I.] Harvard Med Sch, Harvard Stem Cell Inst, Childrens Hosp Boston, Pediat Hematol Oncol DFCI,Stem Cell Program, Boston, MA 02115 USA.
[Zhou, Yi; Hu, Bella; Choudhuri, Avik; Trompouki, Eirini; Yang, Song; Zon, Leonard I.] Harvard Med Sch, Harvard Stem Cell Inst, Childrens Hosp Boston, Pediat Hematol Oncol DFCI,Div Hematol Oncol, Boston, MA 02115 USA.
[Zhou, Yi; Hu, Bella; Choudhuri, Avik; Trompouki, Eirini; Yang, Song; Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 AC Leiden, Netherlands.
[Trompet, Stella] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 AC Leiden, Netherlands.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
[Keller, Margaux F.; Nalls, Michael A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Chang, Li-Ching; Wu, Jer-Yuarn; Chen, Chien-Hsiun; Chen, Yuan-Tsong] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan.
[Schmidt, Helena; Saba, Yasaman] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
[Yang, Min-Lee; Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Dept Internal Med, Div Cardiovasc Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Chen, Ming-Huei; Johnson, Andrew D.; Fox, Caroline S.; Levy, Daniel; Yang, Qiong; O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Populat Sci Branch, Div Intramural Res,NIH, Framingham, MA 01702 USA.
[Hayes, James; Klein, Robert J.; Zeller, Tanja] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Icahn Inst Multiscale Biol, New York, NY 10029 USA.
[Mueller, Christian; Zeller, Tanja] Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany.
[Lange, Leslie] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Floyd, James S.; Brody, Jennifer A.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Ghanbari, Mohsen] Mashhad Univ Med Sci, Sch Med, Dept Genet, Mashhad 91375345, Iran.
[Zonderman, Alan B.; Patel, Kushang V.] NIA, NIH, Bethesda, MD 20892 USA.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Desch, Karl C.; Ozel, Ayse B.; Ginsburg, David; Li, Jun Z.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Snively, Beverly M.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA.
[Wu, Jer-Yuarn; Chen, Chien-Hsiun; Tsai, Fuu-Jen] China Med Univ, Sch Chinese Med, Taichung 40402, Taiwan.
[Schmidt, Reinhold; Hofer, Edith] Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, A-8010 Graz, Austria.
[Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA.
[Matsuda, Koichi] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Mol Med, Tokyo 1088639, Japan.
[Kamatani, Naoyuki; Takahashi, Atsushi; Kamatani, Yoichiro; Okada, Yukinori] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa 2300045, Japan.
[Wild, Philipp S.; Grossmann, Vera] Univ Med Ctr Mainz, CTH, D-55131 Mainz, Germany.
[Wild, Philipp S.] German Ctr Cardiovasc Res DZHK, Partner Site RhineMain, Mainz, Germany.
[Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, Prevent Cardiol & Prevent Med, D-55131 Mainz, Germany.
[Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland.
[Slagboom, P. Eline] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Dept Med Stat & Bioinformat, NL-2300 AC Leiden, Netherlands.
[Yang, Jaden] Stanford Univ, Sch Med, Quantitat Sci Unit, Palo Alto, CA 94304 USA.
[Chu, Audrey Y.; Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
[Chu, Audrey Y.; Chasman, Daniel I.; Ridker, Paul M.] Harvard Med Sch, Boston, MA 02215 USA.
[Lambert, Amy J.; Peters, Luanne L.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
[Hofer, Edith] Med Univ Graz, Inst Med Informat Stat & Documentat, A-8010 Graz, Austria.
[Keating, Brendan] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Keating, Brendan] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
[Schick, Ursula M.; Reiner, Alexander P.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA.
[Schick, Ursula M.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Chen, Zhao] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Dept Epidemiol & Biostat, Tucson, AZ 85724 USA.
[Mueller, Christian] German Ctr Cardiovasc Res DZHK, Partner Site Hamburg, D-20246 Hamburg, Germany.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Chasman, Daniel I.] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.
[Chasman, Daniel I.; Ridker, Paul M.] Harvard Med Sch, Boston, MA 02115 USA.
[Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa 2300045, Japan.
[Li, Jin] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, LABioMed, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90502 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, LABioMed, Inst Translat Genom & Populat Sci, Dept Med, Torrance, CA 90502 USA.
[Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.
[Tang, Hua] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Li-Gao, Ruifang; Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 AC Leiden, Netherlands.
[Evans, Michelle K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA.
[Trompouki, Eirini] Max Planck Inst Immunobiol & Epigenet, D-79108 Freiburg, Germany.
[Abraham, Brian J.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
[Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Biostat & Biomath, Seattle, WA 98109 USA.
[Jee, Sun Ha] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Seoul 03722, South Korea.
[Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, George W Comstock Ctr Publ Hlth Res & Prevent, Comstock Ctr & Cardiovasc Epidemiol, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
[Longo, Dan L.] NIA, Lab Genet & Genom, NIH, Baltimore, MD 21225 USA.
[Yang, Qiong; Cupples, L. Adrienne] Boston Univ Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Mook-Kanamori, Dennis O.] King Faisal Specialist Hosp & Res Ctr, Epidemiol Sect, Dept BESC, Riyadh, Saudi Arabia.
[Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 AC Leiden, Netherlands.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Dehghan, Abbas] Imperial Coll, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Biostat & Epidemiol, London W2 1PG, England.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Block F,Waterhouse Bldg,1-5 Brownlow St, Liverpool L69 3GL, Merseyside, England.
[Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
[Okada, Yukinori] Osaka Univ, Grad Sch Med, Dept Stat Genet, Suita, Osaka 5650871, Japan.
[Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Ganesh, SK (reprint author), Univ Michigan, Dept Human Genet, Dept Internal Med, Div Cardiovasc Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM sganesh@umich.edu
RI Floyd, James/G-7563-2015
FU manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale
Open Data Access project - Johnson Johnson
FX B.M.P. serves on the DSMB of a clinical trial funded by the manufacturer
(Zoll LifeCor) and on the Steering Committee of the Yale Open Data
Access project funded by Johnson & Johnson.
NR 67
TC 0
Z9 0
U1 5
U2 5
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 JAN 5
PY 2017
VL 100
IS 1
BP 51
EP 63
DI 10.1016/j.ajhg.2016.11.016
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA EH6UX
UT WOS:000391910500005
PM 28017375
ER
PT J
AU Chao, HT
Davids, M
Burke, E
Pappas, JG
Rosenfeld, JA
McCarty, AJ
Davis, T
Wolfe, L
Toro, C
Tifft, C
Xia, F
Stong, N
Johnson, TK
Warr, CG
Yamamoto, S
Adams, DR
Markello, TC
Gahl, WA
Bellen, HJ
Wangler, MF
Malicdan, MCV
AF Chao, Hsiao-Tuan
Davids, Mariska
Burke, Elizabeth
Pappas, John G.
Rosenfeld, Jill A.
McCarty, Alexandra J.
Davis, Taylor
Wolfe, Lynne
Toro, Camilo
Tifft, Cynthia
Xia, Fan
Stong, Nicholas
Johnson, Travis K.
Warr, Coral G.
Yamamoto, Shinya
Adams, David R.
Markello, Thomas C.
Gahl, William A.
Bellen, Hugo J.
Wangler, Michael F.
Malicdan, May Christine V.
CA Undiag Dis Network
TI A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in
EBF3
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID LINKED MENTAL-RETARDATION; INTELLECTUAL DISABILITY; NEURONAL
DIFFERENTIATION; TRANSCRIPTION FACTORS; TRUNCATING MUTATIONS; ABNORMAL
GENITALIA; GENE; DROSOPHILA; ARX; FAMILY
AB Early B cell factor 3 (EBF3) is a member of the highly evolutionarily conserved Collier/Olf/EBF (COE) family of transcription factors. Prior studies on invertebrate and vertebrate animals have shown that EBF3 homologs are essential for survival and that loss-of-function mutations are associated with a range of nervous system developmental defects, including perturbation of neuronal development and migration. Interestingly, aristaless-related homeobox (ARX), a homeobox-containing transcription factor critical for the regulation of nervous system development, transcriptionally represses EBF3 expression. However, human neurodevelopmental disorders related to EBF3 have not been reported. Here, we describe three individuals who are affected by global developmental delay, intellectual disability, and expressive speech disorder and carry de novo variants in EBF3. Associated features seen in these individuals include congenital hypotonia, structural CNS malformations, ataxia, and genitourinary abnormalities. The de novo variants affect a single conserved residue in a zinc finger motif crucial for DNA binding and are deleterious in a fly model. Our findings indicate that mutations in EBF3 cause a genetic neurodevelopmental syndrome and suggest that loss of EBF3 function might mediate a subset of neurologic phenotypes shared by ARX-related disorders, including intellectual disability, abnormal genitalia, and structural CNS malformations.
C1 [Chao, Hsiao-Tuan] Baylor Coll Med, Dept Pediat, Sect Child Neurol, Houston, TX 77030 USA.
[Chao, Hsiao-Tuan; Yamamoto, Shinya; Bellen, Hugo J.; Wangler, Michael F.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
[Davids, Mariska; McCarty, Alexandra J.; Wolfe, Lynne; Toro, Camilo; Tifft, Cynthia; Adams, David R.; Markello, Thomas C.; Gahl, William A.; Malicdan, May Christine V.] NHGRI, Undiagnosed Dis Program, NIH Common Fund, Off Director,NIH, Bethesda, MD 20892 USA.
[Burke, Elizabeth; Davis, Taylor; Wolfe, Lynne; Toro, Camilo; Tifft, Cynthia; Adams, David R.; Markello, Thomas C.; Gahl, William A.; Malicdan, May Christine V.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Pappas, John G.] NYU, Dept Pediat, Langone Med Ctr, New York, NY 10016 USA.
[Rosenfeld, Jill A.; Xia, Fan; Yamamoto, Shinya; Bellen, Hugo J.; Wangler, Michael F.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Xia, Fan] Baylor Genet Labs, Houston, TX 77030 USA.
[Stong, Nicholas] Columbia Univ, Inst Genom Med, New York, NY 10032 USA.
[Johnson, Travis K.; Warr, Coral G.] Monash Univ, Sch Biol Sci, Melbourne, Vic 3800, Australia.
[Yamamoto, Shinya; Bellen, Hugo J.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
[Yamamoto, Shinya; Bellen, Hugo J.; Wangler, Michael F.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
[Bellen, Hugo J.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA.
RP Wangler, MF (reprint author), Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.; Malicdan, MCV (reprint author), NHGRI, Undiagnosed Dis Program, NIH Common Fund, Off Director,NIH, Bethesda, MD 20892 USA.; Malicdan, MCV (reprint author), NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.; Wangler, MF (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM mw147467@bcm.edu; maychristine.malicdan@nih.gov
OI Pappas, John/0000-0001-5625-2598
FU NIH [U54NS093793, R24OD022005, R01GM067858, U01HG007709]; Intramural
Research Program of the National Human Genome Research Institute; Common
Fund of the NIH Office of the Director; Wellcome Trust
FX We thank the families and clinical staff at the Undiagnosed Diseases
Program (UDP), Baylor College of Medicine (BCM), and New York University
for participating in this study. This work was supported in part by NIH
grants U54NS093793, R24OD022005, and R01GM067858 to H.J.B, by the
Intramural Research Program of the National Human Genome Research
Institute, and by the Common Fund of the NIH Office of the Director.
H.J.B. is an investigator of the Howard Hughes Medical Institute (HHMI).
F.X. and J.A.R. are supported by NIH grant U01HG007709. The Department
of Molecular and Human Genetics at BCM derives revenue from the clinical
exome sequencing offered at Baylor Genetics. We are thankful for the
technical assistance provided by Y. Huang (NIH UDP Translational
Laboratory) for Sanger sequencing; A. Weech (NIH UDP Translational
Laboratory) for input on protein modeling; H. Pan (HHMI, BCM) for fly
embryo injections; S. Nagarkar-Jaiswal, P. Lee, Y. He, J. Li, Z. Wang,
Q. Gao, and L. Wang (BCM) for creating the 15,000 MIMIC insertion
stocks; and W. Lin (BCM) for T2A-GAL4 conversion. We thank the
Bloomington Drosophila Stock Center, Drosophila Genomics and Genetic
Resources, and FIyORF for numerous stocks and the Developmental Studies
Hybridoma Bank for antibodies. This study made use of data generated by
the DECIPHER community. A full list of centers that contributed to the
generation of the data is available at http://decipher.sanger.ac.uk and
via email at decipher@sanger.ac.uk. Funding for the project was provided
by the Wellcome Trust.
NR 56
TC 1
Z9 1
U1 1
U2 1
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 JAN 5
PY 2017
VL 100
IS 1
BP 128
EP 137
DI 10.1016/j.ajhg.2016.11.018
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA EH6UX
UT WOS:000391910500011
PM 28017372
ER
PT J
AU Wang, H
Russell, LJ
Kelly, KM
Wang, S
Thipphawong, J
AF Wang, Hao
Russell, Lucille J.
Kelly, Kathleen M.
Wang, Steven
Thipphawong, John
TI Fulranumab in patients with interstitial cystitis/bladder pain syndrome:
observations from a randomized, double-blind, placebo-controlled study
SO BMC UROLOGY
LA English
DT Article
DE Fulranumab; Pain; Analgesia; Interstitial cystitis; Bladder
ID NERVE GROWTH-FACTOR; CYSTITIS/PAINFUL BLADDER SYNDROME;
PROOF-OF-CONCEPT; NEUROPATHIC PAIN; CLINICAL-TRIAL; EFFICACY; SAFETY;
MANAGEMENT; TANEZUMAB; PREVALENCE
AB Background: This study was designed to evaluate the efficacy and safety of fulranumab, a fully human monoclonal antibody directed against nerve growth factor (NGF), for pain relief in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).
Methods: In this multicenter, double-blind study, adults with IC/BPS (i.e., interstitial cystitis symptom index [ ICSI] total score >= 8) accompanied by chronic, moderate-to-severe pain were randomized to fulranumab 9 mg or matching placebo, administered subcutaneously at weeks 1, 5, and 9. The primary efficacy endpoint was change from baseline to study endpoint (week 12 or at withdrawal) in average daily pain intensity score. Key secondary endpoints included change from baseline to study endpoint in worst pain intensity score, ICSI total score, Pelvic Pain and Urgency/Frequency total score, Patient Perception of Bladder Condition score, and global response assessment.
Results: This study was terminated prematurely based on concern that this class may be associated with rapidly progressing osteoarthritis or osteonecrosis. Thirty-one patients (of the targeted 70 patients) were randomized, 17 to placebo and 14 to fulranumab, with 15 and 10 patients, respectively, receiving all 3 doses of double-blind treatment. In ANOVA analyses, there was no statistically significant difference between treatment groups for the primary endpoint (LS mean difference [95% CI] vs. placebo, -0.2 [-1.52, 1.10]) or any of the secondary endpoints. Fulranumab was well tolerated, with no patient discontinuing due to an adverse event or experiencing a joint-related serious adverse event over a 26-week follow-up period. No events related to the neurologic or motor systems were reported.
Conclusions: Efficacy was not demonstrated in the present study with the single dose tested and a limited sample size, leading to lack of statistical power. These findings do not exclude the possibility that fulranumab would provide clinical benefit in a larger study and/or specific populations (phenotypes) in this difficult to treat pain condition.
C1 [Russell, Lucille J.; Kelly, Kathleen M.; Wang, Steven; Thipphawong, John] Janssen Res & Dev LLC, Raritan, NJ 08869 USA.
[Wang, Hao] NINDS, Off Translat Res, Bethesda, MD USA.
RP Thipphawong, J (reprint author), Janssen Res & Dev LLC, Raritan, NJ 08869 USA.
EM JThippha@its.jnj.com
FU Janssen Research & Development, LLC
FX This study was funded by Janssen Research & Development, LLC.
NR 35
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2490
J9 BMC UROL
JI BMC Urol.
PD JAN 5
PY 2017
VL 17
AR 2
DI 10.1186/s12894-016-0193-z
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA EH2ZR
UT WOS:000391637800002
PM 28056917
ER
PT J
AU Jiang, ZP
Heinrich, F
McGlinchey, RP
Gruschus, JM
Lee, JC
AF Jiang, Zhiping
Heinrich, Frank
McGlinchey, Ryan P.
Gruschus, James M.
Lee, Jennifer C.
TI Segmental Deuteration of alpha-Synuclein for Neutron Reflectometry on
Tethered Bilayers
SO JOURNAL OF PHYSICAL CHEMISTRY LETTERS
LA English
DT Article
ID PARKINSONS-DISEASE; LIPID MEMBRANES; IN-VITRO; BINDING; FLUORESCENCE;
SPECTROSCOPY; REFLECTIVITY; AGGREGATION; BIOPHYSICS; SCATTERING
AB Neutron reflectometry (NR) is uniquely suited for studying protein interaction with phospholipid bilayers along the bilayer normal on an angstrom scale. However, NR on its own cannot discern specific membrane-bound regions due to a lack of scattering contrast within a protein. Here we report the successful coupling of native chemical ligation (NCL) and NR to study a-synuclein (alpha-syn), a membrane-binding neuronal protein central in Parkinson's disease. Two alpha-syn variants were generated where either the first 86 or last 54 residues are deuterated, allowing for region-specific contrast within the protein and the identification of membrane interacting residues by NR Residues 1-86 are positioned at the hydrocarbon/headgroup interface of the outer leaflet, whereas the density distribution of the 54 C-terminal residues ranges from the hydrocarbon region to the aqueous environment. Coupling of NCL and NR should have broad utility in studies of membrane protein folding.
C1 [Jiang, Zhiping; McGlinchey, Ryan P.; Gruschus, James M.; Lee, Jennifer C.] NHLBI, Lab Prot Conformat & Dynam, NIH, Bethesda, MD 20892 USA.
[Heinrich, Frank] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
[Heinrich, Frank] NIST, Gaithersburg, MD 20899 USA.
RP Lee, JC (reprint author), NHLBI, Lab Prot Conformat & Dynam, NIH, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
RI Heinrich, Frank/A-5339-2010
OI Heinrich, Frank/0000-0002-8579-553X
FU Intramural Research Program at the NIH, NHLBI; NIST IMS program
"Precision Measurements for Integral Membrane Proteins"
FX This work is supported by the Intramural Research Program at the NIH,
NHLBI and by the NIST IMS program "Precision Measurements for Integral
Membrane Proteins". NR was performed on the NG-7 reflectometer at the
NIST Neutron Center for Neutron Research and the NIST Center for
Nanoscale Science and Technology. Parts of this research were performed
at the NHLBI Biophysics (CD and DLS) and Biochemistry (ES-MS) Cores. We
thank Nico Tjandra for the use of 800 MHz Bruker spectrometer. Certain
commercial materials, equipment, and instruments are identified in this
work to describe the experimental procedure as completely as possible.
In no case does such an identification imply a recommendation or
endorsement by NIST, nor does it imply that the materials, equipment, or
instrument identified are necessarily the best available for the
purpose.
NR 42
TC 0
Z9 0
U1 9
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7185
J9 J PHYS CHEM LETT
JI J. Phys. Chem. Lett.
PD JAN 5
PY 2017
VL 8
IS 1
BP 29
EP 34
DI 10.1021/acs.jpclett.6b02304
PG 6
WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science,
Multidisciplinary; Physics, Atomic, Molecular & Chemical
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA EH3EJ
UT WOS:000391653200005
PM 27936328
ER
PT J
AU Saloustros, E
Liu, SS
Mertz, EL
Bhattacharyya, N
Starost, MF
Salpea, P
Nesterova, M
Collins, M
Leikin, S
Stratakis, CA
AF Saloustros, Emmanouil
Liu, Sisi
Mertz, Edward L.
Bhattacharyya, Nisan
Starost, Matthew F.
Salpea, Paraskevi
Nesterova, Maria
Collins, Michael
Leikin, Sergey
Stratakis, Constantine A.
TI Celecoxib treatment of fibrous dysplasia (FD) in a human FD cell line
and FD-like lesions in mice with protein kinase A (PKA) defects
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article
DE Cyclic AMP; Prostaglandin E2; Cyclooxygenase-2 (COX-2); Bone tumors;
McCune-Albright syndrome; Carney complex
ID TOTAL HIP-ARTHROPLASTY; CARNEY COMPLEX; CYCLIC-AMP; OSTEOBLAST LINEAGE;
BONE; CANCER; PRKAR1A; MUTATIONS; ALPHA; DIFFERENTIATION
AB Osteochondromyxomas (OMX) in the context of Carney complex (CNC) and fibrous dysplasia (FD)-like lesions (FDLL) in mice, as well as isolated myxomas in humans may be caused by inactivation of PRKAR1A, the gene coding for the type 1a regulatory subunit (R1 a) of cAMP dependent protein kinase (PKA). OMXs and FDLL in mice lacking Prkar1 alpha grow from abnormal proliferation of adult bone stromal cells (aBSCs). Prkarla and Prkaca (coding for C alpha) haploinsufficiency leads to COX2 activation and prostaglandin E2 (PGE2) production that, in turn, activates proliferation of aBSC5. Celecoxib is a cyclooxygenase-2 (COX2) inhibitor. We hypothesized that COX-2 inhibition may have an effect in FD and FDLL. In vitro treatment of a human cell line prepared from a FD patient with Celecoxib resulted in decreased PGE2 and cell proliferation. Treatment of mice haploinsufficient for R1 alpha and C alpha with 1500 mg/ kg Celecoxib led to decreased PGE2 and proliferation and increased apoptosis, with a corresponding gene expression profile, resulting in dramatic reduction of tumor growth. Furthermore, the treatment improved the organization of cortical bone that was adjacent to the tumor. We conclude that, in vitro and in vivo, Celecoxib had an inhibitory effect on FD cell proliferation and in mouse FDLL structure, respectively. We speculate that COX-2 inhibitors offer an attractive alternative to current treatments for benign tumors such as OMX and FD that, apart from tumor suppression, may mechanically stabilize affected bones. Published by Elsevier Ireland Ltd.
C1 [Saloustros, Emmanouil; Liu, Sisi; Salpea, Paraskevi; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet SEGEN, NIH, Bethesda, MD 20892 USA.
[Mertz, Edward L.; Leikin, Sergey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Phys Biochem, Off Sci Director, NIH, Bethesda, MD 20892 USA.
[Bhattacharyya, Nisan; Collins, Michael] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIH, ORS, DVR, OD, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NICHD, SEGEN, PDEGEN, NIH,Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
OI Saloustros, Emmanouil /0000-0002-0485-0120
FU Intramural Research Program (IRP) of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), National
Institutes of Health (NIH), Bethesda, MD USA [Z01-HD008920-01]; Hellenic
Society of Medical Oncology
FX This work was supported by the Intramural Research Program (IRP) of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health (NIH)
(Z01-HD008920-01), Bethesda, MD 20892 USA and a grant by the Hellenic
Society of Medical Oncology (to Dr. Saloustros).
NR 47
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD JAN 5
PY 2017
VL 439
IS C
BP 165
EP 174
DI 10.1016/j.mce.2016.08.004
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA EH3CX
UT WOS:000391647800018
PM 27498419
ER
PT J
AU Habib, T
Sadoun, A
Nader, N
Suzuki, S
Liu, W
Jithesh, PV
Kino, T
AF Habib, Tanwir
Sadoun, Ameera
Nader, Nancy
Suzuki, Shigeru
Liu, Wei
Jithesh, Puthen V.
Kino, Tomoshige
TI AKT1 has dual actions on the glucocorticoid receptor by cooperating with
14-3-3
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article
DE Histone modification; Nuclear translocation; Phosphorylation;
Protein-protein interaction; Transcriptomics
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSCRIPTIONAL ACTIVITY;
SUBCELLULAR-LOCALIZATION; SIGNALING PATHWAY; INDUCED APOPTOSIS;
SKELETAL-MUSCLE; BINDING DOMAINS; NUCLEAR EXPORT; PHOSPHORYLATION;
PROTEIN
AB Glucocorticoids are important therapeutic compounds for acute lymphoblastic leukemia (ALL). AIM or the protein kinase B is frequently activated in ALL, and contributes to the development of glucocorticoid resistance. We examined impact of AKT1 on glucocorticoid receptor (GR)-induced transcriptional activity in cooperation with phospho-serine/threonine-binding protein 14-3-3. AKT1 has two distinct actions on GR transcriptional activity, one through segregation of GR in the cytoplasm by phosphorylating GR at Ser-134 and subsequent association of 14-3-3, and the other through direct modulation of GR transcriptional activity in the nucleus. For the latter, AKT1 and 14-3-3 are attracted to DNA -bound GR, accompanied by AKT1-dependent p300 phosphorylation, H3S10 phosphorylation and H3K14 acetylation at the DNA site. These two actions of AKT1 regulate distinct sets of glucocorticoid-responsive genes. Our results suggest that specific inhibition of the AKT1/14-3-3 activity on the cytoplasmic retention of GR may be a promising target for treating glucocorticoid resistance observed in ALL (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Habib, Tanwir; Jithesh, Puthen V.] Sidra Med & Res Ctr, Div Syst Biol, Out Patient Clin, POB 26999,Al Luqta St,Educ City North Campus, Doha, Qatar.
[Sadoun, Ameera; Kino, Tomoshige] Sidra Med & Res Ctr, Div Translat Med, Out Patient Clin, POB 26999,Al Luqta St,Educ City North Campus, Doha, Qatar.
[Nader, Nancy] Weill Cornell Univ Qatar, Physiol & Biophys, POB 24144,Al Luqta St,Educ City North Campus, Doha, Qatar.
[Suzuki, Shigeru; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,Rm 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
[Suzuki, Shigeru] Asahikawa Med Univ, Dept Pediat, Asahikawa, Hokkaido 0788510, Japan.
[Liu, Wei] Sidra Med & Res Ctr, Div Genom Core, Out Patient Clin, POB 26999,Al Luqta St,Educ City North Campus, Doha, Qatar.
RP Kino, T (reprint author), Sidra Med & Res Ctr, Div Translat Med, Out Patient Clin, POB 26999,Al Luqta St,Educ City North Campus, Doha, Qatar.
EM thabib@sidra.org; asadoun@sidra.org; nan2017@qatar-med.cornell.edu;
shige5p@asahikawa-med.ac.jp; wliu@sidra.org; pjithesh@sidra.org;
tkino@sidra.org
OI Jithesh, Puthen Veettil/0000-0001-7747-0930; Kino,
Tomoshige/0000-0003-0220-9396
FU Intramural Research Program of the Sidra Medical and Research Center,
Doha, Qatar; Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health, Bethesda, MD [Z01
HD008732-05 HNT]
FX This study was funded by the Intramural Research Program of the Sidra
Medical and Research Center, Doha, Qatar, and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (Z01
HD008732-05 HNT), National Institutes of Health, Bethesda, MD.
NR 62
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD JAN 5
PY 2017
VL 439
IS C
BP 431
EP 443
DI 10.1016/j.mce.2016.10.002
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA EH3CX
UT WOS:000391647800044
PM 27717743
ER
PT J
AU Hanif, A
Edin, ML
Zeldin, DC
Morisseau, C
Falck, JR
Nayeem, MA
AF Hanif, Ahmad
Edin, Matthew L.
Zeldin, Darryl C.
Morisseau, Christophe
Falck, John R.
Nayeem, Mohammed A.
TI Vascular Endothelial Over-Expression of Human Soluble Epoxide Hydrolase
(Tie2-sEH Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of
Oxylipins and omega-Hydroxylases
SO PLOS ONE
LA English
DT Article
ID BLOOD-PRESSURE REGULATION; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS;
EPOXYEICOSATRIENOIC ACIDS; CARDIAC-HYPERTROPHY; PPAR-GAMMA; RECEPTORS;
ACTIVATION; CHANNELS; DISEASE
AB Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega-(omega)-terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas omega-terminal HETEs induce vasoconstriction and vascular dysfunction. We evaluated the effect of these oxylipins on post-ischemic vasodilation known as coronary reactive hyperemia (CRH). CRH prevents the potential harm associated with transient ischemia. The beneficial effects of EETs are reduced after their hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). omega-terminal HETEs are formed by omega-hydroxylase family members. The relationship among endothelial over-expression of sEH (Tie2-sEH Tr), the changes in oxylipins it may produce, the pharmacologic inhibition of omega-hydroxylases, activation of PPAR gamma, and CRH response to a brief ischemia is not known. We hypothesized that CRH is attenuated in isolated mouse hearts with endothelial sEH over-expression through modulation of oxylipin profiles, whereas both inhibition of omega-hydroxylases and activation of PPAR gamma enhance CRH. Compared to WT mice, Tie2-sEH Tr mice had decreased CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05), whereas inhibition of omega-hydroxylases increased these same CRH parameters in Tie2-sEH Tr mice. Inhibition of sEH with t-AUCB reversed the decreased CRH in Tie2-sEH Tr mice. Endothelial over expression of sEH significantly changed oxylipin profiles, including decreases in DHETs, mid-chain HETEs, and prostaglandins (P < 0.05). Treatment with rosiglitazone, PPAR gamma-agonist, enhanced CRH (P < 0.05) in both Tie2-sEH Tr and wild type (WT) mice. These data demonstrate that endothelial over-expression of sEH (through changing the oxylipin profiles) attenuates CRH, whereas inhibition of omega-hydroxylases and activation of PPAR gamma enhance it.
C1 [Hanif, Ahmad; Nayeem, Mohammed A.] West Virginia Univ, Ctr Basic & Translat Stroke Res, Sch Pharm, Basic Pharmaceut Sci, Morgantown, WV 26506 USA.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Morisseau, Christophe] Univ Calif Davis, 1 Shields Ave, Davis, CA 95616 USA.
[Falck, John R.] Univ Texas Southwestern Med Ctr Dallas, Biochem, Dallas, TX 75390 USA.
RP Nayeem, MA (reprint author), West Virginia Univ, Ctr Basic & Translat Stroke Res, Sch Pharm, Basic Pharmaceut Sci, Morgantown, WV 26506 USA.
EM mnayeem@hsc.wvu.edu
FU National Institutes of Health [HL-114559)]; Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences [Z01
ES025034]
FX This work was supported by National Institutes of Health (HL-114559) to
MAN, and the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (Z01 ES025034 to DCZ).
NR 72
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 5
PY 2017
VL 12
IS 1
AR e0169584
DI 10.1371/journal.pone.0169584
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH3AE
UT WOS:000391639100056
PM 28056085
ER
PT J
AU Mangino, M
Roederer, M
Beddall, MH
Nestle, FO
Spector, TD
AF Mangino, Massimo
Roederer, Mario
Beddall, Margaret H.
Nestle, Frank O.
Spector, Tim D.
TI Innate and adaptive immune traits are differentially affected by genetic
and environmental factors
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SYSTEM; AUTOIMMUNITY; DISEASE; TWIN
AB The diversity and activity of leukocytes is controlled by genetic and environmental influences to maintain balanced immune responses. However, the relative contribution of environmental compared with genetic factors that affect variations in immune traits is unknown. Here we analyse 23,394 immune phenotypes in 497 adult female twins. 76% of these traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, gamma delta Tcells and NKT cells, whereas dendritic cells, B2 cells, CD4(+) T and CD8(+) T cells are more influenced by genetics. Although leukocyte subsets are influenced by genetics and environment, adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment.
C1 [Mangino, Massimo; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
[Mangino, Massimo; Nestle, Frank O.] Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England.
[Roederer, Mario; Beddall, Margaret H.] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20817 USA.
[Nestle, Frank O.] Kings Coll London, St Johns Inst Dermatol, Cutaneous Med Unit, London SE1 9RT, England.
RP Nestle, FO (reprint author), Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England.; Roederer, M (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20817 USA.; Nestle, FO (reprint author), Kings Coll London, St Johns Inst Dermatol, Cutaneous Med Unit, London SE1 9RT, England.
EM roederer@nih.gov; frank.nestle@kcl.ac.uk
NR 12
TC 0
Z9 0
U1 6
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN 5
PY 2017
VL 8
AR 13850
DI 10.1038/ncomms13850
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6SQ
UT WOS:000391176900001
PM 28054551
ER
PT J
AU Angmo, S
Tripathi, N
Abbat, S
Sharma, S
Singh, SS
Halder, A
Yadav, K
Shukla, G
Sandhir, R
Rishi, V
Bharatam, PV
Yadav, H
Singhal, NK
AF Angmo, Stanzin
Tripathi, Neha
Abbat, Sheenu
Sharma, Shailesh
Singh, Shelley Sardul
Halder, Avishek
Yadav, Kamalendra
Shukla, Geeta
Sandhir, Rajat
Rishi, Vikas
Bharatam, Prasad V.
Yadav, Hariom
Singhal, Nitin Kumar
TI Identification of Guanosine 5 '-diphosphate as Potential Iron Mobilizer:
Preventing the Hepcidin-Ferroportin Interaction and Modulating the
Interleukin-6/Stat-3 Pathway
SO SCIENTIFIC REPORTS
LA English
DT Article
ID INFLAMMATION-INDUCED ANEMIA; CHRONIC DISEASE; DEFICIENCY ANEMIA; PEPTIDE
HEPCIDIN; MOUSE MODEL; METABOLISM; EXPRESSION; GENE; INTERNALIZATION;
MOLECULES
AB Hepcidin, a peptide hormone, is a key regulator in mammalian iron homeostasis. Increased level of hepcidin due to inflammatory conditions stimulates the ferroportin (FPN) transporter internalization, impairing the iron absorption; clinically manifested as anemia of inflammation (AI). Inhibiting hepcidin-mediated FPN degradation is proposed as an important strategy to combat AI. A systematic approach involving in silico, in vitro, ex vivo and in vivo studies is employed to identify hepcidin-binding agents. The virtual screening of 68,752 natural compounds via molecular docking resulted into identification of guanosine 5'-diphosphate (GDP) as a promising hepcidin-binding agent. The molecular dynamics simulations helped to identify the important hepcidin residues involved in stabilization of hepcidin-GDP complex. The results gave a preliminary indication that GDP may possibly inhibit the hepcidin-FPN interactions. The in vitro studies revealed that GDP caused FPN stabilization (FPN-GFP cell lines) and increased the FPN-mediated cellular iron efflux (HepG2 and Caco-2 cells). Interestingly, the co-administration of GDP and ferrous sulphate (FeSO4) ameliorated the turpentine-induced AI in mice (indicated by increased haemoglobin level, serum iron, FPN expression and decreased ferritin level). These results suggest that GDP a promising natural small-molecule inhibitor that targets Hepcidin-FPN complex may be incorporated with iron supplement regimens to ameliorate AI.
C1 [Angmo, Stanzin; Sharma, Shailesh; Singh, Shelley Sardul; Yadav, Kamalendra; Rishi, Vikas; Singhal, Nitin Kumar] Natl Agrifood Biotechnol Inst, Sas Nagar, Punjab, India.
[Tripathi, Neha; Abbat, Sheenu; Bharatam, Prasad V.] NIPER, Sect 67, Sas Nagar, Punjab, India.
[Halder, Avishek; Sandhir, Rajat] Panjab Univ, Dept Biochem, Chandigarh, India.
[Shukla, Geeta] Panjab Univ, Dept Microbiol, Chandigarh, Punjab, India.
[Yadav, Hariom] NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Singhal, NK (reprint author), Natl Agrifood Biotechnol Inst, Sas Nagar, Punjab, India.; Yadav, H (reprint author), NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM yadav@mail.nih.gov; nitin@nabi.res.in
OI Yadav, Hariom/0000-0003-4504-1597
FU Department of Science and Technology (DST); Council of Scientific and
Industrial Research, New Delhi, India; Department of Biotechnology
(DBT); CSIR; University Grants Commission (UGC)
FX Authors thank the Department of Science and Technology (DST) and the
Council of Scientific and Industrial Research, New Delhi, India for
financial support. Stanzin Angmo, Neha Tripathi, Sheenu Abbat and
Avishek Halder thank Department of Biotechnology (DBT), CSIR and
University Grants Commission (UGC) for their fellowships.
NR 45
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 5
PY 2017
VL 7
AR 40097
DI 10.1038/srep40097
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG9NK
UT WOS:000391385500001
PM 28054602
ER
PT J
AU Barski, A
Cuddapah, S
Kartashov, AV
Liu, C
Imamichi, H
Yang, WJ
Peng, WQ
Lane, HC
Zhao, KJ
AF Barski, Artem
Cuddapah, Suresh
Kartashov, Andrey V.
Liu, Chong
Imamichi, Hiromi
Yang, Wenjing
Peng, Weiqun
Lane, H. Clifford
Zhao, Keji
TI Rapid Recall Ability of Memory T cells is Encoded in their Epigenome
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CYTOKINE GENE-EXPRESSION; TRANSCRIPTION FACTOR; CHIP-SEQ; HELPER-CELLS;
HUMAN GENOME; RNA-SEQ; DIFFERENTIATION; ELEMENTS; ANTIGEN; LOCUS
AB Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naive and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the naive cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting naive, central and effector memory T cells using ChIP-Seq and found that unlike the naive cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory.
C1 [Barski, Artem; Kartashov, Andrey V.; Liu, Chong] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA.
[Barski, Artem; Kartashov, Andrey V.; Liu, Chong] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA.
[Barski, Artem; Kartashov, Andrey V.; Liu, Chong] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA.
[Cuddapah, Suresh] NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY 10987 USA.
[Imamichi, Hiromi; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Yang, Wenjing; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
[Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Barski, A (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA.; Barski, A (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA.; Barski, A (reprint author), Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA.; Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM artem.barski@cchmc.org; zhaok@nhlbi.nih.gov
FU NIH Director's New Innovator Award [DP2 GM119134]; NIH R01 grants
[ES023174, ES024727]; NIH P30 grant [DK078392]; Division of Intramural
Research of NHLBI; Division of Intramural Research of NIAID
FX Authors thank David Hildeman (CCHMC) for critically reading the
manuscript. This research was supported in part by NIH Director's New
Innovator Award to AB DP2 GM119134, NIH R01 grants ES023174 and ES024727
to SC, P30 grant DK078392 and Divisions of Intramural Research of NHLBI
and NIAID.
NR 54
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 5
PY 2017
VL 7
AR 39785
DI 10.1038/srep39785
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6UT
UT WOS:000391182500001
PM 28054639
ER
PT J
AU Del Bello, F
Bonifazi, A
Giannella, M
Giorgioni, G
Piergentili, A
Petrelli, R
Cifani, C
Di Bonaventura, MVM
Keck, TM
Mazzolari, A
Vistoli, G
Cilia, A
Poggesi, E
Matucci, R
Quaglia, W
AF Del Bello, Fabio
Bonifazi, Alessandro
Giannella, Mario
Giorgioni, Gianfabio
Piergentili, Alessandro
Petrelli, Riccardo
Cifani, Carlo
Di Bonaventura, Maria Vittoria Micioni
Keck, Thomas M.
Mazzolari, Angelica
Vistoli, Giulio
Cilia, Antonio
Poggesi, Elena
Matucci, Rosanna
Quaglia, Wilma
TI The replacement of the 2-methoxy substituent of
N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-ami
ne improves the selectivity for 5-HT1A receptor over
alpha(1)-adrenoceptor and D-2-like receptor subtypes
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE 5-HT1A receptor; alpha(1)-Adrenoceptor subtypes; D-2-like receptor
subtypes; Selective 5-HT1A receptor agonists; Docking studies;
Anxiolytic effect
ID CENTRAL-NERVOUS-SYSTEM; ADRENERGIC-RECEPTOR; 1,4-DIOXANE RING; LIGANDS;
ANTAGONISTS; SEROTONIN; DERIVATIVES; BINDING; POTENT; DOPAMINE
AB N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-amine (3) is a potent 5-HT1A receptor and alpha(1d)-adrenoceptor (alpha(1d)-AR) ligand. Analogues 5-10 were rationally designed and prepared to evaluate whether electronic and/or lipophilic properties of substituents in the ortho position of its phenoxy moiety exert any favorable effects on the affinity/activity at 5-HT1A, receptor and improve selectivity over alpha(1)-ARs. To rationalize the experimental observations and derive information about receptor-ligand interactions of the reported ligands, docking studies, using 5-HT1A and alpha(1d)-AR models generated by homology techniques, and a retrospective computational study were performed. The results highlighted that proper substituents in position 2 of the phenoxy moiety of 3 selectively address the ligands toward 5-HT1A receptor with respect to alpha(1)-ARs and D-2-like receptor subtypes. Methoxymethylenoxy derivative 9 showed the best 5-HT1A selectivity profile and the highest potency at 5-HT1A receptor, behaving as a partial agonist. Finally, 9, tested in light/dark exploration test in mice, significantly reduced anxiety-linked behaviors. Therefore, it may be considered a lead for the design of partial agonists potentially useful in the treatment of disorders in which 5-HT1A receptor is involved. (C) 2016 Elsevier Masson SAS. All rights reserved.
C1 [Del Bello, Fabio; Bonifazi, Alessandro; Giannella, Mario; Giorgioni, Gianfabio; Piergentili, Alessandro; Petrelli, Riccardo; Cifani, Carlo; Di Bonaventura, Maria Vittoria Micioni; Quaglia, Wilma] Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, Italy.
[Bonifazi, Alessandro; Keck, Thomas M.] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
[Keck, Thomas M.] Rowan Univ, Dept Chem & Biochem, Coll Sci & Math, 201 Mullica Hill Rd, Glassboro, NJ 08028 USA.
[Keck, Thomas M.] Rowan Univ, Dept Biomed & Translat Sci, Coll Sci & Math, 201 Mullica Hill Rd, Glassboro, NJ 08028 USA.
[Mazzolari, Angelica; Vistoli, Giulio] Univ Milan, Dipartimento Sci Farmaceut, Via Mangiagalli 25, I-20133 Milan, Italy.
[Cilia, Antonio; Poggesi, Elena] Recordati SpA, Drug Discovery, Via Civitali 1, I-20148 Milan, Italy.
[Matucci, Rosanna] Univ Firenze, Dipartimento Neurosci Psicol Area Farmaco & Salut, Sez Farmacol & Tossicol, Viale Pieraccini 6, I-50139 Florence, Italy.
RP Quaglia, W (reprint author), Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, Italy.
EM wilma.quaglia@unicam.it
FU University of Camerino (Fondo di Ateneo per la Ricerca); NIDA-IRP funds
FX This work was supported by grants from the University of Camerino (Fondo
di Ateneo per la Ricerca 2014-2015) and by NIDA-IRP funds (AB, TMK). We
express our gratitude to Dr Amy H. Newman and Michael P. Ellenberger for
their suggestions and comments for this manuscript.
NR 41
TC 0
Z9 0
U1 2
U2 2
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 JAN 5
PY 2017
VL 125
BP 233
EP 244
DI 10.1016/j.ejmech.2016.09.026
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA EF7FX
UT WOS:000390496600016
PM 27662034
ER
PT J
AU Jatoi, I
Anderson, WF
AF Jatoi, Ismail
Anderson, William F.
TI Breast-Cancer Tumor Size and Screening Effectiveness
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID OVERDIAGNOSIS
C1 [Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Anderson, William F.] NCI, Bethesda, MD 20892 USA.
RP Jatoi, I (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
EM jatoi@uthscsa.edu
OI Brentnall, Adam/0000-0001-6327-4357
NR 3
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 5
PY 2017
VL 376
IS 1
BP 93
EP 93
DI 10.1056/NEJMc1614282
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG6SS
UT WOS:000391177100022
PM 28060474
ER
PT J
AU Welch, HG
Prorok, PC
Kramer, BS
AF Welch, H. Gilbert
Prorok, Philip C.
Kramer, Barnett S.
TI Breast-Cancer Tumor Size and Screening Effectiveness REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Welch, H. Gilbert] Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH 03755 USA.
[Prorok, Philip C.; Kramer, Barnett S.] NCI, Bethesda, MD 20892 USA.
RP Welch, HG (reprint author), Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH 03755 USA.
EM h.gilbert.welch@dartmouth.edu
NR 3
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 5
PY 2017
VL 376
IS 1
BP 94
EP 95
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG6SS
UT WOS:000391177100025
PM 28052230
ER
PT J
AU Nogueira, MAF
Peer, CJ
Nguyen, J
McCalla, A
Helman, L
Figg, WD
AF Ferraz Nogueira Filho, Marco A.
Peer, Cody J.
Nguyen, Jeffers
McCalla, Amy
Helman, Lee
Figg, William D.
TI A simple and rapid UHPLC-MS/MS method for the quantitation of the dual
aurora kinase A/B inhibitor SCH-1473759 in murine plasma
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Aurora kinases; UHPLC-MS/MS pharmacokinetics; Mice
ID SMALL-MOLECULE INHIBITOR; CELL-DIVISION; B KINASE; CHROMOSOMAL
PASSENGERS; SELECTIVE INHIBITOR; PHASE-II; ALISERTIB; AZD1152; TUMORS;
CANCER
AB The Aurora kinase family facilitates cell division through various processes and is overexpressed in a wide variety of human cancers, leading to aneuploidy. For that reason, these enzymes are currently targets of a rising class of anticancer drugs, with some molecules already in therapeutic use. In this study, a new UHPLC-MS/MS method was developed and validated to quantitate a new pan Aurora kinase inhibitor still in preclinical development, SCH-1473759. This bioanalytical method employed a liquid-liquid extraction from plasma using ethyl acetate before evaporation. Calibration range encompassed 0.5-2500 ng/mL. The inter- and intra-day accuracy and precision were assessed over five quality control levels; all within limits required by the FDA guidelines. Assay applicability was demonstrated in a first-in-animals study with oral administration, where the maximum plasma concentration (34 ng/mL) occurred at 1 h, the half-life (1 h) was consistent with a previous IV study, and oral bioavailability was poor (F=0.002). (C) 2016 Published by Elsevier B.V.
C1 [Ferraz Nogueira Filho, Marco A.; Peer, Cody J.; Nguyen, Jeffers; Figg, William D.] NCI, Clin Pharmacol Program, Off Clin Director, Bethesda, MD 20892 USA.
[Ferraz Nogueira Filho, Marco A.] Minist Educ Brazil, CAPES Fdn, Brasilia, DF, Brazil.
[McCalla, Amy; Helman, Lee] NCI, Mol Oncol Sect, Pediat 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
NR 19
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JAN 5
PY 2017
VL 132
BP 223
EP 226
DI 10.1016/j.jpba.2016.10.003
PG 4
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA ED7DK
UT WOS:000389015700030
ER
PT J
AU Agarwala, R
Barrett, T
Beck, J
Benson, DA
Bollin, C
Bolton, E
Bourexis, D
Brister, JR
Bryant, SH
Canese, K
Charowhas, C
Clark, K
DiCuccio, M
Dondoshansky, I
Feolo, M
Funk, K
Geer, LY
Gorelenkov, V
Hlavina, W
Hoeppner, M
Holmes, B
Johnson, M
Khotomlianski, V
Kimchi, A
Kimelman, M
Kitts, P
Klimke, W
Krasnov, S
Kuznetsov, A
Landrum, MJ
Landsman, D
Lee, JM
Lipman, DJ
Lu, ZY
Madden, TL
Madej, T
Marchler-Bauer, A
Karsch-Mizrachi, I
Murphy, T
Orris, R
Ostell, J
O'Sullivan, C
Palanigobu, V
Panchenko, AR
Phan, L
Pruitt, KD
Rodarmer, K
Rubinstein, W
Sayers, EW
Schneider, V
Schoch, CL
Schuler, GD
Sherry, ST
Sirotkin, K
Siyan, K
Slotta, D
Soboleva, A
Soussov, V
Starchenko, G
Tatusova, T
Todorov, K
Trawick, BW
Vakatov, D
Wang, YL
Ward, M
Wilbur, WJ
Yaschenko, E
Zbicz, K
AF Agarwala, Richa
Barrett, Tanya
Beck, Jeff
Benson, Dennis A.
Bollin, Colleen
Bolton, Evan
Bourexis, Devon
Brister, J. Rodney
Bryant, Stephen H.
Canese, Kathi
Charowhas, Chad
Clark, Karen
DiCuccio, Michael
Dondoshansky, Ilya
Feolo, Michael
Funk, Kathryn
Geer, Lewis Y.
Gorelenkov, Viatcheslav
Hlavina, Wratko
Hoeppner, Marilu
Holmes, Brad
Johnson, Mark
Khotomlianski, Viatcheslav
Kimchi, Avi
Kimelman, Michael
Kitts, Paul
Klimke, William
Krasnov, Sergey
Kuznetsov, Anatoliy
Landrum, Melissa J.
Landsman, David
Lee, Jennifer M.
Lipman, David J.
Lu, Zhiyong
Madden, Thomas L.
Madej, Tom
Marchler-Bauer, Aron
Karsch-Mizrachi, Ilene
Murphy, Terence
Orris, Rebecca
Ostell, James
O'Sullivan, Christopher
Palanigobu, Vasuki
Panchenko, Anna R.
Phan, Lon
Pruitt, Kim D.
Rodarmer, Kurt
Rubinstein, Wendy
Sayers, Eric W.
Schneider, Valerie
Schoch, Conrad L.
Schuler, Gregory D.
Sherry, Stephen T.
Sirotkin, Karl
Siyan, Karanjit
Slotta, Douglas
Soboleva, Alexandra
Soussov, Vladimir
Starchenko, Grigory
Tatusova, TatianaA.
Todorov, Kamen
Trawick, Bart W.
Vakatov, Denis
Wang, Yanli
Ward, Minghong
Wilbur, W. John
Yaschenko, Eugene
Zbicz, Kerry
CA NCBI Resource Coordinators
TI Database Resources of the National Center for Biotechnology
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SEQUENCE; TOOL
AB The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank((R)) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. The Entrez system provides search and retrieval operations for most of these data from 37 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. New resources released in the past year include iCn3D, MutaBind, and the Antimicrobial Resistance Gene Reference Database; and resources that were updated in the past year include My Bibliography, SciENcv, the Pathogen Detection Project, Assembly, Genome, the Genome Data Viewer, BLAST and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
C1 [Sayers, Eric W.; NCBI Resource Coordinators] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM sayers@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 11
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D12
EP D17
DI 10.1093/nar/gkw1071
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500002
ER
PT J
AU Benson, DA
Cavanaugh, M
Clark, K
Karsch-Mizrachi, I
Lipman, DJ
Ostell, J
Sayers, EW
AF Benson, Dennis A.
Cavanaugh, Mark
Clark, Karen
Karsch-Mizrachi, Ilene
Lipman, David J.
Ostell, James
Sayers, Eric W.
TI GenBank
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID NCBI TAXONOMY DATABASE; SINGLE-MOLECULE; DNA; ARCHIVE; GENOMES; BLAST
AB GenBank((R)) (www.ncbi.nlm.nih.gov/genbank/) is a comprehensive database that contains publicly available nucleotide sequences for 370 000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or the NCBI Submission Portal. GenBank staff assign accession numbers upon data receipt. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Nucleotide database, which links to related information such as taxonomy, genomes ,protein sequences and structures, and biomedical journal literature in PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. Recent updates include changes to policies regarding sequence identifiers, an improved 16S submission wizard, targeted loci studies, the ability to submit methylation and BioNano mapping files, and a database of anti-microbial resistance genes.
C1 [Benson, Dennis A.; Cavanaugh, Mark; Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM sayers@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 19
TC 1
Z9 1
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D37
EP D42
DI 10.1093/nar/gkw1070
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500006
PM 27899564
ER
PT J
AU Nguyen, DT
Mathias, S
Bologa, C
Brunak, S
Fernandez, N
Gaulton, A
Hersey, A
Holmes, J
Jensen, LJ
Karlsson, A
Liu, GX
Ma'ayan, A
Mandava, G
Mani, S
Mehta, S
Overington, J
Patel, J
Rouillard, AD
Schurer, S
Sheils, T
Simeonov, A
Sklar, LA
Southall, N
Ursu, O
Vidovic, D
Waller, A
Yang, J
Jadhav, A
Oprea, TI
Guha, R
AF Dac-Trung Nguyen
Mathias, Stephen
Bologa, Cristian
Brunak, Soren
Fernandez, Nicolas
Gaulton, Anna
Hersey, Anne
Holmes, Jayme
Jensen, Lars Juhl
Karlsson, Anneli
Liu, Guixia
Ma'ayan, Avi
Mandava, Geetha
Mani, Subramani
Mehta, Saurabh
Overington, John
Patel, Juhee
Rouillard, Andrew D.
Schurer, Stephan
Sheils, Timothy
Simeonov, Anton
Sklar, Larry A.
Southall, Noel
Ursu, Oleg
Vidovic, Dusica
Waller, Anna
Yang, Jeremy
Jadhav, Ajit
Oprea, Tudor I.
Guha, Rajarshi
TI Pharos: Collating protein information to shed light on the druggable
genome
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DATABASE; ONTOLOGY; TARGETS; BIOLOGY; UPDATE
AB The 'druggable genome' encompasses several protein families, but only a subset of targets within them have attracted significant research attention and thus have information about them publicly available. The Illuminating the Druggable Genome (IDG) program was initiated in 2014, has the goal of developing experimental techniques and a Knowledge Management Center (KMC) that would collect and organize information about protein targets from four families, representing the most common druggable targets with an emphasis on understudied proteins. Here, we describe two resources developed by the KMC: the Target Central Resource Database (TCRD) which collates many heterogeneous gene/protein datasets and Pharos (https://pharos.nih.gov), a multimodal web interface that presents the data from TCRD. We briefly describe the types and sources of data considered by the KMC and then highlight features of the Pharos interface designed to enable intuitive access to the IDG knowledgebase. The aim of Pharos is to encourage 'serendipitous browsing', whereby related, relevant information is made easily discoverable. We conclude by describing two use cases that highlight the utility of Pharos and TCRD.
C1 [Dac-Trung Nguyen; Mandava, Geetha; Sheils, Timothy; Simeonov, Anton; Southall, Noel; Jadhav, Ajit; Guha, Rajarshi] Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
[Fernandez, Nicolas; Ma'ayan, Avi; Rouillard, Andrew D.] Icahn Sch Med Mt Sinai, Dept Pharmacol Sci, Mt Sinai Ctr Bioinformat, One Gustave L Levy Pl,Box 1603, New York, NY 10029 USA.
[Mathias, Stephen; Bologa, Cristian; Holmes, Jayme; Liu, Guixia; Mani, Subramani; Patel, Juhee; Sklar, Larry A.; Ursu, Oleg; Waller, Anna; Yang, Jeremy; Oprea, Tudor I.] Univ New Mexico, Sch Med, Translat Informat Div, Albuquerque, NM 87131 USA.
[Sklar, Larry A.; Waller, Anna] Univ New Mexico, Ctr Canc, Ctr Mol Discovery, Albuquerque, NM 87131 USA.
[Mehta, Saurabh; Schurer, Stephan; Vidovic, Dusica] Univ Miami, Ctr Computat Sci, Coral Gables, FL 33146 USA.
[Mehta, Saurabh] Delhi Technol Univ, Dept Appl Chem, Delhi 110042, India.
[Schurer, Stephan; Vidovic, Dusica] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA.
[Brunak, Soren; Jensen, Lars Juhl] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Prot Res, DK-2200 Copenhagen, Denmark.
[Gaulton, Anna; Hersey, Anne] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Hinxton CB10 1SD, Cambs, England.
[Liu, Guixia] East China Univ Sci & Technol, Dept Pharmaceut Sci, Shanghai, Peoples R China.
[Patel, Juhee] Univ New Mexico, Sch Med, BA MD Program, Albuquerque, NM 87131 USA.
[Karlsson, Anneli; Overington, John] BenevolentAI, 40 Churchway, London NW1 1LW, England.
RP Guha, R (reprint author), Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.; Oprea, TI (reprint author), Univ New Mexico, Sch Med, Translat Informat Div, Albuquerque, NM 87131 USA.
EM toprea@salud.unm.edu; guhar@mail.nih.gov
OI Overington, John/0000-0002-5859-1064
FU National Institutes of Health (NIH) Common Fund [CA189205]; NIH Common
Fund [CA189201]; Novo Nordisk Foundation [NNF14CC0001]; NIH
FX National Institutes of Health (NIH) Common Fund [CA189205 to T.O.]; NIH
Common Fund [CA189201 to A.M.]; Novo Nordisk Foundation [NNF14CC0001 to
S.B. and L.J.J.]. Intramural Research Program, NCATS [DTN, GM, TS, AS,
NS, AJ, RG]. Funding for open access charge: NIH.
NR 22
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D995
EP D1002
DI 10.1093/nar/gkw1072
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500137
PM 27903890
ER
PT J
AU Finn, RD
Attwood, TK
Babbitt, PC
Bateman, A
Bork, P
Bridge, AJ
Chang, HY
Dosztanyi, Z
El-Gebali, S
Fraser, M
Gough, J
Haft, D
Holliday, GL
Huang, HZ
Huang, XS
Letunic, I
Lopez, R
Lu, SN
Marchler-Bauer, A
Mi, HY
Mistry, J
Natale, DA
Necci, M
Nuka, G
Orengo, CA
Park, Y
Pesseat, S
Piovesan, D
Potter, SC
Rawlings, ND
Redaschi, N
Richardson, L
Rivoire, C
Sangrador-Vegas, A
Sigrist, C
Sillitoe, I
Smithers, B
Squizzato, S
Sutton, G
Thanki, N
Thomas, PD
Tosatto, SCE
Wu, CH
Xenarios, I
Yeh, LS
Young, SY
Mitchell, AL
AF Finn, Robert D.
Attwood, Teresa K.
Babbitt, Patricia C.
Bateman, Alex
Bork, Peer
Bridge, Alan J.
Chang, Hsin-Yu
Dosztanyi, Zsuzsanna
El-Gebali, Sara
Fraser, Matthew
Gough, Julian
Haft, David
Holliday, Gemma L.
Huang, Hongzhan
Huang, Xiaosong
Letunic, Ivica
Lopez, Rodrigo
Lu, Shennan
Marchler-Bauer, Aron
Mi, Huaiyu
Mistry, Jaina
Natale, Darren A.
Necci, Marco
Nuka, Gift
Orengo, Christine A.
Park, Youngmi
Pesseat, Sebastien
Piovesan, Damiano
Potter, Simon C.
Rawlings, Neil D.
Redaschi, Nicole
Richardson, Lorna
Rivoire, Catherine
Sangrador-Vegas, Amaia
Sigrist, Christian
Sillitoe, Ian
Smithers, Ben
Squizzato, Silvano
Sutton, Granger
Thanki, Narmada
Thomas, Paul D.
Tosatto, Silvio C. E.
Wu, Cathy H.
Xenarios, Ioannis
Yeh, Lai-Su
Young, Siew-Yit
Mitchell, Alex L.
TI InterPro in 2017-beyond protein family and domain annotations
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID METABOLIC PATHWAYS; DATABASE; RESOURCE; GENOME; CLASSIFICATION;
DISORDER; GENE; PREDICTION; SEQUENCES; SYSTEM
AB InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, in-cluding the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences.
C1 [Finn, Robert D.; Bateman, Alex; Chang, Hsin-Yu; El-Gebali, Sara; Fraser, Matthew; Lopez, Rodrigo; Mistry, Jaina; Nuka, Gift; Park, Youngmi; Pesseat, Sebastien; Potter, Simon C.; Rawlings, Neil D.; Richardson, Lorna; Sangrador-Vegas, Amaia; Squizzato, Silvano; Young, Siew-Yit; Mitchell, Alex L.] EBI, EMBL, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
[Attwood, Teresa K.] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England.
[Babbitt, Patricia C.; Holliday, Gemma L.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Bork, Peer] European Mol Biol Lab, Biocomp, Meyerhofstasse 1, D-69117 Heidelberg, Germany.
[Bridge, Alan J.; Redaschi, Nicole; Rivoire, Catherine; Sigrist, Christian; Xenarios, Ioannis] CMU, SIB, Swiss Prot Grp, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland.
[Dosztanyi, Zsuzsanna] Eotvos Lorand Univ, Dept Biochem, MTA ELTE Lendulet Bioinformat Res Grp, Pazmany Peter Setany 1-C, Budapest, Hungary.
[Gough, Julian; Smithers, Ben] Univ Bristol, Dept Comp Sci, Woodland Rd, Bristol BS8 1UB, Avon, England.
[Haft, David; Sutton, Granger] J Craig Venter Inst, Bioinformat Dept, 9714 Med Ctr Dr, Rockville, MD 20850 USA.
[Huang, Hongzhan; Wu, Cathy H.] Univ Delaware, Ctr Bioinformat & Computat Biol, Newark, DE 19711 USA.
[Huang, Xiaosong; Mi, Huaiyu; Thomas, Paul D.] Univ Southern Calif, Dept Prevent Med, Div Bioinformat, Los Angeles, CA 90033 USA.
[Letunic, Ivica] Biobyte Solut GmbH, Bothestr 142, D-69126 Heidelberg, Germany.
[Lu, Shennan; Marchler-Bauer, Aron; Thanki, Narmada] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH Bldg,38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
[Natale, Darren A.; Yeh, Lai-Su] Georgetown Univ, Med Ctr, 3300 Whitehaven St NW, Washington, DC 20007 USA.
[Necci, Marco; Piovesan, Damiano; Tosatto, Silvio C. E.] Univ Padua, Dept Biomed Sci, Via U Bassi 58-B, I-35131 Padua, Italy.
[Necci, Marco; Piovesan, Damiano; Tosatto, Silvio C. E.] Univ Padua, CRIBI Biotech Ctr, Via U Bassi 58-B, I-35131 Padua, Italy.
[Orengo, Christine A.; Sillitoe, Ian] UCL, Struct & Mol Biol, Darwin Bldg, London WC1E 6BT, England.
[Tosatto, Silvio C. E.] CNR, Inst Neurosci, Via U Bassi 58-B, I-35131 Padua, Italy.
RP Finn, RD (reprint author), EBI, EMBL, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
EM rdf@ebi.ac.uk
OI Bridge, Alan/0000-0003-2148-9135
FU BBSRC [BB/L024136/1, BB/N00521X/1]; Wellcome Trust [108433/Z/15/Z];
National Sciences Foundation [DBI 1458808]; Intramural Research Program
of the National Library of Medicine at National Institutes of
Health/DHHS; COST Action [BM1405]; European Molecular Biology
Laboratories core funds; Research Councils UK
FX BBSRC [BB/L024136/1, BB/N00521X/1]; Wellcome Trust [108433/Z/15/Z];
National Sciences Foundation [DBI 1458808]; Intramural Research Program
of the National Library of Medicine at National Institutes of
Health/DHHS; COST Action [BM1405]; European Molecular Biology
Laboratories core funds. Funding for open access charge: Research
Councils UK.
NR 47
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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 JAN 4
PY 2017
VL 45
IS D1
BP D190
EP D199
DI 10.1093/nar/gkw1107
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500029
PM 27899635
ER
PT J
AU Galperin, MY
Fernandez-Suarez, XM
Rigden, DJ
AF Galperin, Michael Y.
Fernandez-Suarez, Xose M.
Rigden, Daniel J.
TI The 24th annual Nucleic Acids Research database issue: a look back and
upcoming changes
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PROTEIN FAMILIES DATABASE; MODEL ORGANISM DATABASE; GENOME DATABASE;
FUNCTIONAL ANNOTATIONS; INFORMATION RESOURCE; INTERACTION NETWORKS;
ANALYSIS TOOLS; THE DATABASE; 2016 UPDATE; DATA-BANK
AB This year's Database Issue of Nucleic Acids Re-search contains 152 papers that include descriptions of 54 new databases and update papers on 98 databases, of which 16 have not been previously featured in NAR. As always, these databases cover a broad range of molecular biology subjects, including genome structure, gene expression and its regulation, proteins, protein domains, and protein-protein interactions. Following the recent trend, an increasing number of new and established databases deal with the issues of human health, from cancer causing mutations to drugs and drug targets. In accordance with this trend, three recently compiled databases that have been selected by NAR reviewers and editors as `breakthrough' contributions, DENOVODB, the Monarch Initiative, and Open Targets, cover human de novo gene variants, disease-related phenotypes in model organisms, and a bioinformatics platform for therapeutic target identification and validation, respectively. We expect these databases to attract the attention of numerous researchers working in various areas of genetics and genomics. Looking back at the past 12 years, we present here the 'golden set' of databases that have consistently served as authoritative, comprehensive, and convenient data resources widely used by the entire community and offer some lessons on what makes a successful database. The Database Issue is freely available online at the https://academic.oup.com/narwebsite. An updated version of the NAR Molecular Biology Database Collection is available at http://www.oxfordjournals.org/nar/database/a/.
C1 [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Fernandez-Suarez, Xose M.] Thermo Fisher Sci, Inchinnan Business Pk, Paisley PA4 9RF, Renfrew, Scotland.
[Rigden, Daniel J.] Univ Liverpool, Inst Integrat Biol, Crown St, Liverpool L69 7ZB, Merseyside, England.
RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.; Rigden, DJ (reprint author), Univ Liverpool, Inst Integrat Biol, Crown St, Liverpool L69 7ZB, Merseyside, England.
EM nardatabase@gmail.com; drigden@liv.ac.uk
OI Galperin, Michael/0000-0002-2265-5572
FU NIH Intramural Research Program at the National Library of Medicine
FX The NIH Intramural Research Program at the National Library of Medicine
(to M.Y.G.). The open access publication charge for this paper has been
waived by Oxford University Press.
NR 116
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PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
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J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D1
EP D11
DI 10.1093/nar/gkw1188
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500001
PM 28053160
ER
PT J
AU Grazziotin, AL
Koonin, EV
Kristensen, DM
AF Grazziotin, Ana Laura
Koonin, Eugene V.
Kristensen, David M.
TI Prokaryotic Virus Orthologous Groups (pVOGs): a resource for comparative
genomics and protein family annotation
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID STRANDED DNA VIRUSES; VIRAL GENOMES; CLUSTERS; BACTERIOPHAGES;
EVOLUTION; GENES; CLASSIFICATION; RECONSTRUCTION; METAGENOMES;
REPERTOIRE
AB Viruses are the most abundant and diverse biological entities on earth, and while most of this diversity remains completely unexplored, advances in genome sequencing have provided unprecedented glimpses into the virosphere. The Prokaryotic Virus Orthologous Groups (pVOGs, formerly called Phage Orthologous Groups, POGs) resource has aided in this task over the past decade by using automated methods to keep pace with the rapid increase in genomic data. The uses of pVOGs include functional annotation of viral proteins, identification of genes and viruses in uncharacterized DNA samples, phylogenetic analysis, large-scale comparative genomics projects, and more. The pVOGs database represents a comprehensive set of orthologous gene families shared across multiple complete genomes of viruses that infect bacterial or archaeal hosts (viruses of eukaryotes will be added at a future date). The pVOGs are constructed within the Clusters of Orthologous Groups (COGs) framework that is widely used for orthology identification in prokaryotes. Since the previous release of the POGs, the size has tripled to nearly 3000 genomes and 300 000 proteins, and the number of conserved orthologous groups doubled to 9518. User-friendly webpages are available, including multiple sequence alignments and HMM profiles for each VOG. These changes provide major improvements to the pVOGs database, at a time of rapid advances in virus genomics. The pVOGs database is hosted jointly at the University of Iowa at http://dmk-brain.ecn.uiowa.edu/pVOGs and the NCBI at ftp://ftp.ncbi.nlm.nih.gov/pub/kristensen/pVOGs/home.html.
C1 [Grazziotin, Ana Laura; Kristensen, David M.] Univ Iowa, Dept Biomed Engn, Coll Engn, Iowa City, IA 52242 USA.
[Koonin, Eugene V.; Kristensen, David M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Kristensen, DM (reprint author), Univ Iowa, Dept Biomed Engn, Coll Engn, Iowa City, IA 52242 USA.; Kristensen, DM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM david-kristensen@uiowa.edu
FU Department of Biomedical Engineering at the University of Iowa (Iowa
City, USA); Intramural Research Program of the National Library of
Medicine at the National Institutes of Health (NIH) (Bethesda, USA); NIH
FX D.M.K. and A.L.G. are supported by the Department of Biomedical
Engineering at the University of Iowa (Iowa City, USA). E.V.K. is
supported by the Intramural Research Program of the National Library of
Medicine at the National Institutes of Health (NIH) (Bethesda, USA).
Funding for open access charge: NIH.
NR 50
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U1 3
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D491
EP D498
DI 10.1093/nar/gkw975
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500070
PM 27789703
ER
PT J
AU Hatcher, EL
Zhdanov, SA
Bao, YM
Blinkova, O
Nawrocki, EP
Ostapchuck, Y
Schaffer, AA
Brister, JR
AF Hatcher, Eneida L.
Zhdanov, Sergey A.
Bao, Yiming
Blinkova, Olga
Nawrocki, Eric P.
Ostapchuck, Yuri
Schaffer, Alejandro A.
Brister, J. Rodney
TI Virus Variation Resource - improved response to emergent viral outbreaks
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GROUP-A ROTAVIRUSES; WEST NILE VIRUS; GENOME ANNOTATION; BIOTECHNOLOGY
INFORMATION; NATIONAL CENTER; SEQUENCE; DATABASE; WEB; CLASSIFICATION
AB The Virus Variation Resource is a value-added viral sequence data resource hosted by the National Center for Biotechnology Information. The resource is located at http://www.ncbi.nlm.nih.gov/genome/viruses/variation/ and includes modules for seven viral groups: influenza virus, Dengue virus, West Nile virus, Ebolavirus, MERS coronavirus, Rotavirus A and Zika virus. Each module is supported by pipelines that scan newly released GenBank records, annotate genes and proteins and parse sample descriptors and then map them to controlled vocabulary. These processes in turn support a purpose-built search interface where users can select sequences based on standardized gene, protein and metadata terms. Once sequences are selected, a suite of tools for downloading data, multi-sequence alignment and tree building supports a variety of user directed activities. This manuscript describes a series of features and functionalities recently added to the Virus Variation Resource.
C1 [Hatcher, Eneida L.; Zhdanov, Sergey A.; Bao, Yiming; Blinkova, Olga; Nawrocki, Eric P.; Ostapchuck, Yuri; Schaffer, Alejandro A.; Brister, J. Rodney] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Brister, JR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM jamesbr@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Library of Medicine
FX Intramural Research Program of the National Institutes of Health;
National Library of Medicine. Funding for open access charge: Intramural
Research Program of the National Institutes of Health; National Library
of Medicine.
NR 32
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U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D482
EP D490
DI 10.1093/nar/gkw1065
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500069
PM 27899678
ER
PT J
AU Kristensen, DM
Wolf, YI
Koonin, EV
AF Kristensen, David M.
Wolf, Yuri I.
Koonin, Eugene V.
TI ATGC database and ATGC-COGs: an updated resource for micro- and
macro-evolutionary studies of prokaryotic genomes and protein family
annotation
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID MAXIMUM-LIKELIHOOD; ARCHAEAL GENOMES; BACTERIAL; GENES; ISLANDS;
SYSTEMS; SEARCH; BLAST; TREES; LIFE
AB The Alignable Tight Genomic Clusters (ATGCs) database is a collection of closely related bacterial and archaeal genomes that provides several tools to aid research into evolutionary processes in the microbialworld. Each ATGC is a taxonomy-independent cluster of 2 or more completely sequenced genomes that meet the objective criteria of a high degree of local gene order (synteny) and a small number of synonymous substitutions in the protein-coding genes. As such, each ATGC is suited for analysis of microevolutionary variations within a cohesive group of organisms (e.g. species), whereas the entire collection of ATGCs is useful for macroevolutionary studies. The ATGC database includes many forms of pre-computed data, in particular ATGC-COGs (Clusters of Orthologous Genes), multiple sequence alignments, a set of 'index' orthologs representing the most well-conserved members of each ATGC-COG, the phylogenetic tree of the organisms within each ATGC, etc. Although the ATGC database contains several million proteins from thousands of genomes organized into hundreds of clusters (roughly a 4-fold increase since the last version of the ATGC database), it is now built with completely automated methods and will be regularly updated following new releases of the NCBI RefSeq database. The ATGC database is hosted jointly at the University of Iowa at dmk-brain.ecn.uiowa.edu/ATGC/ and the NCBI at ftp.ncbi.nlm.nih.gov/pub/kristensen/ATGC/atgc_home.html.
C1 [Kristensen, David M.] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA.
[Kristensen, David M.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Kristensen, DM (reprint author), Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA.; Kristensen, DM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM david-kristensen@uiowa.edu
FU Intramural Research Program of the U.S. National Institutes of Health at
the National Library of Medicine; Department of Biomedical Engineering
at the University of Iowa (IowaCity, USA); NIH
FX Intramural Research Program of the U.S. National Institutes of Health at
the National Library of Medicine (to D.M.K. and E.V.K.); Department of
Biomedical Engineering at the University of Iowa (IowaCity, USA) (to
D.M.K.). Funding for open access charge: NIH.
NR 41
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U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D210
EP D218
DI 10.1093/nar/gkw934
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500032
PM 28053163
ER
PT J
AU Lea, IA
Gong, H
Paleja, A
Rashid, A
Fostel, J
AF Lea, Isabel A.
Gong, Hui
Paleja, Anand
Rashid, Asif
Fostel, Jennifer
TI CEBS: a comprehensive annotated database of toxicological data
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BIOLOGICAL-SYSTEMS; RAT-LIVER; DESIGN; TOXICOGENOMICS; METABOLITES;
MICROARRAY; TOXICITY; ASSAYS
AB The Chemical Effects in Biological Systems database (CEBS) is a comprehensive and unique toxicology resource that compiles individual and summary animal data from the National Toxicology Program (NTP) testing program and other depositors into a single electronic repository. CEBS has undergone significant updates in recent years and currently contains over 11 000 test articles (exposure agents) and over 8000 studies including all available NTP car-cinogenicity, short-term toxicity and genetic toxicity studies. Study data provided to CEBS are manually curated, accessioned and subject to quality assurance review prior to release to ensure high quality. The CEBS database has two main components: data collection and data delivery. To accommodate the breadth of data produced by NTP, the CEBS data collection component is an integrated relational design that allows the flexibility to capture any type of electronic data ( to date). The data delivery component of the database comprises a series of dedicated user interface tables containing pre-processed data that support each component of the user interface. The user interface has been updated to include a series of nine Guided Search tools that allow access to NTP summary and conclusion data and larger non-NTP datasets. The CEBS database can be accessed online at http://www.niehs.nih.gov/research/resources/databases/cebs/.
C1 [Lea, Isabel A.; Gong, Hui; Paleja, Anand; Rashid, Asif] ASRCFed Vistronix, 430 Davis Dr,Suite 260, Morrisville, NC 27569 USA.
[Fostel, Jennifer] NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Lea, IA (reprint author), ASRCFed Vistronix, 430 Davis Dr,Suite 260, Morrisville, NC 27569 USA.; Fostel, J (reprint author), NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
EM Isabel.lea@nih.gov; fostel@niehs.nih.gov
FU ASRC Federal Vistronix under National Institute of Environmental Health
Sciences (NIEHS) [HHSN31620120054W, HHSN273201000063U GS06F0629Z];
National Institute of Environmental Health Sciences
FX ASRC Federal Vistronix under National Institute of Environmental Health
Sciences (NIEHS) contracts 'Support for Toxicological Data for the
National Toxicology Program (NTP)' [HHSN31620120054W and
HHSN273201000063U GS06F0629Z]. Funding for open access charge: National
Institute of Environmental Health Sciences.
