FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Klysz, D
   Tai, XG
   Robert, PA
   Craveiro, M
   Cretenet, G
   Oburoglu, L
   Mongellaz, C
   Floess, S
   Fritz, V
   Matias, MI
   Yong, C
   Surh, N
   Marie, JC
   Huehn, J
   Zimmermann, V
   Kinet, S
   Dardalhon, V
   Taylor, N
AF Klysz, Dorota
   Tai, Xuguang
   Robert, Philippe A.
   Craveiro, Marco
   Cretenet, Gaspard
   Oburoglu, Leal
   Mongellaz, Cedric
   Floess, Stefan
   Fritz, Vanessa
   Matias, Maria I.
   Yong, Carmen
   Surh, Natalie
   Marie, Julien C.
   Huehn, Jochen
   Zimmermann, Valerie
   Kinet, Sandrina
   Dardalhon, Valerie
   Taylor, Naomi
TI Glutamine-dependent alpha-ketoglutarate production regulates the balance
   between T helper 1 cell and regulatory T cell generation
SO SCIENCE SIGNALING
LA English
DT Article
ID FOXP3 EXPRESSION; GENE-EXPRESSION; TUMOR-IMMUNITY; GLUCOSE-UPTAKE;
   CUTTING EDGE; MTOR KINASE; REG CELLS; AKT-MTOR; ACTIVATION;
   DIFFERENTIATION
AB T cell activation requires that the cell meet increased energetic and biosynthetic demands. We showed that exogenous nutrient availability regulated the differentiation of naive CD4(+) T cells into distinct subsets. Activation of naive CD4(+) T cells under conditions of glutamine deprivation resulted in their differentiation into Foxp3(+) (forkhead box P3-positive) regulatory T (T-reg) cells, which had suppressor function in vivo. Moreover, glutamine-deprived CD4(+) T cells that were activated in the presence of cytokines that normally induce the generation of T helper 1 (T-H(1)) cells instead differentiated into Foxp3(+) Treg cells. We found that alpha-ketoglutarate (alpha KG), the glutamine-derived metabolite that enters into the mitochondrial citric acid cycle, acted as a metabolic regulator of CD4(+) T cell differentiation. Activation of glutamine-deprived naive CD4(+) T cells in the presence of a cell-permeable alpha KG analog increased the expression of the gene encoding the T-H(1) cell-associated transcription factor Tbet and resulted in their differentiation into T-H(1) cells, concomitant with stimulation of mammalian target of rapamycin complex 1 (mTORC1) signaling. Together, these data suggest that a decrease in the intracellular amount of alpha KG, caused by the limited availability of extracellular glutamine, shifts the balance between the generation of T-H(1) and Treg cells toward that of a T-reg phenotype.
C1 [Klysz, Dorota; Robert, Philippe A.; Craveiro, Marco; Cretenet, Gaspard; Oburoglu, Leal; Mongellaz, Cedric; Fritz, Vanessa; Matias, Maria I.; Yong, Carmen; Surh, Natalie; Zimmermann, Valerie; Kinet, Sandrina; Dardalhon, Valerie; Taylor, Naomi] Univ Montpellier, CNRS, UMR 5535, Inst Genet Mol Montpellier, F-34293 Montpellier, France.
   [Tai, Xuguang] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA.
   [Robert, Philippe A.] Braunschweig Integrated Ctr Syst Biol, Dept Syst Immunol, D-38124 Braunschweig, Germany.
   [Floess, Stefan; Huehn, Jochen] Helmholtz Ctr Infect Res, Dept Expt Immunol, D-38124 Braunschweig, Germany.
   [Yong, Carmen] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Canc Immunol Res Program, Parkville, Vic 3010, Australia.
   [Marie, Julien C.] Univ Lyon 1, CNRS 5286, INSERM, Canc Res Ctr Lyon,U1052, F-69373 Lyon 03, France.
   [Marie, Julien C.] DKFZ German Canc Res Ctr, D-69121 Heidelberg, Germany.