NR 25
TC 0
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U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D964
EP D971
DI 10.1093/nar/gkw1077
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500133
PM 27899660
ER
PT J
AU MacArthur, J
Bowler, E
Cerezo, M
Gil, L
Hall, P
Hastings, E
Junkins, H
McMahon, A
Milano, A
Morales, J
Pendlington, ZM
Welter, D
Burdett, T
Hindorff, L
Flicek, P
Cunningham, F
Parkinson, H
AF MacArthur, Jacqueline
Bowler, Emily
Cerezo, Maria
Gil, Laurent
Hall, Peggy
Hastings, Emma
Junkins, Heather
McMahon, Aoife
Milano, Annalisa
Morales, Joannella
Pendlington, Zoe May
Welter, Danielle
Burdett, Tony
Hindorff, Lucia
Flicek, Paul
Cunningham, Fiona
Parkinson, Helen
TI The new NHGRI-EBI Catalog of published genome-wide association studies
(GWAS Catalog)
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DIABETES SUSCEPTIBILITY; LOCI; METAANALYSIS; UPDATE; VARIANTS; DISEASES;
DATABASE; INSIGHT; TRAITS; RISK
AB The NHGRI-EBI GWAS Catalog has provided data from published genome-wide association studies since 2008. In 2015, the database was redesigned and relocated to EMBL-EBI. The new infrastructure includes a new graphical user interface (www.ebi.ac.uk/gwas/), ontology supported search functionality and an improved curation interface. These developments have improved the data release frequency by increasing automation of curation and providing scaling improvements. The range of available Catalog data has also been extended with structured ancestry and recruitment information added for all studies. The infrastructure improvements also support scaling for larger arrays, exome and sequencing studies, allowing the Catalog to adapt to the needs of evolving study design, genotyping technologies and user needs in the future.
C1 [MacArthur, Jacqueline; Bowler, Emily; Cerezo, Maria; Gil, Laurent; Hastings, Emma; McMahon, Aoife; Milano, Annalisa; Morales, Joannella; Pendlington, Zoe May; Welter, Danielle; Burdett, Tony; Flicek, Paul; Cunningham, Fiona; Parkinson, Helen] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England.
[Hall, Peggy; Junkins, Heather; Hindorff, Lucia] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
RP Parkinson, H (reprint author), European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England.
EM parkinson@ebi.ac.uk
OI Welter, Danielle/0000-0003-1058-2668
FU National Human Genome Research Institute; National Heart, Lung and Blood
Institute; National Institutes of Health Common Fund [U54-HG004028,
U41-HG006104, U41-HG007823]; European Molecular Biology Laboratory;
National Institutes of Health
FX National Human Genome Research Institute, National Heart, Lung and Blood
Institute; National Institutes of Health Common Fund [U54-HG004028,
U41-HG006104, U41-HG007823]; European Molecular Biology Laboratory;
L.H., P.H. and H.J. are employees of the National Human Genome Research
Institute. Funding for open access charge: National Institutes of
Health.
NR 21
TC 1
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U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D896
EP D901
DI 10.1093/nar/gkw1133
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500124
PM 27899670
ER
PT J
AU Marchler-Bauer, A
Bo, Y
Han, LY
He, JE
Lanczycki, CJ
Lu, SN
Chitsaz, F
Derbyshire, MK
Geer, RC
Gonzales, NR
Gwadz, M
Hurwitz, DI
Lu, F
Marchler, GH
Song, JS
Thanki, N
Wang, ZX
Yamashita, RA
Zhang, DC
Zheng, CJ
Geer, LY
Bryant, SH
AF Marchler-Bauer, Aron
Bo, Yu
Han, Lianyi
He, Jane
Lanczycki, Christopher J.
Lu, Shennan
Chitsaz, Farideh
Derbyshire, Myra K.
Geer, Renata C.
Gonzales, Noreen R.
Gwadz, Marc
Hurwitz, David I.
Lu, Fu
Marchler, Gabriele H.
Song, James S.
Thanki, Narmada
Wang, Zhouxi
Yamashita, Roxanne A.
Zhang, Dachuan
Zheng, Chanjuan
Geer, Lewis Y.
Bryant, Stephen H.
TI CDD/SPARCLE: functional classification of proteins via subfamily domain
architectures
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DATABASE
AB NCBI's Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints. An archive of pre-computed domain annotation is maintained for proteins tracked by NCBI's Entrez database, and live search services are offered as well. CDD curation staff supplements a comprehensive collection of protein domain and protein family models, which have been imported from external providers, with representations of selected domain families that are curated in-house and organized into hierarchical classifications of functionally distinct families and sub-families. CDD also supports comparative analyses of protein families via conserved domain architectures, and a recent curation effort focuses on providing functional characterizations of distinct subfamily architectures using SPARCLE: Subfamily Protein Architecture Labeling Engine.
C1 [Marchler-Bauer, Aron; Bo, Yu; Han, Lianyi; He, Jane; Lanczycki, Christopher J.; Lu, Shennan; Chitsaz, Farideh; Derbyshire, Myra K.; Geer, Renata C.; Gonzales, Noreen R.; Gwadz, Marc; Hurwitz, David I.; Lu, Fu; Marchler, Gabriele H.; Song, James S.; Thanki, Narmada; Wang, Zhouxi; Yamashita, Roxanne A.; Zhang, Dachuan; Zheng, Chanjuan; Geer, Lewis Y.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Marchler-Bauer, A (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM bauer@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Library of Medicine at
National Institutes of Health/DHHS; Intramural Research Program of the
National Library of Medicine, National Institutes of Health
FX Intramural Research Program of the National Library of Medicine at
National Institutes of Health/DHHS. Funding for open access charge:
Intramural Research Program of the National Library of Medicine,
National Institutes of Health.
NR 9
TC 0
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U1 5
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D200
EP D203
DI 10.1093/nar/gkw1129
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500030
PM 27899674
ER
PT J
AU Van Doorslaer, K
Li, Z
Xirasagar, S
Maes, P
Kaminsky, D
Liou, D
Sun, Q
Kaur, R
Huyen, Y
McBride, AA
AF Van Doorslaer, Koenraad
Li, Zhiwen
Xirasagar, Sandhya
Maes, Piet
Kaminsky, David
Liou, David
Sun, Qiang
Kaur, Ramandeep
Huyen, Yentram
McBride, Alison A.
TI The Papillomavirus Episteme: a major update to the papillomavirus
sequence database
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CAPSID PROTEIN; E7 PROTEINS; E5 PROTEINS; CLASSIFICATION; E6;
LOCALIZATION; PERFORMANCE; EXPRESSION
AB The Papillomavirus Episteme (PaVE) is a database of curated papillomavirus genomic sequences, accompanied by web-based sequence analysis tools. This update describes the addition of major new features. The papillomavirus genomes within PaVE have been further annotated, and now includes the major spliced mRNA transcripts. Viral genes and transcripts can be visualized on both linear and circular genome browsers. Evolutionary relationships among PaVE reference protein sequences can be analysed using multiple sequence alignments and phylogenetic trees. To assist in viral discovery, PaVE offers a typing tool; a simplified algorithm to determine whether a newly sequenced virus is novel. PaVE also now contains an image library containing gross clinical and histopathological images of papillomavirus infected lesions. Database URL: https://pave.niaid.nih.gov/.
C1 [Van Doorslaer, Koenraad; McBride, Alison A.] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Viral Dis Lab, IDNA Tumor Virus Sect, Bethesda, MD 20989 USA.
[Li, Zhiwen; Xirasagar, Sandhya; Kaminsky, David; Liou, David; Sun, Qiang; Kaur, Ramandeep; Huyen, Yentram] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Bioinformat & Computat Biosciences Branch, Off Cyber Infrastructure & Computat Biol, Bethesda, MD 20989 USA.
[Maes, Piet] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Clin Virol, B-3000 Leuven, Belgium.
RP McBride, AA (reprint author), Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Viral Dis Lab, IDNA Tumor Virus Sect, Bethesda, MD 20989 USA.; McBride, AA (reprint author), Univ Arizona, Sch Anim & Comparat Biomed Sci, Koenraad Doorslaer, Tucson, AZ USA.; McBride, AA (reprint author), Intel Corp, Yentram Huyen, Amer Hlth & Life Sci Solut & Strategy, Fairfax, VA USA.
EM amcbride@nih.gov
FU Intramural Research Program of the National Institutes of Allergy and
Infectious Diseases [1ZIAAI001071]; BCBB Support Services
Contract-National Institutes of Allergy and Infectious Diseases,
National Institutes of Health [GS35F0373X]; National Institutes of
Allergy and Infectious Diseases [1ZIAAI001071]
FX Intramural Research Program [1ZIAAI001071] of the National Institutes of
Allergy and Infectious Diseases; BCBB Support Services Contract
[GS35F0373X] funded by the National Institutes of Allergy and Infectious
Diseases, National Institutes of Health. Funding for open access charge:
National Institutes of Allergy and Infectious Diseases [1ZIAAI001071].
NR 46
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D499
EP D506
DI 10.1093/nar/gkw879
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500071
PM 28053164
ER
PT J
AU Wang, YL
Bryant, SH
Cheng, TJ
Wang, JY
Gindulyte, A
Shoemaker, BA
Thiessen, PA
He, SQ
Zhang, J
AF Wang, Yanli
Bryant, Stephen H.
Cheng, Tiejun
Wang, Jiyao
Gindulyte, Asta
Shoemaker, Benjamin A.
Thiessen, Paul A.
He, Siqian
Zhang, Jian
TI PubChem BioAssay: 2017 update
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID 6-PHOSPHOGLUCONATE DEHYDROGENASE; TUMOR-GROWTH; DNA-REPAIR; DATABASE;
PROTEIN; DISCOVERY; SCREENS; PHARMACOLOGY; INFORMATION; RECEPTORS
AB PubChem's BioAssay database (https://pubchem.ncbi.nlm.nih.gov) has served as a public repository for small-molecule and RNAi screening data since 2004 providing open access of its data content to the community. PubChem accepts data submission from worldwide researchers at academia, industry and government agencies. PubChem also collaborates with other chemical biology database stake-holders with data exchange. With over a decade's development effort, it becomes an important information resource supporting drug discovery and chemical biology research. To facilitate data discovery, PubChem is integrated with all other databases at NCBI. In this work, we provide an update for the PubChem BioAssay database describing several recent development including added sources of research data, redesigned BioAssay record page, new BioAssay classification browser and new features in the Upload system facilitating data sharing.
C1 [Wang, Yanli; Bryant, Stephen H.; Cheng, Tiejun; Wang, Jiyao; Gindulyte, Asta; Shoemaker, Benjamin A.; Thiessen, Paul A.; He, Siqian; Zhang, Jian] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Wang, YL; Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
National Library of Medicine (NLM); National Center for Biotechnology
Information (NCBI)
FX Intramural Research Program of the National Institutes of Health (NIH);
National Library of Medicine (NLM). Funding for open access charge:
National Center for Biotechnology Information (NCBI).
NR 38
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D955
EP D963
DI 10.1093/nar/gkw1118
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500132
PM 27899599
ER
PT J
AU Wong, KM
Langlais, K
Tobias, GS
Fletcher-Hoppe, C
Krasnewich, D
Leeds, HS
Rodriguez, LL
Godynskiy, G
Schneider, VA
Ramos, EM
Sherry, ST
AF Wong, Kira M.
Langlais, Kristofor
Tobias, Geoffrey S.
Fletcher-Hoppe, Colette
Krasnewich, Donna
Leeds, Hilary S.
Rodriguez, Laura Lyman
Godynskiy, Georgy
Schneider, Valerie A.
Ramos, Erin M.
Sherry, Stephen T.
TI The dbGaP data browser: a new tool for browsing dbGaP controlled-access
genomic data
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PHENOTYPES; GENOTYPES; ARCHIVE
AB The database of Genotypes and Phenotypes (dbGaP) Data Browser (https://www.ncbi.nlm.nih.gov/gap/ddb/) was developed in response to requests from the scientific community for a resource that enable view-only access to summary-level information and individual-level genotype and sequence data associated with phenotypic features maintained in the controlled-access tier of dbGaP. Until now, the dbGaP controlled-access environment required investigators to submit a data access request, wait for Data Access Committee review, download each data set and locally examine them for potentially relevant information. Existing unrestricted-access genomic data browsing resources (e.g.http://evs.gs.washington.edu/EVS/,http://exac.broadinstitute.org/) provide only summary statistics or aggregate allele frequencies. The dbGaP Data Browser serves as a third solution, providing researchers with view-only access to a compilation of individual-level data from general research use (GRU) studies through a simplified controlled-access process. The National Institutes of Health (NIH) will continue to improve the Browser in response to user feedback and believes that this tool may decrease unnecessary download requests, while still facilitating responsible genomic data-sharing.
C1 [Wong, Kira M.; Fletcher-Hoppe, Colette; Rodriguez, Laura Lyman; Ramos, Erin M.] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20814 USA.
[Langlais, Kristofor; Leeds, Hilary S.] Natl Inst Hlth, Off Sci Policy, Bethesda, MD 20814 USA.
[Tobias, Geoffrey S.] Natl Canc Inst, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Krasnewich, Donna] Natl Inst Gen Med Sci, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Godynskiy, Georgy; Schneider, Valerie A.; Sherry, Stephen T.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Ramos, EM (reprint author), Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20814 USA.; Sherry, ST (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM ramoser@mail.nih.gov; sherry@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Library of Medicine at the
National Institutes of Health (NIH); Intramural Research Program of the
National Institutes of Health, National Library of Medicine
FX Intramural Research Program of the National Library of Medicine at the
National Institutes of Health (NIH) [in part]. Funding for open access
charge: Intramural Research Program of the National Institutes of
Health, National Library of Medicine.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN 4
PY 2017
VL 45
IS D1
BP D819
EP D826
DI 10.1093/nar/gkw1139
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO3DQ
UT WOS:000396575500114
PM 27899644
ER
PT J
AU Tejeda, HA
Wu, J
Kornspun, AR
Pignatelli, M
Kashtelyan, V
Krashes, MJ
Lowell, BB
Carlezon, WA
Bonci, A
AF Tejeda, Hugo A.
Wu, Jocelyn
Kornspun, Alana R.
Pignatelli, Marco
Kashtelyan, Vadim
Krashes, Michael J.
Lowell, Brad B.
Carlezon, William A., Jr.
Bonci, Antonello
TI Pathway-and Cell-Specific Kappa-Opioid Receptor Modulation of
Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens
Neuron Activity
SO NEURON
LA English
DT Article
ID LONG-TERM DEPRESSION; MESSENGER-RNA EXPRESSION; NUCLEUS-ACCUMBENS;
DOPAMINE NEURONS; PROJECTION NEURONS; SPINY NEURONS;
SYNAPTIC-TRANSMISSION; PARKINSONS-DISEASE; COCAINE REWARD; PLACE
AVERSION
AB Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases the excitatory drive of D1 MSN activity by the amygdala, but not the hippocampus. Conversely, presynaptic inhibition by KORs of inhibitory synapses on D2 MSNs enhances integration of excitatory drive by the amygdala and hippocampus. In conclusion, we describe a circuit-based mechanism showing differential gating of afferent control of D1 and D2 MSN activity by KORs in a pathway-specific manner.
C1 [Tejeda, Hugo A.; Wu, Jocelyn; Kornspun, Alana R.; Pignatelli, Marco; Krashes, Michael J.; Bonci, Antonello] NIDA, Synapt Plast Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Kashtelyan, Vadim] NIDA, Neuronal Networks Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Lowell, Brad B.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Carlezon, William A., Jr.] Harvard Med Sch, McLean Hosp, Dept Psychiat, Behav Genet Lab, Belmont, MA 02578 USA.
[Bonci, Antonello] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
RP Bonci, A (reprint author), NIDA, Synapt Plast Sect, Intramural Res Program, Baltimore, MD 21224 USA.; Bonci, A (reprint author), Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
EM antonello.bonci@nih.gov
FU NIDA Intramural Research Program; NIH; NIDDK [R01 DK096010, R01
DK089044, R01 DK071051, R01 DK075632]
FX We thank members of the Bonci laboratory, Drs. Alex Hoffman, Carl
Lupica, and Roy Wise, for helpful discussions. We thank Drs. Yeka Aponte
and Zheng-Xiong Xi for sharing equipment. We thank Dr. Marisela Morales
for reagents, resources, and guidance on FG and radioactive in situ
hybridization experiments. We thank Drs. Carlos Mejias-Aponte, Bing Liu,
and Hui-Ling Wang for assistance with FG and radioactive in situ
hybridization experiments. We thanks Drs. Robert Steiner and Sasha
Kauffman for generously providing KOR cDNA. We thank Drs. Bruce Cohen,
Anita Bechtholt, and Ashlee Van't Veer for their roles in developing
KOR-floxed mice. This work was funded by the NIDA Intramural Research
Program and grants to B.B.L. from the NIH and NIDDK (R01 DK096010, R01
DK089044, R01 DK071051, and R01 DK075632).
NR 60
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JAN 4
PY 2017
VL 93
IS 1
BP 147
EP 163
DI 10.1016/j.neuron.2016.12.005
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA EO0ZR
UT WOS:000396427800015
PM 28056342
ER
PT J
AU Hong, SG
Yada, RC
Choi, K
Carpentier, A
Liang, TJ
Merling, RK
Sweeney, CL
Malech, HL
Jung, M
Corat, MAF
AlJanahi, AA
Lin, YS
Liu, HM
Tunc, I
Wang, XJ
Palisoc, M
Pittaluga, S
Boehm, M
Winkler, T
Zou, JZ
Dunbar, CE
AF Hong, So Gun
Yada, Ravi Chandra
Choi, Kyujoo
Carpentier, Arnaud
Liang, T. Jake
Merling, Randall K.
Sweeney, Colin L.
Malech, Harry L.
Jung, Moonjung
Corat, Marcus A. F.
AlJanahi, Aisha A.
Lin, Yongshun
Liu, Huimin
Tunc, Ilker
Wang, Xujing
Palisoc, Maryknoll
Pittaluga, Stefania
Boehm, Manfred
Winkler, Thomas
Zou, Jizhong
Dunbar, Cynthia E.
TI Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of
Transgenes in Differentiated Cells of All Germ Layers
SO MOLECULAR THERAPY
LA English
DT Article
ID EMBRYONIC STEM-CELLS; NONHUMAN PRIMATE MODEL; CAS9 NUCLEASES; AAVS1
LOCUS; CRISPR/CAS9; SPECIFICITY; MONKEY; THERAPY; DISEASE; INTEGRATION
AB Nonhuman primate (NHP) induced pluripotent stem cells (iPSCs) offer the opportunity to investigate the safety, feasibility, and efficacy of proposed iPSC-derived cellular delivery in clinically relevant in vivo models. However, there is need for stable, robust, and safe labeling methods for NHP iPSCs and their differentiated lineages to study survival, proliferation, tissue integration, and biodistribution following transplantation. Here we investigate the utility of the adenoassociated virus integration site 1 (AAVS1) as a safe harbor for the addition of transgenes in our rhesus macaque iPSC (RhiPSC) model. A clinically relevant marker gene, human truncated CD19 (h Delta CD19), or GFP was inserted into the AAVS1 site in RhiPSCs using the CRISPR/Cas9 system. Genetically modified RhiPSCs maintained normal karyotype and pluripotency, and these clones were able to further differentiate into all three germ layers in vitro and in vivo. In contrast to transgene delivery using randomly integrating viral vectors, AAVS1 targeting allowed stable transgene expression following differentiation. Off -target mutations were observed in some edited clones, highlighting the importance of careful characterization of these cells prior to downstream applications. Genetically marked RhiPSCs will be useful to further advance clinically relevant models for iPSC-based cell therapies.
C1 [Hong, So Gun; Yada, Ravi Chandra; Choi, Kyujoo; Jung, Moonjung; Corat, Marcus A. F.; AlJanahi, Aisha A.; Winkler, Thomas; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Carpentier, Arnaud; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Merling, Randall K.; Sweeney, Colin L.; Malech, Harry L.] NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Corat, Marcus A. F.] Univ Estadual Campinas, Multidisciplinar Ctr Biol Res, BR-13083877 Campinas, SP, Brazil.
[AlJanahi, Aisha A.] Georgetown Univ, Dept Chem & Mol & Cellular Biol, Washington, DC 20057 USA.
[Lin, Yongshun; Liu, Huimin; Zou, Jizhong] NHLBI, iPSC Core, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Tunc, Ilker; Wang, Xujing] NHLBI, Syst Biol Core, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Palisoc, Maryknoll; Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Boehm, Manfred] NHLBI, Lab Cardiovasc Regenerat Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Hong, SG (reprint author), NHLBI, NIH, Bld 10-CRC,Room 3-3216,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sogun.hong@nih.gov
FU Division of Intramural Research at the National Heart, Lung and Blood
Institute (NHLBI) at the NIH
FX This research was supported by funding from the Division of Intramural
Research at the National Heart, Lung and Blood Institute (NHLBI) at the
NIH. We thank Gianpietro Dotti for sharing the pCDH-iCasp9-2A-h ACD19
lentiviral vector. We thank the NHLBI Pathology core for tissue
processing and Building 50 staff for provision of excellent animal care.
We also thank Shiqin Judy Yu for assisting with the iPSC culture,
Macallister Harris for his support during the Southern blot analysis,
and Alec Nicholls for feedback on neural stem cell staining.
NR 44
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD JAN 4
PY 2017
VL 25
IS 1
BP 44
EP 53
DI 10.1016/j.ymthe.2016.10.007
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA EH6RM
UT WOS:000391901600007
PM 28129126
ER
PT J
AU Abdelmegeed, MA
Choi, Y
Godlewski, G
Ha, SK
Banerjee, A
Jang, S
Song, BJ
AF Abdelmegeed, Mohamed A.
Choi, Youngshim
Godlewski, Grzegorz
Ha, Seung-Kwon
Banerjee, Atrayee
Jang, Sehwan
Song, Byoung-Joon
TI Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NONALCOHOLIC FATTY LIVER; ENDOPLASMIC-RETICULUM STRESS; METABOLIC
SYNDROME; OXIDATIVE STRESS; STELLATE CELLS; STEATOHEPATITIS; MICE;
CHOLESTEROL; DISEASE; CYP2E1
AB Cytochrome P450-2E1 (CYP2E1) increases oxidative stress. High hepatic cholesterol causes nonalcoholic steatohepatitis (NASH) and fibrosis. Thus, we aimed to study the role of CYP2E1 in promoting liver fibrosis by high cholesterol-containing fast-food (FF). Male wild-type (WT) and Cyp2e1-null mice were fed standard chow or FF for 2, 12, and 24 weeks. Various parameters of liver fibrosis and potential mechanisms such as oxidative and endoplasmic reticulum (ER) stress, inflammation, and insulin resistance (IR) were studied. Indirect calorimetry was also used to determine metabolic parameters. Liver histology showed that only WT fed FF (WT-FF) developed NASH and fibrosis. Hepatic levels of fibrosis protein markers were significantly increased in WT-FF. The nitroxidative stress marker iNOS, but not CYP2E1, was significantly elevated only in FF-fed WT. Serum endotoxin, TLR-4 levels, and inflammatory markers were highest in WT-FF. FAS, PPAR-alpha, PPAR-gamma, and CB1-R were markedly altered in WT-FF. Electron microscopy and immunoblot analyses showed significantly higher levels of ER stress in FF-fed WT. Indirect calorimetry showed that Cyp2e1-null-mice fed FF exhibited consistently higher total energy expenditure (TEE) than their corresponding WT. These results demonstrate that CYP2E1 is important in fast food-mediated liver fibrosis by promoting nitroxidative and ER stress, endotoxemia, inflammation, IR, and low TEE.
C1 [Abdelmegeed, Mohamed A.; Choi, Youngshim; Ha, Seung-Kwon; Banerjee, Atrayee; Jang, Sehwan; Song, Byoung-Joon] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
[Godlewski, Grzegorz] NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA.
RP Abdelmegeed, MA; Song, BJ (reprint author), NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
EM abdelmegeedm@mail.nih.gov; bj.song@nih.gov
FU Intramural Research Program of National Institute on Alcohol Abuse and
Alcoholism; Korean Biomedical Scientist Fellowship Program from Korea
Research Institute of Bioscience and Biotechnology, Republic of Korea
FX This research was supported by the Intramural Research Program of
National Institute on Alcohol Abuse and Alcoholism. Youngshim Choi was
supported by the Korean Biomedical Scientist Fellowship Program from
Korea Research Institute of Bioscience and Biotechnology, Republic of
Korea.
NR 47
TC 1
Z9 1
U1 8
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 4
PY 2017
VL 7
AR 39764
DI 10.1038/srep39764
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6BU
UT WOS:000391129600001
PM 28051126
ER
PT J
AU Kumarasamy, S
Solanki, S
Atolagbe, OT
Joe, B
Birnbaumer, L
Vazquez, G
AF Kumarasamy, Sivarajan
Solanki, Sumeet
Atolagbe, Oluwatomisin T.
Joe, Bina
Birnbaumer, Lutz
Vazquez, Guillermo
TI Deep Transcriptomic Profiling of M1 Macrophages Lacking Trpc3
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ATHEROSCLEROTIC PLAQUES; NETRIN-1; CHANNELS; RETENTION; SURVIVAL;
DISEASE; GENE; KEGG
AB In previous studies using mice with macrophage-specific loss of TRPC3 we found a significant, selective effect of TRPC3 on the biology of M1, or inflammatory macrophages. Whereas activation of some components of the unfolded protein response and the pro-apoptotic mediators CamkII and Stat1 was impaired in Trpc3-deficient M1 cells, gathering insight about other molecular signatures within macrophages that might be affected by Trpc3 expression requires an alternative approach. In the present study we conducted RNA-seq analysis to interrogate the transcriptome of M1 macrophages derived from mice with macrophage-specific loss of TRPC3 and their littermate controls. We identified 160 significantly differentially expressed genes between the two groups, of which 62 were upregulated and 98 downregulated in control vs. Trpc3-deficient M1 macrophages. Gene ontology analysis revealed enrichment in processes associated to cellular movement and lipid signaling, whereas the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included networks for calcium signaling and cell adhesion molecules, among others. This is the first deep transcriptomic analysis of macrophages in the context of Trpc3 deficiency and the data presented constitutes a unique resource to further explore functions of TRPC3 in macrophage biology.
C1 [Kumarasamy, Sivarajan; Solanki, Sumeet; Atolagbe, Oluwatomisin T.; Joe, Bina; Vazquez, Guillermo] Univ Toledo, Dept Physiol & Pharmacol, Coll Med & Life Sci, Hlth Sci Campus,3000 Transverse Dr, Toledo, OH 43614 USA.
[Kumarasamy, Sivarajan; Solanki, Sumeet; Atolagbe, Oluwatomisin T.; Joe, Bina; Vazquez, Guillermo] Univ Toledo, Ctr Hypertens & Personalized Med, Coll Med & Life Sci, Hlth Sci Campus,3000 Transverse Dr, Toledo, OH 43614 USA.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
[Birnbaumer, Lutz] Inst Biomed Res BIOMED UCA CONICET, Fac Med Sci, Av Alicia Moreau de Justo 1600,C1107AFF, Buenos Aires, DF, Argentina.
RP Vazquez, G (reprint author), Univ Toledo, Dept Physiol & Pharmacol, Coll Med & Life Sci, Hlth Sci Campus,3000 Transverse Dr, Toledo, OH 43614 USA.; Vazquez, G (reprint author), Univ Toledo, Ctr Hypertens & Personalized Med, Coll Med & Life Sci, Hlth Sci Campus,3000 Transverse Dr, Toledo, OH 43614 USA.
EM Guillermo.Vazquez@utoledo.edu
FU NIH [R01HL111877-04, HL-076709, HL-112641, HL-020176]; Intramural
Research Program of the NIH [Z01-ES101684]
FX This work was supported by NIH grant R01HL111877-04 to G.V., HL-076709,
HL-112641 and HL-020176 to B.J., and by the Intramural Research Program
of the NIH ( project Z01-ES101684 to L.B.).
NR 23
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 4
PY 2017
VL 7
AR 39867
DI 10.1038/srep39867
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6YW
UT WOS:000391193200001
PM 28051144
ER
PT J
AU Journy, NMY
Lee, C
Harbron, RW
McHugh, K
Pearce, MS
de Gonzalez, AB
AF Journy, Neige M. Y.
Lee, Choonsik
Harbron, Richard W.
McHugh, Kieran
Pearce, Mark S.
de Gonzalez, Amy Berrington
TI Projected cancer risks potentially related to past, current, and future
practices in paediatric CT in the United Kingdom, 1990-2020
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE computed tomography; public health; paediatrics; radiation exposures;
risk assessment; cancer
ID ATOMIC-BOMB SURVIVORS; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE;
SUBSEQUENT RISK; DOSE REDUCTION; BRAIN-TUMORS; SCANS; LEUKEMIA;
CHILDHOOD; IMPACT
AB Background: To project risks of developing cancer and the number of cases potentially induced by past, current, and future computed tomography (CT) scans performed in the United Kingdom in individuals aged <20 years.
Methods: Organ doses were estimated from surveys of individual scan parameters and CT protocols used in the United Kingdom. Frequencies of scans were estimated from the NHS Diagnostic Imaging Dataset. Excess lifetime risks (ELRs) of radiation-related cancer were calculated as cumulative lifetime risks, accounting for survival probabilities, using the RadRAT risk assessment tool.
Results: In 2000-2008, ELRs ranged from 0.3 to 1 per 1000 head scans and 1 to 5 per 1000 non-head scans. ELRs per scan were reduced by 50-70% in 2000-2008 compared with 1990-1995, subsequent to dose reduction over time. The 130 750 scans performed in 2015 in the United Kingdom were projected to induce 64 (90% uncertainty interval (UI): 38-113) future cancers. Current practices would lead to about 300 (90% UI: 230-680) future cancers induced by scans performed in 2016-2020.
Conclusions: Absolute excess risks from single exposures would be low compared with background risks, but even small increases in annual CT rates over the next years would substantially increase the number of potential subsequent cancers.
C1 [Journy, Neige M. Y.; Lee, Choonsik; de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,MSC 9776, Bethesda, MD 20892 USA.
[Harbron, Richard W.; Pearce, Mark S.] Newcastle Univ, Inst Hlth & Soc, Royal Victoria Infirm, Queen Victoria Rd, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[Harbron, Richard W.; Pearce, Mark S.] Newcastle Univ, NIHR Hlth Protect Res Unit Chem & Radiat Threats, Newcastle Upon Tyne, Tyne & Wear, England.
[McHugh, Kieran] Great Ormond St Hosp Sick Children, Great Ormond St, London WC1N 3JH, England.
RP Journy, NMY (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,MSC 9776, Bethesda, MD 20892 USA.
EM neige.journy@nih.gov
FU US National Cancer Institute intramural research program; UK Department
of Health; Cancer Research UK
FX This study used data from the Diagnostic Imaging Dataset released by the
National Health Service (NHS) England. We thank the NHS England for
providing us detailed data on frequencies of paediatric CT scans. The
interpretation and reporting of these data are the sole responsibility
of the authors and do not necessarily reflect the view of the NHS.
Likewise, the views expressed by the authors do not necessarily reflect
those of the National Institute for Health Research (NIHR), the
Department of Health or Public Health England, to which MSP and RWH are
affiliated or collaborate with. The estimated frequencies of CT scans
provided in this paper might differ from official statistics because we
applied our own methodology to handle missing data on patients'
characteristics. This study was financially supported by the US National
Cancer Institute intramural research program, the UK Department of
Health, and Cancer Research UK. The funding sources and sponsor had no
role in design and conduct of the study; collection, management,
analysis, and interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit the manuscript for
publication.
NR 47
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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 JAN 3
PY 2017
VL 116
IS 1
BP 109
EP 116
DI 10.1038/bjc.2016.351
PG 8
WC Oncology
SC Oncology
GA EL1VE
UT WOS:000394408700016
PM 27824812
ER
PT J
AU Wang, PY
Li, J
Walcott, FL
Kang, JG
Starost, MF
Talagala, SL
Zhuang, J
Park, JH
Huffstutler, RD
Bryla, CM
Mai, PL
Pollak, M
Annunziata, CM
Savage, SA
Fojo, AT
Hwang, PM
AF Wang, Ping-Yuan
Li, Jie
Walcott, Farzana L.
Kang, Ju-Gyeong
Starost, Matthew F.
Talagala, S. Lalith
Zhuang, Jie
Park, Ji-Hoon
Huffstutler, Rebecca D.
Bryla, Christina M.
Mai, Phuong L.
Pollak, Michael
Annunziata, Christina M.
Savage, Sharon A.
Fojo, Antonio Tito
Hwang, Paul M.
TI Inhibiting mitochondrial respiration prevents cancer in a mouse model of
Li-Fraumeni syndrome
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID B-CELL LYMPHOMA; OXIDATIVE STRESS; MUTANT P53; METFORMIN; METABOLISM;
MUTATIONS; ACTIVATION; GENERATION; MICE; DNA
AB Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mitochondrial metabolism in patients. However, the implications of altered mitochondrial function for tumorigenesis in LFS are unclear. Here, we have reported that genetic or pharmacologic disruption of mitochondrial respiration improves cancer-free survival in a mouse model of LFS that expresses mutant p53. Mechanistically, inhibition of mitochondrial function increased autophagy and decreased the aberrant proliferation signaling caused by mutant p53. In a pilot study, LFS patients treated with metformin exhibited decreases in mitochondrial activity concomitant with activation of antiproliferation signaling, thus reproducing the effects of disrupting mitochondrial function observed in LFS mice. These observations indicate that a commonly prescribed diabetic medicine can restrain mitochondrial metabolism and tumorigenesis in an LFS model, supporting its further consideration for cancer prevention in LFS patients.
C1 [Wang, Ping-Yuan; Li, Jie; Kang, Ju-Gyeong; Zhuang, Jie; Park, Ji-Hoon; Huffstutler, Rebecca D.; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bldg 10 CRC,Room 5-5330, Bethesda, MD 20892 USA.
[Walcott, Farzana L.; Mai, Phuong L.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Walcott, Farzana L.] George Washington Univ, Dept Internal Med, Washington, DC USA.
[Starost, Matthew F.] NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA.
[Talagala, S. Lalith] NINDS, NIH MRI Res Facil, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bryla, Christina M.; Annunziata, Christina M.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pollak, Michael] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Pollak, Michael] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Fojo, Antonio Tito] Columbia Univ, Med Ctr, Div Hematol Oncol, New York, NY USA.
EM hwangp@mail.nih.gov
FU Division of Intramural Research, NHLBI-NIH [HL005101]
FX This work was supported by the Division of Intramural Research,
NHLBI-NIH (HL005101 to P.M. Hwang). We thank J. Stolinski, R. Hill, and
H. Merkle for MRS studies; J. Chavez, R. Fleischmann, A. Merriweather,
and C. King for pathology services; T. Finkel for helpful comments and
the Polg+/mut mouse created by T.A. Prolla; M.A. Waclawiw for
advice with statistical analysis; and N.A. Long and W.M. Kamp for
technical and editorial assistance.
NR 27
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U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN 3
PY 2017
VL 127
IS 1
BP 132
EP 136
DI 10.1172/JCI88668
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EI1UK
UT WOS:000392271300017
PM 27869650
ER
PT J
AU Kim, W
Khan, SK
Gvozdenovic-Jeremic, J
Kim, Y
Dahlman, J
Kim, H
Park, O
Ishitani, T
Jho, EH
Gao, B
Yang, Y
AF Kim, Wantae
Khan, Sanjoy Kumar
Gvozdenovic-Jeremic, Jelena
Kim, Youngeun
Dahlman, Jason
Kim, Hanjun
Park, Ogyi
Ishitani, Tohru
Jho, Eek-Hoon
Gao, Bin
Yang, Yingzi
TI Hippo signaling interactions with Wnt/beta-catenin and Notch signaling
repress liver tumorigenesis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID STEM-CELL PROLIFERATION; HUMAN HEPATOCELLULAR-CARCINOMA; BETA-CATENIN;
ADHERENS JUNCTIONS; STAT3 ACTIVATION; DUAL FUNCTIONS; GAMMA-CATENIN;
SIZE-CONTROL; IN-VIVO; KAPPA-B
AB Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/beta-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC). Ablation of the mammalian Hippo kinases Mst1 and Mst2 in liver led to rapid HCC formation and activated Yes-associated protein/WW domain containing transcription regulator 1 (YAP/TAZ), STAT3, Wnt/beta-catenin, and Notch signaling. Previous work has shown that abnormal activation of these downstream pathways can lead to HCC. Rigorous genetic experiments revealed that Notch signaling forms a positive feedback loop with the Hippo signaling effector YAP/TAZ to promote severe hepatomegaly and rapid HCC initiation and progression. Surprisingly, we found that Wnt/beta-catenin signaling activation suppressed HCC formation by inhibiting the positive feedback loop between YAP/TAZ and Notch signaling. Furthermore, we found that STAT3 in hepatocytes is dispensable for HCC formation when mammalian sterile 20-like kinase 1 and 2 (Mst1 and Mst2) were removed. The molecular network we have identified provides insights into HCC molecular classifications and therapeutic developments for the treatment of liver tumors caused by distinct genetic mutations.
C1 [Kim, Wantae; Khan, Sanjoy Kumar; Gvozdenovic-Jeremic, Jelena; Dahlman, Jason; Kim, Hanjun; Yang, Yingzi] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Kim, Wantae; Khan, Sanjoy Kumar; Kim, Hanjun; Yang, Yingzi] Harvard Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA.
[Kim, Youngeun; Jho, Eek-Hoon] Univ Seoul, Dept Life Sci, Seoul, South Korea.
[Park, Ogyi; Gao, Bin] NIAAA, Sect Liver Biol, NIH, Bethesda, MD USA.
[Ishitani, Tohru] Kyushu Univ, Med Inst Bioregulat, Div Cell Regulat Syst, Fukuoka, Japan.
EM yingzi_yang@hsdm.harvard.edu
FU intramural research program of the NHGRI; HSDM; Korean Visiting
Scientist Training Award (KVSTA) fellowship from the Korean Health
Industry Development Institute (KHIDI) [HI13C1274, HI13C1276]; National
R&D Program for Cancer Control of the Ministry of Health and Welfare of
Korea [1420060]
FX We thank members of the Yang laboratory for stimulating discussions and
J. Jiang for reagents (University of Texas Southwestern Medical Center,
Dallas, Texas). This study was supported by grants from the intramural
research program of the NHGRI and the HSDM and by a Korean Visiting
Scientist Training Award (KVSTA) fellowship from the Korean Health
Industry Development Institute (KHIDI) (HI13C1274, to WK and HI13C1276,
to HK). This research was partially supported by the National R&D
Program for Cancer Control of the Ministry of Health and Welfare of
Korea (1420060, to EHJ).
NR 82
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U1 3
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN 3
PY 2017
VL 127
IS 1
BP 137
EP 152
DI 10.1172/JCI88486
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EI1UK
UT WOS:000392271300018
PM 27869648
ER
PT J
AU Keir, LS
Firth, R
Aponik, L
Feitelberg, D
Sakimoto, S
Aguilar, E
Welsh, GI
Richards, A
Usui, Y
Satchell, SC
Kuzmuk, V
Coward, RJ
Goult, J
Bull, KR
Sharma, R
Bharti, K
Westenskow, PD
Michael, IP
Saleem, MA
Friedlander, M
AF Keir, Lindsay S.
Firth, Rachel
Aponik, Lyndsey
Feitelberg, Daniel
Sakimoto, Susumu
Aguilar, Edith
Welsh, Gavin I.
Richards, Anna
Usui, Yoshihiko
Satchell, Simon C.
Kuzmuk, Valeryia
Coward, Richard J.
Goult, Jonathan
Bull, Katherine R.
Sharma, Ruchi
Bharti, Kapil
Westenskow, Peter D.
Michael, Iacovos P.
Saleem, Moin A.
Friedlander, Martin
TI VEGF regulates local inhibitory complement proteins in the eye and
kidney
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM;
MEMBRANE-ATTACK-COMPLEX; HEMOLYTIC-UREMIC SYNDROME; MACULAR
DEGENERATION; FACTOR-H; GEOGRAPHIC ATROPHY; IN-VITRO;
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; CHOROIDAL NEOVASCULARIZATION
AB Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-alpha/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF inhibition could reduce cellular complement regulatory capacity. VEGF antagonism also increased markers of endothelial cell activation, which was partially reduced by genetic complement inhibition. Together, these results suggest that VEGF protects the retinal and glomerular microvasculature, not only through VEGFR2-mediated vasculotrophism, but also through modulation of local complement proteins that could protect against complement-mediated damage. Though further study is warranted, these findings could be relevant for patients receiving VEGF antagonists.
C1 [Keir, Lindsay S.; Aponik, Lyndsey; Feitelberg, Daniel; Sakimoto, Susumu; Aguilar, Edith; Usui, Yoshihiko; Westenskow, Peter D.; Friedlander, Martin] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA.
[Keir, Lindsay S.; Firth, Rachel; Welsh, Gavin I.; Satchell, Simon C.; Kuzmuk, Valeryia; Coward, Richard J.; Saleem, Moin A.] Univ Bristol, Sch Clin Sci, Acad Renal Unit, Bristol, Avon, England.
[Richards, Anna] Univ Edinburgh, Queens Med Res Inst, Edinburgh, Midlothian, Scotland.
[Usui, Yoshihiko] Tokyo Med Univ Hosp, Tokyo, Japan.
[Goult, Jonathan; Bull, Katherine R.] Univ Oxford, Ctr Cellular & Mol Physiol, Oxford OX1 2JD, England.
[Sharma, Ruchi; Bharti, Kapil] NEI, NIH, Bethesda, MD 20892 USA.
[Westenskow, Peter D.] Lowy Med Res Inst, La Jolla, CA USA.
[Michael, Iacovos P.] Ecole Polytech Fed Lausanne, Lausanne, Switzerland.
EM m.saleem@bristol.ac.uk; friedlan@scripps.edu
FU medical research council clinical research training fellowship
[G0901987]; University of Bristol MRC Centenary award; NIHR clinical
lecturer post; Wellcome Trust intermediate clinical training fellowship
[WT085226]; National Eye Institute of the NIH [EY011254]; Lowy Medical
Research Institute
FX We would like to thank all collaborators who provided samples and
reagents as listed in the manuscript; the Wolfson biomedical imaging
facility at the University of Bristol; the flow cytometry facility at
the Scripps Research Institute; Lea Scheppke, Salome Murinello, and Alys
Belcher for review of the manuscript; and Stacey Moreno, Carli
Wittgrove, Mauricio Rosenfeld, and Lan Ni for excellent technical
assistance. LSK was funded by a medical research council clinical
research training fellowship (G0901987), a University of Bristol MRC
Centenary award, and an NIHR clinical lecturer post. AR was funded by a
Wellcome Trust intermediate clinical training fellowship (WT085226;
2009-2014). This work was also funded by grants to MF from the National
Eye Institute of the NIH (EY011254) and the Lowy Medical Research
Institute.
NR 92
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PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN 3
PY 2017
VL 127
IS 1
BP 199
EP 214
DI 10.1172/JCI86418
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EI1UK
UT WOS:000392271300022
PM 27918307
ER
PT J
AU Mace, EM
Bigley, V
Gunesch, JT
Chinn, IK
Angelo, LS
Care, MA
Maisuria, S
Keller, MD
Togi, S
Watkin, LB
LaRosa, DF
Jhangiani, SN
Muzny, DM
Stray-Pedersen, A
Akdemir, ZC
Smith, JB
Hernandez-Sanabria, M
Le, DT
Hogg, GD
Cao, TN
Freud, AG
Szymanski, EP
Savic, S
Collin, M
Cant, AJ
Gibbs, RA
Holland, SM
Caligiuri, MA
Ozato, K
Paust, S
Doody, GM
Lupski, JR
Orange, JS
AF Mace, Emily M.
Bigley, Venetia
Gunesch, Justin T.
Chinn, Ivan K.
Angelo, Laura S.
Care, Matthew A.
Maisuria, Sheetal
Keller, Michael D.
Togi, Sumihito
Watkin, Levi B.
LaRosa, David F.
Jhangiani, Shalini N.
Muzny, Donna M.
Stray-Pedersen, Asbjorg
Akdemir, Zeynep Coban
Smith, Jansen B.
Hernandez-Sanabria, Mayra
Le, Duy T.
Hogg, Graham D.
Cao, Tram N.
Freud, Aharon G.
Szymanski, Eva P.
Savic, Sinisa
Collin, Matthew
Cant, Andrew J.
Gibbs, Richard A.
Holland, Steven M.
Caligiuri, Michael A.
Ozato, Keiko
Paust, Silke
Doody, Gina M.
Lupski, James R.
Orange, Jordan S.
TI Biallelic mutations in IRF8 impair human NK cell maturation and function
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID NATURAL-KILLER-CELLS; SEQUENCE-BINDING-PROTEIN; LEUKEMIA-LIKE SYNDROME;
T-CELL; TRANSCRIPTION FACTOR; IN-VIVO; DENDRITIC CELLS; B-CELL;
IMMUNOLOGICAL SYNAPSE; SIGNALING PATHWAYS
AB Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56(dim) NK cells and an increase in the frequency of the immature CD56(bright) NK cells, and this impairment in terminal maturation was also observed in Irf8(-/-), but not Irf8(+/-), mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense.
C1 [Mace, Emily M.; Gunesch, Justin T.; Chinn, Ivan K.; Angelo, Laura S.; Watkin, Levi B.; Smith, Jansen B.; Hernandez-Sanabria, Mayra; Le, Duy T.; Hogg, Graham D.; Cao, Tram N.; Orange, Jordan S.] Texas Childrens Hosp, Ctr Human Immunobiol, Houston, TX 77030 USA.
[Mace, Emily M.; Chinn, Ivan K.; Lupski, James R.; Orange, Jordan S.] Baylor Coll Med, Dept Pediat, Houston, TX USA.
[Mace, Emily M.; Gunesch, Justin T.; Orange, Jordan S.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX USA.
[Bigley, Venetia; Collin, Matthew] Univ Newcastle, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
[Chinn, Ivan K.; Jhangiani, Shalini N.; Muzny, Donna M.; Stray-Pedersen, Asbjorg; Akdemir, Zeynep Coban; Gibbs, Richard A.; Lupski, James R.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Care, Matthew A.; Doody, Gina M.] Univ Leeds, Leeds Inst Canc & Pathol, Sect Expt Haematol, Leeds, W Yorkshire, England.
[Maisuria, Sheetal] St James Univ Hosp, Dept Clin Immunol & Allergy, Leeds, W Yorkshire, England.
[Keller, Michael D.] Childrens Natl Hlth Syst, Ctr Canc & Immunol Res, Div Allergy & Immunol, Washington, DC USA.
[Togi, Sumihito; Ozato, Keiko] NIH, Natl Inst Child Hlth & Human Dev, Lab Mol Growth Regulat, Program Genom Differentiat, Bethesda, MD 20892 USA.
[LaRosa, David F.] Univ Penn, Childrens Hosp, Sch Med, Philadelphia Res Inst,Dept Pediat, Philadelphia, PA 19104 USA.
[Stray-Pedersen, Asbjorg; Akdemir, Zeynep Coban; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Freud, Aharon G.; Paust, Silke] Ohio State Univ, Dept Pathol, Div Hematopathol, Columbus, OH 43210 USA.
[Freud, Aharon G.; Caligiuri, Michael A.] Ohio State Univ, James Canc Hosp & Solove Res Ctr, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Szymanski, Eva P.; Holland, Steven M.] NIH, NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Cant, Andrew J.] Great North Childrens Hosp, Dept Paediat Immunol & Bone Marrow Transplantat, Newcastle Upon Tyne, Tyne & Wear, England.
[Caligiuri, Michael A.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
[Paust, Silke; Orange, Jordan S.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
EM orange@bcm.edu
FU Genomic and RNA Profiling Core at Baylor College of Medicine;
NIH-National Institute of Allergy and Infectious Diseases grants
[R01AI067946, R01 AI120989]; Jeffrey Modell Foundation; NIH (National
Human Genome Research Institute/National Heart, Lung, and Blood
Institute) [U54HG006542]
FX The authors thank all the patients and their families, particularly the
proband's, for their engagement in this study. The authors also thank
Linda Monaco-Shawver for technical assistance. This project was
supported by the Genomic and RNA Profiling Core at Baylor College of
Medicine and the expert assistance of the core director, Lisa D. White,
and Mylinh Bernardi. This work was supported by NIH-National Institute
of Allergy and Infectious Diseases grants R01AI067946 and R01 AI120989
to JSO, the Jeffrey Modell Foundation, and NIH (National Human Genome
Research Institute/National Heart, Lung, and Blood Institute) grant
U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics.
NR 75
TC 1
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U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN 3
PY 2017
VL 127
IS 1
BP 306
EP 320
DI 10.1172/JCI86276
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EI1UK
UT WOS:000392271300030
PM 27893462
ER
PT J
AU Cao, J
Tyburczy, ME
Moss, J
Darling, TN
Widlund, HR
Kwiatkowski, DJ
AF Cao, Juxiang
Tyburczy, Magdalena E.
Moss, Joel
Darling, Thomas N.
Widlund, Hans R.
Kwiatkowski, David J.
TI Tuberous sclerosis complex inactivation disrupts melanogenesis via
mTORC1 activation
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR LEF-1; B16
MELANOMA-CELLS; BETA-CATENIN; NEURAL CREST; TSC1-TSC2 COMPLEX; SIGNALING
PATHWAY; HUMAN MELANOCYTES; PROTEIN; MITF
AB Tuberous sclerosis complex (TSC) is an autosomal dominant tumor-suppressor gene syndrome caused by inactivating mutations in either TSC1 or TSC2, and the TSC protein complex is an essential regulator of mTOR complex 1 (mTORC1). Patients with TSC develop hypomelanotic macules (white spots), but the molecular mechanisms underlying their formation are not fully characterized. Using human primary melanocytes and a highly pigmented melanoma cell line, we demonstrate that reduced expression of either TSC1 or TSC2 causes reduced pigmentation through mTORC1 activation, which results in hyperactivation of glycogen synthase kinase 3 beta (GSK3 beta), followed by phosphorylation of and loss of beta-catenin from the nucleus, thereby reducing expression of microphthalmia-associated transcription factor (MITF), and subsequent reductions in tyrosinase and other genes required for melanogenesis. Genetic suppression or pharmacological inhibition of this signaling cascade at multiple levels restored pigmentation. Importantly, primary melanocytes isolated from hypomelanotic macules from 6 patients with TSC all exhibited reduced TSC2 protein expression, and 1 culture showed biallelic mutation in TSC2, one of which was germline and the second acquired in the melanocytes of the hypomelanotic macule. These findings indicate that the TSC/mTORC1/AKT/GSK3 beta/beta-catenin/MITF axis plays a central role in regulating melanogenesis. Interventions that enhance or diminish mTORC1 activity or other nodes in this pathway in melanocytes could potentially modulate pigment production.
C1 [Cao, Juxiang; Tyburczy, Magdalena E.; Kwiatkowski, David J.] Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Pulm & Crit Care Med & Genet, Boston, MA 02115 USA.
[Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
[Widlund, Hans R.] Brigham & Womens Hosp, Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.
EM dk@rics.bwh.harvard.edu
FU National Cancer Institute (NCI), NIH [1P01CA120964, R01AR062080];
Intramural Research Program of the NHLBI, NIH
FX We thank Brendan Manning's laboratory (T.H. Chan School of Public
Health, Harvard University, Boston, Massachusetts, USA) for providing
TSC2-knockdown cells, cDNA constructs, and GSK3 beta inhibitors and Ken
Inoki for providing beta-catenin constructs. We also thank the members
of DJK's laboratory for helpful comments and suggestions. This work was
supported by grants from the National Cancer Institute (NCI), NIH
(1P01CA120964, to DJK and R01AR062080, to TND). JM was supported by the
Intramural Research Program of the NHLBI, NIH.
NR 94
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U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN 3
PY 2017
VL 127
IS 1
BP 349
EP 364
DI 10.1172/JCI84262
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EI1UK
UT WOS:000392271300033
PM 27918305
ER
PT J
AU Lu, SS
Grigoryan, H
Edmands, WMB
Hu, W
Iavarone, AT
Hubbard, A
Rothman, N
Vermeulen, R
Lan, Q
Rappaport, SM
AF Lu, Sixin S.
Grigoryan, Hasmik
Edmands, William M. B.
Hu, Wei
Iavarone, Anthony T.
Hubbard, Alan
Rothman, Nathaniel
Vermeulen, Roel
Lan, Qing
Rappaport, Stephen M.
TI Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in
Xuanwei and Fuyuan, China
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID LUNG-CANCER RISK; COAL COMBUSTION EMISSIONS; HOUSEHOLD AIR-POLLUTION;
HUMAN PLASMA; EXPOSURE; WEI; GLUTATHIONE; GENOTYPES; COUNTIES; TISSUES
AB Xuanwei and Fuyuan counties in China have the highest lung cancer rates in the world due to household air pollution from combustion of smoky coal for cooking and heating. To discover potential biomarkers of indoor combustion products, we profiled adducts at the Cys34 locus of human serum albumin (HSA) in 29 nonsmoking Xuanwei and Fuyuan females who used smoky coal, smokeless coal, or wood and 10 local controls who used electricity or gas fuel. Our untargeted "adductomics" method detected 50 tryptic peptides of HSA, containing Cys34 and prominent post-translational modifications. Putative adducts included Cys34 oxidation products, mixed disulfides, rearrangements, and truncations. The most significant differences in adduct levels across fuel types were observed for S-glutathione (S-GSH) and S-gamma-glutamylcysteine (S-gamma-GluCys), both of which were present at lower levels in subjects exposed to combustion products than in controls. After adjustment for age and personal measurements of airborne benzo(a)pyrene, the largest reductions in levels of S-GSH and S-gamma-GluCys relative to controls were observed for users of smoky coal, compared to users, of smokeless coal and wood. These results point to possible depletion of GSH, an essential antioxidant, and its precursor gamma-GluCys in nonsmoking females exposed to indoor-combustion products in Xuanwei and Fuyuan, China.
C1 [Lu, Sixin S.] Univ Calif Berkeley, Coll Nat Resources, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Grigoryan, Hasmik; Edmands, William M. B.; Rappaport, Stephen M.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Hu, Wei; Rothman, Nathaniel; Lan, Qing] NCI, US Dept HHS, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Iavarone, Anthony T.] Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA.
[Hubbard, Alan] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA.
[Vermeulen, Roel] Univ Utrecht, Div Environm Epidemiol, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.
RP Rappaport, SM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
EM srappaport@berkeley.edu
RI Vermeulen, Roel/F-8037-2011;
OI Vermeulen, Roel/0000-0003-4082-8163; Lu, Sixin/0000-0001-9951-1721
FU National Cancer Institute of the U.S. National Institutes of Health;
National Institute for Environmental Health Sciences [U54ES016115,
R44ES022360]; [R33CA191159]
FX This work was supported by Grant R33CA191159 and by the intramural
program of the National Cancer Institute of the U.S. National Institutes
of Health. The authors also acknowledge support from Grants U54ES016115
and R44ES022360 from the National Institute for Environmental Health
Sciences. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
NR 42
TC 0
Z9 0
U1 9
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
EI 1520-5851
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD JAN 3
PY 2017
VL 51
IS 1
BP 46
EP 57
DI 10.1021/acs.est.6b03955
PG 12
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA EG8ZR
UT WOS:000391346900007
PM 27936627
ER
PT J
AU Esposito, G
Manian, N
Truzzi, A
Bornstein, MH
AF Esposito, Gianluca
Manian, Nanmathi
Truzzi, Anna
Bornstein, Marc H.
TI Response to Infant Cry in Clinically Depressed and Non-Depressed Mothers
SO PLOS ONE
LA English
DT Article
ID OXYTOCIN RECEPTOR GENE; MATERNAL SENSITIVITY; POSTNATAL DEPRESSION;
POSTPARTUM DEPRESSION; ATTACHMENT SECURITY; PARENTING BEHAVIOR;
CHRONOLOGICAL AGE; MEDIATING ROLE; DISTRESS; METAANALYSIS
AB Background
Bowlby and Ainsworth hypothesized that maternal responsiveness is displayed in the context of infant distress. Depressed mothers are less responsive to infant distress vocalizations (cry) than non-depressed mothers. The present study focuses on acoustical components of infant cry that give rise to responsive caregiving in clinically depressed (n = 30) compared with non-depressed mothers (n = 30) in the natural setting of the home.
Methods
Analyses of infant and mother behaviors followed three paths: (1) tests of group differences in acoustic characteristics of infant cry, (2) tests of group differences of mothers' behaviors during their infant's crying, and (3) tree-based modeling to ascertain which variable(s) best predict maternal behaviors during infant cry.
Results
(1) Infants of depressed mothers cried as frequently and for equal durations as infants of non-depressed mothers; however, infants of depressed mothers cried with a higher fundamental frequency (fO) and in a more restricted range of fO. (2) Depressed mothers fed, rocked, and touched their crying infants less than non-depressed mothers, and depressed mothers were less responsive to their infants overall. (3) Novel tree-based analyses confirmed that depressed mothers engaged in less caregiving during their infants' cry and indicated that depressed mothers responded only to cries at higher fOs and shorter durations. Older non-depressed mothers were the most interactive with infants.
Conclusions
Clinical depression affects maternal responsiveness during infant cry, leading to patterns of action that appear poorly attuned to infant needs.
C1 [Esposito, Gianluca; Truzzi, Anna] Univ Trento, Dept Psychol & Cognit Sci, Rovereto, Trentino, Italy.
[Esposito, Gianluca] Nanyang Technol Univ, Sch Humanities & Social Sci, Div Psychol, Singapore, Singapore.
[Manian, Nanmathi] Westat Corp, Rockville, MD USA.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Bethesda, MD USA.
RP Esposito, G (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Rovereto, Trentino, Italy.; Esposito, G (reprint author), Nanyang Technol Univ, Sch Humanities & Social Sci, Div Psychol, Singapore, Singapore.; Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Bethesda, MD USA.
EM gianluca.esposito@unitn.it; Marc_H_Bornstein@nih.gov
FU FP7 PEOPLE-Marie Curie Career Integration Grants [GA-2013-630166];
Intramural Research Program of the NIH, NICHD; Westat, a commercial
company
FX This research was supported by grants from the FP7 PEOPLE-Marie Curie
Career Integration Grants (GA-2013-630166) and the Intramural Research
Program of the NIH, NICHD. Westat, a commercial company, provided
financial support in the form of salary for author NM. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 69
TC 0
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U1 5
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 3
PY 2017
VL 12
IS 1
AR e0169066
DI 10.1371/journal.pone.0169066
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH2QJ
UT WOS:000391612300105
PM 28046020
ER
PT J
AU Peavey, MC
Reynolds, CL
Szwarc, MM
Gibbons, WE
Valdese, CT
DeMayo, FJ
Lydon, JP
AF Peavey, Mary C.
Reynolds, Corey L.
Szwarc, Maria M.
Gibbons, William E.
Valdese, Cecilia T.
DeMayo, Francesco J.
Lydon, John P.
TI Three-Dimensional High-Frequency Ultrasonography for Early Detection and
Characterization of Embryo Implantation Site Development in the Mouse
SO PLOS ONE
LA English
DT Article
ID RECURRENT PREGNANCY LOSS; ULTRASOUND; GROWTH; MICE; SCIENCE; MODELS;
CANCER; 3RS
AB Ultrasonography is a powerful tool to non-invasively monitor in real time the development of the human fetus in utero. Although genetically engineered mice have served as valuable in vivo models to study both embryo implantation and pregnancy progression, such studies usually require sacrifice of parous mice for subsequent phenotypic analysis. To address this issue, we used three-dimensional (3-D) reconstruction in silico of high-frequency ultrasound (HFUS) imaging data for early detection and characterization of murine embryo implantation sites and their development in utero. With HFUS imaging followed by 3-D reconstruction, we were able to precisely quantify embryo implantation site number and embryonic developmental progression in pregnant C57BL6J/129S mice from as early as 5.5 days post coitus (d.p.c.) through to 9.5 d.p.c. using a VisualSonics Vevo 2100 (MS550S) transducer. In addition to measurements of implantation site number, location, volume and spacing, embryo viability via cardiac activity monitoring was also achieved. A total of 12 dams were imaged with HFUS with approximately 100 embryos examined per embryonic day. For the post implantation period (5.5 to 8.5 d.p.c.), 3-D reconstruction of the gravid uterus in mesh or solid overlay format enabled visual representation in silico of implantation site location, number, spacing distances, and site volume within each uterine horn. Therefore, this short technical report describes the feasibility of using 3-D HFUS imaging for early detection and analysis of post-implantation events in the pregnant mouse with the ability to longitudinally monitor the development of these early pregnancy events in a non-invasive manner. As genetically engineered mice continue to be used to characterize female reproductive phenotypes, we believe this reliable and non-invasive method to detect, quantify, and characterize early implantation events will prove to be an invaluable investigative tool for the study of female infertility and subfertility phenotypes based on a defective uterus.
C1 [Peavey, Mary C.; Szwarc, Maria M.; Lydon, John P.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Peavey, Mary C.; Gibbons, William E.; Valdese, Cecilia T.] Baylor Coll Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Houston, TX 77030 USA.
[Reynolds, Corey L.] Baylor Coll Med, Mouse Phenotyping Core, Houston, TX 77030 USA.
[DeMayo, Francesco J.] NIEHS, Reprod & Dev Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Lydon, JP (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.; DeMayo, FJ (reprint author), NIEHS, Reprod & Dev Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM francesco.demayo@nih.gov; jlydon@bcm.tmc.edu
FU NIH/NICHD [RO1: HD-042311]; Burroughs Wellcome Fund; NIH [U54 HG006348]
FX This project was supported by NIH/NICHD RO1: HD-042311 (to JPL) and the
Burroughs Wellcome Fund (to FJD). Ultrasound imaging was conducted in
the Mouse Phenotyping Core at Baylor College of Medicine with funding
from the NIH (U54 HG006348). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 30
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U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 3
PY 2017
VL 12
IS 1
AR e0169312
DI 10.1371/journal.pone.0169312
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH2QJ
UT WOS:000391612300164
PM 28046063
ER
PT J
AU Slike, BM
Creegan, M
Marovich, M
Ngauy, V
AF Slike, Bonnie M.
Creegan, Matthew
Marovich, Mary
Ngauy, Viseth
TI Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood
versus Adult Immunization on Vaccinia Vector Vaccine Development in
Military Populations
SO PLOS ONE
LA English
DT Article
ID PREEXISTING POXVIRUS IMMUNITY; HIV-1 NEUTRALIZING ANTIBODIES;
IMMUNOLOGICAL RESPONSE; HVTN 503/PHAMBILI; DENDRITIC CELLS;
SOUTH-AFRICA; PHASE 2H; MVA-B; VIRUS; HIV/AIDS
AB Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax (R). These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 1020 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax (R) as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia na ve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.
C1 [Slike, Bonnie M.; Creegan, Matthew] US Mil HIV Res Program, Silver Spring, MD USA.
[Slike, Bonnie M.; Creegan, Matthew] Henry M Jackson Adv Mil Med, Bethesda, MD USA.
[Marovich, Mary] NIAID, Div Aids, Bethesda, MD USA.
[Ngauy, Viseth] Tripler Army Med Ctr, Honolulu, HI 96859 USA.
RP Ngauy, V (reprint author), Tripler Army Med Ctr, Honolulu, HI 96859 USA.
EM Viseth.ngauy.mil@mail.mil
FU Henry M. Jackson Foundation for the Advancement of Military Medicine,
Inc. [W81XWH-07-2-0067]; U.S. Department of Defense [W81XWH-07-2-0067];
Infectious Disease Clinical Research Program (IDCRP); Department of
Defense (DoD) program executed through the Uniformed Services University
of the Health Sciences from the National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH) [Y1-AI-5072];
Military Vaccine Program (MILVAX)
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, the Infectious
Disease Clinical Research Program (IDCRP), a Department of Defense (DoD)
program executed through the Uniformed Services University of the Health
Sciences from the National Institute of Allergy and Infectious Diseases,
National Institutes of Health (NIH), under Inter-Agency Agreement
Y1-AI-5072, and the Military Vaccine Program (MILVAX). The views
expressed are those of the authors and should not be construed to
represent the positions of the U.S. Army or DoD.
NR 34
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U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 3
PY 2017
VL 12
IS 1
AR e0169247
DI 10.1371/journal.pone.0169247
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH2QJ
UT WOS:000391612300152
PM 28046039
ER
PT J
AU Rabkin, CS
Goedert, JJ
AF Rabkin, Charles S.
Goedert, James J.
TI Chronic Hepatitis and Non-Hodgkin Lymphoma Among People With HIV:
Implications for Screening, Treatment, and Prevention
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID ANTIRETROVIRAL THERAPY; C VIRUS; COHORT; RISK; METAANALYSIS; INFECTION;
ERA
C1 [Rabkin, Charles S.; Goedert, James J.] NCI, Bethesda, MD 20892 USA.
[Rabkin, Charles S.; Goedert, James J.] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
RP Rabkin, CS (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
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 JAN 3
PY 2017
VL 166
IS 1
BP 69
EP +
DI 10.7326/M16-2340
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA EH0QD
UT WOS:000391467900010
PM 27750296
ER
PT J
AU Xu, ZL
Langie, SAS
De Boever, P
Taylor, JA
Niu, L
AF Xu, Zongli
Langie, Sabine A. S.
De Boever, Patrick
Taylor, Jack A.
Niu, Liang
TI RELIC: a novel dye-bias correction method for Illumina Methylation
BeadChip
SO BMC GENOMICS
LA English
DT Article
DE RELIC; DNA methylation; Dye-bias correction; Illumina
HumanMethylation450; Illumina MethylationEPIC; Data preprocessing
ID PROBE DESIGN BIAS; NORMALIZATION; ARRAY; QUANTILE
AB Background: The Illumina Infinium HumanMethylation450 BeadChip and its successor, Infinium MethylationEPIC BeadChip, have been extensively utilized in epigenome-wide association studies. Both arrays use two fluorescent dyes (Cy3-green/Cy5-red) to measure methylation level at CpG sites. However, performance difference between dyes can result in biased estimates of methylation levels.
Results: Here we describe a novel method, called REgression on Logarithm of Internal Control probes (RELIC) to correct for dye bias on whole array by utilizing the intensity values of paired internal control probes that monitor the two color channels. We evaluate the method in several datasets against other widely used dye-bias correction methods. Results on data quality improvement showed that RELIC correction statistically significantly outperforms alternative dye-bias correction methods. We incorporated the method into the R package ENmix, which is freely available from the Bioconductor website(https://www.bioconductor.org/packages/release/bioc/html/ENmix.html).
Conclusions: RELIC is an efficient and robust method to correct for dye-bias in Illumina Methylation BeadChip data. It outperforms other alternative methods and conveniently implemented in R package ENmix to facilitate DNA methylation studies.
C1 [Xu, Zongli; Taylor, Jack A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC USA.
[Langie, Sabine A. S.; De Boever, Patrick] Flemish Inst Technol Res VITO, Environm Risk & Hlth Unit, Mol, Belgium.
[Langie, Sabine A. S.; De Boever, Patrick] Hasselt Univ, Fac Sci, Diepenbeek, Belgium.
[Taylor, Jack A.] Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC USA.
[Niu, Liang] Univ Cincinnati, Coll Med, Dept Environm Hlth, Div Biostat & Bioinformat, Cincinnati, OH 45267 USA.
RP Niu, L (reprint author), Univ Cincinnati, Coll Med, Dept Environm Hlth, Div Biostat & Bioinformat, Cincinnati, OH 45267 USA.
EM niulg@ucmail.uc.edu
OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398
FU Center for Environmental Genetics grant (National Institute of
Environmental Health Sciences) [P30-ES00606]; Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
[Z01 ES049033, Z01 ES049032]; VITO-FWO post-doctoral fellowship
[12L5216N]
FX This work was supported by the Center for Environmental Genetics grant
(National Institute of Environmental Health Sciences award P30-ES00606),
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (Z01 ES049033, and Z01 ES049032), and
VITO-FWO post-doctoral fellowship (12L5216N).
NR 14
TC 0
Z9 0
U1 6
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JAN 3
PY 2017
VL 18
AR 4
DI 10.1186/s12864-016-3426-3
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA EG8UG
UT WOS:000391332000004
PM 28049437
ER
PT J
AU Karyadi, DM
Geybels, MS
Karlins, E
Decker, B
Mcntosh, L
Hutchinson, A
Kolb, S
McDonnell, SK
Hicks, B
Middha, S
FitzGerald, LM
DeRycke, MS
Yeager, M
Schaid, DJ
Chanock, SJ
Thibodeau, SN
Bernd, SI
Stanford, JL
Ostrander, EA
AF Karyadi, Danielle M.
Geybels, Milan S.
Karlins, Eric
Decker, Brennan
Mcntosh, Laura
Hutchinson, Amy
Kolb, Suzanne
McDonnell, Shannon K.
Hicks, Belynda
Middha, Sumit
FitzGerald, Liesel M.
DeRycke, Melissa S.
Yeager, Meredith
Schaid, Daniel J.
Chanock, Stephen J.
Thibodeau, Stephen N.
Bernd, Sonja I.
Stanford, Janet L.
Ostrander, Elaine A.
TI Whole exome sequencing in 75 high-risk families with validation and
replication in independent case-control studies identifies TANGO2,
OR5H14, and CHAD as new prostate cancer susceptibility genes
SO ONCOTARGET
LA English
DT Article
DE whole exome sequencing; cancer susceptibility; high-risk families;
case-control association; prostate cancer
ID GENOME-WIDE SCAN; INTERNATIONAL CONSORTIUM; METABOLIC CRISES; MUTATIONS;
LINKAGE; GENETICS; AGGRESSIVENESS; ASSOCIATION; FRAMEWORK; VARIANTS
AB Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families. Analysis of 341 candidate risk variants identified nine variants significantly associated with increased PCa risk in a population-based, case-control study of 2,495 men. In an independent nested case-control study of 7,121 men, there was risk association evidence for TANGO2 p. Ser17Ter and the established HOXB13 p. Gly84Glu variant. Meta-analysis combining the case-control studies identified two additional variants suggestively associated with risk, OR5H14 p. Met59Val and CHAD p. Ala342Asp. The TANGO2 and HOXB13 variants co-occurred in cases more often than expected by chance and never in controls. Finally, TANGO2 p. Ser17Ter was associated with aggressive disease in both case-control studies separately. Our analyses identified three new PCa susceptibility alleles in the TANGO2, OR5H14 and CHAD genes that not only segregate in multiple high-risk families but are also of importance in altering disease risk for men from the general population. This is the first successful study to utilize sequencing in high-risk families for the express purpose of identifying low-frequency, moderately penetrant PCa risk mutations.
C1 [Karyadi, Danielle M.; Karlins, Eric; Decker, Brennan; Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Geybels, Milan S.; Mcntosh, Laura; Kolb, Suzanne; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Karlins, Eric; Hutchinson, Amy; Hicks, Belynda; Yeager, Meredith; Chanock, Stephen J.; Bernd, Sonja I.] NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[McDonnell, Shannon K.; Middha, Sumit; Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[FitzGerald, Liesel M.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia.
[DeRycke, Melissa S.; Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Ostrander, EA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Decker, Brennan/0000-0003-4516-7421; Ostrander,
Elaine/0000-0001-6075-9738
FU Intramural Program of the National Human Genome Research Institute;
National Cancer Institute; National Cancer Institute, NIH [R01 CA056678,
R01 CA092579, R01 CA080122, U01 CA89600]; Fred Hutchinson Cancer
Research Center; Prostate Cancer Foundation; Dutch Cancer Society
Fellowship [BUIT 2014-6645]; NIH [HHSN268200782096C]
FX This work was supported by the Intramural Program of the National Human
Genome Research Institute (D.M. Karyadi, E. Karlins, B. Decker, E. A.
Ostrander) and National Cancer Institute (E. Karlins, A. Hutchinson, B.
Hicks, M. Yeager, S.J. Chanock, S. I. Berndt), by grants from the
National Cancer Institute, NIH (R01 CA056678, R01 CA092579, and R01
CA080122 to J.L. Stanford; U01 CA89600 to S.N. Thibodeau) with
additional support from the Fred Hutchinson Cancer Research Center and
the Prostate Cancer Foundation and by a Dutch Cancer Society Fellowship
(BUIT 2014-6645 to M. Geybels). The Center for Inherited Disease
Research, which provided sequencing services for 19 families, is funded
through a contact from NIH to The Johns Hopkins University (contract
number HHSN268200782096C). Sequencing of the 56 families at Mayo Clinic
was supported by a grant from the National Cancer Institute, NIH (U01
CA89600).
NR 38
TC 0
Z9 0
U1 3
U2 3
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JAN 3
PY 2017
VL 8
IS 1
BP 1495
EP 1507
DI 10.18632/oncotarget.13646
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EH1DH
UT WOS:000391503300116
PM 27902461
ER
PT J
AU Pope, HG
Khalsa, JH
Bhasin, S
AF Pope, Harrison G., Jr.
Khalsa, Jag H.
Bhasin, Shalender
TI Body Image Disorders and Abuse of Anabolic-Androgenic Steroids Among Men
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID MUSCLE DYSMORPHIA; USERS
C1 [Pope, Harrison G., Jr.] Harvard Med Sch, McLean Hosp, Biol Psychiat Lab, Belmont, MA USA.
[Khalsa, Jag H.] NIDA, Med Consequences Branch, Div Therapeut & Med Consequences, NIH, Bethesda, MD 20892 USA.
[Bhasin, Shalender] Harvard Med Sch, Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, 221 Longwood Ave, Boston, MA 02115 USA.
RP Bhasin, S (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, 221 Longwood Ave, Boston, MA 02115 USA.
EM sbhasin@bwh.harvard.edu
NR 10
TC 0
Z9 0
U1 10
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 3
PY 2017
VL 317
IS 1
BP 23
EP 24
DI 10.1001/jama.2016.17441
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG4JE
UT WOS:000391009100011
PM 27930760
ER
PT J
AU Himelstein, AL
Foster, JC
Khatcheressian, JL
Roberts, JD
Seisler, DK
Novotny, PJ
Qin, R
Go, RS
Grubbs, SS
O'Connor, T
Velasco, MR
Weckstein, D
O'Mara, A
Loprinzi, CL
Shapiro, CL
AF Himelstein, Andrew L.
Foster, Jared C.
Khatcheressian, James L.
Roberts, John D.
Seisler, Drew K.
Novotny, Paul J.
Qin, Rui
Go, Ronald S.
Grubbs, Stephen S.
O'Connor, Tracey
Velasco, Mario R., Jr.
Weckstein, Douglas
O'Mara, Ann
Loprinzi, Charles L.
Shapiro, Charles L.
TI Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on
Skeletal Events in Patients With Bone Metastases A Randomized Clinical
Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; BREAST-CANCER; PREVENTION; CARCINOMA; PHASE-3
AB IMPORTANCE Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.
OBJECTIVE To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.
DESIGN, SETTING, PARTICIPANTS Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.
INTERVENTIONS Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years.
MAIN OUTCOMES AND MEASURES The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels).
RESULTS Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3%[1-sided 95% CI, -4% to infinity]; P<.001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.
CONCLUSIONS AND RELEVANCE Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option.
C1 [Himelstein, Andrew L.; Grubbs, Stephen S.] Canc Ctr & Res Inst, 4701 Ogletown Stanton Rd,Ste 3400, Newark, DE 19713 USA.
[Foster, Jared C.; Seisler, Drew K.; Novotny, Paul J.; Qin, Rui] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA.
[Khatcheressian, James L.] Virginia Canc Inst, Richmond, VA USA.
[Roberts, John D.] VCU Massey Canc Ctr, Richmond, VA USA.
[Roberts, John D.] Yale Univ, New Haven, CT USA.
[Qin, Rui] Regeneron Pharmaceut, Basking Ridge, NJ USA.
[Go, Ronald S.] Gundersen Hlth Syst, La Crosse, WI USA.
[Go, Ronald S.; Loprinzi, Charles L.] Mayo Clin, Rochester, MN USA.
[Grubbs, Stephen S.] Amer Soc Clin Oncol, Alexandria, VA USA.
[O'Connor, Tracey] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Velasco, Mario R., Jr.] Decatur Mem Hosp, Decatur, IL USA.
[Weckstein, Douglas] New Hampshire Oncol Hematol PA, Hooksett, NH USA.
[O'Mara, Ann] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Shapiro, Charles L.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
RP Himelstein, AL (reprint author), Canc Ctr & Res Inst, 4701 Ogletown Stanton Rd,Ste 3400, Newark, DE 19713 USA.
EM ahimelstein@cbg.org
FU National Cancer Institute, National Institutes of Health [UG1CA189823,
U10CA016359, U10CA037404, U10CA037447, U10CA059518, U10CA180790,
U10CA045418, U10CA180866, UG1CA189819]; National Center for Advancing
Translational Sciences, National Institutes of Health [UL1TR001070]
FX This research was supported by grants UG1CA189823 (awarded to the
Alliance for Clinical Trials in Oncology), U10CA016359, U10CA037404,
U10CA037447, U10CA059518, U10CA180790, U10CA045418, U10CA180866, and
UG1CA189819 from the National Cancer Institute, National Institutes of
Health. The C-terminal telopeptide assays were supported by grant
UL1TR001070 from the National Center for Advancing Translational
Sciences, National Institutes of Health.
NR 19
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 3
PY 2017
VL 317
IS 1
BP 48
EP 58
DI 10.1001/jama.2016.19425
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG4JE
UT WOS:000391009100019
PM 28030702
ER
PT J
AU Soethoudt, M
Grether, U
Fingerle, J
Grim, TW
Fezza, F
de Petrocellis, L
Ullmer, C
Rothenhausler, B
Perret, C
van Gils, N
Finlay, D
MacDonald, C
Chicca, A
Gens, MD
Stuart, J
de Vries, H
Mastrangelo, N
Xia, LZ
Alachouzos, G
Baggelaar, MP
Martella, A
Mock, ED
Deng, H
Heitman, LH
Connor, M
Di Marzo, V
Gertsch, J
Lichtman, AH
Maccarrone, M
Pacher, P
Glass, M
van der Stelt, M
AF Soethoudt, Marjolein
Grether, Uwe
Fingerle, Juergen
Grim, Travis W.
Fezza, Filomena
de Petrocellis, Luciano
Ullmer, Christoph
Rothenhausler, Benno
Perret, Camille
van Gils, Noortje
Finlay, David
MacDonald, Christa
Chicca, Andrea
Gens, Marianela Dalghi
Stuart, Jordyn
de Vries, Henk
Mastrangelo, Nicolina
Xia, Lizi
Alachouzos, Georgios
Baggelaar, Marc P.
Martella, Andrea
Mock, Elliot D.
Deng, Hui
Heitman, Laura H.
Connor, Mark
Di Marzo, Vincenzo
Gertsch, Jurg
Lichtman, Aron H.
Maccarrone, Mauro
Pacher, Pal
Glass, Michelle
van der Stelt, Mario
TI Cannabinoid CB2 receptor ligand profiling reveals biased signalling and
off-target activity
SO NATURE COMMUNICATIONS
LA English
DT Article
ID HEPATIC ISCHEMIA/REPERFUSION INJURY; DIACYLGLYCEROL LIPASE-ALPHA;
ENDOCANNABINOID SYSTEM; MOLECULAR CHARACTERIZATION; BIOLOGICAL
EVALUATION; TRICYCLIC PYRAZOLES; THERAPEUTIC TARGET; IN-VIVO;
ANANDAMIDE; INHIBITION
AB The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB2R agonists to study the role of CB2R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research.
C1 [Soethoudt, Marjolein; Alachouzos, Georgios; Baggelaar, Marc P.; Martella, Andrea; Mock, Elliot D.; Deng, Hui; van der Stelt, Mario] Leiden Univ, Leiden Inst Chem, Dept Mol Physiol, Einsteinweg 55, NL-2333 CC Leiden, Netherlands.
[Soethoudt, Marjolein; van Gils, Noortje; de Vries, Henk; Xia, Lizi; Heitman, Laura H.] Leiden Univ, Leiden Acad Ctr Drug Res, Dept Med Chem, Einsteinweg 55, NL-2333 CC Leiden, Netherlands.
[Grether, Uwe; Ullmer, Christoph; Rothenhausler, Benno; Perret, Camille] F Hoffmann La Roche Inc, Roche Innovat Ctr Basel, Grenzachterstr 124, CH-4070 Basel, Switzerland.
[Fingerle, Juergen] Univ Tubingen, NMI, Dept Biochem, Markwiesenstr 55, D-72770 Reutlingen, Germany.
[Grim, Travis W.; Lichtman, Aron H.] Dept Pharmacol & Toxicol, 1220 East Broad St,POB 980613, Richmond, VA 23298 USA.
[Fezza, Filomena] Univ Roma Tor Vergata, Dept Expt Med & Surg, Via Montpellier 1, I-00133 Rome, Italy.
[Fezza, Filomena; Maccarrone, Mauro] IRCCS Santa Lucia Fdn, European Ctr Brain Res, Via Fosso Fiorano 65, I-00143 Rome, Italy.
[de Petrocellis, Luciano; Di Marzo, Vincenzo] CNR, Endocannabinoid Res Grp, Inst Biomol Chem, Via Campi Flegrei 34, I-80078 Pozzuoli, Italy.
[Finlay, David; MacDonald, Christa; Glass, Michelle] Univ Auckland, Fac Med & Hlth Sci, Dept Pharmacol & Clin Pharmacol, 85 Pk Rd, Auckland 1023, New Zealand.
[Chicca, Andrea; Gens, Marianela Dalghi; Gertsch, Jurg] Univ Bern, Inst Biochem & Mol Med, Buhlstr 28, CH-3012 Bern, Switzerland.
[Stuart, Jordyn; Connor, Mark] Macquarie Univ, Fac Med & Hlth Sci, Dept Biomed Sci, N Ryde, NSW 2109, Australia.
[Mastrangelo, Nicolina; Martella, Andrea; Maccarrone, Mauro] Campus Biomed Univ Rome, Dept Med, Via Alvaro del Portillo 21, I-00128 Rome, Italy.
[Pacher, Pal] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
RP van der Stelt, M (reprint author), Leiden Univ, Leiden Inst Chem, Dept Mol Physiol, Einsteinweg 55, NL-2333 CC Leiden, Netherlands.; Glass, M (reprint author), Univ Auckland, Fac Med & Hlth Sci, Dept Pharmacol & Clin Pharmacol, 85 Pk Rd, Auckland 1023, New Zealand.; Pacher, P (reprint author), NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
EM pacher@mail.nih.gov; m.glass@auckland.ac.nz;
m.van.der.stelt@chem.leidenuniv.nl
OI Connor, Mark/0000-0003-2538-2001; Glass, Michelle/0000-0002-5997-6898
FU ECHO-STIP grant from Dutch Research Council-Chemical Sciences; RPF
program; Ministero dell'Istruzione, dell'Universita e della Ricerca
(PRIN grant); Intramural Research Program of NIH/NIAAA; NIH [P30
DA033934, T32DA007027]
FX This paper is dedicated to Prof Dr Raphael Mechoulam, the founder of
cannabinoid research. M.S., L.H.H. and M.v.d.S. were supported by an
ECHO-STIP grant from the Dutch Research Council-Chemical Sciences. A.M.
was supported by the RPF program. Partial support from Ministero
dell'Istruzione, dell'Universita e della Ricerca (PRIN 2010-2011 grant
to M.M.) is gratefully acknowledged. P.P. was supported by the
Intramural Research Program of NIH/NIAAA. Mark Rau (laboratory J.G.) is
acknowledged for measuring AEA uptake inhibition. Pharmacokinetics in
vivo laboratories, Drug Disposition and Safety laboratories.
Pharmaceutical Sciences pRED and F. Hoffmann-La Roche Ltd, Basel,
Switzerland are acknowledged for performing the in vitro DMPK and in
vivo studies. T.W.G and A.H.L were supported by NIH grants P30 DA033934
and T32DA007027.
NR 69
TC 0
Z9 0
U1 6
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN 3
PY 2017
VL 8
AR 13958
DI 10.1038/ncomms13958
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG5CS
UT WOS:000391061700001
PM 28045021
ER
PT J
AU Mahmoodi, BK
Cushman, M
Naess, IA
Allison, MA
Bos, WJ
Braekkan, SK
Cannegieter, SC
Gansevoort, RT
Gona, PN
Hammerstrom, J
Hansen, JB
Heckbert, S
Holst, AG
Lakoski, SG
Lutsey, PL
Manson, JE
Martin, LW
Matsushita, K
Meijer, K
Overvad, K
Prescott, E
Puurunen, M
Rossouw, JE
Sang, YY
Severinsen, MT
ten Berg, J
Folsom, AR
Zakai, NA
AF Mahmoodi, Bakhtawar K.
Cushman, Mary
Naess, Inger Anne
Allison, Matthew A.
Bos, Willem Jan
Braekkan, Sigrid K.
Cannegieter, Suzanne C.
Gansevoort, Ron T.
Gona, Philimon N.
Hammerstrom, Jens
Hansen, John-Bjarne
Heckbert, Susan
Holst, Anders G.
Lakoski, Susan G.
Lutsey, Pamela L.
Manson, JoAnn E.
Martin, Lisa W.
Matsushita, Kunihiro
Meijer, Karina
Overvad, Kim
Prescott, Eva
Puurunen, Marja
Rossouw, Jacques E.
Sang, Yingying
Severinsen, Marianne T.
ten Berg, Jur
Folsom, Aaron R.
Zakai, Neil A.
TI Association of Traditional Cardiovascular Risk Factors With Venous
Thromboembolism An Individual Participant Data Meta-Analysis of
Prospective Studies
SO CIRCULATION
LA English
DT Article
DE cardiovascular disease; diabetes mellitus; hyperlipidemia; hypertension;
risk factors; smoking; venous thromboembolism
ID DIABETES-MELLITUS; WOMENS HEALTH; THROMBOSIS; POPULATION; DISEASE;
TROMSO; MORTALITY; ARTERIAL
AB BACKGROUND: Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE).
METHODS: We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis.
RESULTS: The studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio= 0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively.
CONCLUSIONS: Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.
C1 [Mahmoodi, Bakhtawar K.; Bos, Willem Jan; ten Berg, Jur] St Antonius Hosp, Dept Cardiol & Internal Med, Nieuwegein, Netherlands.
[Mahmoodi, Bakhtawar K.; Meijer, Karina] Univ Groningen, Univ Med Ctr Groningen, Dept Haematol, NL-9700 AB Groningen, Netherlands.
[Cushman, Mary; Zakai, Neil A.] Univ Vermont, Dept Med, Burlington, VT 05405 USA.
[Cushman, Mary; Zakai, Neil A.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Naess, Inger Anne; Hammerstrom, Jens] Univ Trondheim Hosp, Dept Hematol, Trondheim, Norway.
[Allison, Matthew A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Braekkan, Sigrid K.; Hansen, John-Bjarne] Univ Tromso, Dept Clin Med, KG Jebsen Thrombosis Res & Expertise Ctr, N-9001 Tromso, Norway.
[Cannegieter, Suzanne C.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RA Leiden, Netherlands.
[Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9700 AB Groningen, Netherlands.
[Gona, Philimon N.] Univ Massachusetts, Dept Exercise & Hlth Sci, Boston, MA 02125 USA.
[Heckbert, Susan] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Heckbert, Susan] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Holst, Anders G.] Rigshosp, Copenhagen Univ Hosp, Mol Cardiol Lab, Copenhagen, Denmark.
[Lakoski, Susan G.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent & Cardiol, Houston, TX 77030 USA.
[Lutsey, Pamela L.; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Manson, JoAnn E.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA.
[Martin, Lisa W.] George Washington Univ, Sch Med & Hlth Sci, Div Cardiol, Washington, DC 20052 USA.
[Matsushita, Kunihiro; Sang, Yingying] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Overvad, Kim] Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, DK-8000 Aarhus C, Denmark.
[Overvad, Kim] Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
[Prescott, Eva] Univ Copenhagen, Dept Cardiol, Bispebjerg Hosp, DK-1168 Copenhagen, Denmark.
[Puurunen, Marja] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02215 USA.
[Rossouw, Jacques E.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Severinsen, Marianne T.] Aalborg Univ Hosp, Dept Hematol, Aalborg, Denmark.
RP Mahmoodi, BK (reprint author), St Antonius Hosp, Dept Cardiol, Koekoekslaan 1, NL-3435 CM Nieuwegein, Netherlands.
EM b.k.mahmoodi@umcg.nl
FU Sint Antonius Hospital's research fund [10000]
FX Individual studies were supported by a variety of sources for enrollment
and data collection, including laboratory measurements and follow-up
(online-only Data Supplement). The current meta analysis was sponsored
by a small grant (<$10000) provided by the Sint Antonius Hospital's
research fund. The sponsors had no role in the study design, analysis,
data interpretation, or writing of the article. Dr Mahmoodi had full
access to the output and estimates of the studies and performed the
meta-analysis of the estimates; individual-level data were accessible by
the representing coauthor of the individual studies. All authors had
final responsibility for the decision to submit for publication.
NR 31
TC 1
Z9 1
U1 4
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 3
PY 2017
VL 135
IS 1
BP 7
EP +
DI 10.1161/CIRCULATIONAHA.116.024507
PG 56
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA EF8ED
UT WOS:000390560700005
PM 27831499
ER
PT J
AU Kovacs, ZI
Kim, S
Jikaria, N
Qureshi, F
Milo, B
Lewis, BK
Bresler, M
Burks, SR
Frank, JA
AF Kovacs, Zsofia I.
Kim, Saejeong
Jikaria, Neekita
Qureshi, Farhan
Milo, Blerta
Lewis, Bobbi K.
Bresler, Michele
Burks, Scott R.
Frank, Joseph A.
TI Disrupting the blood-brain barrier by focused ultrasound induces sterile
inflammation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE pulsed focused ultrasound; microbubbles; blood-brain barrier; sterile
inflammation; magnetic resonance imaging
ID FOCAL CEREBRAL-ISCHEMIA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; NF-KAPPA-B;
CONTRAST AGENT; IN-VIVO; ACTIVATED CHANNELS; DRUG-DELIVERY;
IMMUNE-SYSTEM; MOUSE MODEL; INJURY
AB MRI-guided pulsed focused ultrasound (pFUS) combined with systemic infusion of ultrasound contrast agent microbubbles (MB) causes localized blood-brain barrier (BBB) disruption that is currently being advocated for increasing drug or gene delivery in neurological diseases. The mechanical acoustic cavitation effects of opening the BBB by low-intensity pFUS+MB, as evidenced by contrast-enhanced MRI, resulted in an immediate damage-associated molecular pattern (DAMP) response including elevations in heat-shock protein 70, IL-1, IL-18, and TNFa indicative of a sterile inflammatory response (SIR) in the parenchyma. Concurrent with DAMP presentation, significant elevations in proinflammatory, antiinflammatory, and trophic factors along with neurotrophic and neurogenesis factors were detected; these elevations lasted 24 h. Transcriptomic analysis of sonicated brain supported the proteomic findings and indicated that the SIR was facilitated through the induction of the NF kappa B pathway. Histological evaluation demonstrated increased albumin in the parenchyma that cleared by 24 h along with TUNEL+ neurons, activated astrocytes, microglia, and increased cell adhesion molecules in the vasculature. Infusion of fluorescent beads 3 d before pFUS+MB revealed the infiltration of CD68(+) macrophages at 6 d postsonication, as is consistent with an innate immune response. pFUS+MB is being considered as part of a noninvasive adjuvant treatment for malignancy or neurodegenerative diseases. These results demonstrate that pFUS+MB induces an SIR compatible with ischemia or mild traumatic brain injury. Further investigation will be required before this approach can be widely implemented in clinical trials.
C1 [Kovacs, Zsofia I.; Kim, Saejeong; Jikaria, Neekita; Qureshi, Farhan; Milo, Blerta; Lewis, Bobbi K.; Bresler, Michele; Burks, Scott R.; Frank, Joseph A.] NIH, Frank Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Kovacs, Zsofia I.; Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Kovacs, ZI (reprint author), NIH, Frank Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.; Kovacs, ZI (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
EM zsofia.kovacs@nih.gov; jf5z@nih.gov
FU Intramural Research Programs of the Clinical Center; National Institute
of Biomedical Imaging and Bioengineering at the National Institutes of
Health
FX This research was funded by the Intramural Research Programs of the
Clinical Center and the National Institute of Biomedical Imaging and
Bioengineering at the National Institutes of Health.
NR 88
TC 0
Z9 0
U1 13
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 3
PY 2017
VL 114
IS 1
BP E75
EP E84
DI 10.1073/pnas.1614777114
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG5OM
UT WOS:000391093700009
PM 27994152
ER
PT J
AU Petrie, RJ
Harlin, HM
Korsak, LIT
Yamada, KM
AF Petrie, Ryan J.
Harlin, Heather M.
Korsak, Lulu I. T.
Yamada, Kenneth M.
TI Activating the nuclear piston mechanism of 3D migration in tumor cells
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID PROTEOLYSIS; ADHESION; MATRIX; MODES; METASTASIS; PLASTICITY; MOTILITY;
INVASION; MT1-MMP; FORCE
AB Primary human fibroblasts have the remarkable ability to use their nucleus like a piston, switching from low-to high-pressure protrusions in response to the surrounding three-dimensional (3D) matrix. Although migrating tumor cells can also change how they migrate in response to the 3D matrix, it is not clear if they can switch between high-and low-pressure protrusions like primary fibroblasts. We report that unlike primary fibroblasts, the nuclear piston is not active in fibrosarcoma cells. Protease inhibition rescued the nuclear piston mechanism in polarized HT1080 and SW684 cells and generated compartmentalized pressure. Achieving compartmentalized pressure required the nucleoskeleton-cytoskeleton linker protein nesprin 3, actomyosin contractility, and integrin-mediated adhesion, consistent with lobopodia-based fibroblast migration. In addition, this activation of the nuclear piston mechanism slowed the 3D movement of HT1080 cells. Together, these data indicate that inhibiting protease activity during polarized tumor cell 3D migration is sufficient to restore the nuclear piston migration mechanism with compartmentalized pressure characteristic of nonmalignant cells.
C1 [Petrie, Ryan J.; Harlin, Heather M.; Korsak, Lulu I. T.] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA.
[Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Petrie, RJ (reprint author), Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA.
EM rjp336@drexel.edu
FU Intramural Research Program of the National Institutes of Health,
National Institute of Dental and Craniofacial Research; College of Arts
and Sciences of Drexel University; Department of Biology of Drexel
University
FX Work in K.M. Yamada's laboratory is supported by the Intramural Research
Program of the National Institutes of Health, National Institute of
Dental and Craniofacial Research. R.J. Petrie is supported by startup
funds from the College of Arts and Sciences and the Department of
Biology of Drexel University.
NR 30
TC 0
Z9 0
U1 7
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD JAN 2
PY 2017
VL 216
IS 1
BP 93
EP 100
DI 10.1083/jcb.201605097
PG 8
WC Cell Biology
SC Cell Biology
GA EI5TD
UT WOS:000392556800016
PM 27998990
ER
PT J
AU Liu, LK
Choudhary, V
Toulmay, A
Prinz, WA
AF Liu, Li-Ka
Choudhary, Vineet
Toulmay, Alexandre
Prinz, William A.
TI An inducible ER-Golgi tether facilitates ceramide transport to alleviate
lipotoxicity
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID NUCLEUS-VACUOLE JUNCTIONS; MEMBRANE CONTACT SITES;
SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; LIPID TRANSFER;
EXTENDED SYNAPTOTAGMINS; SPHINGOLIPID SYNTHESIS; ALKALINE CERAMIDASE;
ELECTRON-MICROSCOPY; INSULIN-RESISTANCE
AB Ceramides are key intermediates in sphingolipid biosynthesis and potent signaling molecules. However, excess ceramide is toxic, causing growth arrest and apoptosis. In this study, we identify a novel mechanism by which cells prevent the toxic accumulation of ceramides; they facilitate nonvesicular ceramide transfer from the endoplasmic reticulum (ER) to the Golgi complex, where ceramides are converted to complex sphingolipids. We find that the yeast protein Nvi2p promotes the nonvesicular transfer of ceramides from the ER to the Golgi complex. The protein is a tether that generates close contacts between these compartments and may directly transport ceramide. Nvi2p normally resides at contacts between the ER and other organelles, but during ER stress, it relocalizes to and increases ER Golgi contacts. ER Golgi contacts fail to form during ER stress in cells lacking Nvi2p. Our findings demonstrate that cells regulate ER Golgi contacts in response to stress and reveal that nonvesicular ceramide transfer out of the ER prevents the buildup of toxic amounts of ceramides.
C1 [Liu, Li-Ka; Choudhary, Vineet; Toulmay, Alexandre; Prinz, William A.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Toulmay, A; Prinz, WA (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM toulmayal@niddk.nih.gov; prinzw@helix.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 59
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Z9 1
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD JAN 2
PY 2017
VL 216
IS 1
BP 131
EP 147
DI 10.1083/jcb.201606059
PG 17
WC Cell Biology
SC Cell Biology
GA EI5TD
UT WOS:000392556800019
PM 28011845
ER
PT J
AU Perera, L
Beard, WA
Pedersen, LG
Wilson, SH
AF Perera, Lalith
Beard, William A.
Pedersen, Lee G.
Wilson, Samuel H.
TI Hiding in Plain Sight: The Bimetallic Magnesium Covalent Bond in Enzyme
Active Sites
SO INORGANIC CHEMISTRY
LA English
DT Article
ID PARTICLE MESH EWALD; CATALYTIC COMPLEX; MECHANISM; ARGINASE; MG-2(2+);
CLUSTER; IONS
AB The transfer of phosphate groups is an essential function of many intracellular biological enzymes. The transfer is in many cases facilitated by a protein scaffold involving two closely spaced magnesium "ions". It has long been a mystery how these "ions" can retain their closely spaced positions throughout enzymatic phosphate transfer: Coulomb's law would dictate large repulsive forces between these ions at the observed distances. Here we show, however, that the electron density can be borrowed from nearby electron-rich oxygens to populate a bonding molecular orbital that is largely localized between the magnesium "ions". The result is that the Mg-Mg core of these phosphate transfer enzymes is surprisingly similar to a metastable [Mg-2](2+) ion in the gas phase, an ion that has been identified experimentally and studied with high-level quantum-mechanical calculations. This similarity is confirmed by comparative computations of the electron densities of [Mg-2](2+) in the gas phase and the Mg-Mg core in the structures derived from QM/MM studies of high-resolution X-ray crystal structures. That there is a level of covalent bonding between the two Mg "ions" at the core of these enzymes is a novel concept that enables an improved vision of how these enzymes function at the molecular level. The concept is broader than magnesium-other biologically relevant metals (e.g., Mn and Zn) can also form similar stabilizing covalent Me-Me bonds in both organometallic and inorganic crystals.
C1 [Perera, Lalith; Beard, William A.; Pedersen, Lee G.; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Pedersen, Lee G.] Univ North Carolina Chapel Hill, Dept Chem, POB 3290, Chapel Hill, NC 27517 USA.
RP Pedersen, LG; Wilson, SH (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Pedersen, LG (reprint author), Univ North Carolina Chapel Hill, Dept Chem, POB 3290, Chapel Hill, NC 27517 USA.
EM pedersen@ad.unc.edu; wilson5@niehs.nih.gov
FU Research Projects in Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences [Z01-ES043010, Z01-ES050158, Z01-ES050159]; National Institutes
of Health [U19CA105010]
FX This research was supported by Research Projects Z01-ES043010 (to L.P.)
and Z01-ES050158 and Z01-ES050159 (to S.H.W.) in the Intramural Research
Program of the National Institutes of Health, National Institute of
Environmental Health Sciences and in association with National
Institutes of Health Grant U19CA105010.
NR 30
TC 0
Z9 0
U1 9
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0020-1669
EI 1520-510X
J9 INORG CHEM
JI Inorg. Chem.
PD JAN 2
PY 2017
VL 56
IS 1
BP 313
EP 320
DI 10.1021/acs.inorgchem.6b02189
PG 8
WC Chemistry, Inorganic & Nuclear
SC Chemistry
GA EG7SJ
UT WOS:000391248900036
PM 27976880
ER
PT J
AU Levin, MJ
Lindsey, JC
Kaplan, SS
Schimana, W
Lawrence, J
McNeal, MM
Bwakura-Dangarembizi, M
Ogwu, A
Mpabalwani, EM
Sato, P
Siberry, G
Nelson, M
Hille, D
Weinberg, GA
Weinberg, A
AF Levin, Myron J.
Lindsey, Jane C.
Kaplan, Susan S.
Schimana, Werner
Lawrence, Jody
McNeal, Monica M.
Bwakura-Dangarembizi, Mutsa
Ogwu, Anthony
Mpabalwani, Evans M.
Sato, Paul
Siberry, George
Nelson, Margaret
Hille, Darcy
Weinberg, Geoffrey A.
Weinberg, Adriana
TI Safety and immunogenicity of a live attenuated pentavalent rotavirus
vaccine in HIV-exposed infants with or without HIV infection in Africa
SO AIDS
LA English
DT Article
DE HIV exposed; HIV infection; immunogenicity; infants; rotavirus;
rotavirus vaccine; safety
ID ACTIVE-ANTIRETROVIRAL-THERAPY; TREATMENT STRATEGIES; ACQUIRED ROTAVIRUS;
ANTIBODY-RESPONSES; UNINFECTED INFANTS; DIARRHEAL DISEASE; CHILDREN;
IMMUNODEFICIENCY; MEASLES; PROTECTION
AB Objective:Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the WHO recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants.Design/methods:We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in four African countries. Ninety-three percent of HIV+ infants were receiving antiretroviral therapy prior to vaccination. Participants were followed for safety. Immune responses were measured 14 days after three doses of RV5, including serum antirotavirus neutralizing and IgA antibodies, IgA antibody in stool, and antirotavirus memory B and T-cell FluoroSpot. Shedding of RV5 in stool was monitored.Results:A total of 76 HIV+ and 126 HEU infants were enrolled from 2009 to 2013. No significant differences were found in adverse event rates, including grade 3 events, between RV5 and placebo recipients, for either HIV+ or HEU infants. The proportion of antirotavirus IgA responders (at least three-fold increase from baseline) after RV5 administration was 81% in both HIV+ and HEU infants, which was approximately 2.5-fold higher than in placebo recipients (P<0.001). Neutralizing antibody responses to three of five serotypes were significantly higher after RV5 regardless of HIV status, and those of HIV+ infants were equal or greater than responses of HEU infants to all five serotypes. Only one HIV+ RV5 recipient had RV5 isolated from stool.Conclusion:RV5 was immunogenic in both HIV+ and HEU infants and no safety signals were observed.
C1 [Levin, Myron J.; Weinberg, Adriana] Univ Colorado Anschutz Med Campus, Dept Pediat, Sect Pediat Infect Dis, Aurora, CO USA.
[Levin, Myron J.] Univ Colorado Anschutz Med Campus, Dept Med, Sect Pediat Infect Dis, Aurora, CO USA.
[Lindsey, Jane C.] Harvard Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA.
[Kaplan, Susan S.; Nelson, Margaret; Hille, Darcy] Merck & Co Inc, Kenilworth, NJ USA.
[Schimana, Werner] Municipal Munich, Dept Hlth & Environm, Sect Hlth Promot, Munich, Germany.
[Lawrence, Jody] Pfizer Inc, Collegeville, PA USA.
[McNeal, Monica M.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Infect Dis, Cincinnati, OH 45229 USA.
[Bwakura-Dangarembizi, Mutsa] Univ Zimbabwe, Coll Hlth Sci, Dept Paediat & Child Hlth, Harare, Zimbabwe.
[Ogwu, Anthony] Harvard AIDS Inst, Gaborone, Botswana.
[Ogwu, Anthony] Trinity Med Ctr, Port Adelaide, SA, Australia.
[Mpabalwani, Evans M.] Univ Teaching Hosp, Dept Pediat & Child Hlth, Lusaka, Zambia.
[Sato, Paul] NIAID, Maternal Adolescent & Pediat Res Branch, NIH, Rockville, MD USA.
[Sato, Paul] NIH, Off AIDS Res, Bethesda, MD USA.
[Siberry, George] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA.
[Weinberg, Geoffrey A.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Weinberg, Adriana] Univ Colorado Anschutz Med Campus, Dept Med, Sect Pediat Infect Dis, Aurora, CO USA.
[Weinberg, Adriana] Univ Colorado Anschutz Med Campus, Dept Pathol, Sect Pediat Infect Dis, Aurora, CO USA.
RP Levin, MJ (reprint author), Univ Colorado Anschutz Med Campus, 401 Mail Stop C227,1784 Racine St, Aurora, CO 80045 USA.
EM myron.levin@ucdenver.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) of the
National Institutes of Health (NIH) [UM1AI068632, UM1AI068616,
UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD); National Institute of Mental Health
(NIMH); Merck Co., Inc.; Merck & Co., Inc., Kenilworth, NJ, USA
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) of the National Institutes of
Health (NIH) under Award Numbers UM1AI068632 (IMPAACTLOC), UM1AI068616
(IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with cofunding from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and the National Institute of Mental Health (NIMH).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH.; Merck & Co., Inc.
provided financial support. In addition, Barbara Heckman BS (Frontier
Science and Technology Research Foundation, Inc., 4033 Maple RD.,
Amherst, NY 14226, USA) helped with study conduct and manuscript
preparation, Michelle Brown (Merck & Co., Inc.) contributed to the
protocol development, and Jon Stek (Merck & Co., Inc.) for assistance in
preparing the manuscript.; Funding for this research was provided by
Merck & Co., Inc., Kenilworth, NJ, USA (sponsor) in conjunction with the
International Maternal, Pediatric, and Adolescent AIDS Clinical Trials
Network (IMPAACT) of the National Institute of Allergy and Infectious
Diseases, NIH; National Institute of Mental Health, NIH; and the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH.
NR 51
TC 0
Z9 0
U1 5
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 2
PY 2017
VL 31
IS 1
BP 49
EP 59
DI 10.1097/QAD.0000000000001258
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA EF3QY
UT WOS:000390240700006
PM 27662551
ER
PT J
AU Wilson, ML
Fleming, KA
AF Wilson, Michael L.
Fleming, Kenneth A.
TI Improving Global Access to Diagnostic Testing More Steps Forward
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Editorial Material
C1 [Wilson, Michael L.] Denver Hlth, Dept Pathol & Lab Serv, Denver, CO 80204 USA.
[Wilson, Michael L.] Univ Colorado, Sch Med, Dept Pathol, Aurora, CO 80045 USA.
[Fleming, Kenneth A.] NCI, Ctr Global Hlth, Washington, DC USA.
[Fleming, Kenneth A.] Univ Oxford, Green Templeton Coll, Oxford, England.
RP Wilson, ML (reprint author), Denver Hlth, Dept Pathol & Lab Serv, Denver, CO 80204 USA.; Wilson, ML (reprint author), Univ Colorado, Sch Med, Dept Pathol, Aurora, CO 80045 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JAN
PY 2017
VL 147
IS 1
BP 6
EP 7
DI 10.1093/AJCP/AQW219
PG 2
WC Pathology
SC Pathology
GA EP0QI
UT WOS:000397091400001
PM 28171911
ER
PT J
AU Fleming, KA
Naidoo, M
Wilson, M
Flanigan, J
Horton, S
Kuti, M
Looi, LM
Price, C
Ru, K
Ghafur, A
Wang, JX
Lago, N
AF Fleming, Kenneth A.
Naidoo, Mahendra
Wilson, Michael
Flanigan, John
Horton, Susan
Kuti, Modupe
Looi, Lai Meng
Price, Chris
Ru, Kun
Ghafur, Abdul
Wang, Jianxiang
Lago, Nestor
TI An Essential Pathology Package for Low- and Middle-Income Countries
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Review
DE Low-income countries; Middle-income countries; Africa; Asia; Essential
pathology services; Hospital laboratory services
ID SUB-SAHARAN AFRICA; LABORATORY ACCREDITATION; HEALTH; MEDICINE; QUALITY;
COST
AB Objectives: We review the current status of pathology services in low-and middle-income countries and propose an "essential pathology package" along with estimated costs. The purpose is to provide guidance to policy makers as countries move toward universal health care systems.
Methods: Five key themes were reviewed using existing literature (role of leadership; education, training, and continuing professional development; technology; accreditation, management, and quality standards; and reimbursement systems). A tiered system is described, building on existing proposals. The economic analysis draws on the very limited published studies, combined with expert opinion.
Results: Countries have underinvested in pathology services, with detrimental effects on health care. The equipment needs for a tier 1 laboratory in a primary health facility are modest ($ 2-$ 5,000), compared with $ 150,000 to $ 200,000 in a district hospital, and higher in a referral hospital (depending on tests undertaken). Access to a national (or regional) specialized laboratory undertaking disease surveillance and registry is important. Recurrent costs of appropriate laboratories in district and referral hospitals are around 6% of the hospital budget in midsized hospitals and likely decline in the largest hospitals. Primary health facilities rely largely on single-use tests.
Conclusions: Pathology is an essential component of good universal health care.
C1 [Fleming, Kenneth A.; Naidoo, Mahendra; Flanigan, John] NCI, Ctr Global Hlth, Washington, DC USA.
[Fleming, Kenneth A.] Green Templeton Coll, 43 Woodstock Rd, Oxford OX2 6HG, England.
[Price, Chris] Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England.
[Wilson, Michael] Univ Colorado, Sch Med, Dept Pathol, Denver, CO 80262 USA.
[Wilson, Michael] Denver Hlth, Dept Pathol & Lab Serv, Denver, CO USA.
[Horton, Susan] Univ Waterloo, Global Hlth Econ, Waterloo, ON, Canada.
[Kuti, Modupe] Univ Ibadan, Coll Med, Dept Chem Pathol, Ibadan, Nigeria.
[Kuti, Modupe] Univ Coll Hosp, Ibadan, Nigeria.
[Looi, Lai Meng] Univ Malaya, Dept Pathol, Fac Med, Kuala Lumpur, Malaysia.
[Ru, Kun] Chinese Acad Med Sci, Dept Pathol & Lab Med, Beijing, Peoples R China.
[Wang, Jianxiang] Chinese Acad Med Sci, Inst Hematol, Beijing, Peoples R China.
[Ghafur, Abdul] Apollo Hosp, Chennai, Tamil Nadu, India.
[Lago, Nestor] Univ Buenos Aires, Dept Pathol, Buenos Aires, DF, Argentina.
RP Fleming, KA (reprint author), Green Templeton Coll, 43 Woodstock Rd, Oxford OX2 6HG, England.
EM kenneth.fleming@medsci.ox.ac.uk
NR 55
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JAN
PY 2017
VL 147
IS 1
BP 15
EP 32
DI 10.1093/AJCP/AQW143
PG 18
WC Pathology
SC Pathology
GA EP0QI
UT WOS:000397091400003
PM 28158414
ER
PT J
AU Datta, M
Via, L
Chen, W
Baish, J
Xu, L
Barry, C
Jain, R
AF Datta, Meenal
Via, Laura
Chen, Wei
Baish, James
Xu, Lei
Barry, Clfton
Jain, Rakesh
TI Mathematical Model of Oxygen Transport in Tuberculosis Granulomas
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Engineering and Physical Sciences in Oncology
CY JUN 25-28, 2016
CL Boston, MA
SP Amer Assoc Canc Res
C1 [Datta, Meenal; Chen, Wei; Xu, Lei; Jain, Rakesh] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Via, Laura; Barry, Clfton] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Baish, James] Bucknell Univ, Lewisburg, PA 17837 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 JAN
PY 2017
VL 77
SU 2
MA B59
DI 10.1158/1538-7445.EPSO16-B59
PG 2
WC Oncology
SC Oncology
GA EQ1WJ
UT WOS:000397860000093
ER
PT J
AU Lee, JA
Ayat, N
Tandle, A
Lu, ZR
Camphausen, K
AF Lee, Jennifer A.
Ayat, Nadia
Tandle, Anita
Lu, Zheng-Rong
Camphausen, Kevin
TI Silencing of DNA repair proteins with ECO/siRNA nanoparticles for the
enhancement of radiation response in glioblastoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Engineering and Physical Sciences in Oncology
CY JUN 25-28, 2016
CL Boston, MA
SP Amer Assoc Canc Res
C1 [Lee, Jennifer A.; Tandle, Anita; Camphausen, Kevin] NCI, Bethesda, MD USA.
[Ayat, Nadia; Lu, Zheng-Rong] Case Western Reserve Univ, Cleveland, OH 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 JAN
PY 2017
VL 77
SU 2
MA B42
DI 10.1158/1538-7445.EPSO16-B42
PG 2
WC Oncology
SC Oncology
GA EQ1WJ
UT WOS:000397860000082
ER
PT J
AU Zeldow, B
Kim, S
McSherry, G
Cotton, MF
Jean-Philippe, P
Violari, A
Bobat, R
Nachman, S
Mofenson, LM
Madhi, SA
Mitchell, C
AF Zeldow, B.
Kim, S.
McSherry, G.
Cotton, M. F.
Jean-Philippe, P.
Violari, A.
Bobat, R.
Nachman, S.
Mofenson, L. M.
Madhi, S. A.
Mitchell, C.
TI Use of antiretrovirals in HIV-infected children in a tuberculosis
prevention trial: IMPAACT P1041
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE TB; perinatal HIV infection; antiretroviral therapy; mortality
ID MARGINAL STRUCTURAL MODELS; SOUTH-AFRICAN CHILDREN; CHILDHOOD
TUBERCULOSIS; ISONIAZID PROPHYLAXIS; THERAPY; INFANTS; BURDEN; IMPACT;
HAART; EPIDEMIOLOGY
AB SETTING: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1041, a tuberculosis (TB) prevention trial conducted among children enrolled from 2004 to 2008 during South Africa's roll-out of combination antiretroviral therapy (ART).
OBJECTIVE: To estimate TB incidence and mortality and the effect of ART.
DESIGN: Children were pre-screened to exclude TB disease and exposure, actively screened 3-monthly for TB exposure and symptoms, and provided post-exposure isoniazid prophylaxis therapy (IPT). TB diagnoses were definite, probable, or possible, and mortality all cause. Testing was at the 5% significance level.
RESULTS: In 539 children (aged 3-4 months) followed up for a median of 74 weeks (interquartile range [IQR] 48-116), incidence/100 person-years (py) was 10.67 (95%CI 8.47-13.26) for any TB and 2.89 (95%CI 1.85-4.31) for definite/probable TB. Any TB incidence was respectively 9.39, 13.59, and 9.83/100 py before, <180 days after, and >= 180 days after ART initiation. Adjusted analysis showed a non-significant increase in any TB (HR 1.32, 95%CI 0.71-2.52, P = 0.38) and a significant reduction in mortality (HR 0.39, 95%CI 0.17-0.82, P = 0.017) following ART initiation.
CONCLUSIONS: ART reduced mortality but not TB incidence in human immunodeficiency virus (HIV) infected children in IMPAACT P1041, possibly attributable to active screening for TB exposure and symptoms with post-exposure IPT. Research into this as a strategy for TB prevention in high HIV-TB burden settings may be warranted.
C1 [Zeldow, B.; Kim, S.] Harvard Sch Publ Hlth, Ctr Biostat AIDS Res, 655 Huntington Ave, Boston, MA 02115 USA.
[Kim, S.] Rutgers Sch Publ Hlth, Dept Biostat, Newark, NJ USA.
[McSherry, G.] Penn State Univ, Coll Med, Hershey, PA USA.
[Cotton, M. F.] Univ Stellenbosch, Dept Paediat & Child Hlth, Tygerberg, South Africa.
[Jean-Philippe, P.] Henry Jackson Fdn, Nat Inst Allergy & Infect Dis, Bethesda, MD USA.
[Violari, A.] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Bobat, R.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Paediat & Child Hlth, Durban, South Africa.
[Nachman, S.] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Mofenson, L. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
[Mofenson, L. M.] Elizabeth Glaser Pediat AIDS Fdn, Washington, DC USA.
[Madhi, S. A.] Univ Witwatersrand, MRC, Resp & Meningeal Pathogens Res Unit, Johannesburg, South Africa.
[Mitchell, C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Kim, S (reprint author), Harvard Sch Publ Hlth, Ctr Biostat AIDS Res, 655 Huntington Ave, Boston, MA 02115 USA.
EM skim@sdac.harvard.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health,
Bethesda, MD, USA [AI068632]; Statistical and Data Analysis Center at
the Harvard School of Public Health, Boston, MA, USA under NIAID
cooperative agreements; IMPAACT Group [1 U01 AI068616]; NIAID; NICHD
International and Domestic Pediatric and Maternal HIV Clinical Trials
Network (NICHD) [N01-DK-9-001/HHSN267200800001C]; NIAID
[HHSN272200800014C]; Secure the Future Fund, a philanthropy program -
Bristol-Myers Squibb, New York, NY, USA; Pediatric AIDS Clinical Trials
Group [5 U01 AI41110]
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials (IMPAACT) Group was provided by grants from the National
Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and the National Institute of Mental Health,
Bethesda, MD, USA (AI068632). This work was supported by the Statistical
and Data Analysis Center at the Harvard School of Public Health, Boston,
MA, USA, under NIAID cooperative agreements with the Pediatric AIDS
Clinical Trials Group (5 U01 AI41110) and the IMPAACT Group (1 U01
AI068616). Support for the sites was provided by NIAID and the NICHD
International and Domestic Pediatric and Maternal HIV Clinical Trials
Network (NICHD contract number N01-DK-9-001/HHSN267200800001C). Support
for PJP comes from NIAID Contract No. HHSN272200800014C. The study was
also funded by a grant from the Secure the Future Fund, a philanthropy
program sponsored by Bristol-Myers Squibb, New York, NY, USA.
NR 26
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U2 0
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD JAN
PY 2017
VL 21
IS 1
BP 38
EP 45
DI 10.5588/ijtld.16.0149
PG 8
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA EP7JH
UT WOS:000397553600009
PM 28157463
ER
PT J
AU Kumar, NP
Velayutham, B
Nair, D
Babu, S
AF Kumar, N. P.
Velayutham, B.
Nair, D.
Babu, S.
TI Angiopoietins as biomarkers of disease severity and bacterial burden in
pulmonary tuberculosis
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE tuberculosis; angiopoietins angiogenesis; lymphangiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS; GRANULOMA; SERUM; PERMEABILITY;
INFLAMMATION; ACTIVATION
AB BACKGROUND: Circulating angiogenic factors of the vascular endothelial growth factor family are important biomarkers of disease severity in pulmonary tuberculosis (PTB). However, the role of angiopoietins, which are also involved in angiogenesis, in PTB is not known.
OBJECTIVE AND DESIGN: To examine the association of circulating angiopoietins with TB disease or latent tuberculous infection (LTBI), we examined the systemic levels of angiopoietin (Ang) 1, Ang 2 and Tie-2 receptor in individuals with PTB (n = 44), LTBI (n = 44) or no tuberculous infection (NTBI) (n = 44).
RESULTS: Circulating levels of Ang-1, Ang-2 and Tie-2 were significantly higher in PTB than in individuals with LTBI or NTBI. Moreover, Ang-1, Ang-2 and Tie-2 levels were significantly higher in PTB with bilateral disease. The levels of these factors also exhibited a significant positive relationship with bacterial burdens in P 1B. Receiver operating characteristics curve analysis revealed Ang-2 as a marker distinguishing PTB from L1BI or NTBI. Finally, the circulating levels of Ang-1, Ang-2 and Tie-2 were significantly reduced following antituberculosis chemotherapy.
CONCLUSIONS: Our data demonstrate that PTB is associated with elevated levels of circulating angiopoietins, possibly reflecting endothelial dysfunction. In addition, Ang-2 could prove useful as a biomarker to monitor disease severity, bacterial burden and therapeutic responses.
C1 [Kumar, N. P.; Babu, S.] Int Ctr Excellence Res, Natl Inst Res TB, 1 Sathiyamoorthy Rd Chetput, Chennai 600031, Tamil Nadu, India.
[Velayutham, B.; Nair, D.] Natl Inst Res TB, Chennai, Tamil Nadu, India.
[Babu, S.] NIH, Natl Inst Allergy & Infect Dis, Parasit Dis Lab, Bldg 10, Bethesda, MD 20892 USA.
RP Kumar, NP (reprint author), Int Ctr Excellence Res, Natl Inst Res TB, 1 Sathiyamoorthy Rd Chetput, Chennai 600031, Tamil Nadu, India.
EM pavankumarn@nirt.res.in
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD, USA
FX The Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD, USA, supported this work.
NR 26
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U2 0
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD JAN
PY 2017
VL 21
IS 1
BP 93
EP 99
DI 10.5588/ijfld.16.0565
PG 7
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA EP7JH
UT WOS:000397553600017
PM 28157471
ER
PT J
AU Koonin, EV
Zhang, F
AF Koonin, Eugene V.
Zhang, Feng
TI Coupling immunity and programmed cell suicide in prokaryotes:
Life-or-death choices
SO BIOESSAYS
LA English
DT Article
DE genotoxic stress sensing; immunity; programmed cell death; virus-host
coevolution
ID CRISPR-CAS SYSTEMS; RESTRICTION-MODIFICATION SYSTEMS; TOXIN-ANTITOXIN
SYSTEMS; SHORT PALINDROMIC REPEATS; PRRC-ANTICODON NUCLEASE;
TRANSFER-RNA REPAIR; ADAPTIVE IMMUNITY; DEFENSE SYSTEMS;
FUNCTIONAL-CHARACTERIZATION; MODIFICATION ENZYMES
AB Host-pathogen arms race is a universal, central aspect of the evolution of life. Most organisms evolved several distinct yet interacting strategies of anti-pathogen defense including resistance to parasite invasion, innate and adaptive immunity, and programmed cell death (PCD). The PCD is the means of last resort, a suicidal response to infection that is activated when resistance and immunity fail. An infected cell faces a decision between active defense and altruistic suicide or dormancy induction, depending on whether immunity is "deemed" capable of preventing parasite reproduction and consequent infection of other cells. In bacteria and archaea, immunity genes typically colocalize with PCD modules, such as toxins-antitoxins, suggestive of immunity-PCD coupling, likely mediated by shared proteins that sense damage and "predict" the outcome of infections. In type VI CRISPR-Cas systems, the same enzyme that inactivates the target RNA might execute cell suicide, in a case of ultimate integration of immunity and PCD.
C1 [Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Zhang, Feng] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Zhang, Feng] MIT, Dept Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Zhang, Feng] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Zhang, Feng] Dept Brain & Cognit Sci, Cambridge, MA USA.
[Zhang, Feng] Dept Biol Engn, Cambridge, MA USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
NR 95
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Z9 0
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD JAN
PY 2017
VL 39
IS 1
AR UNSP 1600186
DI 10.1002/bies.201600186
PG 9
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA EO7TB
UT WOS:000396891900013
ER
PT J
AU Fleming, KA
Naidoo, M
Wilson, M
Flanigan, J
Horton, S
Kuti, M
Looi, LM
Price, C
Ru, K
Ghafur, A
Wang, JX
Lago, N
AF Fleming, Kenneth A.
Naidoo, Mahendra
Wilson, Michael
Flanigan, John
Horton, Susan
Kuti, Modupe
Looi, Lai Meng
Price, Chris
Ru, Kun
Ghafur, Abdul
Wang, Jianxiang
Lago, Nestor
TI An Essential Pathology Package for Low- and Middle-Income Countries
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Review
DE Low-income countries; Middle-income countries; Africa; Asia; Essential
pathology services; Hospital laboratory services
ID SUB-SAHARAN AFRICA; LABORATORY ACCREDITATION; MEDICINE; QUALITY; COSTS
AB Objectives: We review the current status of pathology services in low- and middle-income countries and propose an "essential pathology package" along with estimated costs. The purpose is to provide guidance to policy makers as countries move toward universal health care systems.
Methods: Five key themes were reviewed using existing literature (role of leadership; education, training, and continuing professional development; technology; accreditation, management, and quality standards; and reimbursement systems). A tiered system is described, building on existing proposals. The economic analysis draws on the very limited published studies, combined with expert opinion.
Results: Countries have underinvested in pathology services, with detrimental effects on health care. The equipment needs for a tier 1 laboratory in a primary health facility are modest ($ 2-$ 5,000), compared with $ 150,000 to $ 200,000 in a district hospital, and higher in a referral hospital (depending on tests undertaken). Access to a national (or regional) specialized laboratory undertaking disease surveillance and registry is important. Recurrent costs of appropriate laboratories in district and referral hospitals are around 6% of the hospital budget in midsized hospitals and likely decline in the largest hospitals. Primary health facilities rely largely on single-use tests.
Conclusions: Pathology is an essential component of good universal health care.
C1 [Fleming, Kenneth A.; Naidoo, Mahendra; Flanigan, John] NCI, Ctr Global Hlth, Washington, DC USA.
[Fleming, Kenneth A.] Univ Oxford, Green Templeton Coll, Oxford, England.
[Price, Chris] Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England.
[Wilson, Michael] Univ Colorado, Sch Med, Dept Pathol, Denver, CO 80262 USA.
[Wilson, Michael] Denver Hlth, Dept Pathol & Lab Serv, Denver, CO USA.
[Horton, Susan] Univ Waterloo, Global Hlth Econ, Waterloo, ON, Canada.
[Kuti, Modupe] Univ Ibadan, Coll Med, Dept Chem Pathol, Ibadan, Nigeria.
[Kuti, Modupe] Univ Coll Hosp, Ibadan, Nigeria.
[Looi, Lai Meng] Univ Malaya, Dept Pathol, Fac Med, Kuala Lumpur, Malaysia.
[Ru, Kun] Chinese Acad Med Sci, Dept Pathol & Lab Med, Beijing, Peoples R China.
[Wang, Jianxiang] Chinese Acad Med Sci, Inst Hematol, Beijing, Peoples R China.
[Ghafur, Abdul] Apollo Hosp, Madras, Tamil Nadu, India.
[Lago, Nestor] Univ Buenos Aires, Dept Pathol, Buenos Aires, DF, Argentina.
RP Fleming, KA (reprint author), Green Templeton Coll, 43 Woodstock Rd, Oxford OX2 6HG, England.
EM kenneth.fleming@medsci.ox.ac.uk
NR 53
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U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JAN
PY 2017
VL 147
IS 1
BP 15
EP 32
DI 10.1093/AJCP/AQW143
PG 18
WC Pathology
SC Pathology
GA EP2PV
UT WOS:000397226500003
ER
PT J
AU Smith, E
Master, Z
AF Smith, Elise
Master, Zubin
TI Best Practice to Order Authors in Multi/Interdisciplinary Health
Sciences Research Publications
SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE
LA English
DT Article
DE Authorship; ethics and public policy; multidisciplinary research teams;
publication; publication ethics; research integrity; responsible conduct
of research
ID RESPONSIBLE CONDUCT; SCIENTIFIC MISCONDUCT; EQUAL CONTRIBUTIONS; MEDICAL
JOURNALS; CREDIT; CONTRIBUTORS; CRITERIA; ETHICS; BIOETHICS; ARTICLES
AB Misunderstanding and disputes about authorship are commonplace among members of multi/interdisciplinary health research teams. If left unmanaged and unresolved, these conflicts can undermine knowledge sharing and collaboration, obscure accountability for research, and contribute to the incorrect attribution of credit. To mitigate these issues, certain researchers suggest quantitative authorship distributions schemes (e.g., point systems), while others wish to replace or minimize the importance of authorship by using contributorshipa system based on authors' self-reporting contributions. While both methods have advantages, we argue that authorship and contributorship will most likely continue to coexist for multiple ethical and practical reasons. In this article, we develop a five-step best practice that incorporates the distribution of both contributorship and authorship for multi/interdisciplinary research. This procedure involves continuous dialogue and the use of a detailed contributorship taxonomy ending with a declaration explaining contributorship, which is used to justify authorship order. Institutions can introduce this approach in responsible conduct of research training as it promotes greater fairness, trust, and collegiality among team members and ultimately reduces confusion and facilitates resolution of time-consuming disagreements.
C1 [Smith, Elise; Master, Zubin] Univ Montreal, Dept Social & Prevent Med, Bioeth Programs, Montreal, PQ, Canada.
[Smith, Elise] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Master, Zubin] Albany Med Coll, Alden March Bioeth Inst, 47 New Scotland Ave,MC 153, Albany, NY 12208 USA.
RP Master, Z (reprint author), Albany Med Coll, Alden March Bioeth Inst, 47 New Scotland Ave,MC 153, Albany, NY 12208 USA.
EM zubin@zubsplace.com
FU Committee on Publication Ethics; Social Sciences and Humanities Research
Council; University of Montreal, Montreal, Canada
FX A research grant from the Committee on Publication Ethics (Master)
partly funded this project. In addition, Smith was supported by
scholarships from the Social Sciences and Humanities Research Council
(Joseph-Armand Bombardier Ph.D. Scholarship) and the University of
Montreal, Montreal, Canada.
NR 92
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U1 3
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0898-9621
EI 1545-5815
J9 ACCOUNT RES
JI Account. Res.
PY 2017
VL 24
IS 4
BP 243
EP 267
DI 10.1080/08989621.2017.1287567
PG 25
WC Medical Ethics
SC Medical Ethics
GA EN0MS
UT WOS:000395704700004
PM 28128975
ER
PT J
AU Spencer, RG
Cortese, BD
Lukas, VA
Pleshko, N
AF Spencer, Richard G.
Cortese, Benjamin D.
Lukas, Vanessa A.
Pleshko, Nancy
TI Point Estimates of Test Sensitivity and Specificity from Sample Means
and Variances
SO AMERICAN STATISTICIAN
LA English
DT Article
DE Diagnostic markers; Discriminant tests; Test characteristics
AB In a wide variety of biomedical and clinical research studies, sample statistics from diagnostic marker measurements are presented as a means of distinguishing between two populations, such as with and without disease. Intuitively, a larger difference between themean values of a marker for the two populations, and a smaller spread of values within each population, should lead to more reliable classification rules based on this marker. We formalize this intuitive notion by deriving practical, new, closed-form expressions for the sensitivity and specificity of three different discriminant tests defined in terms of the sample means and standard deviations of diagnosticmarkermeasurements. The three discriminant tests evaluated are based, respectively, on the Euclidean distance and theMahalanobis distance between means, and a likelihood ratio analysis. Expressions for the effects of measurement error are also presented. Our final expressions assume that the diagnostic markers follow independent normal distributions for the two populations, although it will be clear that other known distributions may be similarly analyzed. We then discuss applications drawn from the medical literature, although the formalism is clearly not restricted to that application.
C1 [Spencer, Richard G.; Lukas, Vanessa A.] NIH, Magnet Resonance Imaging & Spect Sect, Natl Inst Aging, Baltimore, MD USA.
[Cortese, Benjamin D.] Syracuse Univ, Dept Math, Syracuse, NY USA.
[Pleshko, Nancy] Temple Univ, Dept Bioengn, Tissue Imaging & Spect Lab, Philadelphia, PA USA.
RP Spencer, RG (reprint author), NIH, Magnet Resonance Imaging & Spect Sect, Natl Inst Aging, Intramural Res Program, BRC 04B-116, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM spencer@helix.nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging
FX This work was supported by the Intramural Research Program of the NIH,
National Institute on Aging.
NR 15
TC 0
Z9 0
U1 0
U2 0
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.
PY 2017
VL 71
IS 1
BP 81
EP 87
DI 10.1080/00031305.2016.1239589
PG 7
WC Statistics & Probability
SC Mathematics
GA EP2PR
UT WOS:000397226100015
ER
PT J
AU Ossandon, M
Balsam, J
Bruck, HA
Kalpakis, K
Rasooly, A
AF Ossandon, Miguel
Balsam, Joshua
Bruck, Hugh Alan
Kalpakis, Konstantinos
Rasooly, Avraham
TI A computational streak mode cytometry biosensor for rare cell analysis
SO ANALYST
LA English
DT Article
ID SMART-PHONE; TRACKING; MICROSCOPY; CANCER; ARRAY; FLOW; AIR
AB Streak mode imaging flow cytometry for rare cell detection involves imaging moving fluorescently labeled cells in the video mode with a CCD camera. The path of the moving cells results in a "streak", whose length is proportional to the exposure time. The dynamic imaging conditions introduce detection challenges (e.g., images with high signal-to-noise ratio (SNR) backgrounds), especially for enumerating cells using low resolution webcams or smartphone cameras suitable for point of care testing (POCT). To overcome the imaging challenges, a new approach called a "computational biosensor" was developed. It involves combining biosensing hardware with computational algorithms to "computationally transduce" measureable signals from events captured by the hardware. The computational biosensor quantifies potential cells based on the streak intensity, length and relative location of the streaks in consecutive frames. Cell identification consists of three parts: (1) finding streaks, (2) identifying candidate cells, and (3) filtering out spurious cells to identify true cells. Samples of 1 cell per mL were analyzed in batch sizes of 30 mL at flow rates of 10 mL min(1) and imaged at 4 frames per second (fps). The detected cells were annotated, and the SNR was calculated. For images with SNR greater than 4.4 dB, the total detected cells (TD) compared with ground truth (GT) are 98%, while 66% were detected for low SNR. For true positive cells detected compared with ground truth (TP/GT), 91% were detected for high SNR. This demonstrated the new analytical capabilities of the computational biosensor to enumerate rare cells in large volumes not possible with current technologies.
C1 [Ossandon, Miguel; Rasooly, Avraham] NCI, Rockville, MD 20850 USA.
[Ossandon, Miguel; Kalpakis, Konstantinos] Univers Maryland Baltimore Cty, Baltimore, MD USA.
[Balsam, Joshua; Bruck, Hugh Alan] Univ Maryland, College Pk, MD 20742 USA.
RP Rasooly, A (reprint author), NCI, Rockville, MD 20850 USA.
EM ossandom@mail.nih.gov
FU National Cancer Institute (NCI)
FX This work was supported by the National Cancer Institute (NCI).
NR 24
TC 0
Z9 0
U1 0
U2 0
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 0003-2654
EI 1364-5528
J9 ANALYST
JI Analyst
PY 2017
VL 142
IS 4
BP 641
EP 648
DI 10.1039/c6an02517j
PG 8
WC Chemistry, Analytical
SC Chemistry
GA EM9RP
UT WOS:000395649100012
ER
PT S
AU Jaffe, ES
AF Jaffe, Elaine S.
BE Abbas, AK
Aster, JC
Feany, MB
TI The Microscope as a Tool for Disease Discovery-A Personal Voyage
SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12
SE Annual Review of Pathology-Mechanisms of Disease
LA English
DT Review; Book Chapter
DE malignant lymphoma; B cells; T cells; molecular diagnosis; molecular
oncology; cell of origin
ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; GRAY-ZONE LYMPHOMA;
HEALTH-ORGANIZATION CLASSIFICATION; IMMUNOGLOBULIN-GENE REARRANGEMENTS;
REED-STERNBERG CELLS; RED-BLOOD-CELLS; C-MYC GENE; FOLLICULAR LYMPHOMA;
LYMPHOCYTIC LYMPHOMA
AB This review reflects the trajectory of my career in hematopathology, and my personal reflections on scientific advances in the field. During the course of more than 40 years, the approach to classification of hematological malignancies has evolved from descriptive approaches, based on either cytological or clinical features, to a modern approach, which incorporates cutting-edge technologies. My philosophy has focused on defining individual diseases, an approach that can best lead to an understanding of molecular pathogenesis. To quote Carolus Linnaeus (1, p. 19), the father of taxonomy, "The first step in wisdom is to know the things themselves; this notion consists in having a true idea of the objects; objects are distinguished and known by classifying them methodically and giving them appropriate names. Therefore, classification and name-giving will be the foundation of our science."
C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
NR 131
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Z9 0
U1 0
U2 0
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 1553-4006
J9 ANNU REV PATHOL-MECH
JI Annu. Rev. Pathol.-Mech Dis.
PY 2017
VL 12
BP 1
EP 24
DI 10.1146/annurev-pathol-052016-100351
PG 24
WC Pathology
SC Pathology
GA BG9PJ
UT WOS:000393554200001
PM 27959631
ER
PT S
AU Baseler, L
Chertow, DS
Johnson, KM
Feldmann, H
Morens, DM
AF Baseler, Laura
Chertow, Daniel S.
Johnson, Karl M.
Feldmann, Heinz
Morens, David M.
BE Abbas, AK
Aster, JC
Feany, MB
TI The Pathogenesis of Ebola Virus Disease
SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12
SE Annual Review of Pathology-Mechanisms of Disease
LA English
DT Review; Book Chapter
DE Ebola; ebolavirus; epidemic; filovirus; viral disease pathogenesis;
viral hemorrhagic fever
ID DENDRITIC CELL MATURATION; AFRICAN-GREEN MONKEYS; HEMORRHAGIC-FEVER;
SIERRA-LEONE; ZAIRE-EBOLAVIRUS; GUINEA-PIGS; NONHUMAN-PRIMATES;
RHESUS-MONKEYS; MARBURG-VIRUS; VP35 PROTEIN
AB For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.
C1 [Baseler, Laura] Univ Texas MD Anderson Canc Ctr, Dept Vet Med & Surg, Houston, TX 77030 USA.
[Chertow, Daniel S.] NIAID, Dept Crit Care Med, Ctr Clin, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Johnson, Karl M.] Ctr Dis Control & Prevent, Special Pathogens Branch, Placitas, NM 87043 USA.
[Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[Morens, David M.] NIAID, Off Director, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, Off Director, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
NR 176
TC 0
Z9 0
U1 7
U2 7
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 1553-4006
J9 ANNU REV PATHOL-MECH
JI Annu. Rev. Pathol.-Mech Dis.
PY 2017
VL 12
BP 387
EP 418
DI 10.1146/annurev-pathol-052016-100506
PG 32
WC Pathology
SC Pathology
GA BG9PJ
UT WOS:000393554200015
PM 27959626
ER
PT S
AU Metcalfe, DD
Mekori, YA
AF Metcalfe, Dean D.
Mekori, Yoseph A.
BE Abbas, AK
Aster, JC
Feany, MB
TI Pathogenesis and Pathology of Mastocytosis
SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12
SE Annual Review of Pathology-Mechanisms of Disease
LA English
DT Review; Book Chapter
DE KIT; mast cells; mast cell mediators; mastocytosis
ID MAST-CELL DISEASE; ADVANCED SYSTEMIC MASTOCYTOSIS; BONE-MARROW
HISTOPATHOLOGY; TYROSINE KINASE INHIBITORS; CATALYTIC DOMAIN MUTATIONS;
KIT-ACTIVATING MUTATION; SERUM TRYPTASE LEVELS; RECEPTOR-ALPHA CHAIN;
PROTOONCOGENE C-KIT; URTICARIA PIGMENTOSA
AB Systemic mastocytosis is a clonal disorder of mast cells that may variably present with characteristic skin lesions, episodes of mast cell mediator release, and disturbances of hematopoiesis. No curative therapy presently exists. Conventional management has relied on agents that antagonize mediators released by mast cells, inhibit mediator secretion, or modulate mast cell proliferation. Recent advances in the molecular understanding of the pathophysiology of systemic mastocytosis have provided new therapeutic considerations, including new and novel tyrosine kinase inhibitors.
C1 [Metcalfe, Dean D.] NIAID, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Mekori, Yoseph A.] Tel Hai Coll, IL-1220800 Upper Galilee, Israel.
[Mekori, Yoseph A.] Meir Med Ctr, IL-44281 Kefar Sava, Israel.
[Mekori, Yoseph A.] Tel Aviv Univ, Sackler Sch Med, IL-6997801 Tel Aviv, Israel.
RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dmetcalfe@niaid.nih.gov; ymekori@telhai.ac.il
NR 129
TC 0
Z9 0
U1 1
U2 1
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 1553-4006
J9 ANNU REV PATHOL-MECH
JI Annu. Rev. Pathol.-Mech Dis.
PY 2017
VL 12
BP 487
EP 514
DI 10.1146/annurev-pathol-052016-100312
PG 28
WC Pathology
SC Pathology
GA BG9PJ
UT WOS:000393554200018
PM 28135563
ER
PT S
AU Insel, PA
Amara, SG
Blaschke, TF
Meyer, UA
AF Insel, Paul A.
Amara, Susan G.
Blaschke, Terrence F.
Meyer, Urs A.
BE Insel, PA
TI Introduction to the Theme "New Methods and Novel Therapeutic Approaches
in Pharmacology and Toxicology"
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 57
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
ID NEURODEGENERATIVE DISEASES
AB Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e. g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e. g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.
C1 [Insel, Paul A.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Insel, Paul A.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Amara, Susan G.] NIMH, Bethesda, MD 20892 USA.
[Blaschke, Terrence F.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Meyer, Urs A.] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
RP Insel, PA (reprint author), Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.; Insel, PA (reprint author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
NR 15
TC 0
Z9 0
U1 1
U2 1
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0457-7
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2017
VL 57
BP 13
EP 17
DI 10.1146/annurev-pharmtox-091616-023708
PG 5
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BH0QN
UT WOS:000396044800002
PM 27732830
ER
PT S
AU Hutson, PH
Clark, JA
Cross, AJ
AF Hutson, P. H.
Clark, J. A.
Cross, A. J.
BE Insel, PA
TI CNS Target Identification and Validation: Avoiding the Valley of Death
or Naive Optimism?
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 57
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
DE drug discovery; drug development; neurology; psychiatry; translational
research
ID MAJOR DEPRESSIVE DISORDER; P NK1 RECEPTOR; PDE9 INHIBITOR PF-04447943;
PLURIPOTENT STEM-CELLS; PARKINSONS-DISEASE; DRUG DISCOVERY;
ALZHEIMERS-DISEASE; ANIMAL-MODELS; HUNTINGTONS-DISEASE; COGNITIVE
FUNCTION
AB There are many challenges along the path to the approval of new drugs to treat CNS disorders, one of the greatest areas of unmet medical need with a large societal burden and health-care impact. Unfortunately, over the past two decades, few CNS drug approvals have succeeded, leading many pharmaceutical companies to deprioritize this therapeutic area. The reasons for the failures in CNS drug discovery are likely to be multifactorial. However, selecting the most biologically plausible molecular targets that are relevant to the disorder is a critical first step to improve the probability of success. In this review, we outline previous methods for identifying and validating novel targets for CNS drug discovery, and, cognizant of previous failures, we discuss potential new strategies that may improve the probability of success of developing novel treatments for CNS disorders.
C1 [Hutson, P. H.] Teva Pharmaceut, CNS Discovery, Neurobiol, W Chester, PA 19380 USA.
[Clark, J. A.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Cross, A. J.] AstraZeneca, Neurosci Innovat Med, Cambridge, MA 01239 USA.
RP Hutson, PH (reprint author), Teva Pharmaceut, CNS Discovery, Neurobiol, W Chester, PA 19380 USA.
EM peter.hutson@tevapharm.com; Janet.Clark@nih.gov; alan.cross@azneuro.com
NR 115
TC 1
Z9 1
U1 0
U2 0
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0457-7
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2017
VL 57
BP 171
EP 187
DI 10.1146/annurev-pharmtox-010716-104624
PG 17
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BH0QN
UT WOS:000396044800010
PM 27575715
ER
PT S
AU Xie, L
Draizen, EJ
Bourne, PE
AF Xie, Lei
Draizen, Eli J.
Bourne, Philip E.
BE Insel, PA
TI Harnessing Big Data for Systems Pharmacology
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 57
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
DE cloud computing; data science; machine learning; semantic web;
computational modeling; systems biology; systems pharmacology modeling;
NIH Commons
ID GENOME-SCALE MODELS; SEMANTIC WEB TECHNOLOGIES; NEED EXACT SOLVERS;
COMPRESSIVE GENOMICS; CLEARER STANDARDS; LIFE SCIENCES; DRUG TARGETS;
NETWORK; BIOLOGY; DISEASE
AB Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets. More work is needed to interpret and predict a drug response phenotype, which is dependent on many known and unknown factors. To gain a comprehensive understanding of drug actions, SPM requires close collaborations between domain experts from diverse fields and integration of heterogeneous models from biophysics, mathematics, statistics, machine learning, and semantic webs. This creates challenges in model management, model integration, model translation, and knowledge integration. In this review, we discuss several emergent issues in SPM and potential solutions using big data technology and analytics. The concurrent development of high-throughput techniques, cloud computing, data science, and the semantic web will likely allow SPM to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable.
C1 [Xie, Lei] CUNY, Hunter Coll, Dept Comp Sci, New York, NY 10065 USA.
[Xie, Lei] CUNY, Grad Ctr, New York, NY 10016 USA.
[Draizen, Eli J.; Bourne, Philip E.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Draizen, Eli J.] Boston Univ, Program Bioinformat, Boston, MA 02215 USA.
[Bourne, Philip E.] NIH, Off Director, Bethesda, MD 20894 USA.
RP Xie, L (reprint author), CUNY, Hunter Coll, Dept Comp Sci, New York, NY 10065 USA.; Xie, L (reprint author), CUNY, Grad Ctr, New York, NY 10016 USA.
EM lei.xie@hunter.cuny.edu; philip.bourne@nih.gov
NR 89
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U1 1
U2 1
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0457-7
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2017
VL 57
BP 245
EP 262
DI 10.1146/annurev-pharmtox-010716-104659
PG 18
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BH0QN
UT WOS:000396044800013
PM 27814027
ER
PT S
AU Volkow, ND
Hampson, AJ
Baler, RD
AF Volkow, Nora D.
Hampson, Aidan J.
Baler, Ruben D.
BE Insel, PA
TI Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection
of Stress and Reward
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 57
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
DE cannabis; marijuana; endocannabinoids; THC; stress; reward
ID POSITRON-EMISSION-TOMOGRAPHY; VENTRAL TEGMENTAL AREA; ACID AMIDE
HYDROLASE; METABOTROPIC GLUTAMATE RECEPTORS; CB1 RECEPTOR; TYPE-1
RECEPTOR; MOUSE-BRAIN; INDUCED ANALGESIA; DOPAMINE FUNCTION; ENDOGENOUS
CANNABINOIDS
AB Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-a-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i. e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions.
C1 [Volkow, Nora D.; Hampson, Aidan J.; Baler, Ruben D.] NIDA, NIH, Bethesda, MD 20892 USA.
RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
NR 171
TC 0
Z9 0
U1 8
U2 8
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0457-7
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2017
VL 57
BP 285
EP 308
DI 10.1146/annurev-pharmtox-010716-104615
PG 24
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BH0QN
UT WOS:000396044800015
PM 27618739
ER
PT S
AU Vannella, KM
Wynn, TA
AF Vannella, Kevin M.
Wynn, Thomas A.
BE Julius, D
TI Mechanisms of Organ Injury and Repair by Macrophages
SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 79
SE Annual Review of Physiology
LA English
DT Review; Book Chapter
DE fibrosis; pulmonary; hepatic; cardiovascular; gut; brain
ID TISSUE-RESIDENT MACROPHAGES; ALTERNATIVELY ACTIVATED MACROPHAGES;
SKELETAL-MUSCLE REGENERATION; ERYTHRO-MYELOID PROGENITOR;
CENTRAL-NERVOUS-SYSTEM; MURINE LIVER FIBROSIS; SPINAL-CORD-INJURY;
GROWTH-FACTOR; ALVEOLAR MACROPHAGES; ALZHEIMERS-DISEASE
AB Macrophages regulate tissue regeneration following injury. They can worsen tissue injury by producing reactive oxygen species and other toxic mediators that disrupt cell metabolism, induce apoptosis, and exacerbate ischemic injury. However, they also produce a variety of growth factors, such as IGF-1, VEGF-alpha, TGF-beta, and Wnt proteins that regulate epithelial and endothelial cell proliferation, myofibroblast activation, stem and tissue progenitor cell differentiation, and angiogenesis. Proresolving macrophages in turn restore tissue homeostasis by functioning as anti-inflammatory cells, and macrophage-derived matrix metalloproteinases regulate fibrin and collagen turnover. However, dysregulated macrophage function impairs wound healing and contributes to the development of fibrosis. Consequently, the mechanisms that regulate these different macrophage activation states have become active areas of research. In this review, we discuss the common and unique mechanisms by which macrophages instruct tissue repair in the liver, nervous system, heart, lung, skeletal muscle, and intestine and illustrate how macrophages might be exploited therapeutically.
C1 [Vannella, Kevin M.; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Vannella, KM (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kevin.vannella@nih.gov; twynn@niaid.nih.gov
NR 125
TC 0
Z9 0
U1 3
U2 3
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0066-4278
BN 978-0-8243-0379-2
J9 ANNU REV PHYSIOL
JI Annu. Rev. Physiol.
PY 2017
VL 79
BP 593
EP 617
DI 10.1146/annurev-physiol-022516-034356
PG 25
WC Physiology
SC Physiology
GA BH0QP
UT WOS:000396049000026
PM 27959618
ER
PT S
AU Sheeran, P
Klein, WMP
Rothman, AJ
AF Sheeran, Paschal
Klein, William M. P.
Rothman, Alexander J.
BE Fiske, ST
TI Health Behavior Change: Moving from Observation to Intervention
SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 68
SE Annual Review of Psychology
LA English
DT Review; Book Chapter
DE experimental medicine; interventions; trials; theory; construct;
correlational data
ID RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY INTERVENTIONS;
IMPLEMENTATION INTENTIONS; SELF-AFFIRMATION; SMOKING-CESSATION;
PUBLIC-HEALTH; DRINKING BEHAVIOR; CONSORT STATEMENT; REGULATORY FOCUS;
DECISION-MAKING
AB How can progress in research on health behavior change be accelerated? Experimental medicine (EM) offers an approach that can help investigators specify the research questions that need to be addressed and the evidence needed to test those questions. Whereas current research draws predominantly on multiple overlapping theories resting largely on correlational evidence, the EM approach emphasizes experimental tests of targets or mechanisms of change and programmatic research on which targets change health behaviors and which techniques change those targets. There is evidence that engaging particular targets promotes behavior change; however, systematic studies are needed to identify and validate targets and to discover when and how targets are best engaged. The EM approach promises progress in answering the key question that will enable the science of health behavior change to improve public health: What strategies are effective in promoting behavior change, for whom, and under what circumstances?
C1 [Sheeran, Paschal] Univ N Carolina, Dept Psychol & Neurosci, Chapel Hill, NC 27599 USA.
[Klein, William M. P.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
[Rothman, Alexander J.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
RP Sheeran, P (reprint author), Univ N Carolina, Dept Psychol & Neurosci, Chapel Hill, NC 27599 USA.