RP Dardalhon, V (reprint author), Univ Montpellier, CNRS, UMR 5535, Inst Genet Mol Montpellier, F-34293 Montpellier, France.
EM valerie.dardalhon@igmm.cnrs.fr; taylor@igmm.cnrs.fr
RI Taylor, Naomi/H-4016-2014; Marie, Julien/I-5084-2016; 
OI Craveiro, Marco/0000-0002-7405-4621
FU European Marie Curie fellowship (ATTACK); Research Ministry fellowship;
   Ligue Contre le Cancer; Association de la Recherche contre le Cancer
   (ARC); Portuguese Foundation for Science and Technology; Association
   Francaise contre les Myopathies (AFM); Cancer Therapeutics CRC;
   Australian Postgraduate Award; NIH intramural program; CNRS; INSERM;
   European Community [LSHC-CT-2005-018914, PIRG5-GA-2009-249227]; CNRS-NIH
   International Laboratory grant from the CNRS (LIA-BAGEL); ARC; French
   national research grants ANR [ANR-10-LABX-61]; INCa; German Research
   Foundation [KFO250]; French laboratory consortiums (Labex) EpiGenMed;
   GR-EX
FX D.K. was supported by a European Marie Curie fellowship (ATTACK); P.R.
   was supported by a Research Ministry fellowship administered by the
   University of Montpellier II; L.O. and G.C. were supported by
   fellowships from the Ligue Contre le Cancer; L.O. is presently supported
   by the Association de la Recherche contre le Cancer (ARC); M.C. was
   supported by a fellowship from the Portuguese Foundation for Science and
   Technology; V.F. was supported by a fellowship from the Association
   Francaise contre les Myopathies (AFM); C.Y. was supported by a
   fellowship from Cancer Therapeutics CRC and an Australian Postgraduate
   Award; X.T. was supported by the NIH intramural program; C.M., V.Z.,
   S.K., and V.D. were supported by the CNRS; J.M. and N.T. were supported
   by INSERM. This work was supported by generous funding from the European
   Community [contracts LSHC-CT-2005-018914 (ATTACK) and
   PIRG5-GA-2009-249227 (T cell homeostasis)], a CNRS-NIH International
   Laboratory grant from the CNRS (LIA-BAGEL), ARC, French national
   research grants ANR (PolarATTACK, GlutStem, NutriDiff, and
   ANR-10-LABX-61), INCa, German Research Foundation (KFO250), and the
   French laboratory consortiums (Labex) EpiGenMed and GR-EX.
NR 63
TC 16
Z9 16
U1 3
U2 5
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD SEP 29
PY 2015
VL 8
IS 396
AR ra97
DI 10.1126/scisignal.aab2610
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CU1YQ
UT WOS:000363318700002
PM 26420908
ER

PT J
AU Wang, HK
   Treadway, T
   Covey, DP
   Cheer, JF
   Lupica, CR
AF Wang, Huikun
   Treadway, Tyler
   Covey, Daniel P.
   Cheer, Joseph F.
   Lupica, Carl R.
TI Cocaine-Induced Endocannabinoid Mobilization in the Ventral Tegmental
   Area
SO CELL REPORTS
LA English
DT Article
ID MIDBRAIN DOPAMINE NEURONS; CANNABINOID CB1 RECEPTOR; FREELY MOVING RATS;
   NUCLEUS-ACCUMBENS; ENDOGENOUS CANNABINOIDS; EXTRACELLULAR DOPAMINE;
   GLUTAMATERGIC SYNAPSES; METABOTROPIC GLUTAMATE; PRESYNAPTIC INHIBITION;
   RELEASE
AB Cocaine is a highly addictive drug that acts upon the brain's reward circuitry via the inhibition of monoamine uptake. Endogenous cannabinoids (eCB) are lipid molecules released from midbrain dopamine (DA) neurons that modulate cocaine's effects through poorly understood mechanisms. We find that cocaine stimulates release of the eCB, 2-arachidonoylglycerol (2-AG), in the rat ventral midbrain to suppress GABAergic inhibition of DA neurons, through activation of presynaptic cannabinoid CB1 receptors. Cocaine mobilizes 2-AG via inhibition of norepinephrine uptake and promotion of a cooperative interaction between G(q/11)-coupled type-1 metabotropic glutamate and alpha(1)-adrenergic receptors to stimulate internal calcium stores and activate phospholipase C. The disinhibition of DA neurons by cocaine-mobilized 2-AG is also functionally relevant because it augments DA release in the nucleus accumbens in vivo. Our results identify a mechanism through which the eCB system can regulate the rewarding and addictive properties of cocaine.