EM psheeran@email.unc.edu
NR 158
TC 2
Z9 2
U1 0
U2 0
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0066-4308
BN 978-0-8243-0268-9
J9 ANNU REV PSYCHOL
JI Annu. Rev. Psychol
PY 2017
VL 68
BP 573
EP 600
DI 10.1146/annurev-psych-010416-044007
PG 28
WC Psychology; Psychology, Multidisciplinary
SC Psychology
GA BH0QL
UT WOS:000396040000023
PM 27618942
ER
PT J
AU Greer, S
Han, T
Dieguez, C
McLean, N
Saer, R
Reis, I
Levi, J
Marquez, VE
AF Greer, Sheldon
Han, Tieran
Dieguez, Cristina
McLean, Nicola
Saer, Rafael
Reis, Isildinha
Levi, Joe
Marquez, Victor E.
TI Enzyme-Driven Chemo-and Radiation-Therapy with 12 Pyrimidine Nucleoside
Analogs Not Yet in the Clinic
SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
LA English
DT Article
DE Chemotherapy; radiosensitization; activation of prodrugs; dCkinase;
cytidine deaminase; dCMPdeaminase; uridine/cytidine kinase; pyrimidine
nucleoside analogs
ID DNA METHYLTRANSFERASE INHIBITOR; TARGET-DIRECTED THERAPIES; EXPLOIT
HIGH-LEVELS; CYTIDINE DEAMINASE; METHYLATION INHIBITOR;
CYTOSINE-ARABINOSIDE; CANCER-CELLS; E-CADHERIN; IN-VITRO;
DEOXYCYTIDYLATE DEAMINASE
AB Enzymatic activity from tumor and adjacent normal tissue of 200 patients involving deoxycytidine kinase (dCK), uridine/cytidine kinase (U/CK), cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD) was quantified. Patients with brain (17), colon (24), and breast (30) tumors, 53, 67, and 73%, respectively, had an elevated T/N value (Specific Activity of tumor/Specific Activity of normal tissue) involving dCK and dCMPD suggesting chemotherapy with 5-fluorodeoxycytidine (5-FdC) alone or in combination with thymidine plus deoxytetra-hydrouridine, or with the radiosensitizer, 5-chlorodeoxycytidine (5-CldC) plus tetrahydrouridine (H4U). Among patients with colon (19) and pancreatic tumors (40), 53 and 68 %, respectively, displayed T/N values >4 for CD suggesting chemotherapy with 5-FdC, 4-N-methylamino-5-FdC, 5-trifluoromethyldeoxycytidine and radiosensitization with 5-CldC, 4-N-methylamino-5-CldC, 5-iododeoxycytidine and 5-bromodeoxycytidine. The percent of patients with tumors with a T/N value >4 for U/CK in lung (72), colon (23) and breast (28) was 47, 61 and 68, respectively, suggesting zebularine (plus thymidine) treatment for tumors involving gene silencing.
Evidence is presented that the 4-N-alkylamino-dC substituted nucleosides and those with large 5-substitutions are activated only via CD to thymidine kinase (TK) using end-points of cytotoxicity and/or radiosensitization: H4U, the inhibitor of CD is an antagonist, cells with low CD or no TK are resistant to the analogs, the end points are indifferent to the dCK status of cells, they are poor substrates for dCK and good substrates for CD, whereas 5-FdC and 5-CldC are good substrates for both enzymes. The analogs present opportunities for Collateral Sensitivity for 5-azacytidine and gemcitabine resistant tumors.
C1 [Greer, Sheldon; Dieguez, Cristina; Saer, Rafael] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Greer, Sheldon] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA.
[Greer, Sheldon; McLean, Nicola] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA.
[Greer, Sheldon; Han, Tieran] Univ Miami, Miller Sch Med, Sylvester Canc Ctr, Coral Gables, FL 33124 USA.
[Reis, Isildinha] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Coral Gables, FL 33124 USA.
[Levi, Joe] Univ Miami, Miller Sch Med, Dept Surg, Coral Gables, FL 33124 USA.
[Marquez, Victor E.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Greer, S (reprint author), Univ Miami, Miller Sch Med, Dept Microbiol Immunol R138, 1600 NW 10th Ave, Miami, FL 33136 USA.
EM sgreer@miami.edu
FU NIH STTR [CA79279-02]; Women's Cancer Association; Intramural Research
Program of the NIH, NCI, Center for Cancer Research
FX This study was supported mainly by NIH STTR grant CA79279-02 to Dr.
Greer, Professor of Microbiology/Immunology; Biochemistry/Molecular
Biology and Radiation Oncology and CSO of Halogenetics Inc. and, in
part, by a grant from the Women's Cancer Association. Contributors to
the Sylvester Cancer Center of Miami, FL and the Rumbaugh-Goodwin Cancer
Center of Plantation FL are acknowledged. This research was supported,
in part, by the Intramural Research Program of the NIH, NCI, Center for
Cancer Research to Dr. Victor E. Marquez. This paper is dedicated to the
memory of Dr. Eckhard Podack, who served as Chairman of
Microbiology/Immunology at the University of Miami, Miller School of
Medicine for many creative years His dedication to make an impact in
Life Science and the Cancer Problem, which he achieved, was an
inspiration to all who were close to him-and he made many feel close to
him.
NR 76
TC 0
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U1 1
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5206
EI 1875-5992
J9 ANTI-CANCER AGENT ME
JI Anti-Cancer Agents Med. Chem.
PY 2017
VL 17
IS 2
BP 250
EP 264
DI 10.2174/1871520616666161013145853
PG 15
WC Oncology; Chemistry, Medicinal
SC Oncology; Pharmacology & Pharmacy
GA EP2YY
UT WOS:000397250800010
PM 27745548
ER
PT J
AU Funderburg, NT
Xu, DH
Playford, MP
Joshi, AA
Andrade, A
Kuritzkes, DR
Lederman, MM
Mehta, NN
AF Funderburg, Nicholas T.
Xu, Dihua
Playford, Martin P.
Joshi, Aditya A.
Andrade, Adriana
Kuritzkes, Daniel R.
Lederman, Michael M.
Mehta, Nehal N.
TI Treatment of HIV infection with a raltegravir-based regimen increases
LDL levels, but improves HDL cholesterol efflux capacity
SO ANTIVIRAL THERAPY
LA English
DT Article
ID ANTIRETROVIRAL THERAPY ACTG; MONOCYTE ACTIVATION; VASCULAR-DISEASE;
SOLUBLE CD14; NAIVE; INFLAMMATION; INDIVIDUALS; DRIVE
AB Background: Persons infected with HIV often have altered lipid profiles that may be affected by antiretroviral therapies (ART). Traditional lipid measurements may be insufficient to assess cardiovascular disease (CVD) risk in this population.
Methods: We report results from 39 ART-naive participants in a substudy of A5248, a single-arm study of raltegravir, emtricitabine/tenofovir administration. Samples were collected at baseline, 12, 24 and 48 weeks after ART initiation. We performed advanced lipid phenotyping using nuclear magnetic resonance spectroscopy (Liposcience, Raleigh, NC, USA) for lipid particle size and number, and examined high-density lipoprotein (HDL) function measuring reverse cholesterol transport using J774 macrophages.
Results: We report significant increases in total cholesterol (13 mg/dl; P<0.001) and low-density lipoprotein (LDL; 8 mg/dl; P=0.03), with no change in triglycerides and without an increase in LDL particle number (P>0.1 all time points). HDL levels were increased over baseline levels at all time points (P<0.003), but reached a peak at week 12 and subsequently declined. HDL particle numbers also increased from baseline (P<0.002) and HDL function improved at week 48 (7% increase in efflux capacity; P<0.001). Oxidized LDL (oxLDL) levels decreased by week 12, but rose subsequently, and were not different from baseline at later time points.
Conclusions: HDL increases were associated with increases in beneficial HDL particles and HDL cholesterol efflux capacity, which may reduce future CVD events. Persistent inflammation in these HIV+ participants, may be a cause or consequence of oxLDL levels, and may contribute to declining levels of HDL over time.
C1 [Funderburg, Nicholas T.] Ohio State Univ, Div Med Lab Sci, Sch Hlth & Rehabil Sci, Columbus, OH 43210 USA.
[Xu, Dihua; Playford, Martin P.; Joshi, Aditya A.; Mehta, Nehal N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Andrade, Adriana] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA.
[Kuritzkes, Daniel R.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Lederman, Michael M.] Case Western Reserve Univ, Dept Med, Univ Hosp Case Med Ctr, Ctr AIDS Res,Div Infect Dis & HIV Med, Cleveland, OH 44106 USA.
RP Mehta, NN (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM nehal.mehta@nih.gov
FU National Institutes of Health [AI-07164, AI-67039, AI-68636,
R00HL108743, R56HL126563]; Fasenmyer Foundation (Cleveland, OH, USA);
Center for AIDS Research at Case Western Reserve University [AI-36219];
NIH Intramural Grant from the NHLBI [HL006193-01]; National Institute of
Allergy and Infectious Diseases [U01AI068636]; National Institute of
Mental Health (NIMH), National Institute of Dental and Craniofacial
Research (NIDCR)
FX This work was supported by grants from the National Institutes of Health
(grant numbers AI-07164, AI-67039, AI-68636, R00HL108743, R56HL126563),
the Fasenmyer Foundation (Cleveland, OH, USA), the Center for AIDS
Research at Case Western Reserve University AI-36219 and an NIH
Intramural Grant from the NHLBI to NNM (HL006193-01).; The project
described was supported by Award Number U01AI068636 from the National
Institute of Allergy and Infectious Diseases and supported by National
Institute of Mental Health (NIMH), National Institute of Dental and
Craniofacial Research (NIDCR). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institute of Allergy and Infectious Diseases or the
National Institutes of Health.
NR 20
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U1 0
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PU INT MEDICAL PRESS LTD
PI LONDON
PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND
SN 1359-6535
J9 ANTIVIR THER
JI Antivir. Ther.
PY 2017
VL 22
IS 1
BP 71
EP 75
DI 10.3851/IMP3091
PG 5
WC Infectious Diseases; Pharmacology & Pharmacy; Virology
SC Infectious Diseases; Pharmacology & Pharmacy; Virology
GA EO1ZV
UT WOS:000396497300008
PM 27740536
ER
PT J
AU Lee, M
Gouskova, NA
Feuer, EJ
Fine, JP
AF Lee, Minjung
Gouskova, Natalia A.
Feuer, Eric J.
Fine, Jason P.
TI On the choice of time scales in competing risks predictions
SO BIOSTATISTICS
LA English
DT Article
DE Cumulative incidence function; Disease registry data; Left truncation;
Multiple time scales; Population risk; Proportional hazards model
ID MODEL; SURVIVAL; CANCER
AB In the standard analysis of competing risks data, proportional hazards models are fit to the cause-specific hazard functions for all causes on the same time scale. These regression analyses are the foundation for predictions of cause-specific cumulative incidence functions based on combining the estimated cause-specific hazard functions. However, in predictions arising from disease registries, where only subjects with disease enter the database, disease-related mortality may be more naturally modeled on the time since diagnosis time scale while death from other causes may be more naturally modeled on the age time scale. The single time scale methodology may be biased if an incorrect time scale is employed for one of the causes and an alternative methodology is not available. We propose inferences for the cumulative incidence function in which regression models for the cause-specific hazard functions may be specified on different time scales. Using the disease registry data, the analysis of other cause mortality on the age scale requires left truncating the event time at the age of disease diagnosis, complicating the analysis. In addition, standard Martingale theory is not applicable when combining regression models on different time scales. We establish that the covariate conditional predictions are consistent and asymptotically normal using empirical process techniques and propose consistent variance estimators for constructing confidence intervals. Simulation studies show that the proposed two time scales method performs well, outperforming the single time-scale predictions when the time scale is misspecified. The methods are illustrated with stage III colon cancer data obtained from the Surveillance, Epidemiology, and End Results program of National Cancer Institute.
C1 [Lee, Minjung] Kangwon Natl Univ, Dept Stat, Chunchon 24341, South Korea.
[Gouskova, Natalia A.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Feuer, Eric J.] Natl Canc Inst, Div Canc Control & Populat Studies, Stat Res & Applicat Branch, Bethesda, MD 20892 USA.
[Fine, Jason P.] Univ N Carolina, Dept Biostat & Dept Stat, Chapel Hill, NC 27599 USA.
RP Lee, M (reprint author), Kangwon Natl Univ, Dept Stat, Chunchon 24341, South Korea.
EM minjung.lee09@gmail.com
FU Kangwon National University
FX This study was supported by 2016 Research Grant from Kangwon National
University.
NR 19
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2017
VL 18
IS 1
BP 15
EP 31
DI 10.1093/biostatistics/kxw024
PG 17
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EP0FX
UT WOS:000397063700002
PM 27335117
ER
PT J
AU Zhu, H
Ning, J
Shen, Y
Qin, J
AF Zhu, Hong
Ning, Jing
Shen, Yu
Qin, Jing
TI Semiparametric density ratio modeling of survival data from a prevalent
cohort
SO BIOSTATISTICS
LA English
DT Article
DE Conditional pairwise likelihood; Density ratio model; Left-truncated
right-censored data; Prevalent sampling; Profile likelihood
ID REGRESSION-ANALYSIS; PROFILE LIKELIHOOD; TRUNCATED DATA
AB In this article, we consider methods for assessing covariate effects on survival outcome in the target population when data are collected under prevalent sampling. We investigate a flexible semiparametric density ratio model without the constraints of the constant disease incidence rate and discrete covariates as required in Shen and others 2012. For inference, we introduce two likelihood approaches with distinct computational algorithms. We first develop a full likelihood approach to obtain the most efficient estimators by an iterative algorithm. Under the density ratio model, we exploit the invariance property of uncensored failure times from the prevalent cohort and also propose a computationally convenient estimation procedure that uses a conditional pairwise likelihood. The empirical performance and efficiency of the two approaches are evaluated through simulation studies. The proposed methods are applied to the Surveillance, Epidemiology, and End Results Medicare linked data for women diagnosed with stage IV breast cancer.
C1 [Zhu, Hong] Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Div Biostat, Dallas, TX 75390 USA.
[Ning, Jing; Shen, Yu] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Qin, Jing] Natl Inst Allergy & Infect Dis, Biostat Res Branch, Bethesda, MD 20892 USA.
RP Zhu, H (reprint author), Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Div Biostat, Dallas, TX 75390 USA.
EM hong.zhu@utsouthwestern.edu
FU National Institutes of Health; Cancer Center Support Grant from the
National Cancer Institute [2P30CA142543]; National Cancer Institute
[R01CA193878, R01CA07466, P30CA016672]
FX National Institutes of Health; the Cancer Center Support Grant from the
National Cancer Institute (2P30CA142543, to H.Z.) awarded to the Harold
C. Simmons Cancer Center at the University of Texas Southwestern Medical
Center; the National Cancer Institute (R01CA193878, R01CA07466 and
P30CA016672, J.N. and Y.S.).
NR 15
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2017
VL 18
IS 1
BP 62
EP 75
DI 10.1093/biostatistics/kxw028
PG 14
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EP0FX
UT WOS:000397063700005
PM 27354710
ER
PT J
AU Hamilton, DH
David, JM
Dominguez, C
Palena, C
AF Hamilton, Duane H.
David, Justin M.
Dominguez, Charli
Palena, Claudia
TI Development of Cancer Vaccines Targeting Brachyury, a Transcription
Factor Associated with Tumor Epithelial-Mesenchymal Transition
SO CELLS TISSUES ORGANS
LA English
DT Article; Proceedings Paper
CT International EMT Meeting
CY OCT 11-14, 2015
CL Melbourne, AUSTRALIA
DE Epithelial-mesenchymal transition; Brachyury; Cancer vaccines; Immune
resistance
ID CELL LUNG-CANCER; EGFR INHIBITOR RESISTANCE; HUMAN CARCINOMA-CELLS;
PHASE-I TRIAL; AUTOPHAGY INDUCTION; MESODERM FORMATION; PROSTATE-CANCER;
MEDIATED LYSIS; IMMUNE ATTACK; T-GENE
AB Epithelial-mesenchymal transition (EMT) is recognized as a relevant process during the progression of carcinomas towards metastatic disease. Epithelial cancer cells undergoing an EMT program may acquire mesenchymal features, motility, invasiveness, and resistance to a variety of anticancer therapeutics. Preventing or reverting the EMT process in carcinomas has the potential to minimize tumor dissemination and the emergence of therapeutic resistance. One of the strategies currently under investigation to target tumor cells undergoing EMT is the generation of a sustained immune response directed against an essential molecular driver of the process. This review focuses on the current development of immune-mediated anticancer interventions aimed at targeting a transcription factor, brachyury, associated with human tumor EMT. Also presented here is a summary of recent studies demonstrating a role for EMT in tumor resistance to immune effector cytotoxicity, and the study of novel strategies aimed at reverting the EMT to be used in combination with immune-mediated anticancer interventions. (C) 2017 S. Karger AG, Basel
C1 [Hamilton, Duane H.; David, Justin M.; Dominguez, Charli; Palena, Claudia] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Lab Tumor Immunol & Biol, 10 Ctr Dr,Room 8B14,Bethesda, Bethesda, MD 20892 USA.
RP Palena, C (reprint author), Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Lab Tumor Immunol & Biol, 10 Ctr Dr,Room 8B14,Bethesda, Bethesda, MD 20892 USA.
EM palenac@mail.nih.gov
FU NIH Intramural Research Program, National Cancer Institute, Center for
Cancer Research
FX This research was supported by funds of the NIH Intramural Research
Program, National Cancer Institute, Center for Cancer Research.
NR 70
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1422-6405
EI 1422-6421
J9 CELLS TISSUES ORGANS
JI Cells Tissues Organs
PY 2017
VL 203
IS 2
BP 128
EP 138
DI 10.1159/000446495
PG 11
WC Anatomy & Morphology; Cell Biology; Developmental Biology
SC Anatomy & Morphology; Cell Biology; Developmental Biology
GA EL9EM
UT WOS:000394922500007
PM 28214895
ER
PT J
AU Strong, SL
Silson, EH
Gouws, AD
Morland, AB
McKeefry, DJ
AF Strong, Samantha L.
Silson, Edward H.
Gouws, Andre D.
Morland, Antony B.
McKeefry, Declan J.
TI A Direct Demonstration of Functional Differences between Subdivisions of
Human V5/MT+
SO CEREBRAL CORTEX
LA English
DT Article
DE fMRI; psychophysics; transcranial magnetic stimulation; V5/MT+
ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN VISUAL-CORTEX; SUPERIOR
TEMPORAL SULCUS; OPTIC FLOW STIMULI; MT PLUS COMPLEX; PURSUIT
EYE-MOVEMENTS; CORTICAL AREAS MT; MST NEURONS; HUMAN BRAIN; EXTRASTRIATE
CORTEX
AB Two subdivisions of human V5/MT+: one located posteriorly (MT/TO-1) and the other more anteriorly (MST/TO-2) were identified in human participants using functional magnetic resonance imaging on the basis of their representations of the ipsilateral versus contralateral visual field. These subdivisions were then targeted for disruption by the application of repetitive transcranial magnetic stimulation (rTMS). The rTMS was delivered to cortical areas while participants performed direction discrimination tasks involving 3 different types of moving stimuli defined by the translational, radial, or rotational motion of dot patterns. For translational motion, performance was significantly reduced relative to baseline when rTMS was applied to both MT/TO-1 and MST/TO-2. For radial motion, there was a differential effect between MT/TO-1 and MST/TO-2, with only disruption of the latter area affecting performance. The rTMS failed to reveal a complete dissociation between MT/TO-1 and MST/TO-2 in terms of their contribution to the perception of rotational motion. On the basis of these results, MT/TO-1 and MST/TO-2 appear to be functionally distinct subdivisions of hV5/MT+. While both areas appear to be implicated in the processing of translational motion, only the anterior region (MST/TO-2) makes a causal contribution to the perception of radial motion.
C1 [Strong, Samantha L.; McKeefry, Declan J.] Univ Bradford, Sch Optometry & Vis Sci, Bradford BD7 1DP, W Yorkshire, England.
[Strong, Samantha L.; Silson, Edward H.; Gouws, Andre D.; Morland, Antony B.] Univ York, Dept Psychol, York Neuroimaging Ctr, York YO10 5DD, N Yorkshire, England.
[Silson, Edward H.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Morland, Antony B.] Univ York, Hull York Med Sch, Ctr Neurosci, York YO10 5DD, N Yorkshire, England.
RP McKeefry, DJ (reprint author), Univ Bradford, Sch Optometry & Vis Sci, Bradford BD7 1DP, W Yorkshire, England.
EM d.mckeefry@bradford.ac.uk
FU BBSRC award [BB/N003012/1]
FX BBSRC award (BB/N003012/1).
NR 71
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JAN
PY 2017
VL 27
IS 1
BP 1
EP 10
DI 10.1093/cercor/bhw362
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA EP0GI
UT WOS:000397064800001
PM 28365777
ER
PT J
AU Zavala, B
Damera, S
Dong, JW
Lungu, C
Brown, P
Zaghloul, KA
AF Zavala, Baltazar
Damera, Srikanth
Dong, Jian Wilson
Lungu, Codrin
Brown, Peter
Zaghloul, Kareem A.
TI Human Subthalamic Nucleus Theta and Beta Oscillations Entrain Neuronal
Firing During Sensorimotor Conflict
SO CEREBRAL CORTEX
LA English
DT Article
DE conflict; deep brain stimulation; impulsivity; inhibition; theta
oscillations
ID DEEP BRAIN-STIMULATION; ANTERIOR CINGULATE CORTEX; FIELD POTENTIAL
ACTIVITY; INFERIOR FRONTAL GYRUS; STOP-SIGNAL TASK; PARKINSONS-DISEASE;
BASAL GANGLIA; RESPONSE-INHIBITION; DECISION-MAKING; IMPULSE CONTROL
AB Recent evidence has suggested that prefrontal cortical structures may inhibit impulsive actions during conflict through activation of the subthalamic nucleus (STN). Consistent with this hypothesis, deep brain stimulation to the STN has been associated with altered prefrontal cortical activity and impaired response inhibition. The interactions between oscillatory activity in the STN and its presumably antikinetic neuronal spiking, however, remain poorly understood. Here, we simultaneously recorded intraoperative local field potential and spiking activity from the human STN as participants performed a sensorimotor action selection task involving conflict. We identified several STN neuronal response types that exhibited different temporal dynamics during the task. Some neurons showed early, cue-related firing rate increases that remained elevated longer during high conflict trials, whereas other neurons showed late, movement-related firing rate increases. Notably, the high conflict trials were associated with an entrainment of individual neurons by theta-and beta-band oscillations, both of which have been observed in cortical structures involved in response inhibition. Our data suggest that frequency-specific activity in the beta and theta bands influence STN firing to inhibit impulsivity during conflict.
C1 [Zavala, Baltazar; Damera, Srikanth; Dong, Jian Wilson; Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 3D20,10 Ctr Dr, Bethesda, MD 20892 USA.
[Lungu, Codrin] NINDS, Off Clin Director, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Zavala, Baltazar; Brown, Peter] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurol, Expt Neurol Grp, Oxford OX3 9DU, England.
[Brown, Peter] Univ Oxford, MRC, Brain Network Dynam Unit, Oxford OX1 3TH, England.
RP Zaghloul, KA (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 3D20,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kareem.zaghloul@nih.gov
FU National Institutes of Health; Medical Research Council; National
Institute for Health Research Oxford Biomedical Research Centre
FX This work was supported by the National Institutes of Health Intramural
Research Program (B.Z., S.D., J.D., C.L., and K.Z.) as well as by the
Medical Research Council (P.B.) and the National Institute for Health
Research Oxford Biomedical Research Centre (P.B.).
NR 72
TC 3
Z9 3
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JAN
PY 2017
VL 27
IS 1
BP 496
EP 508
DI 10.1093/cercor/bhv244
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA EP0GI
UT WOS:000397064800040
PM 26494798
ER
PT J
AU Roccella, EJ
AF Roccella, Edward J.
TI Giants in Chest Medicine Claude Lenfant, MD
SO CHEST
LA English
DT Biographical-Item
ID CLINICAL-PRACTICE; BLOOD-PRESSURE
C1 [Roccella, Edward J.] NHLBI, Natl High Blood Pressure Educ Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Roccella, EJ (reprint author), NHLBI, Natl High Blood Pressure Educ Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM eroccella@cox.net
NR 21
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JAN
PY 2017
VL 151
IS 1
BP 11
EP 13
DI 10.1016/j.chest.2016.09.048
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA EO0HE
UT WOS:000396378100009
PM 28065248
ER
PT J
AU Balk, RA
Kadri, SS
Cao, Z
Robinson, SB
Lipkin, C
Bozzette, SA
AF Balk, Robert A.
Kadri, Sameer S.
Cao, Zhun
Robinson, Scott B.
Lipkin, Craig
Bozzette, Samuel A.
TI Effect of Procalcitonin Testing on Health-care Utilization and Costs in
Critically Ill Patients in the United States
SO CHEST
LA English
DT Article
DE antibiotic use; cost of care; intensive care unit; procalcitonin; sepsis
ID RESPIRATORY-TRACT INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; GUIDED
ANTIBIOTIC-THERAPY; SEPTIC SHOCK; SEVERE SEPSIS; BACTERIAL-INFECTION;
SERUM PROCALCITONIN; METAANALYSIS; ALGORITHMS; DURATION
AB BACKGROUND: There is a growing use of procalcitonin (PCT) to facilitate the diagnosis and management of severe sepsis. We investigated the impact of one to two PCT determinations on ICU day 1 on health-care utilization and cost in a large research database.
METHODS: A retrospective, propensity score-matched multivariable analysis was performed on the Premier Healthcare Database for patients admitted to the ICU with one to two PCT evaluations on day 1 of ICU admission vs patients who did not have PCT testing.
RESULTS: A total of 33,569 PCT-managed patients were compared with 98,543 propensity score-matched non-PCT patients. In multivariable regression analysis, PCT utilization was associated with significantly decreased total length of stay (11.6 days [95% CI, 11.4 to 11.7] vs 12.7 days [95% CI, 12.6 to 12.8]; 95% CI for difference, 1 to 1.3; P < .001) and ICU length of stay (5.1 days [95% CI, 5.1 to 5.2] vs 5.3 days [95% CI, 5.3 to 5.4]; 95% CI for difference, 0.1 to 0.3; P < .03), and lower hospital costs ($30,454 [95% CI, 29,968 to 31,033] vs $33,213 [95% CI, 32,964 to 33,556); 95% CI for difference, 2,159 to 3,321; P < .001). There was significantly less total antibiotic exposure (16.2 days [95% CI, 16.1 to 16.5] vs 16.9 days [95% CI, 16.8 to 17.1]; 95% CI for difference, -0.9 to 0.4; P = 0.006) in PCT-managed patients. Patients in the PCT group were more likely to be discharged to home (44.1% [95% CI, 43.7 to 44.6] vs 41.3% [95% CI, 41 to 41.6]; 95% CI for difference, 2.3 to 3.3; P = .006). Mortality was not different in an analysis including the 96% of patients who had an independent measure of mortality risk available (19.1% [95% CI, 18.7 to 19.4] vs 19.1% [95% CI, 18.9 to 19.3]; 95% CI for difference, -0.5 to 0.4; P = .93).
CONCLUSIONS: Use of PCT testing on the first day of ICU admission was associated with significantly lower hospital and ICU lengths of stay, as well as decreased total, ICU, and pharmacy cost of care. Further elucidation of clinical outcomes requires additional data.
C1 [Balk, Robert A.] Rush Med Coll, Div Pulm & Crit Care Med, Chicago, IL 60612 USA.
Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Bozzette, Samuel A.] BioMerieux USA, Med Affairs Amer East Asia & Global Hlth Econ & O, Durham, NC USA.
[Bozzette, Samuel A.] Univ Calif San Diego, Med & Int Relat, San Diego, CA 92103 USA.
[Bozzette, Samuel A.] Univ N Carolina, Hlth Policy & Management, Raleigh, NC USA.
[Cao, Zhun; Robinson, Scott B.; Lipkin, Craig] Premier Res Serv Inc, Charlotte, NC USA.
[Kadri, Sameer S.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Balk, RA (reprint author), Rush Univ, Med Ctr, Div Pulm & Crit Care Med, 1725 W Harrison St,Ste 054, Chicago, IL 60612 USA.
EM rbalk@rush.edu
FU bioMerieux USA
FX This study was funded by bioMerieux USA.
NR 33
TC 2
Z9 2
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JAN
PY 2017
VL 151
IS 1
BP 23
EP 33
DI 10.1016/j.chest.2016.06.046
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA EO0HE
UT WOS:000396378100014
PM 27568580
ER
PT J
AU Small, AM
Mehta, NN
Rader, DJ
AF Small, Aeron M.
Mehta, Nehal N.
Rader, Daniel J.
TI The Role of Emerging Biomarkers in Unraveling the Complex Biology
Underlying Associations between HDL Cholesterol and Cardiovascular
Diseases
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
ID INFLAMMATION; GLYCA; RISK; EVENTS
C1 [Small, Aeron M.; Rader, Daniel J.] Univ Penn, Dept Med, Hosp Univ Penn, Div Cardiol,Perelman Sch Med, Philadelphia, PA 19104 USA.
[Mehta, Nehal N.] NHLBI, Cardiovasc & Pulm Branch, Bldg 10, Bethesda, MD 20892 USA.
[Rader, Daniel J.] Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Rader, DJ (reprint author), Univ Penn, Smilow Ctr Translat Res 11 125, Perelman Sch Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
NR 15
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD JAN
PY 2017
VL 63
IS 1
BP 27
EP 29
DI 10.1373/clinchem.2016.267922
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA EM1AE
UT WOS:000395048800006
PM 27815309
ER
PT J
AU Karathanasis, SK
Freeman, LA
Gordon, SM
Remaley, AT
AF Karathanasis, Sotirios K.
Freeman, Lita A.
Gordon, Scott M.
Remaley, Alan T.
TI The Changing Face of HDL and the Best Way to Measure It
SO CLINICAL CHEMISTRY
LA English
DT Review
ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; CHOLESTEROL EFFLUX
CAPACITY; TRYPANOSOME LYTIC FACTOR; ISCHEMIC-HEART-DISEASE;
APOLIPOPROTEIN-A-I; CHRONIC KIDNEY-DISEASE; NITRIC-OXIDE SYNTHASE; ACUTE
MYOCARDIAL-INFARCTION; HAPTOGLOBIN-RELATED PROTEIN
AB BACKGROUND: HDL cholesterol (HDL-C) is a commonly used lipid biomarker for assessing cardiovascular health. While a central focus has been placed on the role of HDL in the reverse cholesterol transport (RCT) process, our appreciation for the other cardioprotective properties of HDL continues to expand with further investigation into the structure and function of HDL and its specific subfractions. The development of novel assays is empowering the research community to assess different aspects of HDL function, which at some point may evolve into new diagnostic tests.
CONTENT: This review discusses our current understanding of the formation and maturation of HDL particles via RCT, as well as the newly recognized roles of HDL outside RCT. The antioxidative, antiinflammatory, andapoptotic, anti thrombotic, and infective, and vasoprotective effects of HDL are all discussed, as are the related methodologies for assessing these different aspects of HDL function. We elaborate on the importance of protein and lipid composition of HDL in health and disease and highlight potential new diagnostic assays based on these parameters.
SUMMARY: Although multiple epidemiologic studies have confirmed that HDL-C is a strong negative risk marker for cardiovascular disease, several clinical and experimental studies have yielded inconsistent results on the direct role of HDL-C as an antiatherogenic factor. As of yet, our increased understanding of HDL biology has not been translated into successful new therapies, but will undoubtedly depend on the development of alternative ways for measuring HDL besides its cholesterol content. (C) 2016 American Association for Clinical Chemistry
C1 [Karathanasis, Sotirios K.] MedImmune, Cardiovasc & Metab Dis Sect, Gaithersburg, MD USA.
[Freeman, Lita A.; Gordon, Scott M.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bldg 10,Rm 2C433, Bethesda, MD 20814 USA.
RP Remaley, AT (reprint author), NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bldg 10,Rm 2C433, Bethesda, MD 20814 USA.
EM aremaley1@nhlbi.nih.gov
FU Medlmmune; CRADA Research Grant; intramural National Heart, Lung and
Blood Institute of the NIH; MedImmune on LCAT
FX Medical writing support was funded by Medlmmune. L.A. Freeman,
intramural National Heart, Lung and Blood Institute of the NIH; S.M.
Gordon, intramural National Heart, Lung and Blood Institute of the NIH;
A.T. Remaley, CRADA Research Grant with MedImmune on LCAT and intramural
National Heart, Lung and Blood Institute of the NIH.
NR 196
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD JAN
PY 2017
VL 63
IS 1
BP 196
EP 210
DI 10.1373/clinchem.2016.257725
PG 15
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA EM1AE
UT WOS:000395048800028
PM 27879324
ER
PT J
AU Salahudeen, AA
Patel, MI
Baas, P
Curran, WJ
Bradley, JD
Gandara, DR
Goss, GD
Mok, TS
Ramalingam, SS
Vokes, EE
Malik, SM
Wakelee, HA
AF Salahudeen, Ameen Abdulla
Patel, Manali I.
Baas, Paul
Curran, Walter J.
Bradley, Jeffrey D.
Gandara, David R.
Goss, Glenwood D.
Mok, Tony S.
Ramalingam, Suresh S.
Vokes, Everett E.
Malik, Shakun M.
Wakelee, Heather A.
TI Overview of Thoracic Oncology Trials in Cooperative Groups Around the
Globe
SO CLINICAL LUNG CANCER
LA English
DT Review
DE Cooperative group; Mesothelioma; NCTN; NSCLC; SCLC
ID CELL LUNG-CANCER; DOUBLE-BLIND; OPEN-LABEL; CHEMOTHERAPY; MULTICENTER;
ERLOTINIB; ADENOCARCINOMA; GEFITINIB; THERAPY; PLACEBO
AB Survival rates of patients with either early and advanced stage non small-cell lung cancer (NSCLC) have improved with newer systemic therapy and radiation techniques, including combination regimens, targeted therapies, and immunotherapies. The cancer cooperative groups have historically played a critical role in the advancement of NSCLC therapy. Annually, representatives from cooperative groups worldwide convene at the International Lung Cancer Congress (ILCC). In summer 2015, the ILCC reached its 16th anniversary. This article highlights the NSCLC studies presented by participating groups in 2015. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Salahudeen, Ameen Abdulla; Patel, Manali I.; Ramalingam, Suresh S.; Wakelee, Heather A.] Emory Univ, Sch Med, Winship Canc Inst, Hematol & Med Oncol, Atlanta, GA 30322 USA.
[Curran, Walter J.] Emory Univ, Sch Med, Winship Canc Inst, Radiat Oncol, Atlanta, GA USA.
[Baas, Paul] Univ Amsterdam AMC UvA, Antoni van Leeuwenhoek Hosp NKI AVL, Netherlands Canc Inst, Thorac Oncol,Fac Med, Amsterdam, Netherlands.
[Bradley, Jeffrey D.] Washington Univ, Sch Med, S Lee Kling Ctr Proton Therapy, St Louis, MO USA.
[Gandara, David R.] Univ Calif Davis, Ctr Comprehens Canc, Thorac Oncol Program, Davis, CA USA.
[Goss, Glenwood D.] Univ Ottawa, Div Oncol, Dept Med, Ottawa, ON, Canada.
[Mok, Tony S.] Chinese Med Univ Hong Kong, Dept Clin Oncol, Shatin, Hong Kong, Peoples R China.
[Vokes, Everett E.] Univ Chicago, Sch Med, Dept Med, Chicago, IL 60637 USA.
[Malik, Shakun M.] NCI, Clin Invest Branch, CTEP, DCTD,NIH, Rockville, MD USA.
RP Wakelee, HA (reprint author), Stanford Univ, Dept Med, 875 Blake Wilbur Dr,Room 2233, Stanford, CA 94305 USA.; Wakelee, HA (reprint author), Stanford Univ, Dept Oncol, 875 Blake Wilbur Dr,Room 2233, Stanford, CA 94305 USA.
EM hwakelee@stanford.edu
FU NCI NIH HHS [U10 CA180833, U10 CA180888]
NR 17
TC 1
Z9 1
U1 0
U2 0
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1525-7304
EI 1938-0690
J9 CLIN LUNG CANCER
JI Clin. Lung Cancer
PD JAN
PY 2017
VL 18
IS 1
BP 5
EP 12
DI 10.1016/j.cllc.2016.06.007
PG 8
WC Oncology
SC Oncology
GA EK7AW
UT WOS:000394078900002
PM 27473736
ER
PT J
AU Cai, YT
Zijlema, WL
Doiron, D
Blangiardo, M
Burton, PR
Fortier, I
Gaye, A
Gulliver, J
de Hoogh, K
Hveem, K
Mbatchou, S
Morley, DW
Stolk, RP
Elliott, P
Hansell, AL
Hodgson, S
AF Cai, Yutong
Zijlema, Wilma L.
Doiron, Dany
Blangiardo, Marta
Burton, Paul R.
Fortier, Isabel
Gaye, Amadou
Gulliver, John
de Hoogh, Kees
Hveem, Kristian
Mbatchou, Stephane
Morley, David W.
Stolk, Ronald P.
Elliott, Paul
Hansell, Anna L.
Hodgson, Susan
TI Ambient air pollution, traffic noise and adult asthma prevalence: a
BioSHaRE approach
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID RESPIRATORY HEALTH; ENVIRONMENTAL NOISE; ALLERGIC RHINITIS; EXPOSURE;
NO2; COHORT; ROAD; ESCAPE; EUROPE; IMPACT
AB We investigated the effects of both ambient air pollution and traffic noise on adult asthma prevalence, using harmonised data from three European cohort studies established in 2006-2013 (HUNT3, Lifelines and UK Biobank).
Residential exposures to ambient air pollution (particulate matter with aerodynamic diameter <= 10 mu m (PM10) and nitrogen dioxide (NO2)) were estimated by a pan-European Land Use Regression model for 2007. Traffic noise for 2009 was modelled at home addresses by adapting a standardised noise assessment framework (CNOSSOS-EU). A cross-sectional analysis of 646 731 participants aged >= 20 years was undertaken using DataSHIELD to pool data for individual-level analysis via a "compute to the data" approach. Multivariate logistic regression models were fitted to assess the effects of each exposure on lifetime and current asthma prevalence.
PM10 or NO2 higher by 10 mu g center dot m-3 was associated with 12.8% (95% CI 9.5-16.3%) and 1.9% (95% CI 1.1-2.8%) higher lifetime asthma prevalence, respectively, independent of confounders. Effects were larger in those aged. 50 years, ever-smokers and less educated. Noise exposure was not significantly associated with asthma prevalence.
This study suggests that long-term ambient PM10 exposure is associated with asthma prevalence in western European adults. Traffic noise is not associated with asthma prevalence, but its potential to impact on asthma exacerbations needs further investigation.
C1 [Cai, Yutong; Blangiardo, Marta; Morley, David W.; Elliott, Paul; Hansell, Anna L.; Hodgson, Susan] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, IMRC PHE Ctr Environm & Hlth, London, England.
[Zijlema, Wilma L.; Stolk, Ronald P.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Doiron, Dany; Mbatchou, Stephane] McGill Univ Hlth Ctr & Dept Med, McGill Univ, Res Inst, Montreal, PQ, Canada.
[Burton, Paul R.] Univ Bristol, Data Knowledge D2K Res Grp, Bristol, Avon, England.
[Burton, Paul R.] Publ Populat Project Genom & Soc P3G, Montreal, PQ, Canada.
[Gaye, Amadou] Natl Human Genome Res Inst, Cardiovascular & Inflammatory Dis Genom Branch, Metab, Bethesda, MD USA.
[de Hoogh, Kees] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[de Hoogh, Kees] Univ Basel, Basel, Switzerland.
[Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Trondheim, Norway.
[Hansell, Anna L.] Imperial Coll Healthcare NHS Trust, Directorate Publ Hlth & Primary Care, London, England.
[Cai, Yutong] Sch Publ Hlth, Dept Epidemiol & Biostatist, Imperial Coll London, MRC PHE Ctr Environm & Hlth, St Marys Campus,Pl, Norfolk, VA USA.
RP Cai, YT (reprint author), Sch Publ Hlth, Dept Epidemiol & Biostatist, Imperial Coll London, MRC PHE Ctr Environm & Hlth, St Marys Campus,Pl, Norfolk, VA USA.
EM yutong.cai@imperial.ac.uk
FU European Union [261433]; UK Medical Research Council (MRC); Wellcome
Trust; MRC; BBMRI-LPC (European Union Seventh Framework Programme: I3
grant); Netherlands Organisation of Scientific Research NWO
[175.010.2007.006]; Economic Structure Enhancing Fund (FES) of the Dutch
government; Ministry of Economic Affairs; Ministry of Education, Culture
and Science; Ministry for Health, Welfare and Sports; Northern
Netherlands Collaboration of Provinces (SNN); Province of Groningen;
University Medical Center Groningen; University of Groningen; Dutch
Kidney Foundation; Dutch Diabetes Research Foundation; Welsh Assembly
Government; British Heart Foundation; Diabetes UK; European Union
Seventh Framework Programme (FP7) [211250]; Public Health England (PHE)
[MR/L01341X/1]; Imperial College Healthcare National Health Service
Trust; Imperial College London Biomedical Research Centre; NIHR Health
Protection Research Unit on the Health Effects of Environmental Hazards
[HPRU-2012-10030-KCL]; MRC-PHE Centre for Environment and Health
FX The research leading to these results has received funding from the
European Union Seventh Framework Programme (FP7/2007-2013) under grant
agreement 261433 (Biobank Standardisation and Harmonisation for Research
Excellence in the European Union (BioSHaRE)). BioSHaRE is engaged in a
Bioresource Research Impact Factor (BRIF) policy pilot study
(www.bioshare.eu/content/bioresource-impact-factor). DataSHIELD
development is also partly funded under a strategic award from the UK
Medical Research Council (MRC) and Wellcome Trust underpinning the
ALSPAC (Avon Longitudinal Study of Parents and Children) project, and
the Welsh and Scottish Farr Institutes funded by MRC, BBMRI-LPC
(European Union Seventh Framework Programme: I3 grant). The Lifelines
Cohort Study, and generation and management of genomewide association
studies genotype data for the Lifelines Cohort Study, is supported by
the Netherlands Organisation of Scientific Research NWO (grant
175.010.2007.006), the Economic Structure Enhancing Fund (FES) of the
Dutch government, the Ministry of Economic Affairs, the Ministry of
Education, Culture and Science, the Ministry for Health, Welfare and
Sports, the Northern Netherlands Collaboration of Provinces (SNN), the
Province of Groningen, University Medical Center Groningen, the
University of Groningen, Dutch Kidney Foundation and Dutch Diabetes
Research Foundation. Lifelines is a facility that is open for all
researchers. Information on application and data access procedures is
summarised at www.lifelines.nl. UK Biobank was established by the
Wellcome Trust medical charity, MRC, Dept of Health, Scottish Government
and the Northwest Regional Development Agency. It has also had funding
from the Welsh Assembly Government, British Heart Foundation and
Diabetes UK. The ESCAPE (European Study of Cohorts for Air Pollution
Effects) project has received funding from the European Union Seventh
Framework Programme (FP7/2007-2011) under grant agreement 211250. The
MRC-PHE Centre for Environment and Health is funded by the MRC and
Public Health England (PHE) (MR/L01341X/1). P. Elliott is a National
Institute for Health Research (NIHR) Senior Investigator and
acknowledges support from the Imperial College Healthcare National
Health Service Trust and Imperial College London Biomedical Research
Centre, the NIHR Health Protection Research Unit on the Health Effects
of Environmental Hazards (HPRU-2012-10030-KCL), and the MRC-PHE Centre
for Environment and Health. Funding information for this article has
been deposited with the Open Funder Registry.
NR 41
TC 0
Z9 0
U1 1
U2 1
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JAN
PY 2017
VL 49
IS 1
AR 1502127
DI 10.1183/13993003.02127-2015
PG 10
WC Respiratory System
SC Respiratory System
GA EP5MU
UT WOS:000397423500003
ER
PT J
AU Khincha, PP
Bertuch, AA
Agarwal, S
Townsley, DM
Young, NS
Keel, S
Shimamura, A
Boulad, F
Simoneau, T
Justino, H
Kuo, C
Artandi, S
McCaslin, C
Cox, DW
Chaffee, S
Collins, BF
Giri, N
Alter, BP
Raghu, G
Savage, SA
AF Khincha, Payal P.
Bertuch, Alison A.
Agarwal, Suneet
Townsley, Danielle M.
Young, Neal S.
Keel, Sioban
Shimamura, Akiko
Boulad, Farid
Simoneau, Tregony
Justino, Henri
Kuo, Christin
Artandi, Steven
McCaslin, Charles
Cox, Des W.
Chaffee, Sara
Collins, Bridget F.
Giri, Neelam
Alter, Blanche P.
Raghu, Ganesh
Savage, Sharon A.
TI Pulmonary arteriovenous malformations: an uncharacterised phenotype of
dyskeratosis congenita and related telomere biology disorders
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Letter
ID HEPATOPULMONARY SYNDROME; FISTULAS
C1 [Khincha, Payal P.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, Bethesda, MD 20892 USA.
[Bertuch, Alison A.; Justino, Henri] Baylor Coll Med, Houston, TX 77030 USA.
[Agarwal, Suneet; Shimamura, Akiko] Boston Childrens Hosp, Div Haematol Oncol, Boston, MA USA.
[Townsley, Danielle M.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Keel, Sioban] Univ Washington, Dept Med, Div Haematol, Seattle, WA 98195 USA.
[Boulad, Farid] Mem Sloan Kettering Canc Ctr, Dept Paediat, Paediat Oncol & Bone Marrow Transplant Serv, 1275 York Ave, New York, NY 10021 USA.
[Simoneau, Tregony] Connecticut Childrens Med Ctr, Dept Pulmonol, Hartford, CT USA.
[Kuo, Christin] Lucile Packard Childrens Hosp Stanford, Dept Pulmonol, Palo Alto, CA USA.
[Artandi, Steven] Stanford Univ, Sch Med, Canc Biol Program, Palo Alto, CA 94304 USA.
[McCaslin, Charles] Helen DeVos Childrens Hosp, Grand Rapids, MI USA.
[Cox, Des W.] Our Ladys Childrens Hosp, Paediat Resp Med, Dublin, Ireland.
[Chaffee, Sara] Childrens Hosp Dartmouth, Dartmouth Hitchcock Med Ctr, Paediat Haematol Oncol, Lebanon, NH USA.
[Collins, Bridget F.; Raghu, Ganesh] Univ Washington, Ctr Interstitial Lung Dis, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
RP Khincha, PP (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E562,MSC 9772, Bethesda, MD 20892 USA.
EM khinchapp@mail.nih.gov
FU National Cancer Institute (Rockville, MD, USA); National Institutes of
Health (NIH; Bethesda, MD, USA); National Heart, Lung and Blood
Institute, NIH; Translational Research Program at Boston Children's
Hospital (Boston, MA, USA)
FX This work was supported by the intramural research programme of the
National Cancer Institute (Rockville, MD, USA), National Institutes of
Health (NIH; Bethesda, MD, USA), the National Heart, Lung and Blood
Institute, NIH and the Translational Research Program at Boston
Children's Hospital (Boston, MA, USA). Funding information for this
article has been deposited with Open Funder Registry.
NR 15
TC 1
Z9 1
U1 1
U2 1
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JAN
PY 2017
VL 49
IS 1
AR 1601640
DI 10.1183/13993003.01640-2016
PG 4
WC Respiratory System
SC Respiratory System
GA EP5MU
UT WOS:000397423500036
ER
PT J
AU Brooks, KM
George, JM
Kumar, P
AF Brooks, Kristina M.
George, Jomy M.
Kumar, Parag
TI Drug interactions in HIV treatment: complementary & alternative
medicines and over-the-counter products
SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY
LA English
DT Review
DE Antiretrovirals; complementary and alternative medicines (CAMs); drug
interactions; herbals; HIV; over-the-counter (OTC); pharmacokinetics;
supplements
ID ST-JOHNS-WORT; HUMAN-IMMUNODEFICIENCY-VIRUS; PREGNANE-X-RECEPTOR;
GOLDENSEAL HYDRASTIS-CANADENSIS; ACTIVE ANTIRETROVIRAL THERAPY; PROTEASE
INHIBITOR INDINAVIR; CYTOCHROME-P450 3A ACTIVITY; AFRICAN HERBAL
MEDICINES; KAVA PIPER-METHYSTICUM; SEVILLE ORANGE JUICE
AB Introduction: Use of complementary and alternative medicines (CAMs) and over-the-counter (OTC) medications are very common among HIV-infected patients. These products can cause clinically significant drug-drug interactions (DDIs) with antiretroviral (ARV) medications, thereby increasing risk for negative outcomes such as toxicity or loss of virologic control.
Areas covered: This article provides an updated review of the different mechanisms by which CAM and OTC products are implicated in DDIs with ARV medications.
Expert commentary: Much of the literature published to date involves studies of CAMs interacting with older ARV agents via the cytochrome P450 (CYP450) system. However, the HIV treatment and prevention arsenal is continually evolving. Furthermore, our elucidation of the role of non-CYP450 mediated DDIs with ARV medications is greatly increasing. Therefore, clinicians are well served to understand the various mechanisms and extent by which new ARV therapies may be involved in drug interactions with CAMs and OTC medications.
C1 [Brooks, Kristina M.; George, Jomy M.; Kumar, Parag] NIH, Clin Pharmacokinet Res Unit, Clin Ctr Pharm Dept, 10 Ctr Dr Bldg 10,Rm 1C-230G, Bethesda, MD 20892 USA.
RP Kumar, P (reprint author), NIH, Clin Pharmacokinet Res Unit, Clin Ctr Pharm Dept, 10 Ctr Dr Bldg 10,Rm 1C-230G, Bethesda, MD 20892 USA.
EM Parag.kumar@nih.gov
NR 166
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U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1751-2433
EI 1751-2441
J9 EXPERT REV CLIN PHAR
JI Expert Rev. Clin. Pharmacol.
PY 2017
VL 10
IS 1
BP 59
EP 79
DI 10.1080/17512433.2017.1246180
PG 21
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EL3MG
UT WOS:000394522600007
PM 27715369
ER
PT J
AU Ke, SZ
Chen, SZ
Dong, ZH
Hong, CS
Zhang, Q
Tang, L
Yang, PG
Zhai, J
Yan, HX
Shen, F
Zhuang, ZG
Wen, W
Wang, HY
AF Ke, Shizhong
Chen, Shuzhen
Dong, Zihui
Hong, Christopher S.
Zhang, Qi
Tang, Liang
Yang, Pinghua
Zhai, Jian
Yan, Hexin
Shen, Feng
Zhuang, Zhengping
Wen, Wen
Wang, Hongyang
TI Erythrocytosis in Hepatocellular Carcinoma Portends Poor Prognosis by
Respiratory Dysfunction Secondary to Mitochondrial DNA Mutations
SO HEPATOLOGY
LA English
DT Article
ID ERYTHROPOIETIN RECEPTOR; COMPLEX-I; BREAST-CANCER; DOUBLE-BLIND;
EXPRESSION; CELLS; CARDIOMYOPATHY; ENCEPHALOPATHY; DIAGNOSIS; APOPTOSIS
AB Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma. Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. We demonstrate an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas. In the subset of hepatocellular carcinoma patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting in impairment of respiratory metabolism, which sequentially led to depletion of a-ketoglutarate, stabilization of hypoxia inducible factor-alpha, and expression of target genes such as EPO. Cell lines and patient-derived xenograft models were used to demonstrate that EPO promoted cancer stem cell self-renewal and expansion in an autocrine/paracrine manner through enhanced Janus kinase/signal transducer and activator of transcription signaling both in vitro and in vivo. Furthermore, to explore the therapeutic targeting of EPO-induced tumor changes, we found that blocking EPO signaling with soluble EPO receptor extracellular domain Fc fusion protein could inhibit tumor growth both in vitro and in vivo. Conclusion: These findings suggest clinical and therapeutic implications for erythrocytosis in hepatocellular carcinoma. There is an underlying link between mitochondrial function and hypoxia inducible factor alpha signaling, revealing a mechanism of erythrocytosis in a subset of hepatocellular carcinoma patients who may benefit from treatment involving EPO signaling interference.
C1 [Ke, Shizhong; Wang, Hongyang] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst State Key Lab Oncogenes & Rel, Shanghai, Peoples R China.
[Chen, Shuzhen; Dong, Zihui; Tang, Liang; Yan, Hexin; Wen, Wen] Second Mil Med Univ, Natl Ctr Liver Canc, Shanghai, Peoples R China.
[Chen, Shuzhen; Dong, Zihui; Tang, Liang; Yan, Hexin; Wen, Wen; Wang, Hongyang] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Int Cooperat Lab Signal Transduct, 225 Changhai Rd, Shanghai 200438, Peoples R China.
[Hong, Christopher S.] NIH, Surg Neurol Branch, Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Yang, Pinghua; Shen, Feng] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg, Shanghai, Peoples R China.
[Zhai, Jian] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Int Radiol, Shanghai, Peoples R China.
[Wang, Hongyang] Second Mil Med Univ, Minist Educ MOE Key Lab Signaling Regulat & Targe, Shanghai, Peoples R China.
[Hong, Christopher S.] Yale Sch Med, Dept Neurosurg, New Haven, CT USA.
RP Wen, W; Wang, HY (reprint author), Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Int Cooperat Lab Signal Transduct, 225 Changhai Rd, Shanghai 200438, Peoples R China.
EM wenwen_smmu@163.com; hywangk@vip.sina.com
FU National Natural Science Foundation of China [81370061, 81521091,
81572896]; Personalized Medicines-Molecular Signature-based Drug
Discovery and Development, Strategic Priority Research Program of the
Chinese Academy of Sciences [XDA12010201-XDA12020102]
FX Supported by the National Natural Science Foundation of China (81370061,
81521091, and 81572896) and Personalized Medicines-Molecular
Signature-based Drug Discovery and Development, Strategic Priority
Research Program of the Chinese Academy of Sciences, Grant
No.XDA12010201-XDA12020102.
NR 49
TC 0
Z9 0
U1 1
U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2017
VL 65
IS 1
BP 134
EP 151
DI 10.1002/hep.28889
PG 18
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EP3RE
UT WOS:000397298600014
PM 27774607
ER
PT J
AU Navarro, VJ
Khan, I
Bjornsson, E
Seeff, LB
Serrano, J
Hoofnagle, JH
AF Navarro, Victor J.
Khan, Ikhlas
Bjoernsson, Einar
Seeff, Leonard B.
Serrano, Jose
Hoofnagle, Jay H.
TI Liver Injury From Herbal and Dietary Supplements
SO HEPATOLOGY
LA English
DT Review
ID ANABOLIC-ANDROGENIC STEROIDS; GREEN TEA; OXYELITE PRO; PLANT-MATERIAL;
UNITED-STATES; HEPATOTOXICITY; EXPERIENCE; TRENDS; SAFETY
AB Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced liver injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety.
C1 [Navarro, Victor J.; Seeff, Leonard B.] Einstein Healthcare Network, Div Hepatol, Philadelphia, PA USA.
[Khan, Ikhlas] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, Jackson, MS USA.
[Bjoernsson, Einar] Natl Univ Hosp Iceland, Reykjavik, Iceland.
[Bjoernsson, Einar] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Serrano, Jose; Hoofnagle, Jay H.] Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Res Branch, Bethesda, MD USA.
RP Navarro, VJ (reprint author), Einstein Med Ctr, Div Hepatol, 5401 Old York Rd,Suite 505, Philadelphia, PA 19141 USA.
EM Navarrov@einstein.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (NIH); American Association for the Study
of Liver Diseases; Office of Dietary Supplements, Office of the
Director, NIH; National Center for Complementary and Integrative Health,
NIH; National Institute of Environmental Health Services, NIH; US
Department of Agriculture; Centers for Disease Control and Prevention
FX This summary is based upon the research symposium Liver Injury From
Herbal and Dietary Supplements, held May 4-5, 2015, in Bethesda, MD,
which was funded by the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health (NIH), in collaboration
with the American Association for the Study of Liver Diseases with
support from the Office of Dietary Supplements, Office of the Director,
NIH; the National Center for Complementary and Integrative Health, NIH;
the National Institute of Environmental Health Services, NIH; the US
Department of Agriculture; and the Centers for Disease Control and
Prevention, with a special contribution by The National Center for
Natural Products Research, School of Pharmacy, University of Mississippi
(University, MS).
NR 47
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U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2017
VL 65
IS 1
BP 363
EP 373
DI 10.1002/hep.28813
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EP3RE
UT WOS:000397298600031
PM 27677775
ER
PT J
AU Fontana, RJ
Engle, RE
Purcell, RH
Lee, WM
AF Fontana, Robert J.
Engle, Ronald E.
Purcell, Robert H.
Lee, William M.
TI Hepatitis E in Decompensated Alcoholic Cirrhosis REPLY
SO HEPATOLOGY
LA English
DT Letter
ID E VIRUS-INFECTION
C1 [Fontana, Robert J.] Univ Michigan, Med Ctr, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA.
[Engle, Ronald E.; Purcell, Robert H.] NIAID, Bethesda, MD USA.
[Lee, William M.] Univ Texas Southwestern, Dallas, TX USA.
RP Fontana, RJ (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA.
FU Bristol-Myers Squibb; Janssen; Gilead; Merck; Ocera; Exalenz
FX Dr. Fontana received grants from Bristol-Myers Squibb, Janssen, and
Gilead. Dr. Lee consults for Novartis and Sanofi and received grants
from Bristol-Myers Squibb, Gilead, Merck, Ocera, and Exalenz.
NR 5
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U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2017
VL 65
IS 1
BP 389
EP 390
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EP3RE
UT WOS:000397298600038
PM 27616011
ER
PT J
AU Boyce, AM
Collins, MT
Tosi, LL
Gafni, RI
AF Boyce, Alison M.
Collins, Michael T.
Tosi, Laura L.
Gafni, Rachel I.
TI A Subtrochanteric Femoral Stress Fracture following Bisphosphonate
Treatment in an Adolescent Girl
SO HORMONE RESEARCH IN PAEDIATRICS
LA English
DT Article
DE Atypical subtrochanteric and diaphyseal femoral fractures;
Bisphosphonates
ID DIAPHYSEAL FRACTURES; SHAFT; FEMUR; DXA
AB Atypical subtrochanteric and diaphyseal femoral fractures (AFFs) have emerged as a potential complication of bisphosphonate treatment in adults. Despite increasing off-label use of bisphosphonates in children and adolescents for a variety of skeletal disorders, there have been no reports of AFFs in children or adolescents outside of the osteogenesis imperfecta population. We present the case of a 16-year-old girl who developed a subtrochanteric femoral stress fracture following pamidronate treatment for idiopathic juvenile osteoporosis. (C) 2016 S. Karger AG, Basel
C1 [Boyce, Alison M.; Collins, Michael T.; Gafni, Rachel I.] NIDCR, Sect Skeletal Disorders & Mineral Homeostasis, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr Bldg 30,Room 228 MSC 4320, Bethesda, MD 20892 USA.
[Boyce, Alison M.; Tosi, Laura L.] Childrens Natl Hlth Syst, Bone Hlth Program, Div Orthopaed & Sports Med, Washington, DC USA.
[Boyce, Alison M.] Childrens Natl Hlth Syst, Div Endocrinol & Diabet, Washington, DC USA.
RP Boyce, AM (reprint author), NIDCR, Sect Skeletal Disorders & Mineral Homeostasis, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr Bldg 30,Room 228 MSC 4320, Bethesda, MD 20892 USA.
EM boyceam@mail.nih.gov
FU Intramural NIH HHS [Z99 DE999999]
NR 14
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1663-2818
EI 1663-2826
J9 HORM RES PAEDIAT
JI Horm. Res. Paediatr.
PY 2017
VL 87
IS 1
BP 69
EP 72
DI 10.1159/000447425
PG 4
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA EN3GG
UT WOS:000395896400010
PM 27379824
ER
PT J
AU Kamal, A
Sinha, A
Hutfless, SM
Afghani, E
Faghih, M
Khashab, MA
Lennon, AM
Yadav, D
Makary, MA
Andersen, DK
Kalloo, AN
Singh, VK
AF Kamal, Ayesha
Sinha, Amitasha
Hutfless, Susan M.
Afghani, Elham
Faghih, Mahya
Khashab, Mouen A.
Lennon, Anne Marie
Yadav, Dhiraj
Makary, Martin A.
Andersen, Dana K.
Kalloo, Anthony N.
Singh, Vikesh K.
TI Hospital admission volume does not impact the in-hospital mortality of
acute pancreatitis
SO HPB
LA English
DT Article
ID ORGAN FAILURE; UNITED-STATES; NECROTIZING PANCREATITIS; DYNAMIC NATURE;
CLINICAL-DATA; CO-MORBIDITY; RISK; EPIDEMIOLOGY; DYSFUNCTION; PERSISTENT
AB Background: Multiple factors influence mortality in Acute Pancreatitis (AP).
Methods: To evaluate the association of demographic, clinical, and hospital factors with the in-hospital mortality of AP using a population-based administrative database. The Maryland HSCRC database was queried for adult (>= 18 years) admissions with primary diagnosis of AP between 1/94-12/10. Organ failure (OF), interventions, hospital characteristics and referral status were evaluated.
Results: There were 72,601 AP admissions across 48 hospitals in Maryland with 885 (1.2%) deaths. A total of 1657 (2.3%) were transfer patients, of whom 101 (6.1%) died. Multisystem OF was present in 1078 (1.5%), of whom 306 (28.4%) died. On univariable analysis, age, male gender, transfer status, comorbidity, OF, all interventions, and all hospital characteristics were significantly associated with mortality; however, only age, transfer status, OF, interventions, and large hospital size were significant in the adjusted analysis. Patients with commercial health insurance had significantly less mortality than those with other forms of insurance (OR 0.65, 95% Cl: 0.52, 0.82, p = 0.0002). Conclusion: OF is the strongest predictor of mortality in AP after adjusting for demographic, clinical, and hospital characteristics. Admission to HV or teaching hospital has no survival benefit in AP after adjusting for OF and transfer status.
C1 [Makary, Martin A.; Kalloo, Anthony N.; Singh, Vikesh K.] Johns Hopkins Univ, Sch Med, Pancreatitis Ctr, Baltimore, MD USA.
[Kamal, Ayesha; Sinha, Amitasha; Hutfless, Susan M.; Faghih, Mahya; Khashab, Mouen A.; Lennon, Anne Marie; Kalloo, Anthony N.; Singh, Vikesh K.] Johns Hopkins Univ, Sch Med, Div Gastroenterol, Baltimore, MD USA.
[Makary, Martin A.] Johns Hopkins Univ, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21205 USA.
[Yadav, Dhiraj] Univ Pittsburgh, Div Gastroenterol, Sch Med, Pittsburgh, PA USA.
[Andersen, Dana K.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Afghani, Elham] Cedars Sinai Med Ctr, Ctr Digest Dis, Los Angeles, CA 90048 USA.
RP Singh, VK (reprint author), Johns Hopkins Univ Hosp, Div Gastroenterol, 1830 E Monument St,Room 428, Baltimore, MD 21205 USA.
EM vsingh1@jhmi.edu
NR 50
TC 0
Z9 0
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1365-182X
EI 1477-2574
J9 HPB
JI HPB
PD JAN
PY 2017
VL 19
IS 1
BP 21
EP 28
DI 10.1016/j.hpb.2016.10.013
PG 8
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA EK8RZ
UT WOS:000394193100005
PM 27887788
ER
PT J
AU Farag, A
Lu, L
Roth, HR
Liu, JM
Turkbey, E
Summers, RM
AF Farag, Amal
Lu, Le
Roth, Holger R.
Liu, Jiamin
Turkbey, Evrim
Summers, Ronald M.
TI A Bottom-Up Approach for Pancreas Segmentation Using Cascaded
Superpixels and (Deep) Image Patch Labeling
SO IEEE TRANSACTIONS ON IMAGE PROCESSING
LA English
DT Article
DE Abdominal computed tomography (CT); deep convolutional neural networks;
dense image patch labeling; cascaded random forest; pancreas
segmentation
ID FEATURES; ALGORITHM; NETWORKS
AB Robust organ segmentation is a prerequisite for computer-aided diagnosis, quantitative imaging analysis, pathology detection, and surgical assistance. For organs with high anatomical variability (e.g., the pancreas), previous segmentation approaches report low accuracies, compared with well-studied organs, such as the liver or heart. We present an automated bottom-up approach for pancreas segmentation in abdominal computed tomography (CT) scans. The method generates a hierarchical cascade of information propagation by classifying image patches at different resolutions and cascading (segments) superpixels. The system contains four steps: 1) decomposition of CT slice images into a set of disjoint boundary-preserving superpixels; 2) computation of pancreas class probability maps via dense patch labeling; 3) superpixel classification by pooling both intensity and probability features to form empirical statistics in cascaded random forest frameworks; and 4) simple connectivity based post-processing. Dense image patch labeling is conducted using two methods: efficient random forest classification on image histogram, location and texture features; and more expensive (but more accurate) deep convolutional neural network classification, on larger image windows (i.e., with more spatial contexts). Over-segmented 2 - D CT slices by the simple linear iterative clustering approach are adopted through model/parameter calibration and labeled at the superpixel level for positive (pancreas) or negative (non-pancreas or background) classes. The proposed method is evaluated on a data set of 80 manually segmented CT volumes, using six-fold cross-validation. Its performance equals or surpasses other state-of-the-art methods (evaluated by " leave-one-patient-out"), with a dice coefficient of 70.7% and Jaccard index of 57.9%. In addition, the computational efficiency has improved significantly, requiring a mere 6 similar to 8 min per testing case, versus >= 10 h for other methods. The segmentation framework using deep patch labeling confidences is also more numerically stable, as reflected in the smaller performance metric standard deviations. Finally, we implement a multi-atlas label fusion (MALF) approach for pancreas segmentation using the same data set. Under six-fold cross-validation, our bottom-up segmentation method significantly outperforms its MALF counterpart: 70.7 +/- 13.0% versus 52.51 +/- 20.84% in dice coefficients.
C1 [Farag, Amal; Lu, Le; Liu, Jiamin; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Lu, Le; Summers, Ronald M.] NIH, Clin Image Proc Serv, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Roth, Holger R.] Nagoya Univ, Nagoya, Aichi 4648602, Japan.
[Turkbey, Evrim] NIH, Clin Image Proc Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Turkbey, Evrim] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
RP Lu, L (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM le.lu@nih.gov; rms@nih.gov
OI Lu, Le/0000-0002-6799-9416
FU National Institutes of Health Clinical Center
FX This work was supported by the Intramural Research Program of the
National Institutes of Health Clinical Center. The associate editor
coordinating the review of this manuscript and approving it for
publication was Prof. Chunming Li.
NR 49
TC 0
Z9 0
U1 4
U2 4
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1057-7149
EI 1941-0042
J9 IEEE T IMAGE PROCESS
JI IEEE Trans. Image Process.
PD JAN
PY 2017
VL 26
IS 1
BP 386
EP 399
DI 10.1109/TIP.2016.2624198
PG 14
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA EP2OB
UT WOS:000397221700004
ER
PT J
AU Vila, A
Dapas, JI
Rivero, CV
Bocanegra, F
Furnari, RF
Hsu, AP
Holland, SM
AF Vila, Andrea
Dapas, Juan I.
Rivero, Cynthia V.
Bocanegra, Florencia
Furnari, Roberto F.
Hsu, Amy P.
Holland, Steven M.
TI Multiple Opportunistic Infections in a Woman with GATA2 Mutation
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE GATA2 mutation; MonoMAC syndrome; monocytopenia; GATA2 deficiency
ID ACUTE MYELOID-LEUKEMIA; SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT;
MONOMAC SYNDROME; DEFICIENCY; CELL
AB GATA2 deficiency is a genetic disorder caused by inherited or sporadic haploinsufficient mutations in the GATA2 gene. Patients have abnormalities in hematopoiesis, lymphangiogenesis and immunity; encompassing a broad range of clinical syndromes, mainly characterized by monocytopenia, B and NK cell cytopenia, severe or recurrent infections, and a high risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
We report a case of an Argentinean woman who presented with multiple opportunistic infections as her first manifestation of GATA2 deficiency. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
C1 [Vila, Andrea; Dapas, Juan I.; Rivero, Cynthia V.] Hosp Italiano Mendoza, Dept Infect Dis, Ave Acceso Este 1070, San Jose, Mendoza, Argentina.
[Bocanegra, Florencia; Furnari, Roberto F.] Hosp Italiano Mendoza, Dept Internal Med, Ave Acceso Este 1070, San Jose, Mendoza, Argentina.
[Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Vila, A (reprint author), Hosp Italiano Mendoza, Ave Acceso Este Lateral Norte 1070,CP 5519, San Jose, Mendoza, Argentina.
EM santander@arlink.net.ar
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
FX This work was supported in part by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD, USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD JAN
PY 2017
VL 54
BP 89
EP 91
DI 10.1016/j.ijid.2016.11.408
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA EO0YY
UT WOS:000396425800020
PM 27894982
ER
PT J
AU Togias, A
Cooper, SF
Acebal, ML
Assa'ad, A
Baker, JR
Beck, LA
Block, J
Byrd-Bredbenner, C
Chan, ES
Eichenfield, LF
Fleischer, DM
Fuchs, GJ
Furuta, GT
Greenhawt, MJ
Gupta, RS
Habich, M
Jones, SM
Keaton, K
Muraro, A
Plaut, M
Rosenwasser, LJ
Rotrosen, D
Sampson, HA
Schneider, LC
Sicherer, SH
Sidbury, R
Spergel, J
Stukus, DR
Venter, C
Boyce, JA
AF Togias, Alkis
Cooper, Susan F.
Acebal, Maria L.
Assa'ad, Amal
Baker, James R., Jr.
Beck, Lisa A.
Block, Julie
Byrd-Bredbenner, Carol
Chan, Edmond S.
Eichenfield, Lawrence F.
Fleischer, David M.
Fuchs, George J., III
Furuta, Glenn T.
Greenhawt, Matthew J.
Gupta, Ruchi S.
Habich, Michele
Jones, Stacie M.
Keaton, Kari
Muraro, Antonella
Plaut, Marshall
Rosenwasser, Lanny J.
Rotrosen, Daniel
Sampson, Hugh A.
Schneider, Lynda C.
Sicherer, Scott H.
Sidbury, Robert
Spergel, Jonathan
Stukus, David R.
Venter, Carina
Boyce, Joshua A.
TI Addendum guidelines for the prevention of peanut allergy in the United
States: Report of the National Institute of Allergy and Infectious
Diseases-sponsored expert panel
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Food; peanut; allergy; prevention; guidelines
ID FOOD ALLERGY; NUTRITIONAL INTERVENTIONS; ANAPHYLACTIC REACTIONS; GRADING
QUALITY; HIGH-RISK; INFANTS; PREVALENCE; CONSUMPTION; RECOMMENDATIONS;
FEASIBILITY
AB Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.
Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.
Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.
Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
C1 [Togias, Alkis; Cooper, Susan F.; Plaut, Marshall; Rotrosen, Daniel] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Acebal, Maria L.] Food Allergy Res & Educ, Board Directors, Mclean, VA 22102 USA.
[Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45221 USA.
[Baker, James R., Jr.] Food Allergy Res & Educ, Ann Arbor, MI 22102 USA.
[Baker, James R., Jr.] Univ Michigan Hlth Syst, Div Allergy & Clin Immunol, Ann Arbor, MI USA.
[Beck, Lisa A.] Univ Rochester, Med Ctr, Dept Dermatol, Rochester, NY 14627 USA.
[Block, Julie] Natl Eczema Assoc, San Rafael, CA USA.
[Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA.
[Chan, Edmond S.] Univ British Columbia, BC Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Vancouver, WA USA.
[Eichenfield, Lawrence F.] Univ Calif San Diego, Rady Childrens Hosp, San Diego Sch Med, Dept Dermatol, San Diego, CA 92103 USA.
[Eichenfield, Lawrence F.] Univ Calif San Diego, Rady Childrens Hosp, San Diego Sch Med, Dept Pediat, San Diego, CA 92103 USA.
[Fleischer, David M.; Greenhawt, Matthew J.] Univ Colorado, Denver Sch Med, Childrens Hosp Colorado, Dept Pediat,Sect Allergy & Immunol, Aurora, CO USA.
[Fuchs, George J., III] Univ Kentucky, Coll Med, Kentucky Childrens Hosp, Dept Pediat,Div Gastroenterol Hepatol & Nutr, Lexington, KY 40506 USA.
[Furuta, Glenn T.] Childrens Hosp Colorado, Digest Hlth Inst, Aurora, CO 80045 USA.
[Furuta, Glenn T.] Univ Colorado, Denver Sch Med, Sect Pediat Gastroenterol, Aurora, CO 80045 USA.
[Gupta, Ruchi S.] Northwestern Univ, Dept Pediat, Div Acad Gen Pediat & Primary Care, Chicago, IL 60611 USA.
[Gupta, Ruchi S.] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Chicago, IL 60611 USA.
[Habich, Michele] Cent DuPage Hosp, Northwestern Med, Winfield, KS USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Dept Pediat, Div Allergy & Immunol, Arkansas Childrens Hosp, Little Rock, AR 72205 USA.
[Keaton, Kari] Metro DC Food Allergy Support Grp, Rockville, MD 20850 USA.
[Muraro, Antonella] Padua Univ Hosp, Dept Women & Child Hlth, Food Allergy Referral Ctr, Padua, Italy.
[Rosenwasser, Lanny J.] Univ Missouri Kansas City, Sch Med, Kansas City, KS 64110 USA.
[Sampson, Hugh A.] Icahn Sch Med Mt Sinai, Dept Pediat, Div Allergy & Immunol, New York, NY 10029 USA.
[Sicherer, Scott H.] Icahn Sch Med Mt Sinai, Div Pediat Allergy & Immunol, New York, NY 10029 USA.
[Schneider, Lynda C.] Boston Childrens Hosp, Div Allergy & Immunol, Boston, MA 02115 USA.
[Sidbury, Robert] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp,Div Dermatol, Seattle, WA 98195 USA.
[Spergel, Jonathan] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Allergy & Immunol,Dept Pediat, Philadelphia, PA 19104 USA.
[Stukus, David R.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Dept Pediat,Sect Allergy & Immunol, Columbus, OH 43210 USA.
[Venter, Carina] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA.
RP Cooper, SF (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 5601 Fishers Lane,Room 7C28, Rockville, MD 20892 USA.
EM coopersu@niaid.nih.gov
FU DBV Technologies; Aimmune; Stanford Foundation; TEVA Pharmaceuticals;
GlaxoSmithKline; National Institutes of Health (NIH); Astellas; Food
Allergy Research & Education (FARE); Monsanto Company; Nestle Nutrition
Institute; Aimmune Therapeutics; Agency for Healthcare Research and
Quality [1K08HS024599-01]; NIH; FARE; Mylan LLC; NIH/NIAID (Consortium
of Food Allergy Research and Immune Tolerance Network IMPACT Trial);
National Peanut Board; NIAID; Immune Tolerance Network; HAL Allergy;
ACAAI; Pfizer; Sanofi; Mead Johnson; Nestle; Grand Rounds; Kansas City
Allergy Society; Mercy Children's Hospital; Riley Children's Hospital;
Southwester Medical School Children's Medical Center; European Academy
of Allergy & Clinical Immunology; New York Allergy Asthma Society;
University of Iowa Paul M. Seebohm Lectureship in Allergy; Iowa Society
of Allergy; Asthma; Immunology; Taiwanese Dermatological Society;
Dartmouth College; Florida Allergy Society
FX A. Assa' ad received travel support from the American College of
Allergy, Asthma & Immunology (ACAAI); was an elected member of the Board
of Directors for the American Academy of Allergy, Asthma, & Immunology
(AAAAI) from March 2012 to March 2016; has consultant arrangements with
Aimmune; is employed by Cincinnati Children's Hospital Medical Center;
has received grants from DBV Technologies, Aimmune, Stanford Foundation,
TEVA Pharmaceuticals, GlaxoSmithKline, the National Institutes of Health
(NIH), Astellas, and Food Allergy Research & Education (FARE); and has
received payment for lectures from the ACAAI. C. Byrd-Bredbenner and G.
J. Fuchs III have received travel support from the NIH/National
Institute of Allergy and Infectious Disease (MAID). E. S. Chan has
received travel support from the NIAID, has received grants from DBV
Technologies, and has received payment for lectures from Pfizer, Sanofi,
Mead Johnson, and Nestle. D. M. Fleischer has received travel support
from the NIAID; is a board member for the National Peanut Board, the
FAACT Medical Advisory Board, and the FARE Medical Advisory Board; has
consultant arrangements with Adamis Pharmaceuticals Corporation, INSYS
Therapeutics, DBV Technologies, Aimmune Therapeutics, Intrommune
Therapeutics, and Kaleo Pharma; is employed by University Physicians;
has received grants from Monsanto Company, Nestle Nutrition Institute,
DBV Technologies, and Aimmune Therapeutics; has received payment for
lectures from Nestle Nutrition Institute; and has received royalties
from UpToDate. M. J. Greenhawt has received a grant from the Agency for
Healthcare Research and Quality (1K08HS024599-01, Career Development
Award); has received travel support from the MAID and the Joint
Taskforce on Allergy Practice Parameters; has a board membership with
the National Peanut Board; has consultant arrangements with Adamis
Pharmaceuticals, the Canadian Transportation Agency, Nutricia,
Nestle/Gerber, Aimmune, Kaleo Pharmaceutical, and Monsanto; is an
Associate Editor for the Annals of Allergy, Asthma, and Immunology; has
received payment for lectures from the ACAAI, Reach MD, Thermo Fisher
Scientific, the California Society for Allergy and Immunology, the
Allergy and Asthma Network, the New England Society for Allergy,
UCLA/Harbor Heiner Lectureship, Medscape, the Western Michigan School of
Medicine, the Canadian Society of Allergy and Clinical Immunology, and
the Pennsylvania Society for Allergy and Immunology. R. S. Gupta has
consultant arrangements with BEFORE Brands and DBV Technologies; has
received grants from the NIH, FARE, and Mylan LLC; has received payment
for lectures from Grand Rounds; and has received royalties from
Createspace Independent Publishing Platform. S. M. Jones is on the
Research Advisory Board for FARE; is on the Scientific Advisory Board
for Aimmune; has consultant arrangements with Stallergenes; has received
grants from the NIH/NIAID (Consortium of Food Allergy Research and
Immune Tolerance Network IMPACT Trial), FARE, Aimmune Technologies, DBV
Technologies, and the National Peanut Board; has received payment for
lectures from the Kansas City Allergy Society, Mercy Children's
Hospital, Riley Children's Hospital, Southwester Medical School
Children's Medical Center, the European Academy of Allergy & Clinical
Immunology, the New York Allergy & Asthma Society, the University of
Iowa Paul M. Seebohm Lectureship in Allergy, and the Iowa Society of
Allergy, Asthma, and Immunology. A.; Muraro has consultant arrangements
with Meda, Novartis, and Menarini; is employed by Padua University
Hospital; and has received payment for lectures from Meda and Menarini.
L. J. Rosenwasser is a board member for the World Allergy Organization H
A Sampson has consultant arrangements with Allertein Therapeutics,
Genentech/Roche, Sanofi, Stallergenes, Danone, and Merck; is employed
part time as Chief Scientific Officer for DBV Technologies; has received
grants from the NIAID and the Immune Tolerance Network; has received
royalties from UpToDate and Elsevier; has been offered stock options in
DBV Technologies; and is chairman of PhARF Award Selection Committee for
Thermo Fisher. L. C. Schneider is on the Medical Advisory Board for
FARE, has received a grant from DBV Technologies, and has received
stock/stock options in Antera Therapeutics. S. H. Sicherer has received
grants from the NIAID, FARE, and HAL Allergy; has received royalties
from UpToDate; and is serving as Associate Editor for the Journal of
Allergy and Clinical Immunology: In Practice. R. Sidbury has received
travel support from the NIH and the Hawaii Dermatology Seminar, has
consultant arrangements with Anacor, has provided expert witness
testimony on behalf of Roche in Accutane inflammatory bowel disease
cases, has received a grant from Epidermolysis Bullosa Research
Partnership, has received payment for lectures from the Taiwanese
Dermatological Society, and has received royalties from UpToDate. J.
Spergel has consultant arrangements with DBV Technologies and Danone;
has received grants from DBV Technologies, Aimmune Therapeutics, and the
NIH; has received payment for lectures for Dartmouth College, the ACAAI,
and the Florida Allergy Society; and has received stock/stock options in
DBV Technologies. D. R. Stukus has received payment for lectures from
the ACAAI. C. Venter has consultant arrangements with Danone and Nestle,
has received payment for lectures from Mead Johnson, and has received
travel support from Thermo Fisher. The rest of the authors declare that
they have no relevant conflicts of interest.
NR 29
TC 2
Z9 2
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JAN
PY 2017
VL 139
IS 1
BP 29
EP 44
DI 10.1016/j.jaci.2016.10.010
PG 16
WC Allergy; Immunology
SC Allergy; Immunology
GA EK5WM
UT WOS:000393996800004
PM 28065278
ER
PT J
AU Kennedy, EA
Connolly, J
Hourihane, JO
Fallon, PG
McLean, WHI
Murray, D
Jo, JH
Segre, JA
Kong, HH
Irvine, AD
AF Kennedy, Elizabeth A.
Connolly, Jennifer
Hourihane, Jonathan O'B.
Fallon, Padraic G.
McLean, W. H. Irwin
Murray, Deirdre
Jo, Jay-Hyun
Segre, Julia A.
Kong, Heidi H.
Irvine, Alan D.
TI Skin microbiome before development of atopic dermatitis: Early
colonization with commensal staphylococci at 2 months is associated with
a lower risk of atopic dermatitis at 1 year
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Staphylococcus aureus; atopic dermatitis; skin; microbiome; longitudinal
birth cohort; 16S sequencing
ID PARTY DIAGNOSTIC-CRITERIA; HAY-FEVER; ALLERGIC SENSITIZATION; CESAREAN
DELIVERY; BODY HABITATS; CHILDREN; CELLS; DISEASE; AUREUS; LIFE
AB Background: Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown.
Methods: We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological andNutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples.
Results: Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD.
Conclusions: This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD.
C1 [Kennedy, Elizabeth A.; Jo, Jay-Hyun; Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Connolly, Jennifer; Hourihane, Jonathan O'B.; Murray, Deirdre] Univ Coll, Paediat & Child Hlth, Cork, Ireland.
[Fallon, Padraic G.; Irvine, Alan D.] Cork Univ Matern Hosp, Irish Ctr Fetal & Neonatal Translat INFANT Res, Cork, Ireland.
[Fallon, Padraic G.; Irvine, Alan D.] Trin Coll Dublin, Med Clin, Dublin, Ireland.
[Irvine, Alan D.] Univ Dundee, Natl Childrens Res Ctr, Dundee DD1 4HN, Scotland.
[Irvine, Alan D.] Univ Dundee, Paediat Dermatol, Our Ladys Childrens Hosp Crumlin, Dundee DD1 4HN, Scotland.
[McLean, W. H. Irwin] Univ Dundee, Dermatol & Genet Med, Dundee DD1 4HN, Scotland.
[Segre, Julia A.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Irvine, AD (reprint author), Our Ladys Childrens Hosp Crumlin, Natl Childrens Res Ctr, Dublin 12, Ireland.; Kong, HH (reprint author), NCI, Dermatol Branch, CCR, NIH, 10 Ctr Dr,Bldg 10-MSC 1908, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; irvinea@tcd.ie
FU National Children's Research Centre (NCRC), Dublin, Ireland; NCRC; UK
Food Standards Agency (FSA); Intramural Research Program of the National
Institutes of Health's National Cancer Institute; National Human Genome
Research Institute; Korean Health Technology R&D Project, Ministry of
Health and Welfare, Republic of Korea [HI15C1095]
FX A.D.I. is funded by the National Children's Research Centre (NCRC),
Dublin, Ireland. The NCRC is the primary funding source for the ongoing
Cork BASELINE birth cohort. Additional support came from the UK Food
Standards Agency (FSA). The work was also supported by the Intramural
Research Program of the National Institutes of Health's National Cancer
Institute (to E.A.K., J.-H.J., and H.H.K.) and the National Human Genome
Research Institute (to J.A.S.). J.-H.J. is also supported by a grant
from the Korean Health Technology R&D Project, Ministry of Health and
Welfare, Republic of Korea (HI15C1095).
NR 44
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PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JAN
PY 2017
VL 139
IS 1
BP 166
EP 172
DI 10.1016/j.jaci.2016.07.029
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA EK5WM
UT WOS:000393996800018
PM 27609659
ER
PT J
AU Meyer, ML
Palta, P
Tanaka, H
Deal, JA
Wright, J
Knopman, DS
Griswold, ME
Mosley, TH
Heiss, G
AF Meyer, Michelle L.
Palta, Priya
Tanaka, Hirofumi
Deal, Jennifer A.
Wright, Jacqueline
Knopman, David S.
Griswold, Michael E.
Mosley, Thomas H.
Heiss, Gerardo
TI Association of Central Arterial Stiffness and Pressure Pulsatility with
Mild Cognitive Impairment and Dementia: The Atherosclerosis Risk in
Communities Study-Neurocognitive Study (ARIC-NCS)
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Article
DE Alzheimer's disease; brain; cognition; dementia; mild cognitive
impairment; pulse wave velocity
ID PULSE-WAVE VELOCITY; SMALL-VESSEL DISEASE; VASCULAR DEMENTIA;
ALZHEIMERS-DISEASE; OLDER-ADULTS; DIAGNOSTIC GUIDELINES; NATIONAL
INSTITUTE; PHYSICAL-ACTIVITY; UNITED-STATES; NINDS-AIREN
AB Background: The association of central arterial stiffness and pressure pulsatility with mild cognitive impairment (MCI) and dementia is not well characterized in the population-based setting.
Objective: The aim of this study was to quantify the cross-sectional association of arterial stiffness and pressure pulsatility with MCI and dementia among 4,461 older white and black adults from the population-based Atherosclerosis Risk in Communities Study-Neurocognitive Study.
Methods: We used race-stratified multinomial logistic regression to evaluate associations of percentile cut points of carotidfemoral pulse wave velocity, central systolic blood pressure, central pulse pressure, and pulse pressure amplification with MCI and dementia versus no cognitive impairment.
Results: Among whites, those with carotid-femoral pulse wave velocity or central systolic blood pressure >= 75th percentile had a higher prevalence of MCI compared to participants < 75th percentile (conditional odds ratio (OR); 95% confidence interval (CI): 1.27 (1.02, 1.56) and 1.28 (1.04, 1.57), respectively) and those with central pulse pressure >= 25th percentile had a higher prevalence of MCI (OR 1.27 (95% CI: 1.03, 1.58)) and dementia (OR 1.76 (95% CI: 1.06, 2.92) compared to participants < 75th percentile. Also among whites, those with pulse pressure amplification <= 25th percentile had a higher prevalence of dementia compared to participants > 25th percentile (OR 1.65; (95% CI: 1.01, 2.70). Weaker associations were seen among black participants.
Conclusion: Higher arterial stiffness and pulsatility were associated with MCI and dementia in white participants. Longitudinal characterization of the observed associations is warranted to assess whether arterial stiffness and pressure pulsatility predict MCI and dementia among older adults.
C1 [Meyer, Michelle L.; Palta, Priya; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Tanaka, Hirofumi] Univ Texas Austin, Dept Kinesiol & Hlth Educ, Austin, TX 78712 USA.
[Deal, Jennifer A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Wright, Jacqueline] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
RP Meyer, ML (reprint author), Univ N Carolina, Dept Emergency Med, 170 Manning Dr, Chapel Hill, NC 27599 USA.
EM michelle_meyer@med.unc.edu
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; NHLBI T32 training grant [HL-007055]
FX The authors thank the staff and participants of the ARIC study for their
important contributions. The Atherosclerosis Risk in Communities Study
is carried out as a collaborative study supported by National Heart,
Lung, and Blood Institute contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C). Neurocognitive data was collected by U01 HL096812,
HL096814, HL096899, HL096902, and HL096917 with previous brain MRI
examinations funded by R01-HL70825. MLM was supported by the NHLBI T32
training grant HL-007055. The views expressed in this manuscript are
those of the authors and do not necessarily represent the views of the
National Heart, Lung, and Blood Institute; the National Institutes of
Health; or the U.S. Department of Health and Human Services.
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PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 1387-2877
EI 1875-8908
J9 J ALZHEIMERS DIS
JI J. Alzheimers Dis.
PY 2017
VL 57
IS 1
BP 195
EP 204
DI 10.3233/JAD-161041
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA EN8SQ
UT WOS:000396270500017
PM 28222517
ER
PT J
AU Faruque, MU
Chen, GJ
Doumatey, AP
Zhou, J
Huang, HX
Shriner, D
Adeyemo, AA
Rotimi, CN
Dunston, GM
AF Faruque, Mezbah U.
Chen, Guanjie
Doumatey, Ayo P.
Zhou, Jie
Huang, Hanxia
Shriner, Daniel
Adeyemo, Adebowale A.
Rotimi, Charles N.
Dunston, Georgia M.
TI Transferability of genome-wide associated loci for asthma in African
Americans
SO JOURNAL OF ASTHMA
LA English
DT Article
DE Asthma; replication; single nucleotide polymorphism; genetic
association; African Americans; IL33; ethnicity
ID POPULATION DIFFERENTIATION; GENETIC ASSOCIATION; UNITED-STATES; DISEASE;
REPLICATION; IL-33; VARIANTS; CELLS; STRATIFICATION; METAANALYSIS
AB Objective: Transferability of significantly associated loci or GWAS hits adds credibility to genotype-disease associations and provides evidence for generalizability across different ancestral populations. We sought evidence of association of known asthma-associated single nucleotide polymorphisms (SNPs) in an African American population. Methods: Subjects comprised 661 participants (261 asthma cases and 400 controls) from the Howard University Family Study. Forty-eight SNPs previously reported to be associated with asthma by GWAS were selected for testing. We adopted a combined strategy by first adopting an exact approach where we looked-up only the reported index SNP. For those index SNPs missing form our dataset, we used a local approach that examined all the regional SNPs in LD with the index SNP. Results: Out of the 48 SNPs, our cohort had genotype data available for 27, which were examined for exact replication. Of these, two SNPs were found positively associated with asthma. These included: rs10508372 (OR = 1.567 [95%CI, 1.133-2.167], P = 0.0066) and rs2378383 (OR = 2.147 [95%CI, 1.149-4.013], P = 0.0166), located on chromosomal bands 10p14 and 9q21.31, respectively. Local replication of the remaining 21 loci showed association at two chromosomal loci (9p24.1-rs2381413 and 6p21.32-rs3132947; Bonferroni-corrected P values: 0.0033 and 0.0197, respectively). Of note, multiple SNPs in LD with rs2381413 located upstream of IL33 were significantly associated with asthma. Conclusions: This study has successfully transferred four reported asthma-associated loci in an independent African American population. Identification of several asthma-associated SNPs in the upstream of the IL33, a gene previously implicated in allergic inflammation of asthmatic airway, supports the generalizability of this finding.
C1 [Faruque, Mezbah U.; Dunston, Georgia M.] Howard Univ, Coll Med, Natl Human Genome Ctr, Washington, DC 20059 USA.
[Chen, Guanjie; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Shriner, Daniel; Adeyemo, Adebowale A.; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
RP Faruque, MU (reprint author), Howard Univ, Ctr Canc, 2041 Georgia Ave,NW,Rm 612, Washington, DC 20060 USA.
EM mfaruque@howard.edu
FU MBRS/SCORE Program of the National Institute of General Medical
Sciences, National Institutes of Health (NIH) [S06GM008016-320107,
S06GM008016-380111]; National Center for Research Resources (NCRR), NIH
[2M01RR010284]; RCMI Program at Howard University - Division of Research
Infrastructure, NCRR, NIH [RR003048]; Intramural Research Program of the
Center for Research on Genomics and Global Health (CRGGH); National
Human Genome Research Institute; National Institute of Diabetes and
Digestive and Kidney Diseases; Center for Information Technology; Office
of the Director at the NIH [Z01HG200362]
FX The Howard University Family Study (HUFS) was supported by grants
S06GM008016-320107 to C.N.R. and S06GM008016-380111 to A.A.A., both from
the MBRS/SCORE Program of the National Institute of General Medical
Sciences, National Institutes of Health (NIH). Participant enrollment
for the HUFS was carried out at the Howard University General Clinical
Research Center, which is supported by grant 2M01RR010284 from the
National Center for Research Resources (NCRR), NIH. This research was
supported in part by the RCMI Program at Howard University funded by the
Division of Research Infrastructure, NCRR, NIH (RR003048) and by the
Intramural Research Program of the Center for Research on Genomics and
Global Health (CRGGH). The CRGGH is supported by the National Human
Genome Research Institute, the National Institute of Diabetes and
Digestive and Kidney Diseases, the Center for Information Technology,
and the Office of the Director at the NIH (Z01HG200362).
NR 54
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PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0277-0903
EI 1532-4303
J9 J ASTHMA
JI J. Asthma
PY 2017
VL 54
IS 1
BP 1
EP 8
DI 10.1080/02770903.2016.1188941
PG 8
WC Allergy; Respiratory System
SC Allergy; Respiratory System
GA EM1FZ
UT WOS:000395064800001
PM 27177148
ER
PT J
AU Radin, RG
Sjaarda, LA
Perkins, NJ
Silver, RM
Chen, Z
Lesher, LL
Galai, N
Wactawski-Wende, J
Mumford, SL
Schisterman, EF
AF Radin, Rose G.
Sjaarda, Lindsey A.
Perkins, Neil J.
Silver, Robert M.
Chen, Zhen
Lesher, Laurie L.
Galai, Noya
Wactawski-Wende, Jean
Mumford, Sunni L.
Schisterman, Enrique F.
TI Low-Dose Aspirin and Sporadic Anovulation in the EAGeR Randomized Trial
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID IN-VITRO FERTILIZATION; PROSTAGLANDIN SYNTHETASE INHIBITORS;
DOUBLE-BLIND; BLOOD-FLOW; EMBRYO-TRANSFER; OVARIAN RESPONSIVENESS;
EUMENORRHEIC WOMEN; MENSTRUAL-CYCLE; PREGNANCY; UTERINE
AB Context: Among women with a single, recent pregnancy loss, daily preconception low-dose aspirin (LDA) increased the live birth rate with no effect on pregnancy loss. Ovulation is a potentialmechanism underlying this effect.
Objective: Weestimated the effect of LDA on the per-cycle risk of anovulation among eumenorrheic women.
Design: Multicenter, randomized, double-blind, placebo-controlled trial of daily LDA on reproductive outcomes. Preconception follow-up lasted 1 to 6 menstrual cycles (ClinicalTrials. gov, NCT00467363).
Setting: Four US medical centers during 2007 to 2011.
Patients or Other Participants: Healthy women (n = 1214), age 18 to 40, were attempting pregnancy, had regular menstrual cycles (21 to 42 days), and had a history of 1 to 2 documented pregnancy losses, <= 2 live births, and no infertility. All participants completed at least 1 menstrual cycle of follow-up; none withdrew due to adverse events.
Intervention: Aspirin (81 mg) daily for 1 to 6 menstrual cycles.
Main Outcome Measure: Per-cycle risk of anovulation, defined as the absence of both a positive spot-urine pregnancy test and a luteinizing hormone (LH) peak (2.5-fold increase in daily urinary LH). Hypothesis formulation preceded data collection.
Results: Among4340cycles, LDAwasnotassociatedwithanovulation(LDA: 13.4%, placebo: 11.1%; riskratio= 1.16, 95% confidence interval, 0.88 to 1.52). Results were similar among women with a single, recent loss.
Conclusions: Daily LDA had no effect on anovulation among women with a history of 1 to 2 pregnancy losses. LDA may affect fertility via other pathways, and these warrant further study.
C1 [Radin, Rose G.; Sjaarda, Lindsey A.; Perkins, Neil J.; Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20817 USA.
[Silver, Robert M.; Lesher, Laurie L.] Univ Utah, Hlth Sci Ctr, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
[Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20817 USA.
[Galai, Noya] Univ Haifa, Dept Stat, IL-3498838 Haifa, Israel.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14228 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6710B Rockledge Dr, Bethesda, MD 20817 USA.
EM schistee@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland [HHSN267200603423, HHSN267200603424,
HHSN267200603426]
FX 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, Bethesda, Maryland (Contract
Nos. HHSN267200603423, HHSN267200603424, and HHSN267200603426).
NR 51
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PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JAN
PY 2017
VL 102
IS 1
BP 86
EP 92
DI 10.1210/jc.2016-2095
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EP0IV
UT WOS:000397071900012
PM 27754808
ER
PT J
AU Bernard, V
Kherra, S
Francou, B
Fagart, J
Viengchareun, S
Guechot, J
Ladjouze, A
Guiochon-Mantel, A
Korach, KS
Binart, N
Lombes, M
Christin-Maitre, S
AF Bernard, Valerie
Kherra, Sakina
Francou, Bruno
Fagart, Jerome
Viengchareun, Say
Guechot, Jerome
Ladjouze, Asmahane
Guiochon-Mantel, Anne
Korach, Kenneth S.
Binart, Nadine
Lombes, Marc
Christin-Maitre, Sophie
TI Familial Multiplicity of Estrogen Insensitivity Associated With a
Loss-of-Function ESR1 Mutation
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID RECEPTOR KNOCKOUT MICE; HUMAN-DISEASE; GENE; FEMALE; ALPHA;
GUBERNACULUM; DISRUPTION; DEFICIENCY; RESISTANCE; CLONING
AB Context: Estrogens influence many physiological processes in mammals, including reproduction. Estrogen peripheral actions are mainly mediated through estrogen receptors (ERs) a and b, encoded by ESR1 and ESR2 genes, respectively.
Objective: The study's aim was to describe a family in which 3 members presented with estrogen insensitivity.
Design and Setting: Clinical evaluation and genetic and mutational analysis were performed in an academic medical center.
Patients and Interventions: An ESR1 mutation was identified in 2 sisters and 1 brother, originating from a consanguineous Algerian family, who did not enter puberty and presented with delayed bone maturation consistent with estrogen insensitivity. The 2 sisters had enlarged multicystic ovaries. Hormonal evaluation as well as genetic and mutational analysis were performed.
Results: Hormonal evaluation revealed extremely high plasma 17b-estradiol (>50-fold normal range) associated with elevated gonadotropin levels (greater than threefold normal range), highly suggestive of estrogen resistance. The 3 affected patients carried a homozygous mutation of a highly conserved arginine 394 for which histidine was substituted through an autosomal recessive mode of transmission. Structural and functional analysis of the mutant ERa revealed strongly reduced transcriptional activity and the inability to securely anchor the activating hormone, estradiol, compared with wild-type ERa. A group of other potential ER activating ligands were tested, but none overcame the estrogen insensitivity in these patients.
Conclusion: Description and analysis of this family of patients with mutant ERa provide additional clinical findings toward identification and characterization of what was previously thought to be a highly rare clinical condition.
C1 [Bernard, Valerie; Francou, Bruno; Fagart, Jerome; Viengchareun, Say; Guiochon-Mantel, Anne; Binart, Nadine; Lombes, Marc] Univ Paris Saclay, Fac Med Paris Sud, INSERM 1185, F-94270 Le Kremlin Bicetre, France.
[Kherra, Sakina] Hop Nafissa Hamoud, Serv Pediat, Algiers 16040, Algeria.
[Francou, Bruno; Guiochon-Mantel, Anne] CHU Bicetre, Hop Univ Paris Sud, AP HP, Serv Genet Mol Pharmacogenet & Hormonol, F-94270 Le Kremlin Bicetre, France.
[Lombes, Marc] CHU Bicetre, Hop Univ Paris Sud, AP HP, Serv Endocrinol & Malad Reprod, F-94270 Le Kremlin Bicetre, France.
[Guechot, Jerome] Hop Univ Est Parisien, AP HP, Lab Hormonol, Pole Biol Med & Pathol, Site St Antoine, F-75012 Paris, France.
[Ladjouze, Asmahane] Hop Bab El Oued, Serv Pediat, Algiers 16040, Algeria.
[Korach, Kenneth S.] NIEHS, Reprod & Dev Biol Lab, NIH, Durham, NC 27709 USA.
[Christin-Maitre, Sophie] Hop St Antoine, AP HP, Serv Endocrinol & Malad Reprod, F-75012 Paris, France.
[Christin-Maitre, Sophie] Univ Paris 06, INSERM 933, F-75011 Paris, France.
RP Christin-Maitre, S (reprint author), Univ Paris 06, Hop St Antoine, AP HP, Serv Endocrinol & Malad Reprod,Ctr Malad Endocrin, 184 Rue Faubourg St Antoine, F-75011 Paris, France.
EM sophie.christin-maitre@aphp.fr
FU INSERM; Universite Paris Sud; Division of Intramural Research, National
Institute of Environmental Health Sciences/National Institutes of Health
[1ZIAES70065]
FX This work was supported by grants from INSERM and Universite Paris Sud.
V.B. was a recipient of a fellowship (Poste d'accueil-Plan Cancer
2014-2019) from INSERM. K.S.K. received funding from the Division of
Intramural Research, National Institute of Environmental Health
Sciences/National Institutes of Health (grant no. 1ZIAES70065).
NR 24
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PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JAN
PY 2017
VL 102
IS 1
BP 93
EP 99
DI 10.1210/jc.2016-2749
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EP0IV
UT WOS:000397071900013
PM 27754803
ER
PT J
AU Nockel, P
Babic, B
Millo, C
Herscovitch, P
Patel, D
Nilubol, N
Sadowski, SM
Cochran, C
Gorden, P
Kebebew, E
AF Nockel, Pavel
Babic, Bruna
Millo, Corina
Herscovitch, Peter
Patel, Dhaval
Nilubol, Naris
Sadowski, Samira M.
Cochran, Craig
Gorden, Phillip
Kebebew, Electron
TI Localization of Insulinoma Using Ga-68-DOTATATE PET/CT Scan
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID NEUROENDOCRINE TUMORS
AB Context: Reliable localization of insulinoma is critical for successful treatment.
Objective: This study compared the accuracy of (68)Gallium DOTA-(Tyr3)-octreotate (Ga-DOTATATE) positron emission tomography (PET)/computed tomography (CT) to anatomic imaging modalities, selective arterial secretagogue injection (SASI), and intraoperative ultrasound (IO ultrasound) and palpation for localizing insulinoma in patients who were biochemically cured.
Design, Setting, and Patients: We conducted a retrospective analysis of 31 patients who had an insulinoma. The results of CT, magnetic resonance imaging (MRI), ultrasound, IO ultrasound, Ga-68-DOTATATE PET/CT, SASI, and operative findings were analyzed.
Intervention, Main Outcome Measures, and Results: The insulinomas were correctly localized in 17 out of 31 (55%) patients by CT, in 17 out of 28 (61%) by MRI, in 6 out of 28 (21%) by ultrasound, and in 9 out of 10 (90%) by Ga-68-DOTATATE. In 29 of 31 patients (93.5%) who had IO ultrasound, an insulinoma was successfully localized. Thirty patients underwent SASI, and the insulinoma was regionalized in 28 out of 30 patients (93%). In 19 out of 23 patients (83%), manual palpation identified insulinoma. In patients who had all 4 noninvasive imaging studies, CT was concordant with Ga-68-DOTATATE in 6 out of 9 patients (67%), MRI in 8 out of 9 (78%), ultrasound in 0 out of 9; the lesion was only seen by Ga-68-DOTATATE in 1 out of 9 (11%).
Conclusions Ga-68-DOTATATE PET/CT identifies most insulinomas and may be considered as an adjunct imaging study when all imaging studies are negative and when a minimally invasive surgical approach is planned.
C1 [Nockel, Pavel; Babic, Bruna; Patel, Dhaval; Nilubol, Naris; Kebebew, Electron] Natl Canc Inst, Natl Inst Hlth, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
[Millo, Corina; Herscovitch, Peter] Natl Inst Hlth, Ctr Clin, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA.
[Cochran, Craig; Gorden, Phillip] Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA.
[Sadowski, Samira M.] Univ Hosp Geneva, Thorac & Endocrine Surg, CH-1211 Geneva, Switzerland.
RP Nockel, P (reprint author), Natl Canc Inst, Natl Inst Hlth, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
FU intramural research program of the Center for Cancer Research, National
Cancer Institute
FX This research was supported, in part, by the intramural research program
of the Center for Cancer Research, National Cancer Institute.
NR 19
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PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JAN
PY 2017
VL 102
IS 1
BP 195
EP 199
DI 10.1210/jc.2016-3445
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EP0IV
UT WOS:000397071900024
PM 27805844
ER
PT J
AU Vinales, KL
Schlogl, M
Piaggi, P
Hohenadel, M
Graham, A
Bonfiglio, S
Krakoff, J
Thearle, MS
AF Vinales, Karyne Lima
Schlogl, Mathias
Piaggi, Paolo
Hohenadel, Maximilian
Graham, Alexis
Bonfiglio, Susan
Krakoff, Jonathan
Thearle, Marie S.
TI The Consistency in Macronutrient Oxidation and the Role for Epinephrine
in the Response to Fasting and Overfeeding
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID SYMPATHETIC-NERVOUS-SYSTEM; BROWN ADIPOSE-TISSUE; ENERGY-EXPENDITURE;
FOOD-INTAKE; CARBOHYDRATE OXIDATION; RESPIRATORY CHAMBER; CALORIC
RESTRICTION; PIMA-INDIANS; BODY-WEIGHT; NOREPINEPHRINE
AB Context: In humans, dietary vs intraindividual determinants of macronutrient oxidation preference and the role of the sympathetic nervous system (SNS) during short-term overfeeding and fasting are unclear.
Objective: To understand the influence on metabolic changes of diet and SNS during 24 hours of overfeeding.
Design, Setting, Participants, and Interventions: While residing on a clinical research unit, 64 participants with normal glucose regulation were assessed during energy balance, fasting, and four 24-hour overfeeding diets, given in random order. The overfeeding diets contained 200% of energy requirements and varied macronutrient proportions: (1) standard (50% carbohydrate, 20% protein, and 30% fat); (2) 75% carbohydrate; (3) 60% fat; and (4) 3% protein.
Main Outcome Measures: Twenty-four-hour energy expenditure (EE) and macronutrient oxidation rates were measured in an indirect calorimeter during the dietary interventions, with concomitant measurement of urinary catecholamines and free cortisol.
Results: EE decreased with fasting (27.7% 64.8%; P, 0.0001) and increased with overfeeding. The smallest increase occurred during consumption of the diet with 3% protein (2.7% +/- 4.5%; P = 0.001) and the greatest during the diet with 75% carbohydrate (13.8 6 5.7%; P, 0.0001). Approximately 60% of macronutrient oxidation was determined by diet and 20% by intrinsic factors (P < 0.0001). Only urinary epinephrine differed between fasting and overfeeding diets (Delta = 2.25 +/- 2.9 mu g/24h; P < 0.0001). During fasting, higher urinary epinephrine concentrations correlated with smaller reductions in EE (rho = 0.34; P = 0.01).
Conclusions: Independent from dietary macronutrient proportions, there is a strong individual contribution to fuel preference that remains consistent across diets. Higher urinary epinephrine levels may reflect the importance of epinephrine in maintaining EE during fasting.
C1 [Vinales, Karyne Lima; Schlogl, Mathias; Piaggi, Paolo; Hohenadel, Maximilian; Bonfiglio, Susan; Krakoff, Jonathan; Thearle, Marie S.] Natl Inst Diabet & Digest & Kidney Dis, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA.
[Schlogl, Mathias] Univ Zurich Hosp, Dept Geriatr & Aging Res, CH-8091 Zurich, Switzerland.
[Graham, Alexis] Johns Hopkins Sch Med, Baltimore, MD 21205 USA.
RP Vinales, KL (reprint author), Natl Inst Diabet & Digest & Kidney Dis, 4212 N 16th St, Phoenix, AZ 85016 USA.
EM karyne.vinales@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 34
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PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JAN
PY 2017
VL 102
IS 1
BP 279
EP 289
DI 10.1210/jc.2016-3006
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EP0IV
UT WOS:000397071900033
PM 27820654
ER
PT J
AU Kowalczyk, WJ
Wehring, HJ
Burton, G
Raley, H
Feldman, S
Heishman, SJ
Kelly, DL
AF Kowalczyk, William J.
Wehring, Heidi J.
Burton, George
Raley, Heather
Feldman, Stephanie
Heishman, Stephen J.
Kelly, Deanna L.
TI Predictors of the Perception of Smoking Health Risks in Smokers With or
Without Schizophrenia
SO JOURNAL OF DUAL DIAGNOSIS
LA English
DT Article
DE Schizophrenia; cigarette smoking; health risks; perception
ID BIPOLAR DISORDER; ADULT SMOKERS; QUIT SMOKING; QUESTIONNAIRE;
MOTIVATION; CESSATION
AB Objective: This study sought to examine the predictors of health risk perception in smokers with or without schizophrenia. Methods: The health risk subscale from the Smoking Consequences Questionnaire was dichotomized and used to measure health risk perception in smokers with (n D 67) and without schizophrenia (n = 100). A backward stepwise logistic regression was conducted using variables associated at the bivariate level to determine multivariate predictors. Results: Overall, 62.5% of smokers without schizophrenia and 40.3% of smokers with schizophrenia completely recognize the health risks of smoking (p <= .01). Multivariate predictors for smokers without schizophrenia included: sex (Exp (B) = .3; p < .05), Smoking Consequences Questionnaire state enhancement (Exp (B) = .69; p < .01), and craving relief (Exp (B) = 1.8; p < .01). Among smokers with schizophrenia, predictors were education (Exp (B) = .7; p < .05), nicotine dependence (Exp (B) = .5; p < .01), motivation to quit (Exp (B) = 1.8; p <.01), and Smoking Consequences Questionnaire craving relief (Exp (B) = 1.8; p < .01). Conclusions: There was overlap and differences between predictors in smokers with and without schizophrenia. Commonly used techniques for education on the health consequences of cigarettes may work in smokers with schizophrenia, but intervention efforts specifically tailored to smokers with schizophrenia might be more efficacious.
C1 [Kowalczyk, William J.; Burton, George; Heishman, Stephen J.] NIDA, Intramural Res Program, Baltimore, MD USA.
[Wehring, Heidi J.; Raley, Heather; Feldman, Stephanie; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Box 21247, Baltimore, MD 21228 USA.
RP Wehring, HJ (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Box 21247, Baltimore, MD 21228 USA.
EM hwehring@mprc.umaryland.edu
FU Intramural Research Program of the National Institutes of Health;
National Institute on Drug Abuse (NIDA); NIDA Residential Research
Support Services Contract [HHSN271200599091CADB (N01DA-5-9909)]; NIDA
FX Funding for this study was provided by the Intramural Research Program
of the National Institutes of Health, National Institute on Drug Abuse
(NIDA), and NIDA Residential Research Support Services Contract
HHSN271200599091CADB (N01DA-5-9909 Kelly, PI). Both NIDA funds and
personnel supported the design, study methods, and analysis of this
study.
NR 27
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U1 0
U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1550-4263
EI 1550-4271
J9 J DUAL DIAGN
JI J. Dual Diagn.
PY 2017
VL 13
IS 1
BP 29
EP 35
DI 10.1080/15504263.2016.1260190
PG 7
WC Psychology, Clinical; Substance Abuse; Psychiatry
SC Psychology; Substance Abuse; Psychiatry
GA EP2UA
UT WOS:000397237700005
PM 27858591
ER
PT J
AU Wehring, HJ
Heishman, SJ
McMahon, RP
Liu, F
Feldman, S
Raley, H
Weiner, E
Kelly, DL
AF Wehring, Heidi J.
Heishman, Stephen J.
McMahon, Robert P.
Liu, Fang
Feldman, Stephanie
Raley, Heather
Weiner, Elaine
Kelly, Deanna L.
TI Antipsychotic Treatment and Tobacco Craving in People With Schizophrenia
SO JOURNAL OF DUAL DIAGNOSIS
LA English
DT Article
DE Tobacco; craving; schizophrenia; antipsychotic
ID FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE DEPENDENCE;
SMOKING-BEHAVIOR; REDUCES SMOKING; HEAVY SMOKERS; USE DISORDER;
HALOPERIDOL; CLOZAPINE; DSM-5; ARIPIPRAZOLE
AB Objective: Nicotine dependence is high in schizophrenia, and craving is known to impact relapse during quit attempts. Methods: We compared tobacco craving in smokers with schizophrenia treated with different antipsychotics. Results: Mean craving scores were lowest in participants receiving first-generation antipsychotics, although these differences were not statistically significant. Craving with clozapine was not lower than with other antipsychotics. Conclusions: Further research is needed to determine whether differences in craving exist between antipsychotic classes.
C1 [Wehring, Heidi J.; McMahon, Robert P.; Liu, Fang; Feldman, Stephanie; Raley, Heather; Weiner, Elaine; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA.
[Heishman, Stephen J.] NIDA, NIH, Intramural Res Program, Baltimore, MD USA.
RP Wehring, HJ (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA.
EM hwehring@mprc.umaryland.edu
FU National Institute on Drug Abuse (NIDA) Residential Research Services
Contract [HHSN271200599091CADB (N01DA-5-9909)]
FX This study was funded in part by the National Institute on Drug Abuse
(NIDA) Residential Research Services Contract HHSN271200599091CADB
(N01DA-5-9909 Kelly, PI).
NR 47
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U1 0
U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1550-4263
EI 1550-4271
J9 J DUAL DIAGN
JI J. Dual Diagn.
PY 2017
VL 13
IS 1
BP 36
EP 42
DI 10.1080/15504263.2017.1288946
PG 7
WC Psychology, Clinical; Substance Abuse; Psychiatry
SC Psychology; Substance Abuse; Psychiatry
GA EP2UA
UT WOS:000397237700006
PM 28166471
ER
PT J
AU Pierce, KK
Whitehead, SS
Kirkpatrick, BD
Grier, PL
Jarvis, A
Kenney, H
Carmolli, MP
Reynolds, C
Tibery, CM
Lovchik, J
Janiak, A
Luke, CJ
Durbin, AP
Pletnev, AG
AF Pierce, Kristen K.
Whitehead, Stephen S.
Kirkpatrick, Beth D.
Grier, Palmtama L.
Jarvis, Adrienne
Kenney, Heather
Carmolli, Marya P.
Reynolds, Cynthia
Tibery, Cecilia M.
Lovchik, Janece
Janiak, Anna
Luke, Catherine J.
Durbin, Anna P.
Pletnev, Alexander G.
TI A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4 Delta 30,
Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult
Volunteers
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE West Nile virus; vaccine; flavivirus
ID UNITED-STATES; INFECTION; CANDIDATE; GENOTYPE; MONKEYS
AB West Nile virus (WNV) is a major cause of mosquito-borne illness in the United States. Human disease ranges from mild febrile illness to severe fatal neurologic infection. Adults aged > 60 years are more susceptible to neuroinvasive disease accompanied by a high mortality rate or long-lasting neurologic sequelae. A chimeric live attenuated West Nile virus vaccine, rWN/DEN4 Delta 30, was shown to be safe and immunogenic in healthy adults aged 18-50 years. This study evaluated rWN/DEN4 Delta 30 in flavivirus-naive adults aged 50-65 years and found it to be safe and immunogenic. Outbreaks of WNV infection tend to be unpredictable, and a safe and effective vaccine will be an important public health tool.
C1 [Pierce, Kristen K.; Kirkpatrick, Beth D.; Jarvis, Adrienne; Carmolli, Marya P.; Reynolds, Cynthia] Univ Vermont, Robert Larner MD Coll Med, Burlington, VT 05405 USA.
[Whitehead, Stephen S.; Kenney, Heather; Luke, Catherine J.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Grier, Palmtama L.; Tibery, Cecilia M.; Lovchik, Janece; Janiak, Anna; Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD USA.
RP Pierce, KK (reprint author), Univ Vermont, Coll Med, Dept Med, Vaccine Testing Ctr, 89 Beaumont Ave,Given Bldg C205, Burlington, VT 05405 USA.
EM kristen.pierce@uvmhealth.org
FU National Institute of Allergy and Infectious Disease Intramural Research
Program, National Institutes of Health [HHSN272200900010C]
FX This work was supported by the National Institute of Allergy and
Infectious Disease Intramural Research Program, National Institutes of
Health (contract HHSN272200900010C).
NR 15
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 1
PY 2017
VL 215
IS 1
BP 52
EP 55
DI 10.1093/infdis/jiw501
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EP2HH
UT WOS:000397203500010
PM 28077583
ER
PT J
AU Nyombayire, J
Anzala, O
Gazzard, B
Karita, E
Bergin, P
Hayes, P
Kopycinski, J
Omosa-Manyonyi, G
Jackson, A
Bizimana, J
Farah, B
Sayeed, E
Parks, CL
Inoue, M
Hironaka, T
Hara, H
Shu, T
Matano, T
Dally, L
Barin, B
Park, H
Gilmour, J
Lombardo, A
Excler, JL
Fast, P
Laufer, DS
Cox, JH
AF Nyombayire, Julien
Anzala, Omu
Gazzard, Brian
Karita, Etienne
Bergin, Philip
Hayes, Peter
Kopycinski, Jakub
Omosa-Manyonyi, Gloria
Jackson, Akil
Bizimana, Jean
Farah, Bashir
Sayeed, Eddy
Parks, Christopher L.
Inoue, Makoto
Hironaka, Takashi
Hara, Hiroto
Shu, Tsugumine
Matano, Tetsuro
Dally, Len
Barin, Burc
Park, Harriet
Gilmour, Jill
Lombardo, Angela
Excler, Jean-Louis
Fast, Patricia
Laufer, Dagna S.
Cox, Josephine H.
CA S001 Study Team
TI First-in-Human Evaluation of the Safety and Immunogenicity of an
Intranasally Administered Replication-Competent Sendai Virus-Vectored
HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses
in Prime-Boost Regimens
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE replication competent; Sendai virus vector; HIV-1 vaccine; intranasal
delivery; immunogenicity; adenovirus 35; prime-boost; mucosal responses
ID IMMUNE-RESPONSES; MUCOSAL VACCINES; CLINICAL-TRIALS; YOUNG-CHILDREN;
DNA; INFECTION; GENE; DELIVERY; CANDIDATES; PROTEIN
AB Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.
Methods. Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 primeboost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12: 4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (S(L)A); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (S(H)A); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (AS(H)); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH).
Results. All vaccine regimens were well tolerated. Gag-specific IFN-gamma enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (S(L)A and S(H)A) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeVGag (55% and 59 spot-forming units, respectively); responses persisted for >= 8 months after completion of the prime-boost regimen. Functional CD8(+) T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the S(L)A and S(H)A groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the AS(H) group. In contrast, the highest Gag-specific antibody titers were seen in the AS(H) group. Mucosal antibody responses were sporadic.
Conclusions. SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody responses. The prime-boost sequence appears to determine which arm of the immune response is stimulated.
C1 [Nyombayire, Julien; Karita, Etienne; Bizimana, Jean] Projet San Francisco, Kigali, Rwanda.
[Anzala, Omu; Omosa-Manyonyi, Gloria; Farah, Bashir] Kenya AIDS Vaccine Initiat Inst Clin Res, Nairobi, Kenya.
[Gazzard, Brian; Jackson, Akil] Chelsea & Westminster Healthcare NHS Fdn Trust, London, England.
[Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Gilmour, Jill] Int AIDS Vaccine Initiat, Human Immunol Lab, London, England.
[Sayeed, Eddy; Parks, Christopher L.; Park, Harriet; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S.; Cox, Josephine H.] Int AIDS Vaccine Initiat, 125 Broad St,9th Fl, New York, NY 10004 USA.
[Dally, Len; Barin, Burc] Emmes Corp, Rockville, MD USA.
[Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine] ID Pharma, Tsukuba, Ibaraki, Japan.
[Matano, Tetsuro] Univ Tokyo, Tokyo, Japan.
[Matano, Tetsuro] Natl Inst Infect Dis, Tokyo, Japan.
[Excler, Jean-Louis] Int Vaccine Inst, Seoul, South Korea.
[Cox, Josephine H.] NIAID, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Laufer, DS (reprint author), Int AIDS Vaccine Initiat, 125 Broad St,9th Fl, New York, NY 10004 USA.
EM dlaufer@iavi.org
FU United States Agency for International Development (USAID); Ministry of
Finance of Japan; World Bank; Bill and Melinda Gates Foundation;
Ministry of Foreign Affairs of Denmark; Irish Aid; Ministry of Foreign
Affairs of the Netherlands; Norwegian Agency for Development
Cooperation; United Kingdom Department for International Development
FX This work was supported by the United States Agency for International
Development (USAID), the Ministry of Finance of Japan in partnership
with the World Bank; the Bill and Melinda Gates Foundation; the Ministry
of Foreign Affairs of Denmark; Irish Aid; the Ministry of Finance of
Japan, in partnership with the World Bank; the Ministry of Foreign
Affairs of the Netherlands; the Norwegian Agency for Development
Cooperation and the United Kingdom Department for International
Development. The full list of IAVI donors is available at:
http://www.iavi.org.
NR 51
TC 0
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U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 1
PY 2017
VL 215
IS 1
BP 95
EP 104
DI 10.1093/infdis/jiw500
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EP2HH
UT WOS:000397203500016
PM 28077588
ER
PT J
AU Hobbs, CV
Anderson, C
Neal, J
Sahu, T
Conteh, S
Voza, T
Langhorne, J
Borkowsky, W
Duffy, PE
AF Hobbs, Charlotte V.
Anderson, Charles
Neal, Jillian
Sahu, Tejram
Conteh, Solomon
Voza, Tatiana
Langhorne, Jean
Borkowsky, William
Duffy, Patrick E.
TI Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite
Immunization Induces Long-Lived, Homologous, and Heterologous Protective
Immunity Against Sporozoite Challenge
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV; malaria; antiretroviral therapy; liver stages; eradication;
children; trimethoprim-sulfamethoxazole; immunity
ID STAGE PLASMODIUM PARASITES; T-CELL RESPONSES; COTRIMOXAZOLE PROPHYLAXIS;
PROTRACTED PROTECTION; FALCIPARUM; YOELII; MICE; VACCINATION;
INHIBITORS; INFECTION
AB Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8(+) T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis.
C1 [Hobbs, Charlotte V.; Anderson, Charles; Neal, Jillian; Sahu, Tejram; Conteh, Solomon; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Hobbs, Charlotte V.] Univ Mississippi, Med Ctr, Dept Microbiol, Batson Childrens Hosp, Jackson, MS 39216 USA.
[Hobbs, Charlotte V.; Borkowsky, William] NYU, Sch Med, Dept Pediat, Div Infect Dis & Immunol, New York, NY 10003 USA.
[Voza, Tatiana] CUNY, New York City Coll Technol, Dept Biol Sci, New York, NY 10021 USA.
[Langhorne, Jean] Francis Crick Inst, Mill Hill Lab, London, England.
RP Hobbs, CV (reprint author), Dept Pediat, Div Infect Dis, 2500 N State St, Jackson, MS 39216 USA.; Hobbs, CV (reprint author), Dept Microbiol, 2500 N State St, Jackson, MS 39216 USA.
EM chobbs@umc.edu
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, NIH
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, NIH.
NR 49
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 1
PY 2017
VL 215
IS 1
BP 122
EP 130
DI 10.1093/infdis/jiw482
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EP2HH
UT WOS:000397203500019
PM 28077589
ER
PT J
AU Togias, A
Cooper, SF
Acebal, ML
Assa'ad, A
Baker, JR
Beck, LA
Block, J
Byrd-Bredbenner, C
Chan, ES
Eichenfield, LF
Fleischer, DM
Fuchs, GJ
Furuta, GT
Greenhawt, MJ
Gupta, RS
Habich, M
Jones, SM
Keaton, K
Muraro, A
Plaut, M
Rosenwasser, LJ
Rotrosen, D
Sampson, HA
Schneider, LC
Sicherer, SH
Sidbury, R
Spergel, J
Stukus, DR
Venter, C
Boyce, JA
AF Togias, Alkis
Cooper, Susan F.
Acebal, Maria L.
Assa'ad, Amal
Baker, James R. jr
Beck, Lisa A.
Block, Julie
Byrd-Bredbenner, Carol
Chan, Edmond S.
Eichenfield, Lawrence F.
Fleischer, David M.
Fuchs, George J., III
Furuta, Glenn T.
Greenhawt, Matthew J.
Gupta, Ruchi S.
Habich, Michele
Jones, Stacie M.
Keaton, Kari
Muraro, Antonella
Plaut, Marshall
Rosenwasser, Lanny J.
Rotrosen, Daniel
Sampson, Hugh A.
Schneider, Lynda C.
Sicherer, Scott H.
Sidbury, Robert
Spergel, Jonathan
Stukus, David R.
Venter, Carina
Boyce, Joshua A.
TI Addendum Guidelines for the Prevention of Peanut Allergy in the United
States: Report of the National Institute of Allergy and Infectious
Diseases-Sponsored Expert Panel
SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES
LA English
DT Article
DE Food; peanut; allergy; prevention; guidelines
ID NUTRITIONAL INTERVENTIONS; ANAPHYLACTIC REACTIONS; GRADING QUALITY;
HIGH-RISK; INFANTS; RECOMMENDATIONS; CONSUMPTION; FATALITIES; STRENGTH;
CHILDREN
AB Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.
Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.
Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.
Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy. Published by Elsevier Inc.
C1 [Togias, Alkis; Cooper, Susan F.; Plaut, Marshall; Rotrosen, Daniel] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Acebal, Maria L.] Board Directors, Food Allergy Res & Educ, Mclean, VA USA.
[Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH USA.
[Baker, James R. jr] Food Allergy Res & Educ, Mclean, VA USA.
[Baker, James R. jr] Univ Michigan Hlth Syst, Div Allergy & Clin Immunol, Ann Arbor, MI USA.
[Beck, Lisa A.] Univ Rochester, Med Ctr, Dept Dermatol, Rochester, NY 14627 USA.
[Block, Julie] Natl Eczema Assoc, San Rafael, CA USA.
[Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ USA.
[Chan, Edmond S.] Univ British Columbia, Div Allergy & Immunol, Dept Pediat, BC Childrens Hosp, Vancouver, BC, Canada.
[Eichenfield, Lawrence F.] Univ Calif San Diego, San Diego Sch Med, Rady Childrens Hosp, Dept Dermatol, San Diego, CA 92103 USA.
[Eichenfield, Lawrence F.] Univ Calif San Diego, San Diego Sch Med, Rady Childrens Hosp, Dept Pediat, San Diego, CA 92103 USA.
[Fleischer, David M.; Greenhawt, Matthew J.] Univ Colorado Denver, Sch Med, Childrens Hosp Colorado, Sect Allergy & Immunol,Dept Pediat, Aurora, CO USA.
[Fuchs, George J., III] Univ Kentucky, Coll Med, Div Gastroenterol Hepatol & Nutr, Dept Pediat,Kentucky Childrens Hosp, Lexington, KY USA.
[Furuta, Glenn T.] Childrens Hosp Colorado, Digest Hlth Inst, Aurora, CO USA.
[Furuta, Glenn T.] Univ Colorado Denver, Sch Med, Sect Pediat Gastroenterol, Aurora, CO USA.
[Gupta, Ruchi S.] Northwestern Univ, Dept Pediat, Div Acad Gen Pediat & Primary Care, Feinberg Sch Med, Chicago, IL 60611 USA.
[Gupta, Ruchi S.] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Chicago, IL 60611 USA.
[Habich, Michele] Cent DuPage Hosp, Northwestern Med, Winfield, IL USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Div Allergy & Immunol, Dept Pediat, Little Rock, AR 72205 USA.
[Keaton, Kari] Metro DC Food Allergy Support Grp, Rockville, MD USA.
[Muraro, Antonella] Padua Univ Hosp, Food Allergy Referral Ctr, Dept Women & Child Hlth, Padua, Italy.
[Sicherer, Scott H.] Icahn Sch Med Mt Sinai, Div Pediat Allergy & Immunol, New York, NY 10029 USA.
[Rosenwasser, Lanny J.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA.
[Sampson, Hugh A.] Icahn Sch Med Mt Sinai, Div Allergy & Immunol, Dept Pediat, New York, NY 10029 USA.
[Schneider, Lynda C.] Boston Childrens Hosp, Div Allergy & Immunol, Boston, MA USA.
[Sidbury, Robert] Univ Washington, Sch Med, Dept Pediat, Div Dermatol,Seattle Childrens Hosp, Seattle, WA 98195 USA.
[Spergel, Jonathan] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Allergy & Immunol,Perelman Sch Med, Philadelphia, PA 19104 USA.
[Stukus, David R.] Ohio State Univ, Coll Med, Dept Pediat, Sect Allergy & Immunol,Nationwide Childrens Hosp, Columbus, OH 43210 USA.
[Venter, Carina] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Boyce, Joshua A.] Harvard Med Sch, Dept Pediat, Boston, MA USA.
RP Cooper, SF (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM coopersu@niaid.nih.gov
FU American College of Allergy, Asthma & Immunology (ACAAI); DBV
Technologies; Aimmune; Stanford Foundation; TEVA Pharmaceuticals;
GlaxoSmithKline; National Institutes of Health (NIH); Astellas; Food
Allergy Research & Education (FARE); ACAAI. C. Byrd-Bredbenner;
NIH/National Institute of Allergy and Infectious Disease (NIAID); NIAID;
Pfizer; Sanofi; Monsanto Company; Nestle Nutrition Institute; Aimmune
Therapeutics; Agency for Healthcare Research and Quality
[1K08HS024599-01]; Joint Taskforce on Allergy Practice Parameters; NIH;
FARE; Mylan LLC; Grand Rounds; Meda and Menarini; HAL Allergy;
Epidermolysis Bullosa Research Partnership; Taiwanese Dermatological
Society
FX Disclosure of potential conflict of interest: A. Assa'ad received travel
support from the American College of Allergy, Asthma & Immunology
(ACAAI); was an elected member of the Board of Directors for the
American Academy of Allergy, Asthma, & Immunology (AAAAI) from March
2012 to March 2016; has consultant arrangements with Aimmune; is
employed by Cincinnati Children's Hospital Medical Center; has received
grants from DBV Technologies, Aimmune, Stanford Foundation, TEVA
Pharmaceuticals, GlaxoSmithKline, the National Institutes of Health
(NIH), Astellas, and Food Allergy Research & Education (FARE); and has
received payment for lectures from the ACAAI. C. Byrd-Bredbenner and G.
J. Fuchs III have received travel support from the NIH/National
Institute of Allergy and Infectious Disease (NIAID). E. S. Chan has
received travel support from the NIAID, has received grants from DBV
Technologies, and has received payment for lectures from Pfizer, Sanofi,
Mead Johnson, and Nestle. D. M. Fleischer has received travel support
from the NIAID; is a board member for the National Peanut Board, the
FAACT Medical Advisory Board, and the FARE Medical Advisory Board; has
consultant arrangements with Adamis Pharmaceuticals Corporation, INSYS
Therapeutics, DBV Technologies, Aimmune Therapeutics, Intrommune
Therapeutics, and Kaleo Pharma; is employed by University Physicians;
has received grants from Monsanto Company, Nestle Nutrition Institute,
DBV Technologies, and Aimmune Therapeutics; has received payment for
lectures from Nestle Nutrition Institute; and has received royalties
from UpToDate. M. J. Greenhawt has received a grant from the Agency for
Healthcare Research and Quality (1K08HS024599-01, Career Development
Award); has received travel support from the NIAID and the Joint
Taskforce on Allergy Practice Parameters; has a board membership with
the National Peanut Board; has consultant arrangements with Adamis
Pharmaceuticals, the Canadian Transportation Agency, Nutricia,
Nestle/Gerber, Aimmune, Kaleo Pharmaceutical, and Monsanto; is an
Associate Editor for the Annals of Allergy, Asthma, and Immunology; has
received payment for lectures from the ACAAI, Reach MD, Thermo Fisher
Scientific, the California Society for Allergy and Immunology, the
Allergy and Asthma Network, the New England Society for Allergy,
UCLA/Harbor Heiner Lectureship, Medscape, the Western Michigan School of
Medicine, the Canadian Society of Allergy and Clinical Immunology, and
the Pennsylvania Society for Allergy and Immunology. R. S. Gupta has
consultant arrangements with BEFORE Brands and DBV Technologies; has
received grants from the NIH, FARE, and Mylan LLC; has received payment
for lectures from Grand Rounds; and has received royalties from
Createspace Independent Publishing Platform. S. M. Jones is on the
Research Advisory Board for FARE; is on the Scientific Advisory Board
for Aimmune; has consultant arrangements with Stallergenes; has received
grants from the NIH/NIAID (Consortium of Food Allergy Research and
Immune Tolerance Network-IMPACT Trial), FARE, Aimmune Technologies,
DBVTechnologies, and the National Peanut Board; has received payment for
lectures from the Kansas City Allergy Society, Mercy Children's
Hospital, Riley Children's Hospital, Southwester Medical
School-Children's Medical Center, the European Academy of Allergy &
Clinical Immunology, the New York Allergy & Asthma Society, the
University of Iowa Paul M. Seebohm Lectureship in Allergy, and the Iowa
Society of Allergy, Asthma, and Immunology. A.; Muraro has consultant
arrangements with Meda, Novartis, and Menarini; is employed by Padua
University Hospital; and has received payment for lectures from Meda and
Menarini. L. J. Rosenwasser is a board member for the World Allergy
Organization. H. A. Sampson has consultant arrangements with Allertein
Therapeutics, Genentech/Roche, Sanofi, Stallergenes, Danone, and Merck;
is employed part time as Chief Scientific Officer for DBV Technologies;
has received grants from the NIAID and the Immune Tolerance Network; has
received royalties from UpToDate and Elsevier; has been offered stock
options in DBV Technologies; and is chairman of PhARF Award Selection
Committee for Thermo Fisher. L C. Schneider is on the Medical Advisory
Board for FARE, has received a grant from DBV Technologies, and has
received stock/stock options in Antera Therapeutics. S. H. Sicherer has
received grants from the NIAID, FARE, and HAL Allergy; has received
royalties from UpToDate; and is serving as Associate Editor for the
Journal of Allergy and Clinical Immunology: In Practice. R. Sidbury has
received travel support from the NIH and the Hawaii Dermatology Seminar,
has consultant arrangements with Anacor, has provided expert witness
testimony on behalf of Roche in Accutane-inflammatory bowel disease
cases, has received a grant from Epidermolysis Bullosa Research
Partnership, has received payment for lectures from the Taiwanese
Dermatological Society, and has received royalties from UpToDate. J.
Spergel has consultant arrangements with DBV Technologies and Danone;
has received grants from DBV Technologies, Aimmune Therapeutics, and the
NIH; has received payment for lectures for Dartmouth College, the ACAAI,
and the Florida Allergy Society; and has received stock/stock options in
DBV Technologies. D. R. Stukus has received payment for lectures from
the ACAAI. C. Venter has consultant arrangements with Danone and Nestle,
has received payment for lectures from Mead Johnson, and has received
travel support from Thermo Fisher. The rest of the authors declare that
they have no relevant conflicts of interest.
NR 29
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0882-5963
J9 J PEDIATR NURS
JI J. Pediatr. Nurs.
PD JAN-FEB
PY 2017
VL 32
BP 91
EP 98
DI 10.1016/j.pedn.2016.12.006
PG 8
WC Nursing; Pediatrics
SC Nursing; Pediatrics
GA EM5MS
UT WOS:000395356300019
PM 28137368
ER
PT J
AU Walker, V
AF Walker, Verma
TI Implementing a 3D printing service in a biomedical library
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Article
ID SURGERY
AB Three-dimensional (3D) printing is opening new opportunities in biomedicine by enabling creative problem solving, faster prototyping of ideas, advances in tissue engineering, and customized patient solutions. The National Institutes of Health (NIH) Library purchased a Makerbot Replicator 2 3D printer to give scientists a chance to try out this technology. To launch the service, the library offered training, conducted a survey on service model preferences, and tracked usage and class attendance. 3D printing was very popular, with new lab equipment prototypes being the most common model type. Most survey respondents indicated they would use the service again and be willing to pay for models. There was high interest in training for 3D modeling, which has a steep learning curve. 3D printers also require significant care and repairs. NIH scientists are using 3D printing to improve their research, and it is opening new avenues for problem solving in labs. Several scientists found the 3D printer so helpful they bought one for their labs. Having a printer in a central and open location like a library can help scientists, doctors, and students learn how to use this technology in their work.
C1 [Walker, Verma] NIH Lib, Off Res Serv, NIH, Bldg 10,B1L306F,MSC 1150, Bethesda, MD 20892 USA.
RP Walker, V (reprint author), NIH Lib, Off Res Serv, NIH, Bldg 10,B1L306F,MSC 1150, Bethesda, MD 20892 USA.
EM walkerve@mail.nih.gov
NR 24
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U2 2
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD JAN
PY 2017
VL 105
IS 1
BP 55
EP 60
DI 10.5195/jmla.2017.107
PG 6
WC Information Science & Library Science
SC Information Science & Library Science
GA EO0LZ
UT WOS:000396390600010
PM 28096747
ER
PT J
AU Greenberg, SJ
AF Greenberg, Stephen J.
TI History matters
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Editorial Material
C1 [Greenberg, Stephen J.] Natl Lib Med, Publ Serv, Hist Med Div, NIH, Bethesda, MD 20894 USA.
RP Greenberg, SJ (reprint author), Natl Lib Med, Publ Serv, Hist Med Div, NIH, Bethesda, MD 20894 USA.
EM greenbes@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 4
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PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD JAN
PY 2017
VL 105
IS 1
BP 89
EP 90
DI 10.5195/jmla.2017.112
PG 2
WC Information Science & Library Science
SC Information Science & Library Science
GA EO0LZ
UT WOS:000396390600016
PM 28096753
ER
PT J
AU Proano, A
Xu, ZY
Caligiuri, P
Mollura, DJ
Gilman, RH
AF Proano, Alvaro
Xu, Ziyue
Caligiuri, Philip
Mollura, Daniel J.
Gilman, Robert H.
CA TB Working Grp Peru
TI Computer automated algorithm to evaluate cavitary lesions in adults with
pulmonary tuberculosis
SO JOURNAL OF THORACIC DISEASE
LA English
DT Letter
ID DRUG-SUSCEPTIBILITY ASSAY; MICROSCOPIC-OBSERVATION
C1 [Proano, Alvaro] Univ Peruana Cayetano Heredia, Sch Med, Fac Med Alberto Hurtado, Av El Mastil 387 Apt 602-1, Lima, Peru.
[Proano, Alvaro; Gilman, Robert H.] Univ Peruana Cayetano Heredia, Fac Sci, Res & Dev Labs, Lab TB Infect Dis, Lima, Peru.
[Xu, Ziyue; Mollura, Daniel J.] NIH, CIDI, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
[Caligiuri, Philip] Univ Utah, Sch Med, Dept Radiol & Imaging Sci, Salt Lake City, UT USA.
[Gilman, Robert H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA.
RP Proano, A (reprint author), Univ Peruana Cayetano Heredia, Sch Med, Fac Med Alberto Hurtado, Av El Mastil 387 Apt 602-1, Lima, Peru.; Gilman, RH (reprint author), Johns Hopkins Med Inst, Dept Int Hlth, Bloomberg Sch Publ Hlth, 615 N Wolfe St,Rm W5515, Baltimore, MD 21205 USA.
EM alvaro.proano.f@upch.pe; gilmanbob@gmail.com
OI Proano, Alvaro/0000-0002-4057-7686; Comina, German/0000-0003-2114-0486
FU CIDI; National Institute of Allergy and Infectious Diseases (NIAID);
National Institute of Biomedical Imaging and Bioengineering (NIBIB);
National Institutes of Health [5D43TW006581, 5R21AI094143-02,
5D43TW009349-03]
FX This research is supported by CIDI, the intramural research program of
the National Institute of Allergy and Infectious Diseases (NIAID) and
the National Institute of Biomedical Imaging and Bioengineering (NIBIB).
It also received support from the National Institutes of Health
(5D43TW006581 "Infectious Diseases Training Program in Peru",
5R21AI094143-02 " Cougha rapid indicator of response to therapy in
pulmonary TB", and 5D43TW009349-03" Inter-American Training for
Innovations in Emerging Infectious Diseases").
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PU PIONEER BIOSCIENCE PUBL CO
PI HONG KONG
PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG,
00000, PEOPLES R CHINA
SN 2072-1439
EI 2077-6624
J9 J THORAC DIS
JI J. Thorac. Dis.
PD JAN
PY 2017
VL 9
IS 1
BP E93
EP E96
DI 10.21037/jtd.2017.01.35
PG 4
WC Respiratory System
SC Respiratory System
GA EO1XN
UT WOS:000396491300019
PM 28203447
ER
PT J
AU Bouska, A
Zhang, W
Gong, Q
Iqbal, J
Scuto, A
Vose, J
Ludvigsen, M
Fu, K
Weisenburger, DD
Greiner, TC
Gascoyne, RD
Rosenwald, A
Ott, G
Campo, E
Rimsza, LM
Delabie, J
Jaffe, ES
Braziel, RM
Connors, JM
Wu, CI
Staudt, LM
Amore, FD
McKeithan, TW
Chan, WC
AF Bouska, A.
Zhang, W.
Gong, Q.
Iqbal, J.
Scuto, A.
Vose, J.
Ludvigsen, M.
Fu, K.
Weisenburger, D. D.
Greiner, T. C.
Gascoyne, R. D.
Rosenwald, A.
Ott, G.
Campo, E.
Rimsza, L. M.
Delabie, J.
Jaffe, E. S.
Braziel, R. M.
Connors, J. M.
Wu, C-I
Staudt, L. M.
Amore, F. D.
McKeithan, T. W.
Chan, W. C.
TI Combined copy number and mutation analysis identifies oncogenic pathways
associated with transformation of follicular lymphoma
SO LEUKEMIA
LA English
DT Article
ID B-CELL LYMPHOMA; SOMATIC MUTATIONS; EZH2 MUTATIONS; CLONAL EVOLUTION;
CARD11 MUTATIONS; EXPRESSION; PATHOGENESIS; SURVIVAL; FREQUENT; TARGET
AB Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information. We found recurrent mutations of miR-142, which has not been previously been reported to be mutated in FL/tFL. The genes most frequently mutated in tFL included KMT2D (MLL2), CREBBP, EZH2, BCL2 and MEF2B. Many recurrently mutated genes are involved in epigenetic regulation, the Janus-activated kinase-signal transducer and activator of transcription (STAT) or the nuclear factor-kappa B pathways, immune surveillance and cell cycle regulation or are TFs involved in B-cell development. Of particular interest are mutations and CNAs affecting S1P-activated pathways through S1PR1 or S1PR2, which likely regulate lymphoma cell migration and survival outside of follicles. Our custom gene enrichment panel provides high depth of coverage for the study of clonal evolution or divergence.
C1 [Bouska, A.; Zhang, W.; Iqbal, J.; Fu, K.; Greiner, T. C.] Univ Nebraska Med Ctr, Pathol & Microbiol, Omaha, NE USA.
[Gong, Q.; Scuto, A.; Weisenburger, D. D.; McKeithan, T. W.; Chan, W. C.] City Hope Natl Med Ctr, Dept Pathol, 1500 East Duarte Rd, Duarte, CA 91010 USA.
[Vose, J.] Univ Nebraska Med Ctr, Div Hematol & Oncol, Omaha, NE USA.
[Ludvigsen, M.] Aarhus Univ, Dept Biomed, Aarhus, Denmark.
[Gascoyne, R. D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada.
[Rosenwald, A.] Univ Wurzburg, Inst Pathol, Wurzburg, Germany.
[Rosenwald, A.] Comprehens Canc Ctr Mainfranken, Wurzburg, Germany.
[Ott, G.] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Ott, G.] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Campo, E.] Univ Barcelona, Hosp Clin, Hematopathol Unit, IDIBAPS, Barcelona, Spain.
[Rimsza, L. M.] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Delabie, J.] Univ Toronto, Dept Pathol, Toronto, ON, Canada.
[Jaffe, E. S.] NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Braziel, R. M.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Connors, J. M.] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC, Canada.
[Wu, C-I] Chinese Acad Sci, Beijing Inst Genom, Beijing, Peoples R China.
[Wu, C-I] Univ Chicago, Dept Ecol & Evolut, 940 E 57th St, Chicago, IL 60637 USA.
[Staudt, L. M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Amore, F. D.] Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.
RP Chan, WC (reprint author), City Hope Natl Med Ctr, Dept Pathol, 1500 East Duarte Rd, Duarte, CA 91010 USA.
EM jochan@coh.org
OI Campo, elias/0000-0001-9850-9793
FU Lymphoma Research Foundation Follicular Lymphoma initiative; Lymphoma
SPORE [P50CA136411-01-(NCI)]; University of Nebraska Foundation; NCRR
[1S10RR027754-01, 5P20RR016469, RR018788-08]; National Institute for
General Medical Science (NIGMS) [8P20GM103427, GM103471-09]; National
Cancer Institute of the National Institutes of Health [P30CA033572]
FX This work was supported by the Lymphoma Research Foundation Follicular
Lymphoma initiative (to WCC), Lymphoma SPORE P50CA136411-01-(NCI) (to
WCC) and a grant for Global Engagement from the University of Nebraska
Foundation (to WCC). The University of Nebraska DNA Sequencing Core
receives partial support from the NCRR (1S10RR027754-01, 5P20RR016469,
RR018788-08) and the National Institute for General Medical Science
(NIGMS) (8P20GM103427, GM103471-09). Research reported in this
publication was supported in part by the National Cancer Institute of
the National Institutes of Health under award number P30CA033572 and
included work performed in the Bioinformatics Core. Thanks to Adam
Cornish and Robert J Boissy for initial sequencing analysis assistance.
NR 51
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD JAN
PY 2017
VL 31
IS 1
BP 83
EP 91
DI 10.1038/leu.2016.175
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA EK6UD
UT WOS:000394058700011
PM 27389057
ER
PT J
AU Hegde, ML
Bohr, VA
Mitra, S
AF Hegde, Muralidhar L.
Bohr, Vilhelm A.
Mitra, Sankar
TI DNA damage responses in central nervous system and age-associated
neurodegeneration
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Editorial Material
ID STRAND BREAK REPAIR; ATAXIA-TELANGIECTASIA; ALZHEIMERS-DISEASE;
COCKAYNE-SYNDROME; EXCISION-REPAIR; BRAIN; INSTABILITY; DEFICIENCY;
INTEGRITY; MUTATION
C1 [Hegde, Muralidhar L.; Mitra, Sankar] Houston Methodist Res Inst, Dept Radiat Oncol, Houston, TX 77030 USA.
[Hegde, Muralidhar L.] Houston Methodist Neurol Inst, Houston, TX 77030 USA.
[Hegde, Muralidhar L.; Mitra, Sankar] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Hegde, ML (reprint author), 6550 Fannin St, Houston, TX 77030 USA.
FU National institute of Health, USA [R01 NS088645, IRP-NIH/NIA, R01 CA
CA158910]
FX M.L.H. (R01 NS088645), V.A.B. (IRP-NIH/NIA) and S.A. (R01 CA CA158910)
acknowledge the National institute of Health, USA for the support of
their research program.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD JAN
PY 2017
VL 161
SI SI
BP 1
EP 3
DI 10.1016/j.mad.2017.01.010
PN A
PG 3
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA EP0JQ
UT WOS:000397074000001
PM 28212866
ER
PT J
AU Hou, YJ
Song, HD
Croteau, DL
Akbari, M
Bohr, VA
AF Hou, Yujun
Song, Hyundong
Croteau, Deborah L.
Akbari, Mansour
Bohr, Vilhelm A.
TI Genome instability in Alzheimer disease
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE DNA damage; DNA repair; Alzheimer's disease
ID BASE-EXCISION-REPAIR; MILD COGNITIVE IMPAIRMENT; OXIDATIVE DNA-DAMAGE;
AMYLOID PRECURSOR PROTEIN; MITOCHONDRIAL CASCADE HYPOTHESIS;
CYTOCHROME-OXIDASE ACTIVITY; HUMAN NEUROBLASTOMA-CELLS; DOUBLE-STRAND
BREAKS; SMOOTH-MUSCLE-CELLS; MOUSE MODEL
AB Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Autosomal dominant, familial AD (fAD) is very rare and caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2) genes. The pathogenesis of sporadic AD (sAD) is more complex and variants of several genes are associated with an increased lifetime risk of AD. Nuclear and mitochondrial DNA integrity is pivotal during neuronal development, maintenance and function. DNA damage and alterations in cellular DNA repair capacity have been implicated in the aging process and in age-associated neurodegenerative diseases, including AD. These findings are supported by research using animal models of AD and in DNA repair deficient animal models. In recent years, novel mechanisms linking DNA damage to neuronal dysfunction have been identified and have led to the development of noninvasive treatment strategies. Further investigations into the molecular mechanisms connecting DNA damage to AD pathology may help to develop novel treatment strategies for this debilitating disease. Here we provide an overview of the role of genome instability and DNA repair deficiency in AD pathology and discuss research strategies that include genome instability as a component. Published by Elsevier Ireland Ltd.
C1 [Hou, Yujun; Song, Hyundong; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Akbari, Mansour] Univ Copenhagen, Ctr Hlth Aging, SUND, Copenhagen, Denmark.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU Intramural Research Program of National Institute on Aging, National
Institutes of Health
FX This work was supported entirely by Intramural Research Program of
National Institute on Aging, National Institutes of Health. We thank
Qiping Lu and Stephanie Cordonnier for critically reading the
manuscript.