C1 [Wang, Huikun; Treadway, Tyler; Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Cellular Neurobiol Res Branch, Baltimore, MD 21224 USA.
   [Covey, Daniel P.; Cheer, Joseph F.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
RP Lupica, CR (reprint author), NIDA, Electrophysiol Res Sect, Cellular Neurobiol Res Branch, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM clupica@mail.nih.gov
FU NIH/NIDA-Intramural Research Program; NIDA [DA022340, DA033926]
FX The AAV1.Syn.Flex.GCaMP6f.WPRE.SV40 virus was generously made available
   by Vivek Jayaraman, PhD, Rex A. Kerr, PhD, Douglas S. Kim, PhD, Loren L.
   Looger, PhD, Karel Svoboda, PhD, and the GENIE Project, Janelia Farms,
   Howard Hughes Medical Institute. The TH-cre rat breeders were donated by
   Dr. Karl Deisseroth to the NIDA-IRP Optogenetic and Transgenic Core. We
   thank Drs. Antonello Bonci and Alexander Hoffman for critically reading
   the manuscript. The work was funded by the NIH/NIDA-Intramural Research
   Program (C.R.L., H.W., and T.T.), and NIDA extramural grants DA022340,
   DA033926 (J.F.C.).
NR 57
TC 6
Z9 6
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD SEP 29
PY 2015
VL 12
IS 12
BP 1997
EP 2008
DI 10.1016/j.celrep.2015.08.041
PG 12
WC Cell Biology
SC Cell Biology
GA CS4CN
UT WOS:000362022600006
PM 26365195
ER

PT J
AU Wu, TQ
   Shin, HM
   Moseman, EA
   Ji, Y
   Huang, BN
   Harly, C
   Sen, JM
   Berg, LJ
   Gattinoni, L
   McGavern, DB
   Schwartzberg, PL
AF Wu, Tuoqi
   Shin, Hyun Mu
   Moseman, E. Ashley
   Ji, Yun
   Huang, Bonnie
   Harly, Christelle
   Sen, Jyoti M.
   Berg, Leslie J.
   Gattinoni, Luca
   McGavern, Dorian B.
   Schwartzberg, Pamela L.
TI TCF1 Is Required for the T Follicular Helper Cell Response to Viral
   Infection
SO CELL REPORTS
LA English
DT Article
ID GERMINAL CENTER FORMATION; TRANSCRIPTION FACTORS; ANTIBODY-RESPONSES;
   GENE-EXPRESSION; DIFFERENTIATION; BCL6; IMMUNITY; MEMORY; SPECIFICATION;
   LEF-1
AB T follicular helper (T-FH) and T helper 1 (Th1) cells generated after viral infections are critical for the control of infection and the development of immunological memory. However, the mechanisms that govern the differentiation and maintenance of these two distinct lineages during viral infection remain unclear. We found that viral-specific T-FH and Th1 cells showed reciprocal expression of the transcriptions factors TCF1 and Blimp1 early after infection, even before the differential expression of the canonical T-FH marker CXCR5. Furthermore, TCF1 was intrinsically required for the TFH cell response to viral infection; in the absence of TCF1, the T-FH cell response was severely compromised, and the remaining TCF1-deficient TFH cells failed to maintain T-FH-associated transcriptional and metabolic signatures, which were distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1. Our findings demonstrate an essential role of TCF1 in T-FH cell responses to viral infection.
C1 [Wu, Tuoqi; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Shin, Hyun Mu; Berg, Leslie J.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA.