NR 216
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD JAN
PY 2017
VL 161
SI SI
BP 83
EP 94
DI 10.1016/j.mad.2016.04.005
PN A
PG 12
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA EP0JQ
UT WOS:000397074000007
PM 27105872
ER
PT J
AU Shin, HW
Ryu, HS
Kim, J
Kim, MJ
Hallett, M
Chung, SJ
AF Shin, Hae-Won
Ryu, Ho-Sung
Kim, Juyeon
Kim, Mi-Jung
Hallett, Mark
Chung, Sun Ju
TI Sensory Tricks for Cervical Levodopa-induced Dyskinesia in Patients with
Parkinson's Disease
SO MOVEMENT DISORDERS CLINICAL PRACTICE
LA English
DT Article
DE Parkinson's disease; levodopa-induced dyskinesia; cervical dystonia;
sensory tricks
ID CLINICAL CHARACTERISTICS; DYSTONIA
AB Choreiform or dystonic movement in the craniocervical region can occur as levodopa-induced dyskinesia (LID). "Sensory tricks" are various alleviating maneuvers for the relief of abnormal postures in patients who have idiopathic focal dystonia, particularly those who have cervical dystonia. The authors report on three men with Parkinson's disease who had been receiving levodopa for more than 3 years and presented with involuntary neck movements during the drug on period. In all three patients, cervical LIDs appeared during the drug on period and completely disappeared during the drug off period. The effects of using sensory tricks to markedly improve the symptoms of cervical LID were studied. In all patients, the cervical LIDs improved more efficiently when sensory tricks were performed on the patient by another person (passive tricks) than by the patient himself (self-sensory tricks). The unique features of the sensory tricks for cervical LID in the current patients may be important clinical evidence of abnormal sensorimotor integration in patients who have PD with LID.
C1 [Shin, Hae-Won] Chung Ang Univ, Coll Med, Dept Neurol, Seoul, South Korea.
[Ryu, Ho-Sung; Kim, Juyeon; Chung, Sun Ju] Univ Ulsan, Coll Med, Dept Neurol, Asan Med Ctr, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea.
[Kim, Mi-Jung] Univ Ulsan, Coll Med, Hlth Screening & Promot Ctr, Asan Med Ctr, Seoul, South Korea.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Chung, SJ (reprint author), Univ Ulsan, Coll Med, Dept Neurol, Asan Med Ctr, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea.
EM sjchung@amc.seoul.kr
FU Korea Healthcare Technology R&D Project, Ministry of Health and Welfare,
Republic of Korea [HI14C2206]
FX This work was supported by a grant from the Korea Healthcare Technology
R&D Project, Ministry of Health and Welfare, Republic of Korea
(HI14C2206). The authors report no conflicts of interest.
NR 9
TC 1
Z9 1
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2330-1619
J9 MOV DISORD CLIN PRAC
JI MOV. DISORD. CLIN. PRACT.
PD JAN-FEB
PY 2017
VL 4
IS 1
BP 138
EP 140
DI 10.1002/mdc3.12363
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA EO0EF
UT WOS:000396370400029
ER
PT J
AU Kwon-Chung, KJ
Bennett, JE
Wickes, BL
Meyer, W
Cuomo, CA
Wollenburg, KR
Bicanic, TA
Castaneda, E
Chang, YC
Chen, JH
Cogliati, M
Dromer, F
Ellis, D
Filler, SG
Fisher, MC
Harrison, TS
Holland, SM
Kohno, S
Kronstad, JW
Lazera, M
Levitz, SM
Lionakis, MS
May, RC
Ngamskulrongroj, P
Pappas, PG
Perfect, JR
Rickerts, V
Sorrell, TC
Walsh, TJ
Williamson, PR
Xu, JP
Zelazny, AM
Casadevall, A
AF Kwon-Chung, Kyung J.
Bennett, John E.
Wickes, Brian L.
Meyer, Wieland
Cuomo, Christina A.
Wollenburg, Kurt R.
Bicanic, Tihana A.
Castaneda, Elizabeth
Chang, Yun C.
Chen, Jianghan
Cogliati, Massimo
Dromer, Francoise
Ellis, David
Filler, Scott G.
Fisher, Matthew C.
Harrison, Thomas S.
Holland, Steven M.
Kohno, Shigeru
Kronstad, James W.
Lazera, Marcia
Levitz, Stuart M.
Lionakis, Michail S.
May, Robin C.
Ngamskulrongroj, Popchai
Pappas, Peter G.
Perfect, John R.
Rickerts, Volker
Sorrell, Tania C.
Walsh, Thomas J.
Williamson, Peter R.
Xu, Jianping
Zelazny, Adrian M.
Casadevall, Arturo
TI The Case for Adopting the "Species Complex" Nomenclature for the
Etiologic Agents of Cryptococcosis
SO MSPHERE
LA English
DT Article
DE Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; clade;
genetic diversity; new nomenclature; species complex
ID NEOFORMANS; GATTII; FUNGI; POPULATION; HIV/AIDS; REVEALS; HYBRID
AB Cryptococcosis is a potentially lethal disease of humans/animals caused by Cryptococcus neoformans and Cryptococcus gattii. Distinction between the two species is based on phenotypic and genotypic characteristics. Recently, it was proposed that C. neoformans be divided into two species and C. gattii into five species based on a phylogenetic analysis of 115 isolates. While this proposal adds to the knowledge about the genetic diversity and population structure of cryptococcosis agents, the published genotypes of 2,606 strains have already revealed more genetic diversity than is encompassed by seven species. Naming every clade as a separate species at this juncture will lead to continuing nomenclatural instability. In the absence of biological differences between clades and no consensus about how DNA sequence alone can delineate a species, we recommend using "Cryptococcus neoformans species complex" and "C. gattii species complex" as a practical intermediate step, rather than creating more species. This strategy recognizes genetic diversity without creating confusion.
C1 [Kwon-Chung, Kyung J.; Bennett, John E.; Chang, Yun C.; Holland, Steven M.; Lionakis, Michail S.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Wickes, Brian L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Meyer, Wieland] Univ Sydney, Mol Mycol Res Lab, Sydney, NSW, Australia.
[Meyer, Wieland; Sorrell, Tania C.] Westmead Inst Med Res, Westmead, NSW, Australia.
[Cuomo, Christina A.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Wollenburg, Kurt R.] NIAID, Off Cyber Infrastruct & Computat Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bicanic, Tihana A.; Harrison, Thomas S.] St Georges Univ London, Inst Infect & Immun, London, England.
[Castaneda, Elizabeth] Colombia Inst Nacl Salud, Bogota, Colombia.
[Chen, Jianghan] Second Mil Med Univ, Changzheng Hosp, Mycol Ctr, Shanghai, Peoples R China.
[Cogliati, Massimo] Univ Milan, Dipartimento Sci Biomed Salute, Milan, Italy.
[Dromer, Francoise] Inst Pasteur, Mol Mycol Unit, Paris, France.
[Ellis, David] Univ Adelaide, Sch Biol Sci, Adelaide, SA, Australia.
[Filler, Scott G.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA USA.
[Fisher, Matthew C.] Imperial Coll London, Dept Infect Dis Epidemiol, London, England.
[Kohno, Shigeru] Nagasaki Univ, Nagasaki, Japan.
[Kronstad, James W.] Univ British Columbia, Michael Smith Labs, Vancouver, BC, Canada.
[Lazera, Marcia] Fiocruz MS, Inst Nacl Infectol Evandro Chagas, Rio De Janeiro, Brazil.
[Levitz, Stuart M.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[May, Robin C.] Univ Birmingham, Inst Microbiol & Infect, Birmingham, W Midlands, England.
[May, Robin C.] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England.
[Ngamskulrongroj, Popchai] Mahidol Univ, Siriraj Hosp, Fac Med, Bangkok, Thailand.
[Pappas, Peter G.] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL USA.
[Perfect, John R.] Duke Univ, Sch Med, Durham, NC USA.
[Rickerts, Volker] Robert Koch Inst, Berlin, Germany.
[Sorrell, Tania C.] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW, Australia.
[Walsh, Thomas J.] Weill Cornell Med, Dept Med, New York, NY USA.
[Walsh, Thomas J.] Weill Cornell Med, Dept Pediat, New York, NY USA.
[Walsh, Thomas J.] Weill Cornell Med, Dept Microbiol & Immunol, New York, NY USA.
[Xu, Jianping] McMaster Univ, Dept Biol, Hamilton, ON, Canada.
[Xu, Jianping] Hainan Med Coll, Haikou, Hainan, Peoples R China.
[Zelazny, Adrian M.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Casadevall, Arturo] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM june_kwon-chung@nih.gov
FU intramural program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health; NHMRC [APP1031943]; European
Research Council under the European Union's Seventh Framework Program
(FP); ERC [614562]; Royal Society Wolfson Research Merit Award; Lister
Institute Prize Fellowship
FX This work was supported by funds from the intramural program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, to K.J.K.-C., J.E.B., Y.C.C., S.M.H., M.L., and
P.R.W. and an NHMRC grant, APP1031943, to W.M. and T.C.S. R.C.M. is
supported by the European Research Council under the European Union's
Seventh Framework Program (FP/2007-2013) and ERC grant agreement no.
614562 and by a Royal Society Wolfson Research Merit Award and a Lister
Institute Prize Fellowship. T.C.S. is a Sydney Medical School Foundation
Fellow.
NR 40
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2379-5042
J9 MSPHERE
JI mSphere
PD JAN
PY 2017
VL 2
IS 1
AR e00357-16
DI 10.1128/mSphere.00357-16
PG 7
WC Microbiology
SC Microbiology
GA EL3WL
UT WOS:000394549900019
ER
PT J
AU Mahic, M
Mjaaland, S
Bovelstad, HM
Gunnes, N
Susser, E
Bresnahan, M
Oyen, AS
Levin, B
Che, X
Hirtz, D
Reichborn-Kjennerud, T
Schjolberg, S
Roth, C
Magnus, P
Stoltenberg, C
Suren, P
Hornig, M
Lipkin, WI
AF Mahic, Milada
Mjaaland, Siri
Bovelstad, Hege Marie
Gunnes, Nina
Susser, Ezra
Bresnahan, Michaeline
Oyen, Anne-Siri
Levin, Bruce
Che, Xiaoyu
Hirtz, Deborah
Reichborn-Kjennerud, Ted
Schjolberg, Synnve
Roth, Christine
Magnus, Per
Stoltenberg, Camilla
Suren, Pal
Hornig, Mady
Lipkin, W. Ian
TI Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism
Spectrum Disorder in Male Offspring
SO MSPHERE
LA English
DT Article
DE autism; birth cohort; herpes simplex virus; infection; prenatal;
serology
ID EPSTEIN-BARR-VIRUS; CONGENITAL TOXOPLASMOSIS; INTRAUTERINE INFECTION;
INFLAMMATORY CYTOKINES; AUTOIMMUNE-DISEASES; TYPE-2 INFECTION;
AMNIOTIC-FLUID; PRETERM BIRTH; FETAL-DEATH; PREGNANCY
AB Maternal infections during pregnancy are associated with risk of neuro-developmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers of children with ASD were identified, and 464 frequency-matched controls were selected. Immunoglobulin G (IgG) antibodies to Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and HSV-2 in plasma collected at midpregnancy and after delivery were measured by multiplexed immunoassays. High levels of HSV-2 IgG antibodies in maternal midpregnancy plasma were associated with increased risk of ASD in male offspring (an increase in HSV-2 IgG levels from 240 to 640 arbitrary units/ml was associated with an odds ratio of 2.07; 95% confidence interval, 1.06 to 4.06; P = 0.03) when adjusted for parity and child's birth year. No association was found between ASD and the presence of IgG antibodies to Toxoplasma gondii, rubella virus, CMV, or HSV-1. Additional studies are needed to test for replicability of risk and specificity of the sex effect and to examine risk associated with other infections.
IMPORTANCE The cause (or causes) of most cases of autism spectrum disorder is unknown. Evidence from epidemiological studies and work in animal models of neurodevelopmental disorders suggest that both genetic and environmental factors may be implicated. The latter include gestational infection and immune activation. In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection may contribute to the pathogenesis of autism spectrum disorder and have the potential to drive new efforts to monitor women more closely for cryptic gestational infection and to implement suppressive therapy during pregnancy.
C1 [Mahic, Milada; Mjaaland, Siri; Che, Xiaoyu; Hornig, Mady; Lipkin, W. Ian] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10027 USA.
[Mahic, Milada; Mjaaland, Siri; Bovelstad, Hege Marie; Gunnes, Nina; Oyen, Anne-Siri; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Roth, Christine; Magnus, Per; Stoltenberg, Camilla; Suren, Pal] Norwegian Inst Publ Hlth, Oslo, Norway.
[Susser, Ezra; Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10027 USA.
[Susser, Ezra; Bresnahan, Michaeline] Columbia Univ, New York State Psychiat Inst, New York, NY USA.
[Levin, Bruce] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
[Hirtz, Deborah] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Reichborn-Kjennerud, Ted] Univ Oslo, Inst Clin Med, Oslo, Norway.
[Roth, Christine] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway.
[Stoltenberg, Camilla] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Hirtz, Deborah] Univ Vermont, Coll Med, Dept Pediat Neurol, Burlington, VT USA.
RP Lipkin, WI (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10027 USA.; Lipkin, WI (reprint author), Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10027 USA.
EM wil2001@cumc.columbia.edu
FU National Institutes of Health [NS47537, NS086122]; Jane Botsford Johnson
foundation; Simons Foundation Autism Research Initiative; Norwegian
Ministry of Health and Care Services; Norwegian Ministry of Education
and Research; Research Council of Norway [189457, 190694, 196452]
FX This work was supported by National Institutes of Health grants NS47537
and NS086122 (all authors), the Jane Botsford Johnson foundation (all
authors), the Simons Foundation Autism Research Initiative (all
authors), the Norwegian Ministry of Health and Care Services (M.M.,
S.M., H.M.B., N.G., A.-S.O., T.R.-K., S.S., C.R., P.M., C.S., and P.S.),
the Norwegian Ministry of Education and Research (M.M., S.M., H.M.B.,
N.G., A.-S.O., T.R.-K., S.S., C.R., P.M., C.S., and P.S.), and Research
Council of Norway grants 189457, 190694, and 196452 (M.M., S.M., H.M.B.,
N.G., A.-S.O., T.R.-K., S.S., C.R., P.M., C.S., and P.S.). The funders
had no role in study design, data collection and interpretation, or the
decision to submit the work for publication.
NR 69
TC 0
Z9 0
U1 4
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2379-5042
J9 MSPHERE
JI mSphere
PD JAN
PY 2017
VL 2
IS 1
AR e00016-17
DI 10.1128/mSphere.00016-17
PG 10
WC Microbiology
SC Microbiology
GA EL3WL
UT WOS:000394549900005
ER
PT J
AU Song, KH
Cho, H
Kim, S
Lee, HJ
Oh, SJ
Woo, SR
Hong, SO
Jang, HS
Noh, KH
Choi, CH
Chung, JY
Hewitt, SM
Kim, JH
Son, M
Kim, SH
Lee, BI
Park, HC
Bae, YK
Kim, TW
AF Song, K-H
Cho, H.
Kim, S.
Lee, H-J
Oh, S. J.
Woo, S. R.
Hong, S-O
Jang, H. S.
Noh, K. H.
Choi, C. H.
Chung, J-Y
Hewitt, S. M.
Kim, J-H
Son, M.
Kim, S-H
Lee, B. I.
Park, H-C
Bae, Y-K
Kim, T. W.
TI API5 confers cancer stem cell-like properties through the FGF2-NANOG
axis
SO ONCOGENESIS
LA English
DT Article
ID CERVICAL-CANCER; IMMUNE EVASION; SMALL-MOLECULE; APOPTOSIS; AAC-11;
GROWTH; OVEREXPRESSION; IDENTIFICATION; EXPRESSION; INHIBITOR
AB Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity. Critically, these CSC-like properties mediated by API5 are dependent on FGFR1 signaling, which is triggered by E2F1-dependent FGF2 expression. Furthermore, we uncovered the FGF2-NANOG molecular axis as a downstream component of API5 signaling that is conserved in cervical cancer patients. Finally, we found that the blockade of FGFR signaling is an effective strategy to control API5(high) human cancer. Thus, our findings reveal a crucial role of API5 in linking immune resistance and CSC-like properties, and provide the rationale for its therapeutic application for the treatment of API5(+) refractory tumors.
C1 [Song, K-H; Lee, H-J; Oh, S. J.; Woo, S. R.; Hong, S-O; Jang, H. S.; Noh, K. H.; Bae, Y-K; Kim, T. W.] Korea Univ, Grad Sch Med, Dept Biomed Sci, Lab Tumor Immunol, Seoul, South Korea.
[Song, K-H; Lee, H-J; Oh, S. J.; Woo, S. R.; Hong, S-O; Jang, H. S.; Noh, K. H.; Kim, T. W.] Korea Univ, Dept Biochem, Coll Med, Seoul, South Korea.
[Song, K-H; Lee, H-J; Oh, S. J.; Jang, H. S.; Kim, T. W.] Korea Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea.
[Cho, H.; Chung, J-Y; Hewitt, S. M.] NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Cho, H.; Kim, J-H] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul, South Korea.
[Cho, H.; Kim, J-H] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul, South Korea.
[Kim, S.; Park, H-C] Korea Univ, Grad Sch Med, Ansan, South Korea.
[Choi, C. H.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea.
[Son, M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kim, S-H] KRIBB, Immunotherapy Res Ctr, Daejeon, South Korea.
[Lee, B. I.] Natl Canc Ctr, Res Inst, Div Convergence Technol, Biomol Funct Res Branch, Goyang, South Korea.
[Bae, Y-K] Natl Canc Ctr, Res Inst, Div Canc Biol, Comparat Biomed Res Branch, Goyang, South Korea.
RP Bae, YK (reprint author), Natl Canc Ctr, Res Inst, Div Canc Biol, Comparat Biomed Res Branch, 323 Ilsan Ro, Goyang Si 10408, Gyeonggi Do, South Korea.; Kim, TW (reprint author), Korea Univ, Coll Med, Lab Tumor Immunol, Room 319,Moonsook Med Hall,73 Inchon Ro, Seoul 02841, South Korea.
EM zebra@ncc.re.kr; twkim0421@korea.ac.kr
FU National Research Foundation of Korea [NRF-2014R1A2A1A10054205,
NRF-2013M3A9D3045881]
FX This work was funded by the National Research Foundation of Korea
(NRF-2014R1A2A1A10054205 and NRF-2013M3A9D3045881).
NR 32
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2157-9024
J9 ONCOGENESIS
JI Oncogenesis
PD JAN
PY 2017
VL 6
AR e285
DI 10.1038/oncsis.2016.87
PG 13
WC Oncology
SC Oncology
GA EO1AI
UT WOS:000396429500009
PM 28092370
ER
PT J
AU Dolinska, MB
Kus, NJ
Farney, SK
Wingfield, PT
Brooks, BP
Sergeev, YV
AF Dolinska, Monika B.
Kus, Nicole J.
Farney, S. Katie
Wingfield, Paul T.
Brooks, Brian P.
Sergeev, Yuri V.
TI Oculocutaneous albinism type 1: link between mutations, tyrosinase
conformational stability, and enzymatic activity
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE oculocutaneous albinism; tyrosinase; genetic mutations; protein
structure; protein stability; protein unfolding; protein purification
ID HERMANSKY-PUDLAK-SYNDROME; RECESSIVE OCULAR ALBINISM;
ENDOPLASMIC-RETICULUM; KOREAN PATIENTS; GENE-MUTATIONS; HUMAN HOMOLOG;
MOUSE; LOCUS; FORM; OCA1
AB Oculocutaneous albinism type 1 ( OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 have been described: severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes of OCA1 patients. Proteins were prepared using site-directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. The OCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimicking OCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates that OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactivate tyrosinase and result in OCA1B albinism.
C1 [Dolinska, Monika B.; Kus, Nicole J.; Farney, S. Katie; Brooks, Brian P.; Sergeev, Yuri V.] NEI, NIH, Bethesda, MD 20892 USA.
[Wingfield, Paul T.] Natl Inst Artritis & Musculoskeletal & Skin Dis, NIH, Bethesda, MD USA.
RP Sergeev, YV (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM sergeevy@nei.nih.gov
NR 59
TC 0
Z9 0
U1 3
U2 3
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD JAN
PY 2017
VL 30
IS 1
BP 41
EP 52
DI 10.1111/pcmr.12546
PG 12
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA EK5HJ
UT WOS:000393957200008
PM 27775880
ER
PT J
AU Gao, Y
Cao, ZJ
Yang, X
Abdelmegeed, MA
Sun, JC
Chen, S
Beger, RD
Davis, K
Salminen, WF
Song, BJ
Mendrick, DL
Yu, LR
AF Gao, Yuan
Cao, Zhijun
Yang, Xi
Abdelmegeed, Mohamed A.
Sun, Jinchun
Chen, Si
Beger, Richard D.
Davis, Kelly
Salminen, William F.
Song, Byoung-Joon
Mendrick, Donna L.
Yu, Li-Rong
TI Proteomic analysis of acetaminophen-induced hepatotoxicity and
identification of heme oxygenase 1 as a potential plasma biomarker of
liver injury
SO PROTEOMICS CLINICAL APPLICATIONS
LA English
DT Article
DE Acetaminophen; Heme oxygenase 1 (HMOX1); Hepatotoxicity; MS
ID MITOCHONDRIAL PERMEABILITY TRANSITION; UNITED-STATES; IN-VIVO;
QUANTITATIVE PROTEOMICS; THERAPEUTIC TARGET; OXIDATIVE STRESS; PROTEIN
ADDUCT; MOUSE-LIVER; TOXICITY; RATS
AB Purpose: Overdose of acetaminophen (APAP) is a major cause of acute liver failure. This study was aimed to identify pathways related to hepatotoxicity and potential biomarkers of liver injury.
Experimental design: Rats were treated with low (100 mg/kg) and high (1250 mg/kg) doses of APAP, and liver tissues at 6 and 24 h post-treatment were analyzed using a proteomic approach of 16O/18O labeling and 2D-LC-MS/MS.
Results: Molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose-and time-dependent manner upon APAP treatment. Imbalanced expression of hemeoxygenase 1 (HMOX1) and biliverdin reductase A (BLVRA) was associated with hepatotoxicity. Protein abundance changes of a total of 31 proteins were uniquely correlated to liver damage, among which a dramatic increase of HMOX1 levels in plasma was observed. Liver injury-associated significant elevation of plasma HMOX1 was further validated in mice treated with APAP.
Conclusions and clinical relevance: This study unveiled molecular changes associated with APAP-induced liver toxicity at the pathway levels and identified HMOX1 as a potential plasma biomarker of liver injury.
C1 [Gao, Yuan; Cao, Zhijun; Yang, Xi; Sun, Jinchun; Beger, Richard D.; Salminen, William F.; Mendrick, Donna L.; Yu, Li-Rong] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Abdelmegeed, Mohamed A.; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD USA.
[Chen, Si] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Davis, Kelly] US FDA, Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR USA.
RP Yu, LR (reprint author), US FDA, Biomarkers & Alternat Models Branch, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 233, Jefferson, AR 72079 USA.
EM Lirong.Yu@fda.hhs.gov
FU National Center for Toxicological Research, U.S. Food and Drug
Administration (NCTR/FDA), Jefferson, Arkansas; National Institute on
Alcohol Abuse and Alcoholism, Bethesda, Maryland
FX This study was supported with funds from the National Center for
Toxicological Research, U.S. Food and Drug Administration (NCTR/FDA),
Jefferson, Arkansas, and in part with the Intramural funds from National
Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. The
information in this article is not a formal dissemination of information
by FDA and does not represent agency position or policy.
NR 72
TC 0
Z9 0
U1 0
U2 0
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1862-8346
EI 1862-8354
J9 PROTEOM CLIN APPL
JI Proteom. Clin. Appl.
PD JAN
PY 2017
VL 11
IS 1-2
AR UNSP 1600123
DI 10.1002/prca.201600123
PG 17
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EO0NM
UT WOS:000396394800008
ER
PT J
AU Gru, AA
Jaffe, ES
AF Gru, Alejandro A.
Jaffe, Elaine S.
TI The Landscape of Cutaneous Lymphomas in 2016, An Introduction
SO SEMINARS IN DIAGNOSTIC PATHOLOGY
LA English
DT Editorial Material
ID B-CELL LYMPHOMA; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; CLASSIFICATION;
NEOPLASMS; PAPULOSIS
C1 [Gru, Alejandro A.] Univ Virginia, Charlottesville, VA USA.
[Jaffe, Elaine S.] Ctr Canc Res, NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), Ctr Canc Res, NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA.
NR 19
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0740-2570
EI 1930-1111
J9 SEMIN DIAGN PATHOL
JI Semin. Diagn. Pathol.
PD JAN
PY 2017
VL 34
IS 1
BP 1
EP 2
DI 10.1053/j.semdp.2016.11.010
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA EP1VI
UT WOS:000397172000001
PM 27989527
ER
PT J
AU Gru, AA
Jaffe, ES
AF Gru, Alejandro A.
Jaffe, Elaine S.
TI Cutaneous EBV-related lymphoproliferative disorders
SO SEMINARS IN DIAGNOSTIC PATHOLOGY
LA English
DT Article
DE Extranodal NW-cell lymphoma; EBV plus mucocutaneous ulcer; Hydroa
vacciniforme; Chronic active EBV infection
ID EPSTEIN-BARR-VIRUS; NK/T-CELL LYMPHOMA; POSITIVE MUCOCUTANEOUS ULCER;
VACCINIFORME-LIKE LYMPHOMA; OF-THE-LITERATURE; CATENIN GENE-MUTATIONS;
PERIPHERAL T-CELL; ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS; COMPARATIVE
GENOMIC HYBRIDIZATION; ORGAN TRANSPLANT RECIPIENTS
AB This article will focus on the cutaneous lymphoproliferative disorders associated with EBV, with an emphasis on the upcoming changes in the revised 4th Edition of the WHO classification of tumors of the hematopoietic system, many of which deal with cutaneous disorders derived from NK-cells or T-cells. Extranodal NK/T-cell lymphoma usually presents in the upper aerodigestive tract, but can involve the skin secondarily. EBV-associated T- and NK-cell lymphoproliferative disorders (LPD) in the pediatric age group include the systemic diseases, chronic active EBV infection (CAEBV) and systemic EBV+ T-cell lymphoma of childhood. Hydroa vacciniforme (HV)-like LPD is a primarily cutaneous form of CAEBV and encompasses the lesions previously referred to as HV and HV-like lymphoma (HVLL). All the T/NK-cellEBV-associated diseases occur with higher frequency in Asians, and indigenous populations from Central and South America and Mexico. Among the B-cell EBV-associated LPD two major changes have been introduced in the WHO. The previously designated EBV-positive diffuse large B-cell lymphoma (EBVDLBCL) of the elderly, has been changed to EBV-DLBCL with 'not otherwise specified' as a modifier (NOS). A new addition to the WHO system is the more recently identified EBV+ mucocutaneous ulcer, which involves skin and mucosal-associated sites. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Gru, Alejandro A.] Univ Virginia, Hematopathol Sect, Pathol & Dermatol, Charlottesville, VA 22903 USA.
[Gru, Alejandro A.] Univ Virginia, Dermatopathol Sect, Pathol & Dermatol, Charlottesville, VA USA.
[Jaffe, Elaine S.] Natl Canc Inst, Hematopathol, Bethesda, MD USA.
RP Gru, AA (reprint author), Univ Virginia, Hematopathol Sect, Pathol & Dermatol, Charlottesville, VA 22903 USA.; Gru, AA (reprint author), Univ Virginia, Dermatopathol Sect, Pathol & Dermatol, Charlottesville, VA USA.
EM aag4b@virginia.edu
NR 222
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0740-2570
EI 1930-1111
J9 SEMIN DIAGN PATHOL
JI Semin. Diagn. Pathol.
PD JAN
PY 2017
VL 34
IS 1
BP 60
EP 75
DI 10.1053/j.semdp.2016.11.003
PG 16
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA EP1VI
UT WOS:000397172000007
PM 27988064
ER
PT J
AU Bellucci, G
Chernyak, S
Hoffman, M
Deshpande, G
Dal Monte, O
Knutson, KM
Grafman, J
Krueger, F
AF Bellucci, Gabriele
Chernyak, Sergey
Hoffman, Morris
Deshpande, Gopikrishna
Dal Monte, Olga
Knutson, Kristine M.
Grafman, Jordan
Krueger, Frank
TI Effective connectivity of brain regions underlying third-party
punishment: Functional MRI and Granger causality evidence
SO SOCIAL NEUROSCIENCE
LA English
DT Article
DE Third-party punishment; social cognition; prefrontal cortex; temporal
pole; effective connectivity
ID EVENT-RELATED FMRI; MEDIAL PREFRONTAL CORTEX; NEURAL BASIS; SOCIAL
COGNITION; TEXT COMPREHENSION; DECISION-MAKING; JUSTICE; NORMS;
METAANALYSIS; INTUITIONS
AB Third-party punishment (TPP) for norm violations is an essential deterrent in large-scale human societies, and builds on two essential cognitive functions: evaluating legal responsibility and determining appropriate punishment. Despite converging evidence that TPP is mediated by a specific set of brain regions, little is known about their effective connectivity (direction and strength of connections). Applying parametric event-related functional MRI in conjunction with multivariate Granger causality analysis, we asked healthy participants to estimate how much punishment a hypothetical perpetrator deserves for intentionally committing criminal offenses varying in levels of harm. Our results confirmed that TPP legal decisions are based on two domain-general networks: the mentalizing network for evaluating legal responsibility and the central-executive network for determining appropriate punishment. Further, temporal pole (TP) and dorsomedial prefrontal cortex (PFC) emerged as hubs of the mentalizing network, uniquely generating converging output connections to ventromedial PFC, temporo-parietal junction, and posterior cingulate. In particular, dorsomedial PFC received inputs only from TP and both its activation and its connectivity to dorsolateral PFC correlated with degree of punishment. This supports the hypothesis that dorsomedial PFC acts as the driver of the TPP activation pattern, leading to the decision on the appropriate punishment. In conclusion, these results advance our understanding of the organizational elements of the TPP brain networks and provide better insights into the mental states of judges and jurors tasked with blaming and punishing legal wrongs.
C1 [Bellucci, Gabriele; Chernyak, Sergey; Krueger, Frank] George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA.
[Bellucci, Gabriele] Humboldt Univ, Berlin Sch Mind & Brain, Berlin, Germany.
[Hoffman, Morris] Second Judicial Dist, Denver, CO USA.
[Hoffman, Morris] John D & Catherine T MacArthur Fdn Res Network La, Nashville, TN USA.
[Deshpande, Gopikrishna] Auburn Univ, Dept Elect & Comp Engn, AU MRI Res Ctr, Auburn, AL 36849 USA.
[Deshpande, Gopikrishna] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA.
[Dal Monte, Olga] Yale Univ, Dept Psychol, New Haven, CT USA.
[Knutson, Kristine M.] NINDS, Behav Neurol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Grafman, Jordan] Rehabil Inst Chicago, Brain Injury Res Program, Chicago, IL 60611 USA.
[Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
RP Krueger, F (reprint author), George Mason Univ, Dept Psychol, Mol Neurosci Dept, 4400 Univ Dr,Mail Stop 2A1, Fairfax, VA 22030 USA.
EM FKrueger@gmu.edu
FU Intramural Research Program of the CNS/ NINDS/ NIH
FX The work was supported by the Intramural Research Program of the CNS/
NINDS/ NIH.
NR 71
TC 0
Z9 0
U1 4
U2 4
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1747-0919
EI 1747-0927
J9 SOC NEUROSCI-UK
JI Soc. Neurosci.
PY 2017
VL 12
IS 2
BP 124
EP 134
DI 10.1080/17470919.2016.1153518
PG 11
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA EM1ST
UT WOS:000395098000003
PM 26942651
ER
PT J
AU Rigo, P
De Pisapia, N
Bornstein, MH
Putnick, DL
Serra, M
Esposito, G
Venuti, P
AF Rigo, Paola
De Pisapia, Nicola
Bornstein, Marc H.
Putnick, Diane L.
Serra, Mauro
Esposito, Gianluca
Venuti, Paola
TI Brain processes in women and men in response to emotive sounds
SO SOCIAL NEUROSCIENCE
LA English
DT Article
DE Infant and adult crying; adult sensitivity; behavior; default mode
network
ID STIMULUS-INDEPENDENT THOUGHT; DEFAULT MODE NETWORK; SEX-DIFFERENCES;
RESTING-STATE; PHYSIOLOGICAL REACTIVITY; SELF-REFLECTION;
WORKING-MEMORY; INFANT CRIES; BABY-CRY; TASK
AB Adult appropriate responding to salient infant signals is vital to child healthy psychological development. Here we investigated how infant crying, relative to other emotive sounds of infant laughing or adult crying, captures adults' brain resources. In a sample of nulliparous women and men, we investigated the effects of different sounds on cerebral activation of the default mode network (DMN) and reaction times (RTs) while listeners engaged in self-referential decision and syllabic counting tasks, which, respectively, require the activation or deactivation of the DMN. Sounds affect women and men differently. In women, infant crying deactivated the DMN during the self-referential decision task; in men, female adult crying interfered with the DMN during the syllabic counting task. These findings point to different brain processes underlying responsiveness to crying in women and men and show that cerebral activation is modulated by situational contexts in which crying occurs.
C1 [Rigo, Paola; De Pisapia, Nicola; Serra, Mauro; Esposito, Gianluca; Venuti, Paola] Univ Trento, Dept Psychol & Cognit Sci, Via Matteo Ben 5-B, Trento, Italy.
[Rigo, Paola; Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Esposito, Gianluca] Nanyang Technol Univ, Div Psychol, Singapore, Singapore.
RP Rigo, P (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Via Matteo Ben 5-B, Trento, Italy.
EM paola.rigo@unitn.it
OI Putnick, Diane/0000-0002-6323-749X; De Pisapia,
Nicola/0000-0002-1089-8841
FU Intramural Research Program of the NIH, NICHD
FX This research was partially supported by the Intramural Research Program
of the NIH, NICHD.
NR 80
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1747-0919
EI 1747-0927
J9 SOC NEUROSCI-UK
JI Soc. Neurosci.
PY 2017
VL 12
IS 2
BP 150
EP 162
DI 10.1080/17470919.2016.1150341
PG 13
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA EM1ST
UT WOS:000395098000005
PM 26905380
ER
PT J
AU Hunsberger, S
Proschan, MA
AF Hunsberger, Sally
Proschan, Michael A.
TI Simple Approaches to Analyzing Self-Controlled Case Series (SCCS) Data
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Case control; Guillain-Barre Syndrome; Scan statistics; Vaccine studies
ID GUILLAIN-BARRE-SYNDROME; INFLUENZA VACCINE; ASSOCIATION
AB Adverse events that occur at moderate rates can be identified during the development of vaccines. When large populations are vaccinated, new rare adverse events can be observed. Determining whether an observed adverse event is related to a vaccine poses statistical issues. Cohort studies can be biased when comparing vaccinated and unvaccinated cohorts. In self-controlled case series designs, each case acts as his or her own control, eliminating the potential bias between vaccinated and unvaccinated participants in a cohort study. The comparison is whether there is an excess of events close to the time of vaccination versus later in time fromthe vaccination. In this design, one must specify a time point where the excess risk from the vaccine is thought to be over. We explore the effect of misspecifying this time point and develop analysis methods that do not require the specification of the time point. Power and Type I error rates of different analysis methods are simulated.
C1 [Hunsberger, Sally; Proschan, Michael A.] NIAID, Biostat Res Branch, Rockville, MD 20852 USA.
RP Hunsberger, S (reprint author), NIAID, Biostat Res Branch, Rockville, MD 20852 USA.
EM sallyh@mail.nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2017
VL 9
IS 1
BP 65
EP 72
DI 10.1080/19466315.2016.1206034
PG 8
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EP3BV
UT WOS:000397258400007
ER
PT J
AU Song, KH
Fan, AC
Hinkle, JJ
Newman, J
Borden, MA
Harvey, BK
AF Song, Kang-Ho
Fan, Alexander C.
Hinkle, Joshua J.
Newman, Joshua
Borden, Mark A.
Harvey, Brandon K.
TI Microbubble gas volume: A unifying dose parameter in blood-brain barrier
opening by focused ultrasound
SO THERANOSTICS
LA English
DT Article
DE ultrasound contrast agent; drug delivery; gene therapy; pharmacokinetics
ID IN-VIVO; ADENOASSOCIATED VIRUS; TARGETED DELIVERY; DRUG-DELIVERY;
GENE-THERAPY; DISRUPTION; DEPENDENCE; MICE; PERSISTENCE; SIZE
AB Focused ultrasound with microbubbles is being developed to transiently, locally and noninvasively open the blood-brain barrier (BBB) for improved pharmaceutical delivery. Prior work has demonstrated that, for a given concentration dose, microbubble size affects both the intravascular circulation persistence and extent of BBB opening. When matched to gas volume dose, however, the circulation half-life was found to be independent of microbubble size. In order to determine whether this holds true for BBB opening as well, we independently measured the effects of microbubble size (2 vs. 6 mu m diameter) and concentration, covering a range of overlapping gas volume doses (1-40 mu L/kg). We first demonstrated precise targeting and a linear dose-response of Evans Blue dye extravasation to the rat striatum for a set of constant microbubble and ultrasound parameters. We found that dye extravasation increased linearly with gas volume dose, with data points from both microbubble sizes collapsing to a single line. A linear trend was observed for both the initial sonication (R-2=0.90) and a second sonication on the contralateral side (R-2=0.68). Based on these results, we conclude that microbubble gas volume dose, not size, determines the extent of BBB opening by focused ultrasound (1 MHz, similar to 0.5 MPa at the focus). This result may simplify planning for focused ultrasound treatments by constraining the protocol to a single microbubble parameter - gas volume dose - which gives equivalent results for varying size distributions. Finally, using optimal parameters determined for Evan Blue, we demonstrated gene delivery and expression using a viral vector, dsAAV1-CMV-EGFP, one week after BBB disruption, which allowed us to qualitatively evaluate neuronal health.
C1 [Song, Kang-Ho; Fan, Alexander C.; Borden, Mark A.] Univ Colorado, Dept Mech Engn, 1111 Engn Dr, Boulder, CO 80309 USA.
[Song, Kang-Ho; Fan, Alexander C.; Hinkle, Joshua J.; Newman, Joshua; Harvey, Brandon K.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA.
RP Borden, MA (reprint author), Univ Colorado, Dept Mech Engn, 1111 Engn Dr, Boulder, CO 80309 USA.; Harvey, BK (reprint author), Natl Inst Drug Abuse, Glia Neuron Interact Unit, Suite 200,Room 06A729,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mark.borden@colorado.edu; bharvey@mail.nih.gov
FU University of Colorado Boulder; Intramural Research Program at the
National Institute on Drug Abuse
FX This work was supported by the University of Colorado Boulder and the
Intramural Research Program at the National Institute on Drug Abuse. We
would like to thank Mr. Pyry Koivula, Julie Necarsulmer and Dr. Yajun
Zhang for lending their expertise in animal procedures, and Dr. Leslie
Whitaker for assistance with vibratome preparation of brain slices.
NR 27
TC 0
Z9 0
U1 1
U2 1
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2017
VL 7
IS 1
BP 144
EP 152
DI 10.7150/thno.15987
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EO2VK
UT WOS:000396553900013
PM 28042323
ER
PT J
AU Yang, XY
Wang, Z
Zhang, FW
Zhu, GZ
Song, JB
Teng, GJ
Niu, G
Chen, XY
AF Yang, Xiangyu
Wang, Zhe
Zhang, Fuwu
Zhu, Guizhi
Song, Jibin
Teng, Gao-Jun
Niu, Gang
Chen, Xiaoyuan
TI Mapping Sentinel Lymph Node Metastasis by Dual-probe Optical Imaging
SO THERANOSTICS
LA English
DT Article
DE metastasis; sentinel lymph node; optical imaging; hyaluronic acid; EGFR;
HER2
ID BREAST-CANCER; MOLECULAR-MECHANISMS; PROSTATE-CANCER; RECEPTOR; BIOPSY;
CARCINOMA; LYVE-1; LYMPHANGIOGENESIS; NANOPARTICLES; HYALURONAN
AB Purpose: Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Experimental Design: Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Results: Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Conclusions: Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging with the combination of lymphatic mapping agents and tumor targeting agents can identify tumor metastases within SLNs, thus may provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.
C1 [Yang, Xiangyu; Teng, Gao-Jun] Southeast Univ, Zhongda Hosp, Sch Med, Dept Radiol,Jiangsu Key Lab Mol Imaging & Funct I, Nanjing 210009, Jiangsu, Peoples R China.
[Yang, Xiangyu; Wang, Zhe; Zhang, Fuwu; Zhu, Guizhi; Song, Jibin; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Teng, GJ (reprint author), 87 Dingjiaqiao Rd, Nanjing 210009, Jiangsu, Peoples R China.; Niu, G; Chen, XY (reprint author), 35A Convent Dr Rm GD959, Bethesda, MD 20892 USA.
EM gjteng@vip.sina.com; niug@mail.nih.gov; shawn.chen@nih.gov
FU Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering, National Institutes of Health
FX The research was supported by the Intramural Research Program, National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health.
NR 44
TC 0
Z9 0
U1 3
U2 3
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2017
VL 7
IS 1
BP 153
EP 163
DI 10.7150/thno.17085
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EO2VK
UT WOS:000396553900014
PM 28042324
ER
PT J
AU Yu, Y
Sikorski, P
Smith, M
Bowman-Gholston, C
Cacciabeve, N
Nelson, KE
Pieper, R
AF Yu, Yanbao
Sikorski, Patricia
Smith, Madeline
Bowman-Gholston, Cynthia
Cacciabeve, Nicolas
Nelson, Karen E.
Pieper, Rembert
TI Comprehensive Metaproteomic Analyses of Urine in the Presence and
Absence of Neutrophil-Associated Inflammation in the Urinary Tract
SO THERANOSTICS
LA English
DT Article
DE urine; clinical proteomics; urothelial cells; label-free quantitation;
urinary tract infection; neutrophils; inflammation; network analysis;
shotgun proteomics; urine sediment
ID HOST-PATHOGEN INTERACTIONS; MASS-SPECTROMETRY; BIOMARKER DISCOVERY;
PROTEOMIC ANALYSIS; SAMPLE PREPARATION; BLADDER-CANCER; QUANTITATIVE
PROTEOMICS; CLINICAL PROTEOMICS; INFECTION; PROTEINS
AB Inflammation in the urinary tract results in a urinary proteome characterized by a high dynamic range of protein concentrations and high variability in protein content. This proteome encompasses plasma proteins not resorbed by renal tubular uptake, renal secretion products, proteins of immune cells and erythrocytes derived from trans-urothelial migration and vascular leakage, respectively, and exfoliating urothelial and squamous epithelial cells. We examined how such proteins partition into soluble urine (SU) and urinary pellet (UP) fractions by analyzing 33 urine specimens 12 of which were associated with a urinary tract infection (UTI). Using mass spectrometry-based metaproteomic approaches, we identified 5,327 non-redundant human proteins, 2,638 and 4,379 of which were associated with SU and UP fractions, respectively, and 1,206 non-redundant protein orthology groups derived from pathogenic and commensal organisms of the urogenital tract. Differences between the SU and UP proteomes were influenced by local inflammation, supported by respective comparisons with 12 healthy control urine proteomes. Clustering analyses showed that SU and UP fractions had proteomic signatures discerning UTIs, vascular injury, and epithelial cell exfoliation from the control group to varying degrees. Cases of UTI revealed clusters of proteins produced by activated neutrophils. Network analysis supported the central role of neutrophil effector proteins in the defense against invading pathogens associated with subsequent coagulation and wound repair processes. Our study expands the existing knowledge of the urinary proteome under perturbed conditions, and should be useful as reference dataset in the search of biomarkers.
C1 [Yu, Yanbao; Sikorski, Patricia; Smith, Madeline; Nelson, Karen E.; Pieper, Rembert] J Craig Venter Inst, 9714 Med Ctr Dr, Rockville, MD 20850 USA.
[Bowman-Gholston, Cynthia] Quest Diagnost Shady Grove Adventist Hosp, 9901 Med Ctr Dr, Rockville, MD 20850 USA.
[Cacciabeve, Nicolas] Adv Pathol Associates LLC, Shady Grove Adventist Hosp, 9901 Med Ctr Dr, Rockville, MD 20850 USA.
[Sikorski, Patricia] NIAID, Parasit Dis Lab, NIH, 4 Mem Dr, Bethesda, MD 20892 USA.
[Sikorski, Patricia] Georgetown Univ, Dept Microbiol & Immunol, 3900 Reservoir Rd,NW, Washington, DC 20057 USA.
RP Yu, Y; Pieper, R (reprint author), J Craig Venter Inst, 9714 Med Ctr Dr, Rockville, MD 20850 USA.
EM yayu@jcvi.org; rpieper@jcvi.org
OI Yu, Yanbao/0000-0003-2994-1974
FU National Institute of General Medical Sciences, National Institutes of
Health [5R01GM103598-02]; J. Craig Venter Institute
FX We thank the National Institute of General Medical Sciences, National
Institutes of Health, via grant 5R01GM103598-02, the J. Craig Venter
Institute, and Dr. J. Craig Venter for funding the study. We thank the
Ruggles Family Foundation for a contribution to fund the mass
spectrometer used for the research. We thank Tamara Tsitrin for
technical assistance in the laboratory, Dr. Harinder Singh for
assistance with bioinformatics analyses, and David Haft for discussions
on network analysis methods. The funding bodies did not have a role in
study design, data collection and analysis, decision to publish, and
preparation of the manuscript.
NR 63
TC 1
Z9 1
U1 0
U2 0
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2017
VL 7
IS 2
BP 238
EP 252
DI 10.7150/thno.16086
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EO2WE
UT WOS:000396555900001
PM 28042331
ER
PT J
AU Sun, XL
Yan, XF
Jacobson, O
Sun, WJ
Wang, ZT
Tong, X
Xia, YQ
Ling, DS
Chen, XY
AF Sun, Xiaolian
Yan, Xuefeng
Jacobson, Orit
Sun, Wenjing
Wang, Zhantong
Tong, Xiao
Xia, Yuqiong
Ling, Daishun
Chen, Xiaoyuan
TI Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy
SO THERANOSTICS
LA English
DT Article
DE Reticuloendothelial system; Nanoparticle; Liposome blockade; Positron
Emission Tomography; Enhanced tumor uptake
ID DRUG-DELIVERY SYSTEMS; RETICULOENDOTHELIAL SYSTEM; CANCER-THERAPY;
CLINICAL-APPLICATIONS; NANOPARTICLES; NANOMEDICINE; CLEARANCE; VESICLES
AB Minimizing the sequestration of nanomaterials (NMs) by the reticuloendothelial system (RES) can enhance the circulation time of NMs, and thus increase their tumor-specific accumulation. Liposomes are generally regarded as safe (GRAS) agents that can block the RES reversibly and temporarily. With the help of positron emission tomography (PET), we monitored the in vivo tissue distribution of Cu-64-labeled 40 x 10 nm gold nanorods (Au NRs) after pretreatment with liposomes. We systematically studied the effectiveness of liposome administration by comparing (1) differently charged liposomes; (2) different liposome doses; and (3) varying time intervals between liposome dose and NR dose. By pre-injecting 400 mu mol/kg positively charged liposomes into mice 5 h before the Au NRs, the liver and spleen uptakes of Au NRs decreased by 30% and 53%, respectively. Significantly, U87MG tumor uptake of Au NRs increased from 11.5 +/- 1.1 % ID/g to 16.1 +/- 1.3 % ID/g at 27 h post-injection. Quantitative PET imaging is a valuable tool to understand the fate of NMs in vivo and cationic liposomal pretreatment is a viable approach to reduce RES clearance, prolong circulation, and improve tumor uptake.
C1 [Sun, Xiaolian; Sun, Wenjing; Wang, Zhantong] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.
[Sun, Xiaolian; Sun, Wenjing; Wang, Zhantong; Chen, Xiaoyuan] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Peoples R China.
[Sun, Xiaolian; Yan, Xuefeng; Jacobson, Orit; Wang, Zhantong; Tong, Xiao; Xia, Yuqiong; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomedicine LOMIN, NIH, Bethesda, MD 20892 USA.
[Ling, Daishun] Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomedicine LOMIN, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
RI Ling, Daishun/J-4736-2014
OI Ling, Daishun/0000-0002-6814-7370
FU National Key Research and Development Program of China [2016YFA0203600];
National Natural Science Foundation of China [51502251, 81571743];
Fundamental Research Funds for Xiamen University [20720160067]; Science
Foundation of Fujian Province [2014Y2004]; Intramural Research Program
(IRP), National Institute of Biomedical Imaging (NIBIB), National
Institutes of Health (NIH)
FX This work was supported in part, by the National Key Research and
Development Program of China (2016YFA0203600), National Natural Science
Foundation of China (51502251, 81571743), Fundamental Research Funds for
Xiamen University (20720160067), Science Foundation of Fujian Province
(2014Y2004), and the Intramural Research Program (IRP), National
Institute of Biomedical Imaging (NIBIB), National Institutes of Health
(NIH).
NR 38
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U1 4
U2 4
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2017
VL 7
IS 2
BP 319
EP 328
DI 10.7150/thno.18078
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EO2WE
UT WOS:000396555900007
PM 28042337
ER
PT J
AU Yang, SX
Polley, EC
Nguyen, D
AF Yang, Sherry X.
Polley, Eric C.
Nguyen, Dat
TI Association of gamma H2AX at Diagnosis with Chemotherapy Outcome in
Patients with Breast Cancer
SO THERANOSTICS
LA English
DT Article
DE breast cancer; chemotherapy; gamma H2AX expression; overall survival;
standard therapy
ID CLINICAL-PRACTICE GUIDELINES; DNA-DAMAGE; AMERICAN SOCIETY; ONCOLOGY;
THERAPY; RECOMMENDATIONS; METAANALYSIS; EXPRESSION; RELEVANCE; TAMOXIFEN
AB gamma H2AX plays a role in DNA damage response signaling and facilitates the repair of DNA double strand breaks. However, it remains unknown whether constitutive tumor gamma H2AX expression is associated with treatment outcome in patients. gamma H2AX status was detected in primary tumors from 24% of 826 patients with stage I, II and III breast cancer by immunohistochemistry; overall survival was analyzed by Kaplan-Meier method. At median follow-up of 176 months (range 13 282 months), we found substantial survival heterogeneity in gamma H2AX-positive patients (P=0.002) among uniform treatment groups including radiation or endocrine therapy alone and no-treatment, as well as chemotherapy alone (being worst), in contrast to gamma H2AX-negative patients (P=0.2). In the chemotherapy group (n=118), median survival was 63 months (95% confidence interval [CI], 29-83) in patients with gamma H2AX-positive tumors compared with 170 months (95% CI 94-235) in those with gamma H2AX-negative tumors (P=0.0017). gamma H2AX remained a poor prognosis factor in the group by multivariable analysis (adjusted hazard ratio 2.12, P=0.009). Our data demonstrate that constitutive gamma H2AX positivity is significantly associated with survival heterogeneity in patients among uniform treatment groups, and its expression at diagnosis independently predicts poor chemotherapy outcome in breast cancer.
C1 [Yang, Sherry X.; Nguyen, Dat] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Polley, Eric C.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
RP Yang, SX (reprint author), 37 Convent Dr,Bldg 37,Room 1048, Bethesda, MD 20892 USA.
EM Sherry.Yang@nih.gov
FU Division of Cancer Treatment and Diagnosis (DCTD); National Cancer
Institute, National Institutes of Health
FX Supported in part by Division of Cancer Treatment and Diagnosis (DCTD),
National Cancer Institute, National Institutes of Health. We would like
to thank patients who donated their breast cancer specimens for
research, and the CBCTR physicians, pathologists and staff who acquired
specimens and established the database. We are very grateful to the
National Cancer Institute Cancer Diagnosis Program in DCTD for its
design of the prognostic breast cancer tissue microarray and providing
guidance.
NR 30
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PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2017
VL 7
IS 4
BP 945
EP 951
DI 10.7150/thno.19102
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EO2XP
UT WOS:000396559600012
PM 28382166
ER
PT J
AU Kim, YH
Min, KH
Wang, ZT
Kim, JH
Jacobson, O
Huang, P
Zhu, GZ
Liu, YJ
Yung, B
Niu, G
Chen, XY
AF Kim, Young-Hwa
Min, Kyung Hyun
Wang, Zhantong
Kim, Jihoon
Jacobson, Orit
Huang, Peng
Zhu, Guizhi
Liu, Yijing
Yung, Bryant
Niu, Gang
Chen, Xiaoyuan
TI Development of Sialic Acid-coated Nanoparticles for Targeting Cancer and
Efficient Evasion of the Immune System
SO THERANOSTICS
LA English
DT Article
DE sialic acid (N-acetylneuraminic acid, Neu5Ac); anti-recognition effect;
evading phagocytosis; lectin targeting; molecular imaging; positron
emission tomography (PET)
ID PROTEIN-TYROSINE PHOSPHATASES; POLYETHYLENE-GLYCOL; FACTOR-H;
BINDING-SITE; CELLS; COMPLEMENT; DELIVERY; GLYCOSAMINOGLYCANS;
DISCRIMINATION; MACROPHAGES
AB Evading the reticuloendothelial system (RES) remains a critical challenge in the development of efficient delivery and diagnostic systems for cancer. Sialic acid (N-acetylneuraminic acid, Neu5Ac) is recognized as a "self" marker by major serum protein complement factor H and shows reduced interaction with the innate immune system via sialic acid-binding immunoglobulin-like lectin (Siglec), which is known as one of the significant regulators of phagocytic evasion. Accordingly, we prepared different surface-modified gold nanoparticles (AuNPs) and investigated the effects of sialic acid on cellular and immune responses of nanoparticles in vitro and in vivo. Sialic acid modification not only facilitates evasion of the RES by suppressing the immune response, but also enhances tumor accumulation via its active targeting ability. Therefore, sialic acid modification presents a promising strategy to advance nanotechnology towards the prospect of clinical translation.
C1 [Kim, Young-Hwa; Min, Kyung Hyun; Wang, Zhantong; Kim, Jihoon; Jacobson, Orit; Zhu, Guizhi; Liu, Yijing; Yung, Bryant; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Huang, Peng] Shenzhen Univ, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China.
RP Niu, G; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM Gang.Niu@nih.gov; shawn.chen@nih.gov
FU KRIBB Research Initiative Program (Korean Biomedical Scientist
Fellowship Program); Korea Research Institute of Bioscience and
Biotechnology, Republic of Korea; Intramural Research Program (IRP) of
the National Institute of Biomedical Imaging and Bioengineering (NIBIB);
National Institutes of Health (NIH); Global Innovative Research Center
(GiRC) Program of the National Research Foundation of Korea
[2012K1A1A2A01055811]
FX This work was supported by a grant from the KRIBB Research Initiative
Program (Korean Biomedical Scientist Fellowship Program), Korea Research
Institute of Bioscience and Biotechnology, Republic of Korea, and the
Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health (NIH). This research was also supported by the Global Innovative
Research Center (GiRC) Program (2012K1A1A2A01055811) of the National
Research Foundation of Korea.
NR 44
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U1 2
U2 2
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2017
VL 7
IS 4
BP 962
EP 973
DI 10.7150/thno.19061
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EO2XP
UT WOS:000396559600014
PM 28382168
ER
PT J
AU Jiang, Y
Cao, Y
Wang, YB
Li, W
Liu, XY
Lv, YX
Li, XL
Mi, J
AF Jiang, Yang
Cao, Yuan
Wang, Yongbin
Li, Wei
Liu, Xinyi
Lv, Yixuan
Li, Xiaoling
Mi, Jun
TI Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis
SO THERANOSTICS
LA English
DT Article
DE solute carrier SLC3A1; breast cancer; ROS; cysteine; PDK1
ID CYSTINE TRANSPORTER; CELL-PROLIFERATION; REDOX REGULATION; IN-VIVO;
EXPRESSION; PROTEIN; SYSTEM; KIDNEY; SULFASALAZINE; INACTIVATION
AB Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute carrier family 3, member 1 (SLC3A1), the cysteine carrier, tightly correlated with clinical stages and patients' survival. Elevated SLC3A1 expression accelerated the cysteine uptake and the accumulation of reductive glutathione (GSH), leading to reduced reactive oxygen species (ROS). ROS increased the stability and activity of PP2Ac, resulting in decreased AKT activity. Hence, SLC3A1 activated the AKT signaling through inhibiting PP2A phosphatase activity. Consistently, overexpression of SLC3A1 enhanced tumorigenesis of breast cancer cells, whereas blocking SLC3A1 either with specific siRNA or SLC3A1 specific inhibitor sulfasalazine suppressed tumor growth and also abolished dietary NAC-promoted tumor growth. Collectively, our data demonstrate that SLC3A1 promotes cysteine uptake and determines cellular response to antioxidant N-acetylcysteine, suggesting SLC3A1 is a potential therapeutic target for breast cancer.
C1 [Jiang, Yang; Cao, Yuan; Wang, Yongbin; Liu, Xinyi; Lv, Yixuan; Mi, Jun] Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, 280 South Choongqing Rd, Shanghai 200025, Peoples R China.
[Jiang, Yang] Dalian Med Univ, Inst Canc Stem Cell, 9 West South Lvshun Rd, Dalian 116044, Liaoning, Peoples R China.
[Li, Wei] Soochow Univ, Affiliated Hosp 1, 188 Shizi Rd, Suzhou 215006, Jiangsu, Peoples R China.
[Li, Xiaoling] NIEHS, NIH, 111 TW Alexander Dr,Rall Bldg, Res Triangle Pk, NC 27709 USA.
RP Mi, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, 280 South Choongqing Rd, Shanghai 200025, Peoples R China.
EM jmei@sjtu.edu.cn
FU National Program on Key Basic Research Project (973 Program)
[2012CB910102]; Shanghai Committee of Science and Technology
[11DZ2260200]; National Science Foundation of China [81372194, 81572300]
FX We are grateful to Dr. Zhaoyuan Hou and Dr. Xuemei Tong (Shanghai Jiao
Tong University School of Medicine) for valuable discussions. This study
was supported by grants from the National Program on Key Basic Research
Project (973 Program) (2012CB910102), the Shanghai Committee of Science
and Technology (11DZ2260200), and the National Science Foundation of
China (81372194) (81572300) to Dr. Mi.
NR 34
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PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2017
VL 7
IS 4
BP 1036
EP 1046
DI 10.7150/thno.18005
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EO2XP
UT WOS:000396559600020
PM 28382174
ER
PT J
AU Eisenberg, MH
Street, RL
Persky, S
AF Eisenberg, Miriam H.
Street, Richard L., Jr.
Persky, Susan
TI "It runs in my family ... ": The association of perceived family history
with body dissatisfaction and weight bias internalization among
overweight women
SO WOMEN & HEALTH
LA English
DT Article
DE Biological attributions for weight; body acceptance; family history of
overweight; race; weight bias internalization
ID OBESITY; STIGMA; PEOPLE; SIZE; DISORDER; IMAGE; GIRLS; GAIN; WELL
AB Aspects of poor body acceptance (BA), such as internalized weight bias and dissatisfaction with one's shape and size, are the strongest predictors of disordered eating and are associated with reduced engagement in healthy behaviors. Perceiving oneself as having a family history of overweight (PFH) could boost BA by increasing attributions for inherited, biological causes of weight. A community sample of 289 women who were overweight from the Washington, DC metropolitan area who were dissatisfied with their current weight (68% Black; 32% White) enrolled in this study in 2012. PFH of overweight was associated with decreased internalized weight bias among white women and marginally increased body shape satisfaction generally. The relationship between PFH and BA was not explained by biological attributions for weight. Perceptions that overweight runs in one's family can be protective with respect to BA. This is suggestive of the potential benefit of integrating family-based approaches into weight management interventions.
C1 [Eisenberg, Miriam H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B13B, Rockville, MD 20892 USA.
[Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA.
[Street, Richard L., Jr.] Baylor Coll Med, Dept Med, Houston Ctr Qual Care & Utilizat Studies, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Persky, Susan] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Eisenberg, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B13B, Rockville, MD 20892 USA.
EM miriam.eisenberg@nih.gov
OI Eisenberg, Miriam/0000-0002-7133-8805
FU National Human Genome Research Institute, National Institutes of Health;
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
M.H.E's time was also partially supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development. This work is based on data collected in the
Immersive Virtual Environment Testing Area of the Social and Behavioral
Research Branch, NHGRI, NIH.
NR 43
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U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0363-0242
EI 1541-0331
J9 WOMEN HEALTH
JI Women Health
PY 2017
VL 57
IS 4
BP 478
EP 493
DI 10.1080/03630242.2016.1170095
PG 16
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA EP3XN
UT WOS:000397315100005
PM 27015259
ER
PT J
AU Hibbert, D
Aboshaiqah, AE
Sienko, KA
Forestell, D
Harb, AW
Yousuf, SA
Kelley, PW
Brennan, PF
Serrant, L
Leary, A
AF Hibbert, Denise
Aboshaiqah, Ahmad E.
Sienko, Kathy A.
Forestell, Debra
Harb, Adel W.
Yousuf, Shadia A.
Kelley, Patricia W.
Brennan, Patricia F.
Serrant, Laura
Leary, Alison
TI Advancing Nursing Practice: The Emergence of the Role of Advanced
Practice Nurse in Saudi Arabia
SO ANNALS OF SAUDI MEDICINE
LA English
DT Article
ID SPECIALIST
AB BACKGROUND: The roots of advanced practice nursing (APN) can be traced back to the 1890s, but the nurse practitioner (NP) emerged in Western countries during the 1960s in response to the unmet healthcare needs of populations in rural areas. These early NPs utilized the medical model of care to assess, diagnose and treat. Nursing has since grown as a profession, with its own unique and distinguishable, holistic, science-based knowledge, which is complementary within the multidisciplinary team. Today, APNs demonstrate nursing expertise in clinical practice, education, research and leadership, and are no longer perceived as "physician replacements" or assistants. Saudi Arabia has yet to define, legislate or regulate APN.
AIMS: This article aims to disseminate information from a Saudi APN thought leadership meeting, to chronicle the history of APN within Saudi Arabia, while identifying strategies for moving forward.
CONCLUSION: It is important to build an APN model based on Saudi healthcare culture and patient population needs, while recognizing global historical underpinnings. Ensuring that nursing continues to distinguish itself from other healthcare professions, while securing a seat at the multidisciplinary healthcare table will be instrumental in advancing the practice of nursing.
C1 [Hibbert, Denise] King Faisal Specialist Hosp & Res Ctr, Colorectal Therapy Unit, POB 3354, Riyadh 11211, Saudi Arabia.
[Aboshaiqah, Ahmad E.] King Saud Univ, Coll Nursing, Riyadh, Saudi Arabia.
[Sienko, Kathy A.] Aldara Hosp & Med Ctr, Nursing Affairs, Riyadh, Saudi Arabia.
[Forestell, Debra] King Faisal Specialist Hosp & Res Ctr, Dept Nursing, Riyadh, Saudi Arabia.
[Harb, Adel W.] Secur Forces Hosp Program, Dept Nursing, Riyadh, Saudi Arabia.
[Yousuf, Shadia A.] King Abdulaziz Univ, Fac Nursing, Jeddah, Saudi Arabia.
[Kelley, Patricia W.] Duquesne Univ, Fac Nursing, Pittsburgh, PA 15219 USA.
[Brennan, Patricia F.] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Serrant, Laura] Sheffield Hallam Univ, Fac Hlth & Wellbeing, Dept Nursing, Sheffield, S Yorkshire, England.
[Leary, Alison] London South Bank Univ, Dept Hlth & Social Care, London, England.
RP Hibbert, D (reprint author), King Faisal Specialist Hosp & Res Ctr, Colorectal Therapy Unit, POB 3354, Riyadh 11211, Saudi Arabia.
EM denisehibbert@gmail.com
NR 37
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U1 1
U2 1
PU K FAISAL SPEC HOSP RES CENTRE
PI RIYADH
PA PUBLICATIONS OFFICE PO BOX 3354, RIYADH 11211, SAUDI ARABIA
SN 0256-4947
EI 1319-9226
J9 ANN SAUDI MED
JI Ann. Saudi Med.
PD JAN-FEB
PY 2017
VL 37
IS 1
BP 72
EP 78
DI 10.5144/0256-4947.2017.72
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA EO4QE
UT WOS:000396678600011
PM 28151460
ER
PT J
AU Epel, B
Halpern, HJ
AF Epel, Boris
Halpern, Howard J.
TI Imaging
SO EMAGRES
LA English
DT Article
DE electron paramagnetic resonance; imaging; oxygen imaging; pH imaging;
redox imaging; image reconstruction; EPR instrumentation; EPR
methodology; spin probes
ID ELECTRON-PARAMAGNETIC-RESONANCE; NUCLEAR-MAGNETIC-RESONANCE; TIME-DOMAIN
EPR; IN-VIVO; SPIN-PROBE; NONINVASIVE MEASUREMENT; TUMOR OXYGENATION;
TRITYL RADICALS; CYCLING HYPOXIA; 250 MHZ
AB EPR imaging is a well-established method for the study of the spatial distribution and the local environment of electron paramagnetic centers (PC) and spin probes. Although conceptually similar to nuclear MRI, EPR imaging did not receive widespread use due to relatively low availability of endogenous electron PC, especially in vivo. However, the development of injectable spin probes sensitive to various physiological parameters allowed EPR imaging to become a valuable tool for preclinical studies. One of the most important applications of modern EPR imaging is in vivo oximetry. Partial oxygen pressure (pO(2)) levels in tumors are major determinants of the response to cancer therapy and thus need thorough investigation. Other areas of EPR imaging application are imaging pH, thio-redox potentials, and polymer degradation.
C1 [Epel, Boris] Univ Chicago, Dept Radiat & Cellular Oncol, Ctr EPR Imaging Vivo Physiol, Chicago, IL 60637 USA.
Univ Chicago, NIBIB, NIH, Ctr EPR Imaging In Vivo Physiol, Chicago, IL 60637 USA.
RP Epel, B (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Ctr EPR Imaging Vivo Physiol, Chicago, IL 60637 USA.
FU NIH [P41 EB 002034, R01 CA 098575, R50 CA211408]
FX This work was supported by NIH grants P41 EB 002034, R01 CA 098575 and
R50 CA211408.
NR 101
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U1 1
U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2055-6101
J9 EMAGRES
JI eMagRes
PY 2017
VL 6
IS 1
BP 149
EP 160
DI 10.1002/9780470034590.emrstm1512
PG 12
WC Spectroscopy
SC Spectroscopy
GA EO3RJ
UT WOS:000396611600010
ER
PT J
AU Veronese, P
Bogana, G
Cerutti, A
Yeo, L
Romero, R
Gervasi, MT
AF Veronese, Paola
Bogana, Gianna
Cerutti, Alessia
Yeo, Lami
Romero, Roberto
Gervasi, Maria Teresa
TI A Prospective Study of the Use of Fetal Intelligent Navigation
Echocardiography (FINE) to Obtain Standard Fetal Echocardiography Views
SO FETAL DIAGNOSIS AND THERAPY
LA English
DT Article
DE 4D ultrasound; Cardiac screening; Fetal heart; Prenatal diagnosis;
Spatiotemporal image correlation; STIC; STICLoop (TM); Ultrasound;
Virtual Intelligent Sonographer Assistance; VIS-Assistance (R)
ID SPATIOTEMPORAL IMAGE CORRELATION; CONGENITAL HEART-DISEASE; ACQUIRE
CARDIAC VOLUMES; PRENATAL-DIAGNOSIS; 4-DIMENSIONAL ULTRASOUND;
GREAT-ARTERIES; 3-DIMENSIONAL ULTRASOUND; INTERVENTRICULAR SEPTUM;
SONOGRAPHIC EXAMINATION; ANTENATAL DIAGNOSIS
AB Objective: To evaluate the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart in generating standard fetal echocardiography views. Methods: In this prospective cohort study of patients with normal fetal hearts (19-30 gestational weeks), one or more STIC volume datasets were obtained of the apical four chamber view. Each STIC volume successfully obtained was evaluated by STICLoop (TM) to determine its appropriateness before applying the FINE method. Visualization rates for standard fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance (R)) were calculated. Results: One or more STIC volumes (total n = 463) were obtained from 246 patients. A single STIC volume per patient was analyzed using the FINE method. In normal cases, FINE was able to generate nine fetal echocardiography views using: (1) diagnostic planes in 76-100% of the cases, (2) VIS-Assistance (R) in 96-100% of the cases, and (3) a combination of diagnostic planes and/or VISAssistance (R) in 96-100% of the cases. Conclusion: FINE applied to STIC volumes can successfully generate nine standard fetal echocardiography views in 96-100% of cases in the 2nd and 3rd trimesters. This suggests that the technology can be used as a method of screening for congenital heart disease. (C) 2016 S. Karger AG, Basel
C1 [Veronese, Paola; Bogana, Gianna; Gervasi, Maria Teresa] AOP, Dept Womens & Childrens Hlth, Unit Maternal Fetal Med, Padua, Italy.
[Cerutti, Alessia] AOP, Dept Womens & Childrens Hlth, Unit Pediat Cardiol, Padua, Italy.
[Yeo, Lami; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Yeo, Lami; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Yeo, Lami] Wayne State Univ, Hutzel Womens Hosp, Sch Med, Detroit Med Ctr, Detroit, MI 48202 USA.
[Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, 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.
RP Yeo, L (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS Hutzel Womens Hosp, 3990 John R 4 Brush, Detroit, MI 48201 USA.
EM lyeo@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, Department of Health and Human Services
(NICHD/NIH/DHHS)
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, NIH, Department of
Health and Human Services (NICHD/NIH/DHHS).
NR 71
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Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1015-3837
EI 1421-9964
J9 FETAL DIAGN THER
JI Fetal Diagn. Ther.
PY 2017
VL 41
IS 2
BP 89
EP 99
DI 10.1159/000446982
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EO0KN
UT WOS:000396386800002
PM 27309391
ER
PT J
AU Hooker, GW
Umstead, KL
Lewis, KL
Koehly, LK
Biesecker, LG
Biesecker, BB
AF Hooker, Gillian W.
Umstead, Kendall L.
Lewis, Katie L.
Koehly, Laura K.
Biesecker, Leslie G.
Biesecker, Barbara B.
TI Engagement and communication among participants in the ClinSeq Genomic
Sequencing Study
SO GENETICS IN MEDICINE
LA English
DT Article
ID PRECAUTION ADOPTION PROCESS; 1ST-DEGREE RELATIVES; PATIENT ENGAGEMENT;
RANDOMIZED-TRIAL; DECISION AID; CANCER; RISK; IMPACT; BEHAVIOR; DISEASE
AB Purpose: As clinical genome sequencing expand its reach, understanding how individuals engage with this process are of critical importance. In this study, we aimed to describe internal engagement and its correlates among a ClinSeq cohort of adults consented to genome sequencing and receipt of results.
Methods: This study was framed using the precaution adoption process model (PAPM), in which knowledge predicts engagement and engagement predicts subsequent behaviors. Prior to receipt of sequencing results, 630 participants in the study completed a baseline survey. Engagement was assessed as the frequency with which participants thought about their participation in ClinSeq since enrollment.
Results: Results were consistent with the PAPM: those with higher genomics knowledge reported higher engagement (r = 0.13, P = 0.001) and those who were more engaged reported more frequent communication with their physicians (r = 0.28, P < 0.001) and family members (r = 0.35, P < 0.001) about ClinSeq. Characteristics of those with higher engagement included poorer overall health (r = -0.13, P = 0.002), greater seeking of health information (r = 0.16, P < 0.001), and more recent study enrollment (r = -0.21, P < 0.001).
Conclusion: These data support the importance of internal engagement in communication related to genomic sequencing.
C1 [Hooker, Gillian W.; Umstead, Kendall L.; Biesecker, Barbara B.] NHGRI, Genet Serv Res Unit, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Lewis, Katie L.; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
[Koehly, Laura K.] NHGRI, Social Network Methods Sect, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Hooker, Gillian W.] NextGxDx Inc, Franklin, TN USA.
RP Biesecker, BB (reprint author), NHGRI, Genet Serv Res Unit, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
EM barbarab@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health
FX The authors thank the dedicated ClinSeq participants who completed the
baseline survey. This research was funded by the Intramural Research
Program of the National Human Genome Research Institute, National
Institutes of Health. An earlier version of this analysis was presented
by Dr Hooker at the National Society of Genetic Counselors in Anaheim,
California, October 2013.
NR 38
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JAN
PY 2017
VL 19
IS 1
BP 98
EP 103
DI 10.1038/gim.2016.71
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA EH6VD
UT WOS:000391911100014
PM 27763633
ER
PT J
AU Chandler, RJ
Williams, IM
Gibson, AL
Davidson, CD
Incao, AA
Hubbard, BT
Porter, FD
Pavan, WJ
Venditti, CP
AF Chandler, Randy J.
Williams, Ian M.
Gibson, Alana L.
Davidson, Cristin D.
Incao, Arturo A.
Hubbard, Brandon T.
Porter, Forbes D.
Pavan, William J.
Venditti, Charles P.
TI Systemic AAV9 gene therapy improves the lifespan of mice with
Niemann-Pick disease, type C1
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID SPINAL MUSCULAR-ATROPHY; CHOLESTEROL HOMEOSTASIS; NPC1 PROTEIN; MOUSE
MODELS; DELIVERY; NEURODEGENERATION; TRAFFICKING; NEURONS; CYCLODEXTRIN;
PROGRESSION
AB Niemann-Pick disease, type C1 (NPC1) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of NPC1 disease (Npc1(-/-)) displays a rapidly progressing form of NPC1 disease which is characterized by weight loss, ataxia, increased cholesterol storage, loss of cerebellar Purkinje neurons and early lethality. To test the potential efficacy of gene therapy for NPC1, we constructed adeno-associated virus serotype 9 (AAV9) vectors to deliver the NPC1 gene under the transcriptional control of the neuronal-specific (CamKII) or a ubiquitous (EF1a) promoter. The Npc1(-/-) mice that received a single dose of AAV9-CamKII-NPC1 as neonates (2.6 x 10(11)GC) or at weaning (1.3 x 10(12)GC), and the mice that received a single dose of AAV9-EF1a-NPC1 at weaning (1.2 x 10(12)GC), exhibited an increased life span, characterized by delayed weight loss and diminished motor decline. Cholesterol storage and Purkinje neuron loss were also reduced in the central nervous system of AAV9 treated Npc1(-/-) mice. Treatment with AAV9-EF1a-NPC1, as compared to AAV9-CamKII-NPC1, resulted in significantly increased survival (mean survival increased from 69 days to 166 and 97 days, respectively) and growth, and reduced hepatic-cholesterol accumulation. Our results provide the first demonstration that gene therapy may represent a therapeutic option for NPC1 patients and suggest that extraneuronal NPC1 expression can further augment the lifespan of the Npc1(-/-) mice after systemic AAV gene delivery.
C1 [Chandler, Randy J.; Hubbard, Brandon T.; Venditti, Charles P.] NHGRI, Med Genom & Metab Genet Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Williams, Ian M.; Porter, Forbes D.] NICHHD, Eunice Kennedy Shriver, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gibson, Alana L.; Incao, Arturo A.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Davidson, Cristin D.] Albert Einstein Coll Med, Intellectual & Dev Disabil Res Ctr, Rose F Kennedy Ctr, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA.
RP Pavan, WJ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.; Venditti, CP (reprint author), NHGRI, Med Genom & Metab Genet Branch, NIH, Bldg 10 Room 7N248A, Bethesda, MD 20892 USA.
EM bpavan@mail.nih.gov; venditti@mail.nih.gov
RI Davidson, Cristin/F-4889-2017
OI Davidson, Cristin/0000-0002-5508-8113
FU Intramural Research Program of the National Human Genome Research
Institute; Intramural Research Program of the National Institute of
Child Health and Human Development; Support of Accelerated Research for
Niemann-Pick C (Dana's Angels Research Trust, The Hide & Seek Foundation
for Lysosomal Disease Research, Fight NPC); Liferay Foundation; Ara
Parseghian Medical Research Foundation (APMRF)
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute, the Intramural Research
Program of the National Institute of Child Health and Human Development,
Support of Accelerated Research for Niemann-Pick C (Dana's Angels
Research Trust, The Hide & Seek Foundation for Lysosomal Disease
Research, Fight NPC), Liferay Foundation and Ara Parseghian Medical
Research Foundation (APMRF).
NR 45
TC 1
Z9 1
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JAN 1
PY 2017
VL 26
IS 1
BP 52
EP 64
DI 10.1093/hmg/ddw367
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EP0GG
UT WOS:000397064600005
PM 27798114
ER
PT J
AU Akins, MR
Berk-Rauch, HE
Kwan, KY
Mitchell, ME
Shepard, KA
Korsak, LIT
Stackpole, EE
Warner-Schmidt, JL
Sestan, N
Cameron, HA
Fallon, JR
AF Akins, Michael R.
Berk-Rauch, Hanna E.
Kwan, Kenneth Y.
Mitchell, Molly E.
Shepard, Katherine A.
Korsak, Lulu I. T.
Stackpole, Emily E.
Warner-Schmidt, Jennifer L.
Sestan, Nenad
Cameron, Heather A.
Fallon, Justin R.
TI Axonal ribosomes and mRNAs associate with fragile X granules in adult
rodent and human brains
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID OLFACTORY MARKER PROTEIN; MENTAL-RETARDATION; PRESYNAPTIC FMRP; RECEPTOR
NEURONS; SENSORY NEURONS; BETA-CATENIN; MOUSE MODEL; RATS; MICE; BULB
AB Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression in response to extrinsic stimuli. However, the role of local translation in mature CNS axons is unknown. Such a mechanism requires the presence of translational machinery and associated mRNAs in circuit-integrated brain axons. Here we use a combination of genetic, quantitative imaging and super-resolution microscopy approaches to show that mature axons in the mammalian brain contain ribosomes, the translational regulator FMRP and a subset of FMRP mRNA targets. This axonal translational machinery is associated with Fragile X granules (FXGs), which are restricted to axons in a stereotyped subset of brain circuits. FXGs and associated axonal translational machinery are present in hippocampus in humans as old as 57 years. This FXG-associated axonal translational machinery is present in adult rats, even when adult neurogenesis is blocked. In contrast, in mouse this machinery is only observed in juvenile hippocampal axons. This differential developmental expression was specific to the hippocampus, as both mice and rats exhibit FXGs in mature axons in the adult olfactory system. Experiments in Fmr1 null mice show that FMRP regulates axonal protein expression but is not required for axonal transport of ribosomes or its target mRNAs. Axonal translational machinery is thus a feature of adult CNS neurons. Regulation of this machinery by FMRP could support complex behaviours in humans throughout life.
C1 [Akins, Michael R.; Mitchell, Molly E.; Shepard, Katherine A.; Korsak, Lulu I. T.] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA.
[Akins, Michael R.; Berk-Rauch, Hanna E.; Stackpole, Emily E.; Fallon, Justin R.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Kwan, Kenneth Y.; Sestan, Nenad] Yale Sch Med, Dept Neurosci, New Haven, CT USA.
[Kwan, Kenneth Y.; Sestan, Nenad] Yale Sch Med, Kavli Inst Neurosci, New Haven, CT USA.
[Warner-Schmidt, Jennifer L.] Rockefeller Univ, Lab Mol & Cellular Neurosci, 1230 York Ave, New York, NY 10021 USA.
[Cameron, Heather A.] NIMH, Sect Neuroplast, NIH, Bethesda, MD 20892 USA.
[Kwan, Kenneth Y.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
[Kwan, Kenneth Y.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
RP Akins, MR (reprint author), PISB 319,3245 Chestnut St, Philadelphia, PA 19104 USA.
EM Michael.R.Akins@drexel.edu
FU National Institutes of Health [R00 MH090237, R00 MH096939, P50 MH106934,
U01 MH103339, R01 MH109904, R01 HD052083]; NIH, National Institute of
Mental Health [ZIAMH002784]
FX This work was supported by National Institutes of Health grants R00
MH090237 to MRA; R00 MH096939 to KYK; P50 MH106934, U01 MH103339, R01
MH109904 to NS; and R01 HD052083 to JRF. HAC was funded by the
Intramural Program of the NIH, National Institute of Mental Health.
Grant Number: ZIAMH002784.
NR 70
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JAN 1
PY 2017
VL 26
IS 1
BP 192
EP 209
DI 10.1093/hmg/ddw381
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EP0GG
UT WOS:000397064600016
PM 28082376
ER
PT J
AU Heymann, J
Winkler, CA
Hoek, M
Susztak, K
Kopp, JB
AF Heymann, Jurgen
Winkler, Cheryl A.
Hoek, Maarten
Susztak, Katalin
Kopp, Jeffrey B.
TI Therapeutics for APOL1 nephropathies: putting out the fire in the
podocyte
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Review
DE chronic kidney disease; focal segmental glomerulosclerosis;
glomerulosclerosis; inflammation; podocytes
ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; CHRONIC
KIDNEY-DISEASE; RISK VARIANTS; AFRICAN-AMERICANS; PATHOGENESIS;
INHIBITORS; POTASSIUM; ASSOCIATE; KINASES
AB APOL1 nephropathies comprise a range of clinical and pathologic syndromes, which can be summarized as focal segmental glomerulosclerosis, in various guises, and arterionephrosclerosis, otherwise known as hypertensive kidney diseases. Current therapies for these conditions may achieve therapeutic targets, reduction in proteinuria and control of blood pressure, respectively, but often fail to halt the progressive decline in kidney function. It appears that current therapies fail to address certain underlying critical pathologic processes that are driven, particularly in podocytes and microvascular cells, by the APOL1 renal risk genetic variants. Mechanisms hypothesized to be responsible for APOL1 variant-associated cell injury can be summarized in five domains: increased APOL1 gene expression, activation of inflammasomes, activation of protein kinase R, electrolyte flux across plasma or intracellular membranes, and altered endolysosomal trafficking associated with endoplasmic reticulum stress. We briefly review the available evidence for these five mechanisms and suggest possible novel therapeutic approaches.
C1 [Heymann, Jurgen; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Winkler, Cheryl A.] NCI, Mol Genet Epidemiol Sect, Basic Res Lab,NIH, Basic Sci Program,Leidos Biomed Res,Frederick Nat, Frederick, MD 21701 USA.
[Hoek, Maarten] Merck & Co Inc, Merck Res Labs, Kenilworth, NJ USA.
[Susztak, Katalin] Univ Penn, Sch Med, Dept Med, Renal Electrolyte & Hypertens Div,Perelman Sch Me, Philadelphia, PA 19104 USA.
RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
EM Jbkopp@nih.gov
FU NIDDK, NIH; NIDDK Intramural Research Program [ZO1 DK043308, RO1
DK105821]; Intramural Research Program of the NCI, Center for Cancer
Research; National Cancer Institute, National Institutes of Health
[HHSN26120080001E]
FX This work was supported by NIDDK, NIH, including the NIDDK Intramural
Research Program under ZO1 DK043308 and RO1 DK105821 to K.S. The work
was also supported by Intramural Research Program of the NCI, Center for
Cancer Research, in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN26120080001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products or
organizations imply endorsement by the US Government. The authors
appreciate the willingness of members of our laboratories to allow us to
reference data that have only been published in abstract form.
NR 43
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
EI 1460-2385
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD JAN
PY 2017
VL 32
SU 1
BP 65
EP 70
DI 10.1093/ndt/gfw402
PG 6
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA EO9RZ
UT WOS:000397027100009
ER
PT J
AU Juberg, DR
Knudsen, TB
Sander, M
Beck, NB
Faustman, EM
Mendrick, DL
Fowle, JR
Hartung, T
Tice, RR
Lemazurier, E
Becker, RA
Fitzpatrick, SC
Daston, GP
Harrill, A
Hines, RN
Keller, DA
Lipscomb, JC
Watson, D
Bahadori, T
Crofton, KM
AF Juberg, Daland R.
Knudsen, Thomas B.
Sander, Miriam
Beck, Nancy B.
Faustman, Elaine M.
Mendrick, Donna L.
Fowle, John R., III
Hartung, Thomas
Tice, Raymond R.
Lemazurier, Emmanuel
Becker, Richard A.
Fitzpatrick, Suzanne Compton
Daston, George P.
Harrill, Alison
Hines, Ronald N.
Keller, Douglas A.
Lipscomb, John C.
Watson, David
Bahadori, Tina
Crofton, Kevin M.
TI FutureTox III: Bridges for Translation
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE predictive toxicology; in vitro and alternatives; regulatory/policy;
risk assessment; testing alternatives
ID ESTROGEN-RECEPTOR; RISK-ASSESSMENT; TOXICITY; 21ST-CENTURY; TOXICOLOGY;
EXPOSURE; CHEMICALS; VISION; MODELS; PRIORITIZATION
AB Future Tox III, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2015. Building upon Future Tox I and II, Future Tox III was focused on developing the high throughput risk assessment paradigm and taking the science of in vitro data and in silico models forward to explore the question-what progress is being made to address challenges in implementing the emerging big-data toolbox for risk assessment and regulatory decision-making. This article reports on the outcome of the workshop including 2 examples of where advancements in predictive toxicology approaches are being applied within Federal agencies, where opportunities remain within the exposome and AOP domains, and how collectively the toxicology community across multiple sectors can continue to bridge the translation from historical approaches to Tox21 implementation relative to risk assessment and regulatory decision-making.
C1 [Juberg, Daland R.] Dow AgroSci, Indianapolis, IN 46268 USA.
[Knudsen, Thomas B.; Hines, Ronald N.; Crofton, Kevin M.] US EPA, Res Triangle Pk, NC 27711 USA.
[Sander, Miriam] Page One Editorial Serv, Boulder, CO USA.
[Beck, Nancy B.; Becker, Richard A.] Amer Chem Council, Washington, DC USA.
[Faustman, Elaine M.] Univ Washington, Seattle, WA 98195 USA.
[Mendrick, Donna L.] US FDA, Silver Spring, MD USA.
[Fowle, John R., III] Sci Inform LLC, Pittsboro, NC USA.
[Hartung, Thomas] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Tice, Raymond R.] NIEHS, Natl Toxicol Program, Durham, NC USA.
[Lemazurier, Emmanuel] INERIS Chron Risk Div, Verneeuil En Halatte, France.
[Fitzpatrick, Suzanne Compton] US FDA, College Pk, MD USA.
[Daston, George P.] Procter & Gamble Co, Cincinnati, OH USA.
[Harrill, Alison] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Keller, Douglas A.] Sanofi, Bridgewater, NJ USA.
[Lipscomb, John C.] US EPA, Cincinnati, OH 45268 USA.
[Watson, David] Lhasa Ltd, Leeds, W Yorkshire, England.
[Bahadori, Tina] US EPA, Washington, DC 20460 USA.
RP Juberg, DR (reprint author), Dow AgroSci, Indianapolis, IN 46268 USA.
EM drjuberg@dow.com
FU Society of Toxicology; Scientific Liaison Coalition; American Chemistry
Council; Dow AgroSciences, LLC; Hamner Institutes for Health Sciences;
Human Toxicology Project Consortium; Humane Society of the United
States; National Institute of Environmental Health Sciences; U.S. Food
and Drug Administration, Office of the Chief Scientist; National Center
for Toxicological Reseach; Bayer Crop Science; NSF International;
Syngenta Crop Protection LLC; TERA Center; University of Cincinnati;
ToxServices; American Academy of Clinical Toxicology; American College
of Toxicology; CAAT; Johns Hopkins Center for Alternatives to Animal
Testing (CAAT); In Sphero; Lhasa Limited; Ramboll Environ; Safety
Pharmacology Society; Society of Toxicologic Pathology; Teratology
Society
FX FutureTox III Sponsors included Society of Toxicology, Scientific
Liaison Coalition, the American Chemistry Council, Dow AgroSciences,
LLC, The Hamner Institutes for Health Sciences, Human Toxicology Project
Consortium, The Humane Society of the United States, National Institute
of Environmental Health Sciences, U.S. Food and Drug Administration,
Office of the Chief Scientist and the National Center for Toxicological
Reseach, Bayer Crop Science, NSF International, Syngenta Crop Protection
LLC, TERA Center, University of Cincinnati, ToxServices, American
Academy of Clinical Toxicology, American College of Toxicology, CAAT,
Johns Hopkins Center for Alternatives to Animal Testing (CAAT), In
Sphero, Lhasa Limited, Ramboll Environ, Safety Pharmacology Society,
Society of Toxicologic Pathology, The Teratology Society.
NR 41
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JAN
PY 2017
VL 155
IS 1
BP 22
EP 31
DI 10.1093/toxsci/kfw194
PG 10
WC Toxicology
SC Toxicology
GA EO9XL
UT WOS:000397041300003
PM 27780885
ER
PT J
AU Ben-Avraham, D
Karasik, D
Verghese, J
Lunetta, KL
Smith, JA
Eicher, JD
Vered, R
Deelen, J
Arnold, AM
Buchman, AS
Tanaka, T
Faul, JD
Nethander, M
Fornage, M
Adams, HH
Matteini, AM
Callisaya, ML
Smith, AV
Yu, L
De Jager, PL
Evans, DA
Gudnason, V
Hofman, A
Pattie, A
Corley, J
Launer, LJ
Knopman, DS
Parimi, N
Turner, ST
Bandinelli, S
Beekman, M
Gutman, D
Sharvit, L
Mooijaart, SP
Liewald, DC
Houwing-Duistermaat, JJ
Ohlsson, C
Moed, M
Verlinden, VJ
Mellstrom, D
van der Geest, JN
Karlsson, M
Hernandez, D
McWhirter, R
Liu, YM
Thomson, R
Tranah, GJ
Uitterlinden, AG
Weir, DR
Zhao, W
Starr, JM
Johnson, AD
Ikram, MA
Bennett, DA
Cummings, SR
Deary, IJ
Harris, TB
Kardia, SLR
Mosley, TH
Srikanth, VK
Windham, BG
Newman, AB
Walston, JD
Davies, G
Evans, DS
Slagboom, EP
Ferrucci, L
Kiel, DP
Murabito, JM
Atzmon, G
AF Ben-Avraham, Dan
Karasik, David
Verghese, Joe
Lunetta, Kathryn L.
Smith, Jennifer A.
Eicher, John D.
Vered, Rotem
Deelen, Joris
Arnold, Alice M.
Buchman, Aron S.
Tanaka, Toshiko
Faul, Jessica D.
Nethander, Maria
Fornage, Myriam
Adams, Hieab H.
Matteini, Amy M.
Callisaya, Michele L.
Smith, Albert V.
Yu, Lei
De Jager, Philip L.
Evans, Denis A.
Gudnason, Vilmundur
Hofman, Albert
Pattie, Alison
Corley, Janie
Launer, Lenore J.
Knopman, Davis S.
Parimi, Neeta
Turner, Stephen T.
Bandinelli, Stefania
Beekman, Marian
Gutman, Danielle
Sharvit, Lital
Mooijaart, Simon P.
Liewald, David C.
Houwing-Duistermaat, Jeanine J.
Ohlsson, Claes
Moed, Matthijs
Verlinden, Vincent J.
Mellstrom, Dan
van der Geest, Jos N.
Karlsson, Magnus
Hernandez, Dena
McWhirter, Rebekah
Liu, Yongmei
Thomson, Russell
Tranah, Gregory J.
Uitterlinden, Andre G.
Weir, David R.
Zhao, Wei
Starr, John M.
Johnson, Andrew D.
Ikram, M. Arfan
Bennett, David A.
Cummings, Steven R.
Deary, Ian J.
Harris, Tamara B.
Kardia, Sharon L. R.
Mosley, Thomas H.
Srikanth, Velandai K.
Windham, Beverly G.
Newman, Ann B.
Walston, Jeremy D.
Davies, Gail
Evans, Daniel S.
Slagboom, Eline P.
Ferrucci, Luigi
Kiel, Douglas P.
Murabito, Joanne M.
Atzmon, Gil
TI The complex genetics of gait speed: genome-wide meta-analysis approach
SO AGING-US
LA English
DT Article
DE gait speed; meta-analysis; aging; GWAS
ID QUANTITATIVE TRAIT LOCI; LOWER-EXTREMITY FUNCTION; TRANSCRIPT ISOFORM
VARIATION; HUMAN PREFRONTAL CORTEX; MAXIMAL WALKING SPEED; OLDER WOMEN;
WHOLE-BLOOD; PHYSICAL PERFORMANCE; REGULATORY VARIATION; MULTIPLE
TISSUES
AB Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta- analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.
C1 [Ben-Avraham, Dan; Atzmon, Gil] Albert Einstein Coll Med, Dept Med & Genet, Bronx, NY 10461 USA.
[Karasik, David; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.
[Karasik, David; Kiel, Douglas P.] Harvard Med Sch, Boston, MA 02131 USA.
[Karasik, David] Bar Ilan Univ, Fac Med Galilee, Safed, Israel.
[Verghese, Joe] Albert Einstein Coll Med, Montefiore Einstein Ctr Aging Brain, Integrated Div Cognit & Motor Aging Neurol, Bronx, NY 10461 USA.
[Verghese, Joe] Albert Einstein Coll Med, Montefiore Einstein Ctr Aging Brain, Integrated Div Geriatr Med, Bronx, NY 10461 USA.
[Lunetta, Kathryn L.; Eicher, John D.; Johnson, Andrew D.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Smith, Jennifer A.; Zhao, Wei; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Eicher, John D.; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Framingham, MA 01702 USA.
[Vered, Rotem] Univ Haifa, Dept Psychol, Haifa, Israel.
[Deelen, Joris; Beekman, Marian; Moed, Matthijs; Slagboom, Eline P.] Leiden Univ, Med Ctr, Mol Epidemiol, Leiden, Netherlands.
[Deelen, Joris] Max Planck Inst Biol Ageing, Cologne, Germany.
[Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98115 USA.
[Buchman, Aron S.; Yu, Lei; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60614 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Faul, Jessica D.; Weir, David R.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA.
[Nethander, Maria] Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Adams, Hieab H.; Hofman, Albert; Verlinden, Vincent J.; Ikram, M. Arfan] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Adams, Hieab H.; Ikram, M. Arfan] Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.
[Matteini, Amy M.; Walston, Jeremy D.] Johns Hopkins Med Inst, Div Geriatr Med, Baltimore, MD 21224 USA.
[Callisaya, Michele L.; Srikanth, Velandai K.] Cent Clin Sch Frankston, Peninsula Clin Sch, Peninsula Hlth, Med, Melbourne, Vic, Australia.
[Callisaya, Michele L.; McWhirter, Rebekah; Thomson, Russell; Srikanth, Velandai K.] Univ Tasmania, Inst Med Res, Hobart, Tas, Australia.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Iceland Heart Assoc, IS-101 Reykjavik, Iceland.
[De Jager, Philip L.] Broad Inst Harvard & MIT, Cambridge, MA 02139 USA.
[De Jager, Philip L.] Brigham & Womens Hosp, Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA.
[Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Chicago, IL 60612 USA.
[Evans, Denis A.] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Pattie, Alison; Corley, Janie; Deary, Ian J.; Davies, Gail] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Knopman, Davis S.] Mayo Clin, Rochester, MN 55905 USA.
[Parimi, Neeta; Tranah, Gregory J.; Cummings, Steven R.; Evans, Daniel S.] Calif Pacific Med Ctr Res Inst, San Francisco, CA 94107 USA.
[Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Mooijaart, Simon P.] Leiden Univ, Med Ctr, Gerontol & Geriatr, Leiden, Netherlands.
[Liewald, David C.; Starr, John M.; Deary, Ian J.; Davies, Gail] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.
[Houwing-Duistermaat, Jeanine J.] Leiden Univ, Med Ctr, Genet Stat, Leiden, Netherlands.
[Houwing-Duistermaat, Jeanine J.] Univ Leeds, Dept Stat, Leeds LS2 9JT, W Yorkshire, England.
[Ohlsson, Claes; Mellstrom, Dan] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
[van der Geest, Jos N.] Erasmus MC, Dept Neurosci, Rotterdam, Netherlands.
[Karlsson, Magnus] Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.
[Hernandez, Dena] NIA, Lab Neurogenet, Bethesda, MD 20892 USA.
[Liu, Yongmei] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Thomson, Russell] Univ Western Sydney, Sch Comp Engn & Math, Penrith, NSW 1797, Australia.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] NCHA, NGI, Rotterdam, Netherlands.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland.
[Mosley, Thomas H.; Windham, Beverly G.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Newman, Ann B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Kiel, Douglas P.] Broad Inst Harvard & MIT, Boston, MA 02131 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA.
[Gutman, Danielle; Sharvit, Lital; Atzmon, Gil] Univ Haifa, Fac Nat Sci, Dept Human Biol, Haifa, Israel.
RP Atzmon, G (reprint author), Albert Einstein Coll Med, Dept Med & Genet, Bronx, NY 10461 USA.; Murabito, JM (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.; Murabito, JM (reprint author), Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA.; Atzmon, G (reprint author), Univ Haifa, Fac Nat Sci, Dept Human Biol, Haifa, Israel.
EM murabito@bu.edu; gil.atzmon@einstein.yu.edu
FU NIH [N01-AG-1-2100, 271201200022C, R01-HL093029]; NIA Intramural
Research Program, Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); National Heart, Lung, and Blood
Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367,
R01HL086694]; National Human Genome Research Institute [U01HG004402];
National Institutes of Health [HHSN268200625226C, UL1RR025005,
HHSN268200782096C]; NIH Roadmap for Medical Research; Intramural
Research Program of the NIH, National Institute on Aging; NHLBI
[HHSN268201200036C, HHSN268200800007C, HHSN268200960009C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086,
HL080295, HL087652, HL105756]; National Institute of Neurological
Disorders and Stroke (NINDS); National Institute on Aging (NIA)
[AG023629]; CTSI [UL1TR000124]; National Institute of Diabetes and
Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491];
NIA [R01AG29451, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1,
RC2 AG036495, RC4 AG039029]; National Heart, Lung and Blood Institute's
Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-64278];
Robert Dawson Evans Endowment; Framingham Heart Study; NIAMS [RO1
AR41398]; National Institute on Aging [NIA U01AG009740]; "targeted
project" by the Italian Ministry of Health [ICS110.1/RF97.71]; U.S.
National Institute on Aging [263 MD 9164, 263 MD 821336]; UK
Biotechnology and Biological Sciences Research Council (BBSRC); Royal
Society; Chief Scientist Office of the Scottish Government; Research
Into Ageing; BBSRC; Medical Research Council (MRC); National Institutes
of Health; National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS); National Center for Research Resources (NCRR); NIH
Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01
AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01AG027810, UL1
RR024140]; MrOS ancillary study 'Replication of candidate gene
associations and bone strength phenotype in MrOS' [R01-AR051124];
National Institute on Aging grants [P30AG10161, R01AG17917, R01AG15819,
R01AG30146, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01
AG005394, R01 AG027574, R01 AG027576]; Illinois Department of Public
Health [R01NS078009]; Translational Genomics Research Institute;
Netherlands Organisation of Scientific Research NWO Investments
[175.010.2005.011, 911-03-012]; Research Institute for Diseases in the
Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands
Organisation [050-060-810]; 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; Dutch Technology Foundation STW; Ministry of Economic
Affairs; ZonMW [916.13.054]; National Health and Medical Research
Council (NHMRC) of Australia; National Institutes of Health (NIH) USA;
National Heart, Lung and Blood Institute [HL054457, HL087660, HL119443];
National Institute of Neurological Disorders and Stroke [NS041558];
European Union's Seventh Framework Programme (FP7) [259679];
Innovation-Oriented Research Program on Genomics [IGE05007]; Centre for
Medical Systems Biology; Netherlands Consortium for Healthy Ageing
[050-060-810]; Netherlands Organization for Scientific Research (NWO);
Unilever Colworth; BBMRI-NL; Dutch government [NWO 184.021.007]; Swedish
Research Council; Swedish government (under the Avtal om Lakarutbildning
och Medicinsk Forskning [Agreement for Medical Education and Research]);
Lundberg Foundation; Torsten Soderberg Foundation; Novo Nordisk
Foundation; Knut and Alice Wallenberg Foundation; Erasmus Medical Center
Rotterdam; Erasmus University, Rotterdam; [RC2ARO58973]
FX This study has been funded by NIH contracts N01-AG1-2100 and
271201200022C, the NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association), and the Althingi (the Icelandic
Parliament). The study is approved by the Icelandic National Bioethics
Committee, VSN: 00-063. The researchers are indebted to the participants
for their willingness to participate in the study.; The Atherosclerosis
Risk in Communities Study is carried out as a collaborative study
supported by National Heart, Lung, and Blood Institute contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and
R01HL086694; National Human Genome Research Institute contract
U01HG004402; and National Institutes of Health contract
HHSN268200625226C. The authors thank the staff and participants of the
ARIC study for their important contributions. Infrastructure was partly
supported by Grant Number UL1RR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research. This project
was also partially supported from NIH grant R01-HL093029.; The BLSA was
supported by the Intramural Research Program of the NIH, National
Institute on Aging.; The CHS research was supported by NHLBI contracts
HHSN268201200036C, HHSN268200800007C, HHSN268200960009C, 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). A full list of CHS investigators
and institutions can be found at http://chs-nhlbi.org/. The provision of
genotyping data was supported in part by the National Center for
Advancing Translational Sciences, CTSI grant UL1TR000124, and the
National Institute of Diabetes and Digestive and Kidney Disease Diabetes
Research Center (DRC) grant DK063491 to the Southern California Diabetes
Endocrinology Research Center.; The Framingham Heart Study
phenotype-genotype analyses were supported by NIA R01AG29451 (JMM, KLL).
The Framingham Heart Study of the National Heart Lung and Blood
Institute of the National Institutes of Health and Boston University
School of Medicine was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study Contract No. N01-HC-25195 and its
contract with Affymetrix, Inc for genotyping services (Contract No.
N02-HL-64278). Analyses reflect intellectual input and resource
development from the Framingham Heart Study investigators participating
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. The investigators thank the participants and the staff for their
support of the Framingham Heart Study. Dr Kiel's effort was supported by
NIAMS grant RO1 AR41398.; This research was supported by 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 National Institutes of Health to The
Johns Hopkins University, contract number HHSN268200782096C. This
research was supported in part by the Intramural Research Program of the
NIH, National Institute on Aging.; HRS is supported by the National
Institute on Aging (NIA U01AG009740). Genotyping was funded separately
by NIA (RC2 AG036495, RC4 AG039029). Our genotyping was conducted by the
NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins
University. Genotyping quality control and final preparation of the data
were performed by the Genetics Coordinating Center at the University of
Washington.; The InCHIANTI study baseline (1998-2000) was supported as a
"targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health
and in part by the U.S. National Institute on Aging (Contracts: 263 MD
9164 and 263 MD 821336).; We thank the cohort participants and team
members who contributed to these studies. Phenotype collection in the
Lothian Birth Cohort 1921 was supported by the UK Biotechnology and
Biological Sciences Research Council (BBSRC), The Royal Society and The
Chief Scientist Office of the Scottish Government. Phenotype collection
in the Lothian Birth Cohort 1936 was supported by Research Into Ageing
(continues as part of Age UK The Disconnected Mind project). Genotyping
of the cohorts was funded by the BBSRC. The work was undertaken by The
University of Edinburgh Centre for Cognitive Ageing and Cognitive
Epidemiology, part of the cross council Lifelong Health and Wellbeing
Initiative (MR/K026992/1). Funding from the BBSRC and Medical Research
Council (MRC) is gratefully acknowledged.; The Osteoporotic Fractures in
Men (MrOS) Study is supported by National Institutes of Health funding.
The following institutes provide support: the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National
Institute on Aging (NIA), the National Center for Research Resources
(NCRR), and NIH Roadmap for Medical Research under the following grant
numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01
AR45654, U01 AR45583, U01 AG18197, U01AG027810, and UL1 RR024140. The
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) provides funding for the MrOS ancillary study 'Replication of
candidate gene associations and bone strength phenotype in MrOS' under
the grant number R01-AR051124. The National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS) provides funding for the MrOS
ancillary study 'GWAS in MrOS and SOF' under the grant number
RC2ARO58973.; The data from the Rush Alzheimer's Disease Center used in
these analyses was supported by National Institute on Aging grants
P30AG10161, R01AG17917, R01AG15819, R01AG30146, the Illinois Department
of Public Health, R01NS078009 and the Translational Genomics Research
Institute.; The generation and management of GWAS genotype data for the
Rotterdam Study are supported by the Netherlands Organisation of
Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012).
This study is funded by the Research Institute for Diseases in the
Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative
(NGI)/Netherlands Organisation for Scientific Research (NWO) project nr.
050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and
Erasmus University, Rotterdam, Netherlands Organization for the Health
Research and Development (ZonMw), the Research Institute for Diseases in
the Elderly (RIDE), the Ministry of Education, Culture and Science, the
Ministry for Health, Welfare and Sports, the European Commission (DG
XII), and the Municipality of Rotterdam. This research is supported by
the Dutch Technology Foundation STW, which is part of the NWO, and which
is partly funded by the Ministry of Economic Affairs. MAI is supported
by ZonMW grant number 916.13.054.; The Study of Osteoporotic Fractures
(SOF) is supported by National Institutes of Health funding. The
National Institute on Aging (NIA) provides support under the following
grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01
AG005394, R01 AG027574, and R01 AG027576.; All participants and research
staff who took part in TASCOG are duly acknowledged, in addition to
funding bodies including the National Health and Medical Research
Council (NHMRC) of Australia, and the National Institutes of Health
(NIH) USA.; Support for the Genetic Epidemiology Network of Arteriopathy
(GENOA) was provided by the National Heart, Lung and Blood Institute
(HL054457, HL087660, HL119443) and the National Institute of
Neurological Disorders and Stroke (NS041558) of the National Institutes
of Health. Genotyping was performed at the Mayo Clinic (S.T.T, Mariza de
Andrade, Julie Cunningham) and was made possible by the University of
Texas Health Sciences Center (Eric Boerwinkle, Megan Grove-Gaona). We
would also like to thank the families that participated in the GENOA
study.; The research leading to these results has received funding from
the European Union's Seventh Framework Programme (FP7/2007-2011) under
grant agreement number 259679. This study was financially supported by
the Innovation-Oriented Research Program on Genomics (SenterNovem
IGE05007), the Centre for Medical Systems Biology and the Netherlands
Consortium for Healthy Ageing (grant 050060-810), all in the framework
of the Netherlands Genomics Initiative, Netherlands Organization for
Scientific Research (NWO), by Unilever Colworth and by BBMRI-NL, a
Research Infrastructure financed by the Dutch government (NWO
184.021.007).; This study was supported by the Swedish Research Council
and by grants from the Swedish government (under the Avtal om
Lakarutbildning och Medicinsk Forskning [Agreement for Medical Education
and Research]), the Lundberg Foundation, the Torsten Soderberg
Foundation, the Novo Nordisk Foundation and the Knut and Alice
Wallenberg Foundation.
NR 192
TC 0
Z9 0
U1 2
U2 2
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JAN
PY 2017
VL 9
IS 1
BP 209
EP 246
PG 38
WC Cell Biology
SC Cell Biology
GA EK8JW
UT WOS:000394170800016
PM 28077804
ER
PT J
AU Mayer, JE
Fontelo, P
AF Mayer, Jonathan E.
Fontelo, Paul
TI Meta-analysis on the effect of text message reminders for HIV-related
compliance
SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
LA English
DT Article
DE HIV; AIDS; compliance; text message; cell phones
ID RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY ADHERENCE; MOBILE
PHONE REMINDERS; SERVICE SMS TEXTS; APPOINTMENT REMINDERS; RURAL UGANDA;
HIGHER RISK; CARE; INTERVENTION; SUPPORT
AB For the treatment of HIV, compliance in regard to appointment attendance and medication usage is critical. Various methods have been attempted to increased HIV care compliance, and a method that has inspired many published studies is text message reminders. We conducted a meta-analysis of the literature from inception through May 2016 using the following databases: Pubmed, Embase, CINAHL, Web of Science, and Cochrane. Examples of terms used in the search included exploded versions of "HIV, "AIDS", "cell phone","SMS", "text message", "reminder". After abstract and manuscript review, articles were discussed with co-author and included based on consensus. We excluded qualitative analyses, observational studies without an intervention, and studies without a control or pre-intervention group. We used random-effects models to calculate odds ratios (OR) and standardized mean differences (SMDs) for the text message intervention. Thirty-four unique studies were found and included in the meta-analysis. For the seven articles relating to non-attendance, text message reminders significantly reduced the rates of nonattendance (OR, 0.66; 95% CI, 0.48-0.92; P = .01; I-2 = 52%). For the 20 articles on drug adherence, text message reminders significantly increased adherence (SMD, 0.87; 95% CI, 0.06-1.68; P = .04; I-2 = 99%). For the 11 articles with physiologic measures (CD4 count or viral load), text message reminders led to significant improvement (SMD, 1.53; 95% CI, 0.52-2.55; P = .003; I-2 = 99%). This meta-analysis reveals that text message reminders are a promising intervention that can be used to increase HIV care compliance when logistically feasible. Further study should focus on which populations benefit the most from this intervention, and successful implementers could create an established technological infrastructure for other clinics to adopt when seeking to boost compliance.
C1 [Mayer, Jonathan E.] Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Med, 5200 Eastern Ave,Room 342, Baltimore, MD 21224 USA.
[Fontelo, Paul] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD USA.
RP Mayer, JE (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Med, 5200 Eastern Ave,Room 342, Baltimore, MD 21224 USA.
EM jem361@mail.harvard.edu
FU Intramural Research Program of the National Institutes of Health (NIH);
National Library of Medicine (NLM); Lister Hill National Center for
Biomedical Communications (LHNCBC)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Library of Medicine (NLM),
and Lister Hill National Center for Biomedical Communications (LHNCBC).
The views and opinions of the authors expressed herein do not
necessarily state or reflect those of the National Library of Medicine,
National Institutes of Health or the US Department of Health and Human
Services.
NR 54
TC 0
Z9 0
U1 4
U2 4
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0954-0121
EI 1360-0451
J9 AIDS CARE
JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv
PY 2017
VL 29
IS 4
BP 409
EP 417
DI 10.1080/09540121.2016.1214674
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychology, Multidisciplinary; Respiratory System; Social Sciences,
Biomedical
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychology; Respiratory System; Biomedical Social Sciences
GA EL4UL
UT WOS:000394616300001
PM 27477580
ER
PT J
AU Zablotsky, B
Colpe, LJ
Pringle, BA
Kogan, MD
Rice, C
Blumberg, SJ
AF Zablotsky, Benjamin
Colpe, Lisa J.
Pringle, Beverly A.
Kogan, Michael D.
Rice, Catherine
Blumberg, Stephen J.
TI Age of Parental Concern, Diagnosis, and Service Initiation Among
Children With Autism Spectrum Disorder
SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES
LA English
DT Article
DE autism spectrum disorder; national surveys; diagnosis; epidemiology
ID 1ST CONCERNS; IDENTIFICATION; TODDLERS; ACCESS; SURVEILLANCE; SEVERITY;
CARE
AB Children with autism spectrum disorder (ASD) require substantial support to address the core symptoms of ASD and co-occurring behavioral/developmental conditions. This study explores the early diagnostic experiences of school-aged children with ASD using survey data from a large probability-based national sample. Multivariate linear regressions were used to examine age when parent reported developmental concern to doctor, received ASD diagnosis, and first obtained services. Children whose parents had concerns about their child's verbal communication reported earlier ages for all outcomes when compared to children of parents who did not have verbal communication concerns. Children whose parents had concerns about their child's nonverbal communication or unusual gestures/ movements received an earlier diagnosis than children whose parents did not have these specific concerns.
C1 [Zablotsky, Benjamin; Blumberg, Stephen J.] Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Colpe, Lisa J.; Pringle, Beverly A.] Natl Inst Mental Hlth, Bethesda, MD USA.
[Kogan, Michael D.] Maternal & Child Hlth Bur, Ottawa, ON, Canada.
[Rice, Catherine] Emory Univ, Atlanta, GA 30322 USA.
RP Zablotsky, B (reprint author), Natl Ctr Hlth Stat, Hyattsville, MD USA.
EM bzablotsky@cdc.gov
NR 46
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES
PI WASHINGTON
PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA
SN 1944-7515
EI 1944-7558
J9 AJIDD-AM J INTELLECT
JI AJIDD-Am. J. Intellect. Dev. Disabil.
PD JAN
PY 2017
VL 122
IS 1
BP 49
EP 61
DI 10.1352/1944-7558-122.1.49
PG 13
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA EO2LM
UT WOS:000396528000004
PM 28095057
ER
PT J
AU Doernberg, S
Hull, SC
AF Doernberg, Sam
Hull, Sara Chandros
TI Harms of Deception in FMR1 Premutation Genotype-Driven Recruitment
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
C1 [Doernberg, Sam; Hull, Sara Chandros] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Hull, Sara Chandros] NHGRI, Bethesda, MD 20892 USA.
RP Hull, SC (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Suite 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA.
EM shull@mail.nih.gov
NR 8
TC 0
Z9 0
U1 1
U2 1
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PY 2017
VL 17
IS 4
BP 62
EP 63
DI 10.1080/15265161.2017.1284920
PG 2
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA EO9JS
UT WOS:000397005600025
PM 28328354
ER
PT J
AU Doussau, A
Hanmer, CB
AF Doussau, Adelaide
Hanmer, Clark B.
TI A Rationale for Relaxing the Requirement to Undergo a Noncurative
Chemotherapy for Advanced Cancer in a Phase I Immunotherapy Trial
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
C1 [Doussau, Adelaide] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Doussau, A (reprint author), McGill Univ, Biomed Eth Unit, Montreal, PQ, Canada.
EM adelaide.doussau@mail.mcgill.ca
NR 4
TC 0
Z9 0
U1 1
U2 1
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PY 2017
VL 17
IS 4
BP 68
EP 69
DI 10.1080/15265161.2017.1284922
PG 2
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA EO9JS
UT WOS:000397005600028
PM 28328363
ER
PT J
AU Collier, E
Danis, M
AF Collier, Elaine
Danis, Marion
TI Participation of Citizen Scientists in Clinical Research and Access to
Research Ethics Consultation
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
AB This case teaches us two important lessons. The first pertains to the valuable input that patients, prospective and active research participants, and others can provide to the research enterprise. The second pertains to the value of allowing patients as well as prospective and active research participants to request research ethics consultations.
C1 [Collier, Elaine] Natl Ctr Adv Translat Sci, 6701 Democracy Blvd, Bethesda, MD 20892 USA.
[Danis, Marion] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Collier, E (reprint author), Natl Ctr Adv Translat Sci, 6701 Democracy Blvd, Bethesda, MD 20892 USA.
EM ec5x@nih.gov
FU Office of Director, National Center for Advancing Translational Sciences
(NCATS), National Institutes of Health (NIH); intramural program of the
NIH, particularly the Department of Bioethics at the NIH
FX This work was funded in part by the Office of Director, National Center
for Advancing Translational Sciences (NCATS), National Institutes of
Health (NIH), and by the intramural program of the NIH, particularly the
Department of Bioethics at the NIH.
NR 9
TC 0
Z9 0
U1 2
U2 2
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PY 2017
VL 17
IS 4
BP 70
EP 72
DI 10.1080/15265161.2017.1284933
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA EO9JS
UT WOS:000397005600029
PM 28328379
ER
PT J
AU Thomas-White, KJ
Kliethermes, S
Rickey, L
Lukacz, ES
Richter, HE
Moalli, P
Zimmem, P
Norton, P
Kusek, JW
Wolfe, AJ
Brubaker, L
AF Thomas-White, Krystal J.
Kliethermes, Stephanie
Rickey, Leslie
Lukacz, Emily S.
Richter, Holly E.
Moalli, Pamela
Zimmem, Philippe
Norton, Peggy
Kusek, John W.
Wolfe, Alan J.
Brubaker, Linda
CA Natl Inst Diabet Digestive Kidney
TI Evaluation of the urinary microbiota of women with uncomplicated stress
urinary incontinence
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE bladder; estrogen; microbiome; stress urinary incontinence; urgency
urinary incontinence
ID ADULT FEMALE BLADDER; OVERACTIVE BLADDER; INFECTION; ESTROGEN; BACTERIA;
WEIGHT
AB BACKGROUND: Female urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described.
OBJECTIVE: We sought to study the cross-sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery.
STUDY DESIGN: Preoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models.
RESULTS: The majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P =.02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P =.04); and hormonal status (P <.001). No associations were detected with stress urinary incontinence symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone-negative women.
CONCLUSION: Women undergoing stress urinary incontinence surgery have detectable urinary microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms.
C1 [Thomas-White, Krystal J.; Wolfe, Alan J.] Loyola Univ, Dept Microbiol & Immunol, Chicago, IL USA.
[Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Obstet, Chicago, IL USA.
[Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Gynecol, Chicago, IL USA.
[Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Urol, Chicago, IL USA.
[Kliethermes, Stephanie] Loyola Univ Chicago, Stritch Sch Med, Dept Med, Maywood, IL USA.
[Kliethermes, Stephanie] Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL USA.
[Rickey, Leslie] Yale Univ, Dept Urol, New Haven, CT USA.
[Lukacz, Emily S.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA USA.
[Lukacz, Emily S.] Univ Calif San Diego Hlth Syst, San Diego, CA USA.
[Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL USA.
[Moalli, Pamela] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Zimmem, Philippe] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA.
[Norton, Peggy] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Kusek, John W.] Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
RP Wolfe, AJ (reprint author), Loyola Univ, Dept Microbiol & Immunol, Chicago, IL USA.
EM awolfe@luc.edu
FU National Institutes of Health (NIH) [U01 DK58229, R21 DK097435];
Department of Health and Human Services [1G20RR030939-1]; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01
DK58229, U01 DK58225, U01 DK58231, U01 DK58234, U01 DK60379, U01
DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; Office of
Research in Women's Health; NIH [NCT00803959]
FX Supported by National Institutes of Health (NIH) grants U01 DK58229 and
R21 DK097435 (to A.J.W. and L.B.). Loyola University Chicago Stritch
School of Medicine's research computing facility was developed through
grant funds awarded by the Department of Health and Human Services as
award number 1G20RR030939-1. Our funding sources had no role in design
and conduct of the study; collection, management, analysis, and
interpretation of the data; or preparation, review, and approval of the
manuscript. The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) Urinary Incontinence Treatment Network and
investigators were supported by cooperative agreements from the NIDDK,
U01 DK58225, U01 DK58229, U01 DK58231, U01 DK58234, U01 DK60379, U01
DK60380, U01 DK60393, U01 DK60395, U01 DK60397, and U01 DK60401. Support
was also provided by the Office of Research in Women's Health, NIH.
Registered at www. clinicaltrials. gov as NCT00803959.
NR 33
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2017
VL 216
IS 1
AR 55.e1
DI 10.1016/j.ajog.2016.07.049
PG 16
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EO0II
UT WOS:000396381100014
ER
PT J
AU Baker, KC
Dettmer, AM
AF Baker, Kate C.
Dettmer, Amanda M.
TI The Well-Being of Laboratory Non-Human Primates INTRODUCTION
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Editorial Material
DE pair housing; psychological well-being; chronic stress; behavioral
management; primate
ID RHESUS MACAQUES; MACACA-MULATTA; HAIR CORTISOL; FULL-CONTACT; BENEFITS;
MONKEYS
AB The well-being of non-human primates in captivity is of joint concern to scientists, veterinarians, colony managers, caretakers, and researchers working with non-human primates in biomedical research. With increased regulatory, accreditation, and research focus on optimizing the use of social housing for laboratory primates, as well as the advent of techniques to assess indices of chronic stress and related measures of well-being, there is no better time to present the most current advances in the field of non-human primate behavioral management. The collective body of research presented here was inspired in part by a 2014 symposium entitled, "Chronic Hormones and Demographic Variables: Center-Wide Studies on Non-Human Primate Well-Being" held at the American Society of Primatologists' 37th Annual Meeting in Decatur, GA. By aiming to target readership with scientific and/or management oversight of captive primate behavioral management programs, this special issue provides badly-needed guidance for implementing social housing programs in a research environment and leverages collaboration across multiple facilities to address key components of behavioral management, explore refinements in how well-being can be measured, and identify the interrelationships between varying indices. (C) 2016 Wiley Periodicals, Inc.
C1 [Baker, Kate C.] Tulane Natl Primate Res Ctr, Div Vet Med, Covington, LA USA.
[Dettmer, Amanda M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, NIH, Poolesville, MD USA.
RP Dettmer, AM (reprint author), NICHD, Comparat Ethol Lab, NIH, POB 529, Poolesville, MD 20837 USA.
EM dettmera@mail.nih.gov
NR 16
TC 1
Z9 1
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD JAN
PY 2017
VL 79
IS 1
AR UNSP e22520
DI 10.1002/ajp.22520
PG 5
WC Zoology
SC Zoology
GA EL5LB
UT WOS:000394661500001
ER
PT J
AU Dettmer, AM
Rosenberg, K
Menard, MT
El-Mallah, SN
Woodward, RA
Suomi, SJ
Meyer, JS
AF Dettmer, Amanda M.
Rosenberg, Kendra
Menard, Mark T.
El-Mallah, Saif N.
Woodward, Ruth A.
Suomi, Stephen J.
Meyer, Jerrold S.
TI Differential Relationships Between Chronic Hormone Profiles in Pregnancy
and Maternal Investment in Rhesus Monkey Mothers With Hair Loss in the
Neonatal Period
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Article
DE hair loss; alopecia; pregnancy; infant growth; maternal investment
ID MACACA-MULATTA; CORTISOL CONCENTRATIONS; STRESS; MACAQUES; BIOMARKER;
ALOPECIA
AB Hair loss is commonly used as an indicator of well being in primate facilities, yet it has been shown to also occur in otherwise healthy pregnant and postpartum females. There is significant variability in the incidence of hair loss during these important developmental periods, reasons for which remain unclear. We studied female rhesus monkeys (Macaca mulatta, n = 47) with and without hair loss in pregnancy/postpartum. We hypothesized that, similar to previously published reports, pregnancy would result in an increased likelihood of hair loss, and that hair loss would be correlated with higher hair cortisol concentrations (HCCs). We further hypothesized that hair loss among pregnant females is related to differential maternal investment. We studied a subset of monkeys (n = 26) from mid-to-late pregnancy through peak lactation, some of which exhibited hair loss in the perinatal period (n = 15), and some of which did not (n = 11). We examined fetal measurements, infant birth weight, infant growth rate, and milk yield volume (MYV) in the first 30 days as indices of investment. We found that pregnant monkeys showed a greater incidence of hair loss across the study year (x((2))(2) = 6.55, P = 0.038), and that mothers with hair loss had significantly higher HCCs in pregnancy than those without (F-(2,F-28) = 3.8, P = 0.017, eta(2)(p) = 0.21). HCCs in pregnancy were correlated with severity of hair loss in the neonatal period (r((37)) = 0.42, P = 0.008). Moreover, HCCs in pregnancy were positively correlated with infant birth weight (r((12)) = 0.56, P = 0.038), infant growth rate (r((12)) = 0.64, P = 0.014), and MYV((r(11)) = 0.85, P < 0.001) for alopecic but not non-alopecic mothers. These mothers did not differ in fetal measurements, infant birth weight/growth rate, or MYV. Our results suggest that hair loss in some monkeys, especially during the birthing season, may be a signal of greater physiological stress during pregnancy and differential investment by mothers to their offspring. (C) 2015 Wiley Periodicals, Inc.
C1 [Dettmer, Amanda M.; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, NIH, Poolesville, MD USA.
[Rosenberg, Kendra; Menard, Mark T.; El-Mallah, Saif N.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Tobin Hall, Amherst, MA 01003 USA.
[Woodward, Ruth A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Res Anim Management Branch, Div Intramural Res, NIH, Poolesville, MD USA.
RP Dettmer, AM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, NIH, POB 529, Dickerson, MD 20837 USA.
EM dettmera@mail.nih.gov
FU NIH [R24OD011180-15]
FX Contract grant sponsor: NIH; contract grant number: R24OD011180-15.
NR 35
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD JAN
PY 2017
VL 79
IS 1
AR UNSP e22489
DI 10.1002/ajp.22489
PG 8
WC Zoology
SC Zoology
GA EL5LB
UT WOS:000394661500004
ER
PT J
AU Peterson, EJ
Worlein, JM
Lee, GH
Dettmer, AM
Varner, EK
Novak, MA
AF Peterson, Emily J.
Worlein, Julie M.
Lee, Grace H.
Dettmer, Amanda M.
Varner, Elana K.
Novak, Melinda A.
TI Rhesus Macaques (Macaca mulatta) With Self-Injurious Behavior Show Less
Behavioral Anxiety During the Human Intruder Test
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Article
DE self-injury; rhesus macaques; anxiety; human intruder test; blunted
affect
ID NONHUMAN-PRIMATES; STEREOTYPIC BEHAVIOR; RELOCATION STRESS; SUICIDE
ATTEMPTS; MONKEYS; MODEL; ADOLESCENTS; ENVIRONMENT; DEPRESSION; CORTISOL
AB Self-injurious behavior (SIB) has been linked to anxiety in the human literature, but relatively few studies have explored this link in rhesus macaques. A widely used behavioral assessment of anxiety, the human intruder test (HIT), employs the mildly stressful stimulus of an unfamiliar experimenter to assess anxious behavior in macaques. The HIT was conducted on 59 (20 male) laboratory housed rhesus macaques, 30 with a record of SIB (10 male). If monkeys with SIB have a more anxious phenotype, they should show stronger reactions to the HIT. However, contrary to our predictions, monkeys with SIB did not show higher levels of anxious behavior compared to controls. They spent significantly less time showing anxious behavior and displayed little aggression in response to the stare of the intruder. SIB and control monkeys did not differ in a range score (number of unique behaviors expressed per phase); however, SIB monkeys had a lower change score (total number of behaviors expressed including repetitions) than controls. In general, monkeys that paced regardless of SIB status, showed a reduction in pacing when the intruder entered the room. Possible explanations for the failure of SIB monkeys to show increased anxiety in the HIT include greater exposure of SIB monkeys to unfamiliar humans because of their condition, evidence for a subtype of SIB which is not anxiety related, and/or the presence of comorbid depressive-like symptoms. (C) 2016 Wiley Periodicals, Inc.
C1 [Peterson, Emily J.] Univ Massachusetts, Neurosci & Behav Grad Program, Amherst, MA 01003 USA.
[Worlein, Julie M.; Lee, Grace H.] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
[Dettmer, Amanda M.] NICHD, Lab Comparat Ethol, NIH Anim Ctr, NIH, Poolesville, MD USA.
[Varner, Elana K.; Novak, Melinda A.] Univ Massachusetts, Dept Psychol & Brain Sci, 135 Hicks Way, Amherst, MA 01003 USA.
RP Novak, MA (reprint author), Univ Massachusetts, Dept Psychol & Brain Sci, 135 Hicks Way, Amherst, MA 01003 USA.
EM mnovak@psych.umass.edu
FU National Institutes of Health [R24-OD11180]
FX Contract grant sponsor: National Institutes of Health; contract grant
number: R24-OD11180.
NR 32
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD JAN
PY 2017
VL 79
IS 1
AR UNSP e22569
DI 10.1002/ajp.22569
PG 8
WC Zoology
SC Zoology
GA EL5LB
UT WOS:000394661500011
ER
PT J
AU Capparelli, EV
Bricker-Ford, R
Rogers, MJ
McKerrow, JH
Reed, SL
AF Capparelli, Edmund V.
Bricker-Ford, Robin
Rogers, M. John
McKerrow, James H.
Reed, Sharon L.
TI Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
DE auranofin; phase I trial; antiparasitic agents
ID ENTAMOEBA-HISTOLYTICA; DRUG; MECHANISM
AB Under an NIH priority to identify new drugs to treat class B parasitic agents, we performed high-throughput screens, which identified the activity of auranofin (Ridaura) against Entamoeba histolytica and Giardia intestinalis, major causes of water- and foodborne outbreaks. Auranofin, an orally administered, gold (Au)-containing compound that was approved by the FDA in 1985 for treatment of rheumatoid arthritis, was effective in vitro and in vivo against E. histolytica and both metronidazole-sensitive and -resistant strains of Giardia. We now report the results of an NIH-sponsored phase I trial to characterize the pharmacokinetics (PK) and safety of auranofin in healthy volunteers using modern techniques to measure gold levels. Subjects received orally 6 mg (p. o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days. Treatment-associated adverse events were reported by 47% of the subjects, but all were mild and resolved without treatment. The mean gold maximum concentration in plasma (C-max) at day 7 was 0.312 mu g/ml and the half-life (t(1/2)) 35 days, so steadystate blood levels would not be reached in short-term therapy. The highest concentration of gold, 13 mu M (auranofin equivalent), or more than 25 x the 50% inhibitory concentration (IC50) for E. histolytica and 4 x that for Giardia, was in feces at 7 days. Modeling of higher doses (9 and 21 mg/day) was performed for systemic parasitic infections, and plasma gold levels of 0.4 to 1.0 mu g/ml were reached after 14 days of treatment at 21 mg/day. This phase I trial supports the idea of the safety of auranofin and provides important PK data to support its potential use as a broadspectrum antiparasitic drug.
C1 [Capparelli, Edmund V.; Bricker-Ford, Robin; McKerrow, James H.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Rogers, M. John] NIH, Div Microbiol & Infect Dis, Bldg 10, Bethesda, MD 20892 USA.
[Reed, Sharon L.] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA.
[Reed, Sharon L.] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.
RP Reed, SL (reprint author), Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA.; Reed, SL (reprint author), Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.
EM slreed@ucsd.edu
FU National Institutes of Health [HHSN272200800024C, UO1 A1077822, UO1
AI110435]
FX This work was supported by the National Institutes of Health (Study DMID
12-0101 under Phase 1 Unit Contract Number HHSN272200800024C to S.L.R.,
UO1 A1077822 to S.L.R. and J.H.M., and UO1 AI110435 to S.L.R.).
NR 22
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2017
VL 61
IS 1
AR e01947- 16
DI 10.1128/AAC.01947-16
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA EK7HC
UT WOS:000394095800051
ER
PT J
AU Rudramurthy, SM
Seyedmousavi, S
Dhaliwal, M
Chakrabarti, A
Meis, JF
Mouton, JW
AF Rudramurthy, Shivaprakash M.
Seyedmousavi, Seyedmojtaba
Dhaliwal, Manpreet
Chakrabarti, Arunaloke
Meis, Jacques F.
Mouton, Johan W.
TI Pharmacodynamics of Voriconazole against Wild-Type and Azole-Resistant
Aspergillus flavus Isolates in a Nonneutropenic Murine Model of
Disseminated Aspergillosis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
DE voriconazole; Aspergillus flavus; azole resistance; pharmacokinetics;
pharmacodynamics
ID INVASIVE ASPERGILLOSIS; AMPHOTERICIN-B; HUMAN PATHOGEN; FUMIGATUS;
SUSCEPTIBILITY; ISAVUCONAZOLE; PHARMACOKINETICS; ANIDULAFUNGIN;
MUTATIONS; STRAINS
AB Invasive aspergillosis (IA) due to Aspergillus flavus is associated with high mortality. Although voriconazole (VRC) is widely recommended as the first-line treatment for IA, emergence of azole resistance in Aspergillus spp. is translating to treatment failure. We evaluated the efficacy of voriconazole in a nonneutropenic murine model of disseminated A. flavus infection using two voriconazole-resistant isolates (one harboring the Y319H substitution in the cyp51C gene) and two wild-type isolates without mutations. All isolates exhibited a dose-response relationship, and voriconazole treatment improved mouse survival in a dose-dependent manner. At 40 mg/kg of body weight, 100% efficacy was observed for 1 susceptible isolate and 1 resistant isolate (with mutation), whereas for another susceptible isolate and resistant isolate (without mutation), survival rates were 81% and 72%, respectively. The Hill equation with a variable slope fitted the relationship between the area under the concentration-time curve (AUC)/MIC ratio and 14-day survival well for each strain. An F test showed the 50% effective doses to be significantly different from each other (P = 0.0023). However, contrary to expectation, there was a significant difference in exposure-response relationships between strains, and it appeared that the susceptible strains required a relatively higher exposure than the resistant ones to result in the same treatment effect, the 50% effective pharmacokinetic/pharmacodynamic (PK/PD) index (EI50) required being negatively and log-linearly related to the MIC (P = 0.04). We conclude that the efficacy of voriconazole depended on drug exposure and the voriconazole MIC of the isolates, but lower exposures are required for strains with higher MICs. These findings may have profound significance in clinical practice with respect to dosing and drug choice.
C1 [Rudramurthy, Shivaprakash M.; Dhaliwal, Manpreet; Chakrabarti, Arunaloke] Postgrad Inst Med Educ & Res PGIMER, Dept Med Microbiol, Chandigarh, India.
[Seyedmousavi, Seyedmojtaba; Mouton, Johan W.] Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands.
[Seyedmousavi, Seyedmojtaba; Meis, Jacques F.; Mouton, Johan W.] Radboudumc, Dept Med Microbiol, Nijmegen, Netherlands.
[Meis, Jacques F.] Canisius Wilhelmina Hosp, Dept Med Microbiol & Infect Dis, Nijmegen, Netherlands.
[Seyedmousavi, Seyedmojtaba] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Rudramurthy, SM (reprint author), Postgrad Inst Med Educ & Res PGIMER, Dept Med Microbiol, Chandigarh, India.
EM mrshivprakash@yahoo.com
FU Indian Council of Medical Research, New Delhi; Astellas Pharma B.V;
Astellas; Basilea; Gilead Sciences; Merck; Pfizer; United Medical
FX This study was supported in part by Indian Council of Medical Research,
New Delhi.; As potential conflicts of interest, S.S has received a
research grant from Astellas Pharma B.V. J.F.M. and J.W.M have served as
consultants to and have received research grants from Astellas, Basilea,
Gilead Sciences, Merck, Pfizer, and United Medical. All other authors
have no conflicts of interest.
NR 34
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2017
VL 61
IS 1
AR e01491-16
DI 10.1128/AAC.01491-16
PG 10
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA EK7HC
UT WOS:000394095800027
ER
PT J
AU Malloy, LC
Orbach, Y
Lamb, ME
Walker, AG
AF Malloy, Lindsay C.
Orbach, Yael
Lamb, Michael E.
Walker, Anne Graffam
TI "How" and "Why" prompts in forensic investigative interviews with
preschool children
SO APPLIED DEVELOPMENTAL SCIENCE
LA English
DT Article
ID WH-QUESTIONS; SEXUAL-ABUSE; YOUNG-CHILDREN; ACQUISITION
AB Although young children may frequently be asked How and Why questions, it is unclear whether they have the ability to respond well enough to justify the use of these words during investigative interviews. The range of possible uses and interpretations of the words How and Why makes it critical to examine their use when communicatively immature children are interviewed. In this study, police interviews of 3- to 5-year-old suspected victims of sexual abuse (n=49) were examined. The use of How/Why prompts by interviewers and children's responses to interviewers' How/Why prompts were coded. How/Why prompts represented 22% of all interviewer prompts. Of all details provided by children, however, 8.5% were in response to How/Why prompts. In addition, children provided the information sought in response to only 20% of the interviewers' How/Why prompts, whereas uninformative responses were relatively common. Children responded to more How/Why prompts with the information sought by interviewers as they grew older. The findings suggest that How/Why prompts may not be particularly effective when interviewing preschool children.
C1 [Malloy, Lindsay C.] Florida Int Univ, Miami, FL 33199 USA.
[Orbach, Yael] NICHHD, Bethesda, MD 20892 USA.
[Lamb, Michael E.] Univ Cambridge, Cambridge, England.
RP Lamb, ME (reprint author), Univ Cambridge, Dept Psychol, Free Sch Lane, Cambridge CB2 3RQ, England.
EM mel37@cam.ac.uk
NR 38
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1088-8691
EI 1532-480X
J9 APPL DEV SCI
JI Appl. Dev. Sci.
PY 2017
VL 21
IS 1
BP 58
EP 66
DI 10.1080/10888691.2016.1158652
PG 9
WC Psychology, Developmental
SC Psychology
GA EL9WL
UT WOS:000394970700005
ER
PT J
AU Kim, JK
Lee, HM
Park, KS
Shin, DM
Kim, TS
Kim, YS
Suh, HW
Kim, SY
Kim, IS
Kim, JM
Son, JW
Sohn, KM
Jung, SS
Chung, C
Han, SB
Yang, CS
Jo, EK
AF Kim, Jin Kyung
Lee, Hye-Mi
Park, Ki-Sun
Shin, Dong-Min
Kim, Tae Sung
Kim, Yi Sak
Suh, Hyun-Woo
Kim, Soo Yeon
Kim, In Soo
Kim, Jin-Man
Son, Ji-Woong
Sohn, Kyung Mok
Jung, Sung Soo
Chung, Chaeuk
Han, Sang-Bae
Yang, Chul-Su
Jo, Eun-Kyeong
TI MIR144* inhibits antimicrobial responses against Mycobacterium
tuberculosis in human monocytes and macrophages by targeting the
autophagy protein DRAM2
SO AUTOPHAGY
LA English
DT Article
DE AMPK; DRAM2; MIR144*; Mycobacterium tuberculosis; tuberculosis
ID PHAGOSOME MATURATION; IMMUNE-RESPONSE; DEFENSE; PATHWAY; MICRORNA;
EXPRESSION; ROLES; MODULATOR; BACTERIA; RUBICON
AB Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages. Mtb infection downregulated, whereas the autophagy activators upregulated, DRAM2 expression in human monocytes and macrophages by activating AMP-activated protein kinase. In addition, overexpression of MIR144* decreased DRAM2 expression and formation of autophagosomes in human monocytes, whereas inhibition of MIR144* had the opposite effect. Moreover, the levels of MIR144* were elevated, whereas DRAM2 levels were reduced, in human peripheral blood cells and tissues in TB patients, indicating the clinical significance of MIR144* and DRAM2 in human TB. Notably, DRAM2 interacted with BECN1 and UVRAG, essential components of the autophagic machinery, leading to displacement of RUBCN from the BECN1 complex and enhancement of Ptdlns3K activity. Furthermore, MIR144* and DRAM2 were critically involved in phagosomal maturation and enhanced antimicrobial effects against Mtb. Our findings identify a previously unrecognized role of human MIR144* in the inhibition of antibacterial autophagy and the innate host immune response to Mtb. Additionally, these data reveal that DRAM2 is a key coordinator of autophagy activation that enhances antimicrobial activity against Mtb.
C1 [Kim, Jin Kyung; Lee, Hye-Mi; Shin, Dong-Min; Kim, Tae Sung; Kim, Yi Sak; Suh, Hyun-Woo; Kim, Soo Yeon; Kim, In Soo; Jo, Eun-Kyeong] Chungnam Natl Univ, Sch Med, Dept Microbiol, Daejeon, South Korea.
[Kim, Jin Kyung; Kim, Tae Sung; Kim, Yi Sak; Suh, Hyun-Woo; Kim, Soo Yeon; Kim, Jin-Man; Jo, Eun-Kyeong] Chungnam Natl Univ, Sch Med, Dept Med Sci, Daejeon, South Korea.
[Park, Ki-Sun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Kim, Jin-Man] Chungnam Natl Univ, Sch Med, Dept Pathol, Daejeon, South Korea.
[Son, Ji-Woong] Konyang Univ, Dept Internal Med, Daejeon, South Korea.
[Sohn, Kyung Mok] Chungnam Natl Univ, Sch Med, Dept Internal Med, Div Infect Dis, Daejeon, South Korea.
[Jung, Sung Soo; Chung, Chaeuk] Chungnam Natl Univ, Sch Med, Dept Internal Med, Div Pulm & Crit Care, Daejeon, South Korea.
[Han, Sang-Bae] Chungbuk Natl Univ, Coll Pharm, Cheongju, South Korea.
[Yang, Chul-Su] Hanyang Univ, Dept Mol & Life Sci, Ansan, South Korea.
RP Yang, CS (reprint author), Chungnam Natl Univ, Sch Med, Dept Microbiol & Med Sci, 6 Munhwa Dong, Daejeon 301747, South Korea.
EM chulsuyang@hanyang.ac.kr
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF) - Ministry of Education [NRF-2013R1A1A2058116]; Korea
Science & Engineering Foundation through the Korea Health Technology R&D
Project through the Korea Health Industry Development Institute (KHIDI);
Ministry of Health & Welfare, Republic of Korea at Chungnam National
University [HI15C0395]; National Research Foundation of Korea (NRF) -
Korea government (MSIP) [2011-0030049]; Chungnam National University
FX This work was supported by Basic Science Research Program through the
National Research Foundation of Korea (NRF) funded by the Ministry of
Education (NRF-2013R1A1A2058116) and Korea Science & Engineering
Foundation through the Korea Health Technology R&D Project through the
Korea Health Industry Development Institute (KHIDI), funded by the
Ministry of Health & Welfare, Republic of Korea (HI15C0395) at Chungnam
National University. This work was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korea government (MSIP)
(No. 2011-0030049). This work was also supported by a research fund
(2015) of Chungnam National University.
NR 66
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PY 2017
VL 13
IS 2
BP 423
EP 441
DI 10.1080/15548627.2016.1241922
PG 19
WC Cell Biology
SC Cell Biology
GA EM2CY
UT WOS:000395125200015
PM 27764573
ER
PT J
AU Fang, EF
Bohr, VA
AF Fang, Evandro F.
Bohr, Vilhelm A.
TI NAD(+): The convergence of DNA repair and mitophagy
SO AUTOPHAGY
LA English
DT Editorial Material
DE ataxia telangiectasia; ATM; autophagy; DNA damage; mitophagy
AB ATM is a 350kDa serine/threonine kinase best known for its role in DNA repair and multiple cellular homeostasis pathways. Mutation in ATM causes the disease ataxia telangiectasia (A-T) with clinical features including ataxia, severe cerebellar atrophy and Purkinje cell loss. In a cross-species study, using primary rat neurons, the roundworm C. elegans, and a mouse model of A-T, we showed that loss of ATM induces mitochondrial dysfunction and compromised mitophagy due to NAD(+) insufficiency. Remarkably, NAD(+) repletion mitigates both the DNA repair defect and mitochondrial dysfunction in ATM-deficient neurons. In C. elegans, NAD(+) repletion can clear accumulated dysfunctional mitochondria through restoration of compromised mitophagy via upregulation of DCT-1. Thus, NAD(+) ties together DNA repair and mitophagy in neuroprotection and intimates immediate translational applications for A-T and related neurodegenerative DNA repair-deficient diseases.
C1 [Fang, Evandro F.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, 215 Bayview Blvd, Baltimore, MD 21224 USA.
RP Fang, EF; Bohr, VA (reprint author), NIA, NIH, 215 Bayview Blvd, Baltimore, MD 21224 USA.
EM Evandro.fang@nih.gov; vbohr@nih.gov
FU Intramural Research Program of the NIH; National Institute on Aging,
including NIA intra-laboratory grant
FX This research was supported by the Intramural Research Program of the
NIH (VAB), National Institute on Aging, including a 2014-2015 NIA
intra-laboratory grant (EFF, VAB).
NR 0
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PY 2017
VL 13
IS 2
BP 442
EP 443
DI 10.1080/15548627.2016.1257467
PG 2
WC Cell Biology
SC Cell Biology
GA EM2CY
UT WOS:000395125200016
PM 27929719
ER
PT J
AU Schliep, KC
Chen, Z
Stanford, JB
Xie, Y
Mumford, SL
Hammoud, AO
Johnstone, EB
Dorais, JK
Varner, MW
Louis, GMB
Peterson, CM
AF Schliep, K. C.
Chen, Z.
Stanford, J. B.
Xie, Y.
Mumford, S. L.
Hammoud, A. O.
Johnstone, E. Boiman
Dorais, J. K.
Varner, M. W.
Louis, G. M. Buck
Peterson, C. M.
TI Endometriosis diagnosis and staging by operating surgeon and expert
review using multiple diagnostic tools: an inter-rater agreement study
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Review
DE Endometriosis; epidemiology; histology; laparoscopy; magnetic resonance
imaging; reliability
ID ESHRE GUIDELINE; PELVIC PAIN; LAPAROSCOPY; RELIABILITY; WOMEN; ACCURACY
AB Objective To determine agreement on endometriosis diagnosis between real-time laparoscopy and subsequent expert review of digital images, operative reports, magnetic resonance imaging (MRI), and histopathology, viewed sequentially.
Design Inter-rater agreement study. Setting Five urban surgical centres.
Population Women, aged 18-44 years, who underwent a laparoscopy regardless of clinical indication. A random sample of 105 women with and 43 women without a postoperative endometriosis diagnosis was obtained from the ENDO study.
Methods Laparoscopies were diagnosed, digitally recorded, and reassessed.
Main outcome measures Inter-observer agreement of endometriosis diagnosis and staging according to the revised American Society for Reproductive Medicine criteria. Prevalence and bias- adjusted kappa values (kappa) were calculated for diagnosis, and weighted kappa values were calculated for staging.
Results Surgeons and expert reviewers had substantial agreement on diagnosis and staging after viewing digital images (n = 148; mean kappa = 0.67, range 0.61-0.69; mean kappa = 0.64, range 0.53-0.78, respectively) and after additionally viewing operative reports n = 148; mean kappa = 0.88, range 0.85-0.89; mean kappa = 0.85, range 0.84-0.86, respectively). Although additionally viewing MRI findings (n = 36) did not greatly impact agreement, agreement substantially decreased after viewing histological findings (n = 67), with expert reviewers changing their assessment from a positive to a negative diagnosis in up to 20% of cases.
Conclusion Although these findings suggest that misclassification bias in the diagnosis or staging of endometriosis via visualised disease is minimal, they should alert gynaecologists who review operative images in order to make decisions on endometriosis treatment that operative reports/drawings and histopathology, but not necessarily MRI, will improve their ability to make sound judgments.
C1 [Schliep, K. C.; Chen, Z.; Xie, Y.; Mumford, S. L.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
[Schliep, K. C.; Stanford, J. B.] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA.
[Hammoud, A. O.; Johnstone, E. Boiman; Dorais, J. K.; Varner, M. W.; Peterson, C. M.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
RP Schliep, KC (reprint author), Univ Utah, Div Publ Hlth, Dept Family & Prevent Med, 375 Chipeta Way,Suite A, Salt Lake City, UT 84108 USA.
EM karen.schliep@utah.edu
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Intramural Research Program, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
[NO1-DK-6-3428, NO1-DK-6-3427, 10001 406-02]
FX Supported by the Intramural Research Program, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health (contracts NO1-DK-6-3428, NO1-DK-6-3427, and 10001
406-02).
NR 25
TC 0
Z9 0
U1 1
U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1470-0328
EI 1471-0528
J9 BJOG-INT J OBSTET GY
JI BJOG
PD JAN
PY 2017
VL 124
IS 2
SI SI
BP 220
EP 229
DI 10.1111/1471-0528.13854
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EO0HI
UT WOS:000396378500009
PM 26435386
ER
PT J
AU Klein, HG
AF Klein, Harvey G.
TI The red cell storage lesion(s): of dogs and men
SO BLOOD TRANSFUSION
LA English
DT Review
DE transfusion; storage lesion; red blood cells; canine model
ID OLDER STORED-BLOOD; EXCHANGE-TRANSFUSION; CANINE PNEUMONIA;
PATHOPHYSIOLOGY; METAANALYSIS; MORTALITY; OUTCOMES; IMPROVE; SAFETY;
UNITS
AB The advent of preservative solutions permitted refrigerated storage of red blood cells. However, the convenience of having red blood cell inventories was accompanied by a disadvantage. Red cells undergo numerous physical and metabolic changes during cold storage, the "storage lesion(s)". Whereas controlled clinical trials have not confirmed the clinical importance of such changes, ethical and operational issues have prevented careful study of the oldest stored red blood cells. Suggestions of toxicity from meta-analyses motivated us to develop pre-clinical canine models to compare the freshest vs the oldest red blood cells. Our model of canine pneumonia with red blood cell transfusion indicated that the oldest red blood cells increased mortality, that the severity of pneumonia is important, but that the dose of transfused red blood cells is not. Washing the oldest red blood cells reduces mortality by removing senescent cells and remnants, whereas washing fresher cells increases mortality by damaging the red blood cell membrane. An opposite effect was found in a model of haemorrhagic shock with reperfusion injury. Physiological studies indicate that release of iron from old cells is a primary mechanism of toxicity during infection, whereas scavenging of cell-free haemoglobin may be beneficial during reperfusion injury. Intravenous iron appears to have toxicity equivalent to old red blood cells in the pneumonia model, suggesting that intravenous iron and old red blood cells should be administered with caution to infected patients.
C1 [Klein, Harvey G.] NIH, Dept Transfus Med, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Klein, HG (reprint author), NIH, Dept Transfus Med, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hklein@cc.nih.gov
FU National Institutes of Health
FX These studies were performed in collaboration with Drs. Charles
Natanson, Steven Solomon, Irene CortesPuch, Dong Wang, Kenneth Remy, and
Jungfen Sun. The studies were supported by intramural research funding,
the Intramural Research Program, and the National Institutes of Health.
NR 19
TC 0
Z9 0
U1 0
U2 0
PU SIMTI SERVIZI SRL
PI MILAN
PA VIA DESIDERIO 21, MILAN, 20131, ITALY
SN 1723-2007
J9 BLOOD TRANSFUS-ITALY
JI Blood Transf.
PY 2017
VL 15
IS 2
BP 107
EP 111
DI 10.2450/2017.0306-16
PG 5
WC Hematology
SC Hematology
GA EM7QP
UT WOS:000395507700003
PM 28263166
ER
PT J
AU Harburg, L
McCormack, E
Kenney, K
Moore, C
Yang, K
Vos, P
Jacobs, B
Madden, CJ
Diaz-Arrastia, R
Bogoslovsky, T
AF Harburg, Leah
McCormack, Erin
Kenney, Kimbra
Moore, Carol
Yang, Kelly
Vos, Pieter
Jacobs, Bram
Madden, Christopher J.
Diaz-Arrastia, Ramon
Bogoslovsky, Tanya
TI Reliability of the NINDS common data elements cranial tomography (CT)
rating variables for traumatic brain injury (TBI)
SO BRAIN INJURY
LA English
DT Article
DE Traumatic brain injury; common data elements; cranial tomography; CT
scanning; head trauma
ID SEVERE HEAD-INJURY; PROGRESSION; HEMORRHAGE; PREDICTION; CONTUSION;
CLASSIFICATION; VALIDATION; EDEMA; TRIAL; SCAN
AB Background: Non-contrast head computer tomography (CT) is widely used to evaluate eligibility of patients after acute traumatic brain injury (TBI) for clinical trials. The NINDS Common Data Elements (CDEs) TBI were developed to standardize collection of CT variables. The objectives of this study were to train research assistants (RAs) to rate CDEs and then to evaluate their performance. The aim was to assess inter-rater reliability (IRR) of CDEs between trained RAs and a neurologist and to evaluate applicability of CDEs in acute and sub-acute TBI to test the feasibility of using CDE CT ratings in future trials and ultimately in clinical practice. The second aim was to confirm that the ratings of CDEs reflect pathophysiological events after TBI.Methods and results: First, a manual was developed for application of the CDEs, which was used to rate brain CTs (n = 100). An excellent agreement was found in combined kappas between RAs on admission and on 24-hour follow-up CTs (Iota = 0.803 and 0.787, respectively). Good IRR (kappa > 0.61) was shown for six CDEs on admissions and for seven CDEs on follow-up CTs. Low IRR (kappa < 0.4) was determined for five CDEs on admission and for four CDEs on follow-up CT. Combined IRR of each assistant with the neurologist were good on admission (Iota = 0.613 and 0.787) and excellent on follow-up CT (Iota = 0.906 and 0.977). Second, Principal Component Analysis (PCA) was applied to cluster the rated CDEs (n = 255) and five major components were found that explain 53% of the variance.Conclusions: CT CDEs are useful in clinical studies of TBI. Trained RAs can reliably collect variables. PCA identifies CDE clusters with clinical and biologic plausibility.Abbreviations: RA, research assistant; CT, Cranial Tomography; TBI, Traumatic Brain Injury; CDE, Common Data Elements; IRR, inter-rater reliability; PCA, Principal Component Analysis; GCS, Glasgow Coma Scale; R, rater; CI, confidence interval; CCC, Concordance correlation coefficient; IVH, Intraventricular haemorrhage; DCA, Discriminant Component analysis; SAH, Subarachnoid Haemorrhage
C1 [Harburg, Leah; McCormack, Erin; Kenney, Kimbra; Moore, Carol; Diaz-Arrastia, Ramon; Bogoslovsky, Tanya] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA.
[Yang, Kelly] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Vos, Pieter] Slingeland Hosp, Dept Neurol, Doetinchem, Netherlands.
[Jacobs, Bram] Univ Med Ctr Groningen, Groningen, Netherlands.
[Madden, Christopher J.] Univ Texas Southwestern Med Ctr Dallas, Dept Neurol Surg, Dallas, TX 75390 USA.
RP Bogoslovsky, T (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM tanya.bogoslovsky.ctr@usuhs.edu
NR 39
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Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0269-9052
EI 1362-301X
J9 BRAIN INJURY
JI Brain Inj.
PY 2017
VL 31
IS 2
BP 174
EP 184
DI 10.1080/02699052.2016.1225989
PG 11
WC Neurosciences; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA EM2RO
UT WOS:000395163500004
PM 27936952
ER
PT J
AU Yang, JD
Altekruse, SF
Nguyen, MH
Gores, GJ
Roberts, LR
AF Yang, Ju Dong
Altekruse, Sean F.
Nguyen, Mindie H.
Gores, Gregory J.
Roberts, Lewis R.
TI Impact of Country of Birth on Age at the Time of Diagnosis of
Hepatocellular Carcinoma in the United States
SO CANCER
LA English
DT Article
DE Africa; age; early onset; liver cancer; Oceania
ID HEPATITIS-B-VIRUS; LIVER-CANCER; C-VIRUS; ASSOCIATION; AFLATOXIN;
MORTALITY; PATTERNS; AFRICA; RISK
AB BACKGROUND: There is global variation in the onset of hepatocellular carcinoma (HCC). The objective of the current study was to investigate the impact of country of birth on age at the time of HCC diagnosis in the United States. METHODS: Incident HCC cases diagnosed between 2000 and 2012 in the Surveillance, Epidemiology, and End Results program 18 registry were included. Factors associated with very early onset (age at diagnosis< 40 years) and early onset (age at diagnosis< 50 years) were identified by logistic regression. RESULTS: A total of 59,907 patients were included. The median age at the time of diagnosis of HCC was 62 years and 76% of the patients were male. Of the 75% of patients for whom information regarding birth country was available, 29% were foreign born. In multivariate logistic regression, birth in West Africa (adjusted odds ratio [AOR], 16.3; 95% confidence interval [95% CI], 9.2-27.9 [P<. 01]), Central/South/other Africa (AOR, 11.0; 95% CI, 4.5-23.7 [P<. 01]), Oceania (AOR, 4.9; 95% CI, 2.9-8.0 [P<. 01]), and East Africa (AOR, 3.5; 95% CI, 1.5-6.8 [P<. 01]) was found to have the strongest association with very early-onset HCC after adjusting for sex and race/ethnicity. Birth in West Africa, Central/South/other Africa, Oceania, or East Africa also was found to be strongly associated with early-onset HCC. CONCLUSIONS: Birth country was found to be independently associated with age at the time of HCC diagnosis in the United States. Birth in Africa (except for North Africa) and Oceania was strongly associated with very early-onset HCC. These findings have implications for the design of comprehensive HCC surveillance programs in the United States. (C) 2016 American Cancer Society.
C1 [Yang, Ju Dong; Gores, Gregory J.; Roberts, Lewis R.] Mayo Clin, Coll Med, Div Gastroenterol & Hepatol, 200 First St SW, Rochester, MN 55905 USA.
[Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Nguyen, Mindie H.] Stanford Univ, Stanford Canc Inst, Div Gastroenterol & Hepatol, Palo Alto, CA 94304 USA.
[Nguyen, Mindie H.] Stanford Univ, Med Ctr, Ctr Innovat Global Hlth, Palo Alto, CA 94304 USA.
RP Roberts, LR (reprint author), Mayo Clin, Coll Med, Div Gastroenterol & Hepatol, 200 First St SW, Rochester, MN 55905 USA.
EM Roberts.lewis@mayo.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [T32
DK07198]; National Cancer Institute [CA165076]
FX Supported by grant T32 DK07198 from the National Institute of Diabetes
and Digestive and Kidney Diseases (to Ju Dong Yang) and grant CA165076
from the National Cancer Institute (to Lewis R. Roberts). The contents
of this article are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health.
NR 24
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JAN 1
PY 2017
VL 123
IS 1
BP 81
EP 89
DI 10.1002/cncr.30246
PG 9
WC Oncology
SC Oncology
GA EL6GT
UT WOS:000394719100011
PM 27571320
ER
PT J
AU Brooks, PJ
Schuebel, K
AF Brooks, P. J.
Schuebel, Kornel
TI Timeless insights into prevention of acetaldehyde genotoxicity?
SO CELL CYCLE
LA English
DT Editorial Material
DE cancer; crosslinks; DNA; protein; DNA repair; Fanconi anemia
C1 [Brooks, P. J.; Schuebel, Kornel] Natl Inst Hlth, Natl Inst Alcohol Abuse & Alcoholism, Neurogenet Lab, Rockville, MD USA.
RP Brooks, PJ (reprint author), Natl Inst Hlth, Natl Ctr Adv Translat Sci NCATS, Div Clin Innovat, 6701 Democracy Blvd,Rm 924, Bethesda, MD 20892 USA.
EM pjbrooks@mail.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PY 2017
VL 16
IS 4
BP 308
EP 309
DI 10.1080/15384101.2016.1247570
PG 2
WC Cell Biology
SC Cell Biology
GA EL4WK
UT WOS:000394621400006
PM 27764578
ER
PT J
AU Mayer-Barber, KD
Yan, B
AF Mayer-Barber, Katrin D.
Yan, Bo
TI Clash of the Cytokine Titans: counter-regulation of interleukin-1 and
type I interferon-mediated inflammatory responses
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Review
DE cytokines; infection; inflammation; interleukin-1; tuberculosis; type-1
interferons
ID TUMOR-NECROSIS-FACTOR; MYCOBACTERIUM-TUBERCULOSIS INFECTION;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHORIOMENINGITIS VIRUS-INFECTION;
PATTERN-RECOGNITION RECEPTORS; ENTERICA SEROVAR TYPHIMURIUM;
HUMAN-IMMUNODEFICIENCY-VIRUS; TRYPANOSOMA-CRUZI INFECTION; PERSISTENT
LCMV INFECTION; INNATE IMMUNE-RESPONSE
AB Over the past decades the notion of 'inflammation' has been extended beyond the original hallmarks of rubor (redness), calor (heat), tumor (swelling) and dolor (pain) described by Celsus. We have gained a more detailed understanding of the cellular players and molecular mediators of inflammation which is now being applied and extended to areas of biomedical research such as cancer, obesity, heart disease, metabolism, auto-inflammatory disorders, autoimmunity and infectious diseases. Innate cytokines are often central components of inflammatory responses. Here, we discuss how the type I interferon and interleukin-1 cytokine pathways represent distinct and specialized categories of inflammatory responses and how these key mediators of inflammation counter-regulate each other.
C1 [Mayer-Barber, Katrin D.; Yan, Bo] NIAID, Inflammat & Innate Immun Unit, Lab Clin Infect Dis, NIH, Bldg 4,Room 407, Bethesda, MD 20892 USA.
RP Mayer-Barber, KD (reprint author), NIAID, Inflammat & Innate Immun Unit, Lab Clin Infect Dis, NIH, Bldg 4,Room 407, Bethesda, MD 20892 USA.
EM mayerk@niaid.nih.gov
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases
FX We thank Drs. Mahtab Moayeri, Dan Barber and Alan Sher for comments and
critical reading of the article. This work was supported by the
Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases.
NR 236
TC 3
Z9 3
U1 2
U2 2
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
EI 2042-0226
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD JAN
PY 2017
VL 14
IS 1
BP 22
EP 35
DI 10.1038/cmi.2016.25
PG 14
WC Immunology
SC Immunology
GA EL0ZN
UT WOS:000394350400004
PM 27264686
ER
PT J
AU Sher, A
Tosh, K
Jankovic, D
AF Sher, Alan
Tosh, Kevin
Jankovic, Dragana
TI Innate recognition of Toxoplasma gondii in humans involves a mechanism
distinct from that utilized by rodents
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Review
DE human; innate immunity; mouse; phagocytosis; Toxoplasma gondii
ID TOLL-LIKE RECEPTORS; CELL PLASMA-MEMBRANE; DENDRITIC CELLS; OCULAR
TOXOPLASMOSIS; INTERFERON-GAMMA; IFN-GAMMA; CLINICAL CHARACTERISTICS;
INFLAMMATORY MONOCYTES; CYTOKINE PRODUCTION; ACUTE INFECTION
AB Toxoplasma gondii is an intracellular protozoan parasite that infects rodents as part of its natural transmission cycle and induces disease in humans, an end-stage host. As one of the natural hosts of T. gondii, the mouse has been used extensively for elucidating the cellular and molecular basis of immunity to this pathogen while relatively few studies have focused on the response of humans. In our recent work, we identified CD16(+) monocytes and DC1 dendritic cells as the major myeloid cell populations that respond to T. gondii in human peripheral blood. Interestingly, these myeloid subsets represent the opposite counterparts from those triggered by the parasite in mice. Moreover, whereas the innate cytokine response to T. gondii in the mouse involves stimulation of Toll-like receptors by a soluble parasite ligand, the response of human cells instead requires phagocytosis of the live pathogen. We speculate that these marked distinctions in the pathways utilized for innate recognition of toxoplasma in mouse and man reflect the differing roles of the two hosts in the biology of this parasite.
C1 [Sher, Alan; Tosh, Kevin; Jankovic, Dragana] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Sher, A; Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 50,Room 6140, Bethesda, MD 20882 USA.
EM asher@niaid.nih.gov; djankovic@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, NIH
FX We thank Drs Ricardo Gazzinelli, Lis Antonelli, Carl Feng, Jonathan
Howard, Steve Singer and Tom Nutman for helpful discussions. This work
was supported by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, NIH.
NR 48
TC 1
Z9 1
U1 2
U2 2
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
EI 2042-0226
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD JAN
PY 2017
VL 14
IS 1
BP 36
EP 42
DI 10.1038/cmi.2016.12
PG 7
WC Immunology
SC Immunology
GA EL0ZN
UT WOS:000394350400005
PM 27157497
ER
PT J
AU Li, H
Zhang, DL
Gao, MN
Huang, LM
Tang, LG
Li, ZJ
Chen, XY
Zhang, XZ
AF Li, Hua
Zhang, Deliang
Gao, Mengna
Huang, Lumei
Tang, Longguang
Li, Zijing
Chen, Xiaoyuan
Zhang, Xianzhong
TI Highly specific C-C bond cleavage induced FRET fluorescence for in vivo
biological nitric oxide imaging
SO CHEMICAL SCIENCE
LA English
DT Article
ID REACTIVE OXYGEN; LIVING CELLS; NITROSATIVE STRESS; RATIONAL DESIGN;
PROBE; CHEMILUMINESCENCE; CHROMOPHORE; INDICATORS; AGENT; MRI
AB A novel Forster resonance energy transfer (FRET) fluorescence "off-on" system based on the highly specific, sensitive and effective C-C bond cleavage of certain dihydropyridine derivatives was reported for real-time quantitative imaging of nitric oxide (NO). 1,4-Dihydropyridine was synthesized as a novel linker which could connect customized fluorophores and their corresponding quenchers. The specific and quantitative response to NO is confirmed using fluorescence spectrometry with the classical example of fluorescein isothiocyanate (FITC) and[4'-(N,N'-dimethylamino) phenylazo] benzoyl (DABCYL). The fluorescence intensity increased linearly with the increase in the amount of NO. Cells incubated with an exogenous NO donor emitted fluorescence as expected. A high fluorescence intensity was detected in macrophages which generate NO when incubated with lipopolysaccharide (LPS). The in vivo imaging shows about an 8-fold contrast between Freund's adjuvant stimulated feet and normal feet in mice after intravenous injection, which was the first example of in vivo semiquantitative fluorescence imaging of NO in mammals.
C1 [Li, Hua; Zhang, Deliang; Gao, Mengna; Huang, Lumei; Tang, Longguang; Li, Zijing; Zhang, Xianzhong] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Ctr Mol Imaging & Translat Med, Xiamen 361102, Fujian, Peoples R China.
[Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Li, ZJ; Zhang, XZ (reprint author), Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Ctr Mol Imaging & Translat Med, Xiamen 361102, Fujian, Peoples R China.
EM zijing.li@xmu.edu.cn; zhangxzh@xmu.edu.cn
RI Zhang, Xianzhong/A-7754-2012
OI Zhang, Xianzhong/0000-0002-1001-1884
FU National Key Basic Research Program of China [2014CB744503]; National
Natural Science Foundation of China [81501534, 21271030, 81471707];
Fundamental Research Funds for the Central Universities [20720150063];
Science Foundation of Fujian Province [2014Y2004]
FX This study was financially supported by the National Key Basic Research
Program of China (2014CB744503), National Natural Science Foundation of
China (81501534, 21271030, 81471707) and partially by the Fundamental
Research Funds for the Central Universities (20720150063) and the
Science Foundation of Fujian Province (2014Y2004).
NR 40
TC 0
Z9 0
U1 2
U2 2
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2041-6520
EI 2041-6539
J9 CHEM SCI
JI Chem. Sci.
PY 2017
VL 8
IS 3
BP 2199
EP 2203
DI 10.1039/c6sc04071c
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA EN3KH
UT WOS:000395906900065
ER
PT J
AU Simpson, EA
Jakobsen, KV
Damon, F
Suomi, SJ
Ferrari, PF
Paukner, A
AF Simpson, Elizabeth A.
Jakobsen, Krisztina V.
Damon, Fabrice
Suomi, Stephen J.
Ferrari, Pier F.
Paukner, Annika
TI Face Detection and the Development of Own-Species Bias in Infant
Macaques
SO CHILD DEVELOPMENT
LA English
DT Article
ID COGNITIVE-DEVELOPMENT; NONHUMAN-PRIMATES; SOCIAL ATTENTION;
EYE-MOVEMENTS; VISUAL-SEARCH; POP-OUT; PERCEPTION; BIRTH; NEWBORN;
AUTISM
AB In visually complex environments, numerous items compete for attention. Infants may exhibit attentional efficiency-privileged detection, attention capture, and holding-for face-like stimuli. However, it remains unknown when these biases develop and what role, if any, experience plays in this emerging skill. Here, nursery-reared infant macaques' (Macaca mulatta; n = 10) attention to faces in 10-item arrays of nonfaces was measured using eye tracking. With limited face experience, 3-week-old monkeys were more likely to detect faces and looked longer at faces compared to nonfaces, suggesting a robust face detection system. By 3 months, after peer exposure, infants looked faster to conspecific faces but not heterospecific faces, suggesting an own-species bias in face attention capture, consistent with perceptual attunement.
C1 [Simpson, Elizabeth A.] Univ Miami, Coral Gables, FL 33124 USA.
[Jakobsen, Krisztina V.] James Madison Univ, Harrisonburg, VA 22807 USA.
[Damon, Fabrice] Univ Grenoble Alpes, Grenoble, France.
[Suomi, Stephen J.; Paukner, Annika] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Ferrari, Pier F.] Univ Parma, Parma, Italy.
RP Simpson, EA (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon, Coral Gables, FL 33124 USA.
EM simpsone@miami.edu
OI Simpson, Elizabeth/0000-0003-2715-2533
FU Division of Intramural Research, NICHD; Alvin V., Jr. and Nancy C. Baird
Professorship; NICHD [P01HD064653]
FX We thank Scott P. Johnson for constructive feedback on an earlier draft.
Supported by the Division of Intramural Research, NICHD, the Alvin V.,
Jr. and Nancy C. Baird Professorship (KVJ), and NICHD P01HD064653 (PFF).
Elizabeth A. Simpson, Krisztina V. Jakobsen, and Annika Paukner
developed the study concept and design. Elizabeth A. Simpson, Fabrice
Damon, and Annika Paukner collected the data. Elizabeth A. Simpson
analyzed and interpreted the data and drafted the manuscript. All
authors provided critical revisions and approved the final version of
the manuscript for submission.
NR 79
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-3920
EI 1467-8624
J9 CHILD DEV
JI Child Dev.
PD JAN-FEB
PY 2017
VL 88
IS 1
BP 103
EP 113
DI 10.1111/cdev.12565
PG 11
WC Psychology, Educational; Psychology, Developmental
SC Psychology
GA EN4WF
UT WOS:000396006900008
PM 27223687
ER
PT J
AU White, LK
Degnan, KA
Henderson, HA
Perez-Edgar, K
Walker, OL
Shechner, T
Leibenluft, E
Bar-Haim, Y
Pine, DS
Fox, NA
AF White, Lauren K.
Degnan, Kathryn A.
Henderson, Heather A.
Perez-Edgar, Koraly
Walker, Olga L.
Shechner, Tomer
Leibenluft, Ellen
Bar-Haim, Yair
Pine, Daniel S.
Fox, Nathan A.
TI Developmental Relations Among Behavioral Inhibition, Anxiety, and
Attention Biases to Threat and Positive Information
SO CHILD DEVELOPMENT
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PROCESSING BIASES; PEDIATRIC ANXIETY;
SOCIAL PHOBIA; SELECTIVE ATTENTION; CHILDREN; CHILDHOOD; TEMPERAMENT;
DISORDER; WITHDRAWAL
AB This study examined relations between behavioral inhibition (BI) assessed in toddlerhood (n = 268) and attention biases (AB) to threat and positive faces and maternal-reported anxiety assessed when children were 5- and 7-year-old. Results revealed that BI predicted anxiety at age 7 in children with AB toward threat, away from positive, or with no bias, at age 7; BI did not predict anxiety for children displaying AB away from threat or toward positive. Five-year AB did not moderate the link between BI and 7-year anxiety. No direct association between AB and BI or anxiety was detected; moreover, children did not show stable AB across development. These findings extend our understanding of the developmental links among BI, AB, and anxiety.
C1 [White, Lauren K.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Degnan, Kathryn A.] Catholic Univ, Washington, DC USA.
[Henderson, Heather A.] Univ Waterloo, Waterloo, ON, Canada.
[Perez-Edgar, Koraly] Penn State Univ, University Pk, PA 16802 USA.
[Walker, Olga L.; Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA.
[Shechner, Tomer] Univ Haifa, Haifa, Israel.
[Leibenluft, Ellen; Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA.
[Bar-Haim, Yair] Tel Aviv Univ, Tel Aviv, Israel.
RP White, LK (reprint author), Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, 3440 Market St,Suite 410, Philadelphia, PA 19104 USA.
EM whitelk@email.chop.edu
FU National Institutes of Health [MH074454, HD17899]
FX This research was supported by grants from the National Institutes of
Health (MH074454 and HD17899) to Nathan A. Fox. We would like to thank
all the children and parents for their participation in this study. We
would also like to acknowledge all the research assistants for their
contributions.
NR 63
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-3920
EI 1467-8624
J9 CHILD DEV
JI Child Dev.
PD JAN-FEB
PY 2017
VL 88
IS 1
BP 141
EP 155
DI 10.1111/cdev.12696
PG 15
WC Psychology, Educational; Psychology, Developmental
SC Psychology
GA EN4WF
UT WOS:000396006900012
PM 28042902
ER
PT J
AU Schneider, ML
Moore, CF
Adkins, M
Barr, CS
Larson, JA
Resch, LM
Roberts, A
AF Schneider, Mary L.
Moore, Colleen F.
Adkins, Miriam
Barr, Christina S.
Larson, Julie A.
Resch, Leslie M.
Roberts, Andrew
TI Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal
Treatment, and Genetic Influences
SO CHILD DEVELOPMENT
LA English
DT Article
ID LINKED POLYMORPHIC REGION; OVER-RESPONSIVITY; ALCOHOL EXPOSURE;
MACACA-MULATTA; FETAL ALCOHOL; TACTILE DEFENSIVENESS; EARLY EXPERIENCE;
YOUNG-CHILDREN; 5-HTT GENE; STRESS
AB Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D-2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D-2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood.
C1 [Schneider, Mary L.; Adkins, Miriam; Larson, Julie A.; Resch, Leslie M.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA.
[Schneider, Mary L.; Larson, Julie A.; Resch, Leslie M.] Univ Wisconsin, Harlow Ctr Biol Psychol, Madison, WI 53706 USA.
[Schneider, Mary L.; Moore, Colleen F.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA.
[Moore, Colleen F.] Montana State Univ, Dept Psychol, Bozeman, MT 59717 USA.
[Barr, Christina S.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Roberts, Andrew] Minnesota State Univ Mankato, Mankato, MN USA.
RP Schneider, ML (reprint author), Dept Kinesiol, Psychol 22 North Charter St, Madison, WI 53715 USA.; Schneider, ML (reprint author), Harlow Ctr Biol, Psychol 22 North Charter St, Madison, WI 53715 USA.
EM schneider@education.wisc.edu
FU National Institute of Alcohol Abuse and Alcoholism [R01 AA12277];
Wallace Research Foundation
FX This study was supported by the National Institute of Alcohol Abuse and
Alcoholism (R01 AA12277) and the Wallace Research Foundation.
NR 63
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-3920
EI 1467-8624
J9 CHILD DEV
JI Child Dev.
PD JAN-FEB
PY 2017
VL 88
IS 1
BP 183
EP 197
DI 10.1111/cdev.12572
PG 15
WC Psychology, Educational; Psychology, Developmental
SC Psychology
GA EN4WF
UT WOS:000396006900015
PM 27338151
ER
PT J
AU Jensen, K
dela Pena-Ponce, MG
Piatak, M
Shoemaker, R
Oswald, K
Jacobs, WR
Fennelly, G
Lucero, C
Mollan, KR
Hudgens, MG
Amedee, A
Kozlowski, PA
Estes, JD
Lifson, JD
Van Rompay, KKA
Larsen, M
De Paris, K
AF Jensen, Kara
dela Pena-Ponce, Myra Grace
Piatak, Michael, Jr.
Shoemaker, Rebecca
Oswald, Kelli
Jacobs, William R., Jr.
Fennelly, Glenn
Lucero, Carissa
Mollan, Katie R.
Hudgens, Michael G.
Amedee, Angela
Kozlowski, Pamela A.
Estes, Jacob D.
Lifson, Jeffrey D.
Van Rompay, Koen K. A.
Larsen, Michelle
De Paris, Kristina
TI Balancing Trained Immunity with Persistent Immune Activation and the
Risk of Simian Immunodeficiency Virus Infection in Infant Macaques
Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium
bovis BCG Vaccine
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
DE pediatric HIV/SIV; vaccine; immune activation; myeloid cells
ID BACILLUS-CALMETTE-GUERIN; CLASS-I ALLELES; T-LYMPHOCYTE RESPONSES;
INDIAN RHESUS MACAQUE; RECOMBINANT BCG; CELL RESPONSES; PULMONARY
TUBERCULOSIS; NONSPECIFIC PROTECTION; GENETIC POLYMORPHISMS; SIVMAC239
REPLICATION
AB Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4(+) T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants.
C1 [Jensen, Kara; dela Pena-Ponce, Myra Grace; De Paris, Kristina] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
[Jensen, Kara; dela Pena-Ponce, Myra Grace; De Paris, Kristina] Univ N Carolina, Ctr AIDS Res, Sch Med, Chapel Hill, NC USA.
[Piatak, Michael, Jr.; Shoemaker, Rebecca; Oswald, Kelli; Lucero, Carissa; Estes, Jacob D.; Lifson, Jeffrey D.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Jacobs, William R., Jr.; Larsen, Michelle] Albert Einstein Coll Med, New York, NY USA.
[Fennelly, Glenn] Rutgers New Jersey Med Sch, Newark, NJ USA.
[Mollan, Katie R.] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC USA.
[Mollan, Katie R.; Hudgens, Michael G.] Univ N Carolina, Ctr AIDS Res, Chapel Hill, NC USA.
[Hudgens, Michael G.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Amedee, Angela; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA.
[Van Rompay, Koen K. A.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
RP De Paris, K (reprint author), Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
EM abelk@med.unc.edu
FU NIH [1R01 DE019064, T32 AI007419, T32 AI007001-36, 5R24RR016038];
Louisiana Vaccine Center - Louisiana Board of Regents; National Cancer
Institute, NIH [HHSN261200800001E]; National Center for Research
Resources (NCRR); Office of Research Infrastructure Programs/OD [P51
OD011107]; Center for AIDS Research (NIH) [2 P30 AI050410]; UNC Flow
Cytometry Core - Department of Microbiology and Immunology; NCI Center
Core Support [P30 CA06086]
FX These studies were supported by NIH grants 1R01 DE019064 (to K.D.P.,
M.L., and G.F.), T32 AI007419 (Training in Virology), and T32
AI007001-36 (Training in Sexually Transmitted Diseases and AIDS) (to
K.J.), by the Louisiana Vaccine Center funded by the Louisiana Board of
Regents (P.A.K.), and in part with federal funds from the National
Cancer Institute, NIH, under contract HHSN261200800001E. The animal
studies at the CNPRC were supported by NIH grants RR00169 from the
National Center for Research Resources (NCRR; NIH) and the Office of
Research Infrastructure Programs/OD P51 OD011107.Studies at UNC Chapel
Hill were supported by the Center for AIDS Research (NIH grant 2 P30
AI050410), by the UNC Flow Cytometry Core that receives support from the
Department of Microbiology and Immunology and the NCI Center Core
Support Grant P30 CA06086 to the UNC Chapel Hill Lineberger Cancer
Center. The MHC Genotyping Service is supported by NIH grant
5R24RR016038 awarded to David Watkins at the University of Miami Miller
School of Medicine.
NR 97
TC 1
Z9 1
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
EI 1556-679X
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD JAN
PY 2017
VL 24
IS 1
AR UNSP e00360-16
DI 10.1128/CVI.00360-16
PG 27
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EK9DH
UT WOS:000394223700005
ER
PT J
AU de Boer, YS
Kosinski, AS
Urban, TJ
Zhao, Z
Long, NY
Chalasani, N
Kleiner, DE
Hoofnagle, JH
AF de Boer, Ynto S.
Kosinski, Andrzej S.
Urban, Thomas J.
Zhao, Zhen
Long, Nanye
Chalasani, Naga
Kleiner, David E.
Hoofnagle, Jay H.
CA Drug-Induced Liver Injury Network
TI Features of Autoimmune Hepatitis in Patients With Drug-induced Liver
Injury
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Database Analysis; Toxicity; Hepatotoxicity; Immune Response;
Immunoglobulin
ID CAUSALITY ASSESSMENT; NETWORK DILIN; OUTCOMES; FAILURE; HEPATOTOXICITY;
MINOCYCLINE; METHYLDOPA; DIAGNOSIS; TYPE-1; COHORT
AB BACKGROUND & AIMS: Drug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine.
METHODS: We analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH- associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls).
RESULTS: Of the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score >= 2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P <.001) and in autoimmune scores (P <.001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03: 01 (15%) and HLA-DRB1*04: 01 (9%) as controls (12% and 9%, respectively).
CONCLUSIONS: In analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH.
C1 [de Boer, Ynto S.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[de Boer, Ynto S.] Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol & Hepatol, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
[Kosinski, Andrzej S.] Duke Clin Res Inst, Durham, NC USA.
[Urban, Thomas J.; Long, Nanye] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
[Zhao, Zhen] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Chalasani, Naga] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP de Boer, YS (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol & Hepatol, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.; Hoofnagle, JH (reprint author), NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, 6707 Democracy Blvd, Bethesda, MD 20852 USA.
EM y.deboer@vumc.nl; hoofnaglej@extra.niddk.nih.gov
OI de Boer, Ynto/0000-0002-4066-7593
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institutes of Health (NIH) [U01DK065211, U01DK065184,
U01DK065201, U01DK083020, U01DK083027, U01DK100928, U01DK065176];
Intramural Division of the National Cancer Institute (NCI), NIH;
Foundation for the National Institutes of Health
FX The Drug Induced Liver Injury Network (DILIN) is structured as a U01
cooperative agreement supported by the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) and the National Institutes of
Health (NIH) with funds provided by the following grants: U01DK065211
(Indiana University [Purdue]), U01DK065184 (University of Michigan [Ann
Arbor]), U01DK065201 (University of North Carolina [Chapel Hill],
Asheville, Wake Forest Baptist Medical Center), U01DK083020 (University
of Southern California, University of California-Los Angeles [Pfleger
Liver Institute]), U01DK083027 (Albert Einstein Medical Center),
U01DK100928 (Icahn School of Medicine at Mount Sinai), and U01DK065176
(Duke Clinical Research Institute). Additional support was provided by
the Intramural Division of the National Cancer Institute (NCI), NIH.
Partial salary support (Y.D.B.) and funding for reagents for
autoantibody testing were provided by the Foundation for the National
Institutes of Health. A complete listing of participants in DILIN is
provided in the Supplementary Material.
NR 33
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JAN
PY 2017
VL 15
IS 1
BP 103
EP +
DI 10.1016/j.cgh.2016.05.043
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EO1XW
UT WOS:000396492200025
PM 27311619
ER
PT J
AU Yang, JD
Abdelmalek, MF
Guy, CD
Gill, RM
Lavine, JE
Yates, K
Klair, J
Terrault, NA
Clark, JM
Unalp-Arida, A
Diehl, AM
Suzuki, A
AF Yang, Ju Dong
Abdelmalek, Manal F.
Guy, Cynthia D.
Gill, Ryan M.
Lavine, Joel E.
Yates, Katherine
Klair, Jagpal
Terrault, Norah A.
Clark, Jeanne M.
Unalp-Arida, Aynur
Diehl, Anna Mae
Suzuki, Ayako
CA Nonalcoholic Steatohepatitis Clini
TI Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate
With Histologic Severity of Nonalcoholic Steatohepatitis
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Gender Differences; Fibrosis; Risk Factor Analysis.
ID FATTY LIVER-DISEASE; HEPATIC-FIBROSIS; INJURY; PREVALENCE; MENOPAUSE;
PATHWAY
AB BACKGROUND & AIMS: Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation.
METHODS: We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress.
RESULTS: Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P < .01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P < .05).
CONCLUSIONS: Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.
C1 [Yang, Ju Dong] Mayo Clin, Coll Med, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Abdelmalek, Manal F.; Diehl, Anna Mae; Suzuki, Ayako] Duke Univ, Gastroenterol & Hepatol, Durham, NC USA.
[Guy, Cynthia D.] Duke Univ, Dept Pathol, Durham, NC 27706 USA.
[Gill, Ryan M.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Lavine, Joel E.] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
[Yates, Katherine] Johns Hopkins Bloomberg Sch Publ Hlth, Nonalcohol Steatohepatitis Clin Res Network, Data Coordinating Ctr, Baltimore, MD USA.
[Klair, Jagpal] Univ Iowa Hosp & Clin, Div Gastroenterol & Hepatol, Iowa City, IA 52242 USA.
[Terrault, Norah A.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
[Clark, Jeanne M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Clark, Jeanne M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Unalp-Arida, Aynur] NIDDK, Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
[Suzuki, Ayako] Cent Arkansas Vet Healthcare Syst, Gastroenterol, Little Rock, AR USA.
[Suzuki, Ayako] Univ Arkansas Med Sci, Gastroenterol & Hepatol, Little Rock, AR 72205 USA.
RP Suzuki, A (reprint author), Cent Arkansas Vet Healthcare Syst, Div Gastroenterol, 111 HLR, Little Rock, AR 72205 USA.
EM ayako.suzuki@va.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734,
U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Center for
Advancing Translational Sciences (NCATS) [UL1TR000439, UL1TR000077,
UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448,
UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058,
UL1TR000454]; Intramural Research Program of the NIH, National Cancer
Institute.
FX The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731,
U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and
U01DK061713). Additional support is received from the National Center
for Advancing Translational Sciences (NCATS) (grants UL1TR000439,
UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006,
UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423,
UL1TR000058, and UL1TR000454). This research was supported in part by
the Intramural Research Program of the NIH, National Cancer Institute.
NR 15
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U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JAN
PY 2017
VL 15
IS 1
BP 127
EP +
DI 10.1016/j.cgh.2016.07.034
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EO1XW
UT WOS:000396492200028
PM 27523635
ER
PT J
AU Pollett, S
Boscardin, WJ
Azziz-Baumgartner, E
Tinoco, YO
Soto, G
Romero, C
Kok, J
Biggerstaff, M
Viboud, C
Rutherford, GW
AF Pollett, Simon
Boscardin, W. John
Azziz-Baumgartner, Eduardo
Tinoco, Yeny O.
Soto, Giselle
Romero, Candice
Kok, Jen
Biggerstaff, Matthew
Viboud, Cecile
Rutherford, George W.
TI Evaluating Google Flu Trends in Latin America: Important Lessons for the
Next Phase of Digital Disease Detection
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Google Flu Trends; Latin America; digital epidemiology
ID INFLUENZA; SURVEILLANCE; EPIDEMICS; BURDEN; PERU
AB Background. Latin America has a substantial burden of influenza and rising Internet access and could benefit from real-time influenza epidemic prediction web tools such as Google Flu Trends (GFT) to assist in risk communication and resource allocation during epidemics. However, there has never been a published assessment of GFT's accuracy inmost Latin American countries or in any low-to middle-income country. Our aim was to evaluate GFT in Argentina, Bolivia, Brazil, Chile, Mexico, Paraguay, Peru, and Uruguay.
Methods. Weekly influenza-test positive proportions for the eight countries were obtained from FluNet for the period January 2011-December 2014. Concurrent weekly Google-predicted influenza activity in the same countries was abstracted from GFT. Pearson correlation coefficients between observed and Google-predicted influenza activity trends were determined for each country. Permutation tests were used to examine background seasonal correlation between FluNet and GFT by country.
Results. There were frequent GFT prediction errors, with correlation ranging from r = -0.53 to 0.91. GFT-predicted influenza activity best correlated with FluNet data in Mexico follow by Uruguay, Argentina, Chile, Brazil, Peru, Bolivia and Paraguay. Correlation was generally highest in the more temperate countries with more regular influenza seasonality and lowest in tropical regions. A substantial amount of autocorrelation was noted, suggestive that GFT is not fully specific for influenza virus activity.
Conclusions. We note substantial inaccuracies with GFT-predicted influenza activity compared with FluNet throughout Latin America, particularly among tropical countries with irregular influenza seasonality. Our findings offer valuable lessons for future Internet-based biosurveillance tools.
C1 [Pollett, Simon; Boscardin, W. John; Rutherford, George W.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Level 2,Mission Hall,3rd St, San Francisco, CA 94143 USA.
[Pollett, Simon] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.
[Azziz-Baumgartner, Eduardo; Biggerstaff, Matthew] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA.
[Tinoco, Yeny O.; Soto, Giselle; Romero, Candice] US Naval Med Res Unit 6, Dept Virol & Emerging Infect Dis, Callao, Peru.
[Kok, Jen] Westmead Hosp, Ctr Infect Dis, Level 3, Westmead, NSW, Australia.
[Kok, Jen] Westmead Hosp, Microbiol Lab Serv, Inst Clin Pathol & Med Res, Pathol West, Level 3, Westmead, NSW, Australia.
[Viboud, Cecile] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Pollett, S (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, Level 2,Mission Hall,3rd St, San Francisco, CA 94143 USA.
EM spollett@med.usyd.edu.au
FU CDC; US Department of Defense Global Emerging Infections Surveillance
[I0082_09_LI]
FX The Peruvian community-based surveillance data were originally collected
in a study funded by the CDC and the US Department of Defense Global
Emerging Infections Surveillance (grant I0082_09_LI).
NR 22
TC 1
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U1 1
U2 1
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 JAN 1
PY 2017
VL 64
IS 1
BP 34
EP 41
DI 10.1093/cid/ciw657
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EP1CN
UT WOS:000397123100014
PM 27678084
ER
PT J
AU Chen, DP
Davis, BR
Simpson, LM
Cushman, WC
Cutler, JA
Dobre, M
Ford, CE
Louis, GT
Muntner, P
Oparil, S
Piller, LB
Pressel, SL
Sarnak, MJ
Whelton, PK
Wright, JT
Rahman, M
AF Chen, Dhruti P.
Davis, Barry R.
Simpson, Lara M.
Cushman, William C.
Cutler, Jeffrey A.
Dobre, Mirela
Ford, Charles E.
Louis, Gail T.
Muntner, Paul
Oparil, Suzanne
Piller, Linda B.
Pressel, Sara L.
Sarnak, Mark J.
Whelton, Paul K.
Wright, Jackson T.
Rahman, Mahboob
CA ALLHAT Collaborative Res Grp
TI Association between chronic kidney disease and cancer mortality: A
report from the ALLHAT
SO CLINICAL NEPHROLOGY
LA English
DT Article
DE chronic kidney disease; cancer; glomerular filtration rate
ID LIPID-LOWERING TREATMENT; STAGE RENAL-DISEASE; HEART-ATTACK TRIAL;
UNITED-STATES; P-CRESOL; RISK; CKD; POPULATION; COHORT; DEATH
AB Background/objectives: Chronic kidney disease (CKD) and cancer are both common in older patients; whether CKD increases risk for cancer is unclear. This study evaluated CKD as a risk factor for cancer mortality in a large cohort of hypertensive patients. Study design: We did post-hoc analyses of in-trial and post-trial data from participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Setting and participants: Participants were = 55 years old with hypertension and one other additional risk factor for coronary heart disease. Predictor: Baseline estimated glomerular filtration rate (eGFR). Outcomes: Cancer mortality was ascertained by cancer-related deaths reported in national databases during and after the trial. Cox proportional hazard models were used to calculate hazard ratios (HRs) adjusted for possible confounders and were stratified by baseline GFR. Results: Participants' mean age was 66.(years. After a mean follow-up of 8.(years, there were 2,338 reported cancer-related deaths. Participants with GFR < 45 mL/min/1.73 m(2) were at increased risk of cancer mortality compared to those with GFR >= 90 mL/min/1.73 m(2) (adjusted HR 1.54 (1.22 -1.94), p-value for trend 0.004). These findings were consistent across subgroups defined by race, gender, and diabetes. Participants with GFR < 45 mL/min/1.73 m(2) were at higher risk for mortality related to colon cancer (p-value for trend 0.048, HR 2.28 (1.12 -4.62)) and urinary tract cancer (p-value for trend 0.001, adjusted HR 2.95 (1.14 -7.65)). Limitations: This is a post hoc analysis of clinical trial data. Conclusions: In a large cohort of hypertensive patients, GFR < 45 mL/min/1.73 m(2) was associated with a higher risk of cancer-related mortality.
C1 [Chen, Dhruti P.] Case Western Reserve Univ, Dept Med, Univ Hosp Case Med Ctr, Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH 44106 USA.
[Davis, Barry R.; Simpson, Lara M.; Ford, Charles E.; Muntner, Paul; Piller, Linda B.; Pressel, Sara L.] Univ Texas Houston, Sch Publ Hlth, Div Biostat, Coordinating Ctr Clin Trials, Houston, TX USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Prevent Med Sect, Memphis, TN USA.
[Cutler, Jeffrey A.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Dobre, Mirela; Wright, Jackson T.; Rahman, Mahboob] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Louis Stokes Cleveland Vet Affairs Med Ctr, Div Nephrol & Hypertens, Cleveland, OH 44106 USA.
[Louis, Gail T.; Whelton, Paul K.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA.
[Muntner, Paul] UAB, Dept Epidemiol, Birmingham, AL USA.
[Oparil, Suzanne] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA.
[Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
RP Rahman, M (reprint author), Case Western Reserve Univ, Div Nephrol & Hypertens, Univ Hosp Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44106 USA.
EM Mahboob.Rahman@UHhospitals.org
FU US National Heart, Lung, and Blood Institute [N01-HC-35130,
HHSN268201100036C]; Pfizer, Inc.
FX This study was supported by contract N01-HC-35130 and HHSN268201100036C
from the US National Heart, Lung, and Blood Institute. The Institute's
role included involvement in design and conduct of the study;
collection, management, analysis, and interpretation of the data; and
preparation, review, and approval of the manuscript. The ALLHAT
investigators acknowledge contributions of study medications supplied by
Pfizer, Inc., (New York, NY, USA) (amlodipine and doxazosin),
AstraZeneca (London, UK) (atenolol and lisinopril), and Bristol-Myers
Squibb (New York, NY, USA) (pravastatin) and financial support provided
by Pfizer, Inc.
NR 32
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U1 1
U2 1
PU DUSTRI-VERLAG DR KARL FEISTLE
PI DEISENHOFEN-MUENCHEN
PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY
SN 0301-0430
J9 CLIN NEPHROL
JI Clin. Nephrol.
PD JAN
PY 2017
VL 87
IS 1
BP 11
EP 20
DI 10.5414/CN108949
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA EO9TX
UT WOS:000397032100002
PM 27900942
ER
PT J
AU Hourigan, CS
AF Hourigan, Christopher S.
TI Targets for Immunotherapy in Acute Leukemia
SO CURRENT DRUG TARGETS
LA English
DT Editorial Material
ID CANCER
C1 [Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Hourigan, CS (reprint author), NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural Research Program of the National Heart, Lung, Blood Institute
of the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Heart, Lung, Blood Institute of the National Institutes of
Health.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-4501
EI 1873-5592
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PY 2017
VL 18
IS 3
BP 256
EP 256
DI 10.2174/1389450117999151116144835
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EL1NU
UT WOS:000394387900001
PM 28264642
ER
PT J
AU Shah, NN
AF Shah, Nirali N.
TI Antibody Based Therapies in Acute Leukemia
SO CURRENT DRUG TARGETS
LA English
DT Review
DE Acute leukemia; antibody therapy; blinatumomab; gemtuzumab; inotuzumab;
rituximab
ID ACUTE-LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA;
CHILDRENS-ONCOLOGY-GROUP; ACUTE LYMPHOCYTIC-LEUKEMIA; MINIMAL RESIDUAL
DISEASE; B-CELL LYMPHOMA; IMMUNOTOXIN MOXETUMOMAB PASUDOTOX; ANTI-CD33
MONOCLONAL-ANTIBODY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHILDHOOD-CANCER
SURVIVOR
AB Despite great progress in the curative treatment of acute leukemia, outcomes for those with relapsed and/or chemotherapy-refractory disease remain poor. Current intensive cytotoxic therapies can be associated with significant morbidity and novel therapies are needed to improve outcomes. Immunotherapy based approaches provide an alternative mechanism of action in the treatment of acute leukemia. Due to cell surface antigen expression, leukemia in particular is amenable to targeted therapies, such as antibody-based therapy. Based on the potential for non-overlapping toxicity, the possibility of synergistic action with standard chemotherapy, and by providing a novel method to overcome chemotherapy resistance, antibody-based therapies have shown potential for benefit. Modifications to standard monoclonal antibodies, including drug conjugation and linkage to T-cells, may further enhance efficacy of antibody-based therapies. Identifying the ideal timing for incorporation of antibody-based therapies, within standard regimens, may lead to improvement in overall outcomes. This article will provide an overview of antibody-based therapies in clinical development for the treatment of acute leukemia in children and adults, with a particular focus on the current strategies and future developments.
C1 [Shah, Nirali N.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Shah, NN (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Room 1W-3750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Nirali.Shah@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Warren Grant
Magnuson Clinical Center
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research and the Warren Grant Magnuson Clinical Center.
NR 158
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PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-4501
EI 1873-5592
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PY 2017
VL 18
IS 3
BP 257
EP 270
DI 10.2174/1389450117666160905091459
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EL1NU
UT WOS:000394387900002
PM 27593687
ER
PT J
AU Goswami, M
Hourigan, CS
AF Goswami, Meghali
Hourigan, Christopher S.
TI Novel Antigen Targets for Immunotherapy of Acute Myeloid Leukemia
SO CURRENT DRUG TARGETS
LA English
DT Review
DE Acute myeloid leukemia; antigens; immunotherapy
ID STEM-CELL TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL
DISEASE; EXOME ANALYSIS REVEALS; MHC-CLASS-I; T-CELLS; CLONAL
HEMATOPOIESIS; MULTIPLE-MYELOMA; CANCER ANTIGENS; NPM1 MUTATION
AB Acute myeloid leukemia (AML) was the first malignancy for which immunotherapy, in the form of allogeneic hematopoietic stem cell transplantation (allo-HSCT), was integrated into the standard of care. Allo-HSCT however is an imperfect therapy associated with significant morbidity and mortality while offering only incomplete prevention of AML clinical relapse. These limitations have motivated the search for AML-related antigens that might be used as more specific and effective targets of immunotherapy. While historically such investigations have focused on protein targets expressed uniquely in AML or at significantly higher levels than in normal tissues, this article will review recent discoveries which have identified a novel selection of potential antigen targets for AML immunotherapy, such as non-protein targets including lipids and carbohydrates, neo-antigens created from genetic somatic mutations or altered splicing and post-translational modification of protein targets, together with innovative ways to target overexpressed protein targets presented by cell surface peptide-MHC complexes. These novel antigens represent promising candidates for further development as targets of AML immunotherapy.
C1 [Goswami, Meghali; Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Goswami, M (reprint author), NHLBI, Myeloid Malignancies Sect, Room 6C-104,10 Ctr Dr, Bethesda, MD 20892 USA.
EM meg.goswami@nih.gov
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. Meghali Goswami is a predoctoral student in the Institute for
Biomedical Sciences at The George Washington University. This work is
from a dissertation to be presented to the above program in partial
fulfillment of the requirements for the Ph.D. degree.
NR 86
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U1 1
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-4501
EI 1873-5592
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PY 2017
VL 18
IS 3
BP 296
EP 303
DI 10.2174/1389450116666150223120005
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EL1NU
UT WOS:000394387900005
PM 25706110
ER
PT J
AU Gonzalez, FJ
Jiang, CT
Xie, C
Patterson, AD
AF Gonzalez, Frank J.
Jiang, Changtao
Xie, Cen
Patterson, Andrew D.
TI Intestinal Farnesoid X Receptor Signaling Modulates Metabolic Disease
SO DIGESTIVE DISEASES
LA English
DT Article; Proceedings Paper
CT 24th International Bile Acid Meeting on Bile Acids in Health and Disease
CY JUN 17-18, 2016
CL Dusseldorf, GERMANY
DE Bile acids; Farnesoid X receptor; Ceramides; Obesity; Diabetes;
Non-alcoholic fatty liver disease
ID FATTY LIVER-DISEASE; NUCLEAR RECEPTOR; BILE-ACID; OBETICHOLIC ACID;
MICE; FXR; HEPATOCARCINOGENESIS; IDENTIFICATION; PHARMACOLOGY;
INHIBITION
AB Farnesoid X receptor (FXR) regulates the synthesis, transport and enterohepatic circulation of bile acids (BA) by modulating the expression of related genes in the liver and small intestine. The composition of the gut microbiota is correlated with metabolic diseases, notably obesity and non-alcoholic fatty acid disease (NAFLD). Recent studies revealed that bacterial metabolism of BA can modulate FXR signaling in the intestine by altering the composition and concentrations of FXR agonist and antagonist. FXR agonist enhances while FXR antagonist suppresses obesity, NAFLD and insulin resistance. The role of intestinal FXR in metabolic disease was firmly established by the analysis of mice lacking FXR that are metabolic resistant to HFD-induced metabolic disease. This is mediated by FXR modulating in part the expression of genes involved in ceramide synthesis in the small intestine. In ileum of obese mice due to the presence of endogenous FXR agonists produced in the liver, these genes are activated, while in mice with altered levels of specific gut bacteria, levels of an FXR antagonist, tauro-beta-muricholic acid (T-beta-MCA) increase and FXR signaling and ceramide synthesis are repressed. T-beta-MCA, which is metabolized in wild-type mice, led to the discovery of glycine-beta-muricholic acid (Gly-MCA) that is stable in the intestine and a potent inhibitor of FXR signaling. These studies reveal that ceramides produced in the ileum under the control of FXR, influence metabolic disease, and suggest that novel FXR antagonist such as GlyMCA that specifically inhibit intestine FXR, could serve as potential drug for the treatment of metabolic disease. (C) 2017 S. Karger AG, Basel
C1 [Gonzalez, Frank J.; Xie, Cen] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Jiang, Changtao] Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing, Peoples R China.
[Jiang, Changtao] Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
NR 36
TC 0
Z9 0
U1 3
U2 3
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0257-2753
EI 1421-9875
J9 DIGEST DIS
JI Dig. Dis.
PY 2017
VL 35
IS 3
BP 178
EP 184
DI 10.1159/000450908
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EM5MP
UT WOS:000395356000005
PM 28249275
ER
PT J
AU Gonzalez, FJ
Xie, C
Jiang, C
Brocker, C
Patterson, AD
AF Gonzalez, Frank J.
Xie, Cen
Jiang, Changtao
Brocker, Chad
Patterson, Andrew D.
TI THE ROLE OF TOXIC LIPIDS METABOLIC DISEASE
SO DRUG METABOLISM AND PHARMACOKINETICS
LA English
DT Meeting Abstract
C1 [Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Bethesda, MD USA.
[Xie, Cen; Brocker, Chad] Natl Canc Inst, Bethesda, MD USA.
[Jiang, Changtao] Peking Univ, Beijing 100871, Peoples R China.
[Patterson, Andrew D.] Penn State Univ, University Pk, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPANESE SOC STUDY XENOBIOTICS
PI TOKYO
PA INT MED INF CENTER SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI SHINJUKU-KU,
TOKYO, 160-0016, JAPAN
SN 1347-4367
EI 1880-0920
J9 DRUG METAB PHARMACOK
JI Drug Metab. Pharmacokinet.
PD JAN
PY 2017
VL 32
IS 1
SU S
MA S37
BP S11
EP S12
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EO9MW
UT WOS:000397013800043
ER
PT J
AU Wang, RP
Qi, YP
Gu, XQ
Lu, F
Fan, GR
Chai, YF
Gonzalez, FJ
Gengli, D
AF Wang, Renping
Qi, Yunpeng
Gu, Xueqin
Lu, Feng
Fan, Guorong
Chai, Yifeng
Gonzalez, Frank J.
Gengli, Duan, Sr.
TI METABOLOMICS ILLUSTRATES CELASTROL-MEDIATED SUPPRESSION ON COLITIS
SO DRUG METABOLISM AND PHARMACOKINETICS
LA English
DT Meeting Abstract
C1 [Wang, Renping; Qi, Yunpeng; Gu, Xueqin; Lu, Feng; Fan, Guorong; Chai, Yifeng] Second Mil Med Univ, Shanghai, Peoples R China.
[Qi, Yunpeng; Gengli, Duan, Sr.] Fudan Univ, Sch Pharm, Dept Pharmaceut Anal, Shanghai, Peoples R China.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU JAPANESE SOC STUDY XENOBIOTICS
PI TOKYO
PA INT MED INF CENTER SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI SHINJUKU-KU,
TOKYO, 160-0016, JAPAN
SN 1347-4367
EI 1880-0920
J9 DRUG METAB PHARMACOK
JI Drug Metab. Pharmacokinet.
PD JAN
PY 2017
VL 32
IS 1
SU S
MA P121
BP S61
EP S62
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EO9MW
UT WOS:000397013800204
ER
PT J
AU Miranda, RA
Franco, CCD
de Oliveira, JC
Barella, LF
Tofolo, LP
Ribeiro, TA
Pavanello, A
da Conceicao, EPS
Torrezan, R
Armitage, J
Lisboa, PC
de Moura, EG
Mathias, PCD
Vieira, E
AF Miranda, Rosiane Aparecida
da Silva Franco, Claudineia Conationi
de Oliveira, Julio Cezar
Barella, Luiz Felipe
Tofolo, Laize Peron
Ribeiro, Tatiane Aparecida
Pavanello, Audrei
Santos da Conceicao, Ellen Paula
Torrezan, Rosana
Armitage, James
Lisboa, Patricia Cristina
de Moura, Egberto Gaspar
de Freitas Mathias, Paulo Cezar
Vieira, Elaine
TI Cross-fostering reduces obesity induced by early exposure to monosodium
glutamate in male rats
SO ENDOCRINE
LA English
DT Article
DE Cross-fostering; Monosodium glutamate; Obesity
ID HIGH-FAT DIET; PANCREATIC-ISLETS; MATERNAL OBESITY; OFFSPRING
METABOLISM; GLUCOSE-INTOLERANCE; INSULIN-RESISTANCE; LEPTIN RESISTANCE;
MILK-COMPOSITION; GENE-EXPRESSION; FEMALE RATS
AB Maternal obesity programmes a range of metabolic disturbances for the offspring later in life. Moreover, environmental changes during the suckling period can influence offspring development. Because both periods significantly affect long-term metabolism, we aimed to study whether cross-fostering during the lactation period was sufficient to rescue a programmed obese phenotype in offspring induced by maternal obesity following monosodium L-glutamate (MSG) treatment. Obesity was induced in female Wistar rats by administering subcutaneous MSG (4 mg/g body weight) for the first 5 days of postnatal life. Control and obese female rats were mated in adulthood. The resultant pups were divided into control second generation (F-2) (CTLF2), MSG-treated second generation (F-2) (MSGF(2)), which suckled from their CTL and MSG biological dams, respectively, or CTLF2-CR, control offspring suckled by MSG dams and MSGF(2)-CR, MSG offspring suckled by CTL dams. At 120 days of age, fat tissue accumulation, lipid profile, hypothalamic leptin signalling, glucose tolerance, glucose-induced, and adrenergic inhibition of insulin secretion in isolated pancreatic islets were analysed. Maternal MSG-induced obesity led to an obese phenotype in male offspring, characterized by hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, dyslipidaemia, and impaired leptin signalling, suggesting central leptin resistance, glucose intolerance, impaired glucose-stimulated, and adrenergic inhibition of insulin secretion. Cross-fostering normalized body weight, food intake, leptin signalling, lipid profiles, and insulinaemia, but not glucose homeostasis or insulin secretion from isolated pancreatic islets. Our findings suggest that alterations during the lactation period can mitigate the development of obesity and prevent the programming of adult diseases.
C1 [Miranda, Rosiane Aparecida; da Silva Franco, Claudineia Conationi; Tofolo, Laize Peron; Ribeiro, Tatiane Aparecida; Pavanello, Audrei; de Freitas Mathias, Paulo Cezar; Vieira, Elaine] State Univ Maringa UEM, Dept Biotechnol Cell Biol & Genet, Block H67,Room 19,Colombo Ave 5790, Maringa, PR, Brazil.
[Miranda, Rosiane Aparecida] Univ Fed Rio de Janeiro, Carlos Chagas Filho Biophys Inst, Rio De Janeiro, RJ, Brazil.
[de Oliveira, Julio Cezar] Univ Fed Mato Grosso, Hlth Sci Inst, Sinop, MT, Brazil.
[Barella, Luiz Felipe] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Santos da Conceicao, Ellen Paula; Lisboa, Patricia Cristina; de Moura, Egberto Gaspar] Univ Estado Rio De Janeiro, Dept Physiol Sci, Roberto Alcantara Gomes Biol Inst, Rio De Janeiro, RJ, Brazil.
[Torrezan, Rosana] Univ Estadual Maringa, Dept Physiol Sci, Maringa, PR, Brazil.
[Armitage, James] Deakin Univ, Sch Med Optometr, Geelong, Vic 3216, Australia.
RP Miranda, RA (reprint author), State Univ Maringa UEM, Dept Biotechnol Cell Biol & Genet, Block H67,Room 19,Colombo Ave 5790, Maringa, PR, Brazil.; Miranda, RA (reprint author), Univ Fed Rio de Janeiro, Carlos Chagas Filho Biophys Inst, Rio De Janeiro, RJ, Brazil.
EM roapmiranda@yahoo.com.br
RI Barella, Luiz/C-1181-2014
OI Barella, Luiz/0000-0003-2211-3842
FU Brazilian Federal Foundation; Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq); Coordenacao de Aperfeicoamento de
Pessoal de Nivel Superior (CAPES)
FX This work was supported by the Brazilian Federal Foundation, Conselho
Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), and
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES).
NR 60
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-008X
EI 1559-0100
J9 ENDOCRINE
JI Endocrine
PD JAN
PY 2017
VL 55
IS 1
BP 110
EP 121
DI 10.1007/s12020-016-0965-y
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EK9PY
UT WOS:000394257600014
PM 27116693
ER
PT J
AU Mamluk, L
O'Doherty, MG
Orfanos, P
Saitakis, G
Woodside, JV
Liao, LM
Sinha, R
Boffetta, P
Trichopoulou, A
Kee, F
AF Mamluk, L.
O'Doherty, M. G.
Orfanos, P.
Saitakis, G.
Woodside, J. V.
Liao, L. M.
Sinha, R.
Boffetta, P.
Trichopoulou, A.
Kee, F.
CA CHANCES Consortium
TI Fruit and vegetable intake and risk of incident of type 2 diabetes:
results from the consortium on health and ageing network of cohorts in
Europe and the United States (CHANCES)
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID GREEN LEAFY VEGETABLES; PRIMARY PREVENTION; MAGNESIUM INTAKE; DIETARY
NITRATE; MELLITUS; METAANALYSIS; CONSUMPTION; DESIGN; BEETROOT; PROJECT
AB BACKGROUND/OBJECTIVES: There is limited information to support definitive recommendations concerning the role of diet in the development of type 2 Diabetes mellitus (T2DM). The results of the latest meta-analyses suggest that an increased consumption of green leafy vegetables may reduce the incidence of diabetes, with either no association or weak associations demonstrated for total fruit and vegetable intake. Few studies have, however, focused on older subjects.
SUBJECTS/METHODS: The relationship between T2DM and fruit and vegetable intake was investigated using data from the NIH-AARP study and the EPIC Elderly study. All participants below the age of 50 and/or with a history of cancer, diabetes or coronary heart disease were excluded from the analysis. Multivariate logistic regression analysis was used to calculate the odds ratio of T2DM comparing the highest with the lowest estimated portions of fruit, vegetable, green leafy vegetables and cabbage intake.
RESULTS: Comparing people with the highest and lowest estimated portions of fruit, vegetable or green leafy vegetable intake indicated no association with the risk of T2DM. However, although the pooled OR across all studies showed no effect overall, there was significant heterogeneity across cohorts and independent results from the NIH-AARP study showed that fruit and green leafy vegetable intake was associated with a reduced risk of T2DM OR 0.95 (95% CI 0.91,0.99) and OR 0.87 (95% CI 0.87,0.90) respectively.
CONCLUSIONS: Fruit and vegetable intake was not shown to be related to incident T2DM in older subjects. Summary analysis also found no associations between green leafy vegetable and cabbage intake and the onset of T2DM. Future dietary pattern studies may shed light on the origin of the heterogeneity across populations.
C1 [Mamluk, L.; O'Doherty, M. G.; Woodside, J. V.; Kee, F.] Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Northern Ireland, Belfast BT7 1NN, Antrim, North Ireland.
[Orfanos, P.; Saitakis, G.; Trichopoulou, A.] Univ Athens, Dept Hyg Epidemiol & Med Stat, Athens, Greece.
[Liao, L. M.; Sinha, R.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD USA.
[Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst & Inst Translat Epidemiol, New York, NY USA.
[Boffetta, P.; Trichopoulou, A.] Hellen Hlth Fdn, Athens, Greece.
RP Mamluk, L (reprint author), Univ Bristol, Univ Hosp Bristol NHS Fdn Trust, Sch Social & Community Med, NIHR CLAHRC West,MRC Integrat Epidemiol Unit, Oakfield House,9th Floor, Bristol BS1 2NT, Avon, England.
EM l.mamluk@bristol.ac.uk
FU European Community [HEALTH -F3-2010-242244]; Intramural Research Program
of the NIH, National Cancer Institute
FX This work was supported by funding from the European Community's Seventh
Framework Programme (FP7/2007-2013) (grant number HEALTH
-F3-2010-242244). This research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute.
Cancer incidence data from the Atlanta metropolitan area were collected
by the Georgia Center for Cancer Statistics, Department of Epidemiology,
Rollins School of Public Health, Emory University, Atlanta, Georgia.
Cancer incidence data from California were collected by the California
Cancer Registry, California Department of Public Health's Cancer
Surveillance and Research Branch, Sacramento, California. Cancer
incidence data from the Detroit metropolitan area were collected by the
Michigan Cancer Surveillance Program, Community Health Administration,
Lansing, Michigan. The Florida cancer incidence data used in this report
were collected by the Florida Cancer Data System (Miami, Florida) under
contract with the Florida Department of Health, Tallahassee, Florida.
The views expressed herein are solely those of the authors and do not
necessarily reflect those of the FCDC or FDOH. Cancer incidence data
from Louisiana were collected by the Louisiana Tumor Registry, Louisiana
State University Health Sciences Center School of Public Health, New
Orleans, Louisiana. Cancer incidence data from New Jersey were collected
by the New Jersey State Cancer Registry, Cancer Epidemiology Services,
New Jersey State Department of Health, Trenton, New Jersey. Cancer
incidence data from North Carolina were collected by the North Carolina
Central Cancer Registry, Raleigh, North Carolina. Cancer incidence data
from Pennsylvania were supplied by the Division of Health Statistics and
Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania.
The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations or conclusions. Cancer
incidence data from Arizona were collected by the Arizona Cancer
Registry, Division of Public Health Services, Arizona Department of
Health Services, Phoenix, Arizona. Cancer incidence data from Texas were
collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services, Austin,
Texas. Cancer incidence data from Nevada were collected by the Nevada
Central Cancer Registry, Division of Public and Behavioral Health, State
of Nevada Department of Health and Human Services, Carson City,
NevadaNevada. We are indebted to the participants in the NIH-AARP Diet
and Health Study for their outstanding cooperation. We also thank Sigurd
Hermansen and Kerry Grace Morrissey from Westat for study outcomes
ascertainment and management and Leslie Carroll at Information
Management Services for data support and analysis. Ethical standard: All
of the cohorts obtained ethical approval and written informed consent
was obtained from all participants.
NR 38
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
EI 1476-5640
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD JAN
PY 2017
VL 71
IS 1
BP 83
EP 91
DI 10.1038/ejcn.2016.143
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EK6GU
UT WOS:000394023900014
PM 27530474
ER
PT J
AU Wang, S
Meigs, JB
Dupuis, J
AF Wang, Shuai
Meigs, James B.
Dupuis, Josee
TI Joint association analysis of a binary and a quantitative trait in
family samples
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENERALIZED ESTIMATING EQUATIONS; BODY-MASS
INDEX; EXTENDED QUASI-LIKELIHOOD; SUSCEPTIBILITY LOCI; GENETIC
ASSOCIATION; CLUSTERED DATA; METAANALYSIS; MODELS; RISK
AB In recent years, improved genotyping and sequencing technologies have enabled the discovery of new loci associated with various diseases or traits. For instance, by testing the association with each single-nucleotide variant (SNV) separately, genome-wide association studies (GWAS) have achieved tremendous success in identifying SNVs associated with specific traits. However, little is known about the common genetic basis of multiple traits owing to lack of efficient methods. With the use of extended quasi-likelihood, a Wald test has been proposed to perform a bivariate analysis of a continuous and a binary trait in unrelated samples. However, owing to its low computational efficiency, it has not been implemented in real applications to large-scale genetic studies. In this paper, we propose an efficient bivariate robust score test for two traits, one continuous and one binary, based on extended generalized estimating equations. Our approach is applicable to both family-based and unrelated study designs and can be extended to test the association of multiple traits. Our simulation studies demonstrate the type-I error rate of our approach is well controlled in all minor allele frequency (MAF) scenarios, with MAF ranging from 1 to 30%, and the method is more powerful in certain MAF scenarios than univariate testing with correction for multiple testing. Because of the computational advantage of score tests, our approach is readily applicable to GWAS or sequencing studies. Finally, we present a real application to uncover genetic variants associated with body mass index and type-2 diabetes in the Framingham Heart Study.
C1 [Wang, Shuai; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Mass Ave,3rd Floor, Boston, MA 02118 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, James B.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Wang, S (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Mass Ave,3rd Floor, Boston, MA 02118 USA.
EM tutuwang@bu.edu
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195, HHSN268201500001I]; Affymetrix Inc [N02-HL-6-4278];
National Institute of National Institute for Diabetes and Digestive and
Kidney Diseases (NIDDK) [R01 DK078616, DK080140]; American Diabetes
Association Mentor-Based Postdoctoral Fellowship [7-09-MN-32]; NIDDK
[K24 DK080140]
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195 &
HHSN268201500001I) and its contract with Affymetrix, Inc for genotyping
services (Contract No. N02-HL-6-4278), and by grants from the National
Institute of National Institute for Diabetes and Digestive and Kidney
Diseases (NIDDK) R01 DK078616, NIDDK K24 DK080140 and American Diabetes
Association Mentor-Based Postdoctoral Fellowship Award # 7-09-MN-32.
NR 35
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JAN
PY 2017
VL 25
IS 1
BP 130
EP 136
DI 10.1038/ejhg.2016.134
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EK7OW
UT WOS:000394116100020
PM 27782109
ER
PT J
AU Patton, J
Brewer, C
Chien, W
Johnston, JJ
Griffith, AJ
Biesecker, LG
AF Patton, John
Brewer, Carmen
Chien, Wade
Johnston, Jennifer J.
Griffith, Andrew J.
Biesecker, Leslie G.
TI A genotypic ascertainment approach to refute the association of MYO1A
variants with non-syndromic deafness
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID HEARING-LOSS; MUTATIONS; GENE; MEDICINE
AB Variants in the unconventional myosin gene, MYO1A, have been reported to cause non-syndromic sensorineural hearing loss with a pattern of autosomal dominant inheritance. Others have challenged this association. We used a genotypic ascertainment study design to test the association of MYO1A variants with hearing loss. We evaluated MYO1A variants from a cohort of 951 individuals with exome sequencing who were not ascertained for hearing loss. Five individuals had one of two variants claimed to be associated with sensorineural hearing loss in a prior study and 33 individuals had one of 13 predicted deleterious variants. We obtained audiology evaluations for 12 individuals with these variants of interest. The hearing acuity of the participants was compared with age-and sex-matched controls and published age-and sex-specific reference ranges from a large population of otologically screened adults. None of the participants had bilateral sensorineural hearing loss of moderate or greater severity. These data do not support a causal relationship of variants in MYO1A to sensorineural hearing loss. We suggest that the genotypic ascertainment method is useful to objectively evaluate gene-phenotype associations.
C1 [Patton, John; Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, 50 South Dr Room 5140, Bethesda, MD 20892 USA.
[Brewer, Carmen; Chien, Wade; Griffith, Andrew J.] NIDCD, Otolaryngol Branch, NIH, Bethesda, MD USA.
[Patton, John] Des Moines Univ, Coll Osteopath Med, Des Moines, IA USA.
RP Biesecker, LG (reprint author), NHGRI, Med Genom & Metab Genet Branch, NIH, 50 South Dr Room 5140, Bethesda, MD 20892 USA.
EM lesb@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health, the
National Human Genome Research Institute; Intramural Research Program of
the National Institutes of Health, National Institute for Deafness and
Communicative Disorders
FX The authors are grateful to the ClinSeq participants for their
contribution to this work. All authors were supported by the Intramural
Research Program of the National Institutes of Health, either the
National Human Genome Research Institute (LGB, JP, and JJJ) or the
National Institute for Deafness and Communicative Disorders (CB, WC, and
AJG).
NR 16
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JAN
PY 2017
VL 25
IS 1
BP 147
EP 149
DI 10.1038/ejhg.2016.140
PG 3
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EK7OW
UT WOS:000394116100022
PM 27759032
ER
PT J
AU Vrisekoop, N
Artusa, P
Monteiro, JP
Mandl, JN
AF Vrisekoop, Nienke
Artusa, Patricio
Monteiro, Joao P.
Mandl, Judith N.
TI Weakly self-reactive T-cell clones can homeostatically expand when
present at low numbers
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Lymphopenia-induced proliferation; Regulation of homeostasis; T-cell
competition; T-cell diversity; T-cell repertoire
ID PRECURSOR FREQUENCY; POSITIVE SELECTION; CUTTING EDGE; NAIVE CD4(+);
HOMEOSTASIS; PROLIFERATION; RECEPTOR; COMPETITION; SURVIVAL; MICE
AB T-cell division is central to maintaining a stable T-cell pool in adults. It also enables T-cell expansion in neonates, and after depletion by chemotherapy, bone marrow transplantation, or infection. The same signals required for T-cell survival in lymphoreplete settings, IL-7 and T-cell receptor (TCR) interactions with self-peptide MHC (pMHC), induce division when T-cell numbers are low. The strength of reactivity for self-pMHC has been shown to correlate with the capacity of T cells to undergo lymphopenia-induced proliferation (LIP), in that weakly self-reactive T cells are unable to divide, implying that T-cell reconstitution would significantly skew the TCR repertoire toward TCRs with greater self-reactivity and thus compromise T-cell diversity. Here, we show that while CD4(+) T cells with low self-pMHC reactivity experience more intense competition, they are able to divide when present at low enough cell numbers. Thus, at physiological precursor frequencies CD4(+) T cells with low self-pMHC reactivity are able to contribute to the reconstitution of the T-cell pool.
C1 [Vrisekoop, Nienke] Univ Med Ctr Utrecht, Lab Translat Immunol, Dept Resp Med, Utrecht, Netherlands.
[Artusa, Patricio; Mandl, Judith N.] McGill Univ, Complex Traits Grp, Dept Physiol, Montreal, PQ, Canada.
[Monteiro, Joao P.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Vrisekoop, N (reprint author), Univ Med Ctr Utrecht, Lab Translat Immunol, Dept Resp Med, Utrecht, Netherlands.; Mandl, JN (reprint author), McGill Univ, Complex Traits Grp, Dept Physiol, Montreal, PQ, Canada.
EM n.vrisekoop@umcutrecht.nl; judith.mandl@mcgill.ca
FU Intramural Research Program of NIAID; NIH DHHS; McGill University
FX N.V. and J.N.M. performed experiments, analyzed data and wrote the
paper, J.P.M. and P.A. performed experiments. This work was supported by
the Intramural Research Program of NIAID, NIH DHHS and a startup fund
from McGill University (J.N.M.). The authors are grateful to William E.
Paul and Ronald N. Germain (N.I.H.), Heather Melichar (U. of Montreal),
and Jose A. M. Borghans (UMCU) for discussions and feedback, as well as
Julie Edwards in the flow cytometry core at NIH for performing all cell
sorts.
NR 32
TC 0
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JAN
PY 2017
VL 47
IS 1
BP 68
EP 73
DI 10.1002/eji.201646540
PG 6
WC Immunology
SC Immunology
GA EL7ZI
UT WOS:000394839400011
PM 27792294
ER
PT J
AU Callahan, R
Chestnut, BA
Raafat, A
AF Callahan, Robert
Chestnut, Barry A.
Raafat, Ahmed
TI Imatinib mesylate (Gleevec) inhibits Notch and c-Myc signaling: Five-day
treatment permanently rescues mammary development
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Mammary gland development; cancer; Notch; c-Myc; Gleevec; ubiquitin;
proteasome
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; UBIQUITIN-PROTEASOME PATHWAY; TRUNCATED
INT3 GENE; LUMINAL CELL-FATE; EPITHELIAL-CELLS; BREAST-CANCER; GLAND
DEVELOPMENT; PROGESTERONE-RECEPTOR; INTRACELLULAR DOMAIN;
PROTEIN-DEGRADATION
AB Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment. In addition, these mice do not develop mammary tumors. We investigated the mechanism for Gleevec regulation of Notch signaling and found that Gleevec treatment results in a loss of Int3 protein but not of Int3 mRNA in HC11 mouse mammary epithelial cells expressing Int3. The addition of MG-132, a proteasome inhibitor, shows increased ubiquitination of Int3 in the presence of Gleevec. Thus, Gleevec affects the stability of Int3 by promoting the degradation of Int3 via E3 ubiquitin ligases targeting it for the proteasome degradation. Gleevec is a tyrosine kinase inhibitor that acts on c-Kit and PDGFR. Therefore, we investigated the downstream substrate kinase GSK3 beta to ascertain the possible role that this kinase might play in the stability of Int3. Data show that Gleevec degradation of Int3 is GSK3 beta dependent. We have expanded our study of the effects Gleevec has on tumorigenesis of other oncogenes. We have found that anchorage-independent growth of HC11-c-Myc cells as well as tumor growth in nude mice is inhibited by Gleevec treatment. As with Int3, Gleevec treatment appears to destabilize the c-Myc protein but not mRNA. These results indicate that Gleevec could be a potential therapeutic drug for patients bearing Notch4 and/or c-Myc positive breast carcinomas.
C1 [Callahan, Robert; Chestnut, Barry A.; Raafat, Ahmed] NCI, Basic Res Lab, NIH, Bethesda, MD 20814 USA.
RP Raafat, A (reprint author), NCI, Basic Res Lab, NIH, Bethesda, MD 20814 USA.
EM raafata@mail.nih.gov
FU National Cancer Institute's Center for Cancer Research Intramural
Research Program (Bethesda, MD)
FX The authors thank Dr Gilbert H Smith for his advice and thorough reading
of the manuscript, Dr Stefania Santopietro for preliminary data
concerning c-Myc and Dr Avinash Bhandoola for his help in completing
this project and Dr Lawrence Samelson for his support. The National
Cancer Institute's Center for Cancer Research Intramural Research
Program (Bethesda, MD) funded this work.
NR 80
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U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1535-3702
EI 1535-3699
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD JAN
PY 2017
VL 242
IS 1
BP 53
EP 67
DI 10.1177/1535370216665175
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EK9SA