   [Moseman, E. Ashley; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA.
   [Ji, Yun; Harly, Christelle; Gattinoni, Luca] NCI, NIH, Bethesda, MD 20892 USA.
   [Sen, Jyoti M.] NIA, NIH, Baltimore, MD 21224 USA.
RP Wu, TQ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM tuoqiwu@gmail.com; pams@nhgri.nih.gov
RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009
FU NHGRI; NINDS; NCI; NIA; NIH [AI101048]
FX We thank J. Reilley, R. Handon, M. Kirby, S. Anderson, J. Fekecs, and E.
   Stregevsky for excellent technical support. This work was supported by
   funds from the intramural programs of the NHGRI, NINDS, NCI, and NIA, as
   well as NIH grant AI101048 (L.J.B.).
NR 51
TC 13
Z9 14
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD SEP 29
PY 2015
VL 12
IS 12
BP 2099
EP 2110
DI 10.1016/j.celrep.2015.08.049
PG 12
WC Cell Biology
SC Cell Biology
GA CS4CN
UT WOS:000362022600014
PM 26365183
ER

PT J
AU Kugelman, JR
   Kugelman-Tonos, J
   Ladner, JT
   Pettit, J
   Keeton, CM
   Nagle, ER
   Garcia, KY
   Froude, JW
   Kuehne, AI
   Kuhn, JH
   Bavari, S
   Zeitlin, L
   Dye, JM
   Olinger, GG
   Sanchez-Lockhart, M
   Palacios, GF
AF Kugelman, Jeffrey R.
   Kugelman-Tonos, Johanny
   Ladner, Jason T.
   Pettit, James
   Keeton, Carolyn M.
   Nagle, Elyse R.
   Garcia, Karla Y.
   Froude, Jeffrey W.
   Kuehne, Ana I.
   Kuhn, Jens H.
   Bavari, Sina
   Zeitlin, Larry
   Dye, John M.
   Olinger, Gene G.
   Sanchez-Lockhart, Mariano
   Palacios, Gustavo F.
TI Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates
   Treated with the MB-003 Antibody Cocktail
SO CELL REPORTS
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; POSTEXPOSURE PROTECTION; MARBURG VIRUSES;
   GUINEA-PIGS; GLYCOPROTEIN; EBOLAVIRUSES; CHALLENGE; EVOLUTION;
   DISCOVERY; ZMAPP
AB MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape.
C1 [Kugelman, Jeffrey R.; Ladner, Jason T.; Keeton, Carolyn M.; Nagle, Elyse R.; Garcia, Karla Y.; Sanchez-Lockhart, Mariano; Palacios, Gustavo F.] USAMRIID, Ctr Genome Sci, Frederick, MD 21702 USA.
   [Kugelman-Tonos, Johanny; Bavari, Sina] USAMRIID, Mol & Translat Sci Div, Frederick, MD 21702 USA.
   [Froude, Jeffrey W.; Kuehne, Ana I.; Dye, John M.] USAMRIID, Virol Div, Frederick, MD 21702 USA.
   [Pettit, James; Kuhn, Jens H.; Olinger, Gene G.] NIH, Integrated Res Facil Ft Detrick, Natl Inst Allergy & Infect Dis, Frederick, MD 21702 USA.
   [Zeitlin, Larry] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA.
RP Palacios, GF (reprint author), USAMRIID, Ctr Genome Sci, Frederick, MD 21702 USA.
EM gustavo.f.palacios.ctr@mail.mil
RI Palacios, Gustavo/I-7773-2015
OI Palacios, Gustavo/0000-0001-5062-1938
FU Defense Threat Reduction Agency; NIAID [HHSN272200700016I]
FX The authors thank Dr. W. Ian Lipkin for critical review of this
   manuscript, Dr. Krishna Kota for advice on the high content imaging
   systems used in the work, and the USAMRIID technicians: Guido Pelaez and
   Sarah Becker in the USAMRIID Molecular and Translational Sciences
   Division. This work was supported by Defense Threat Reduction Agency.
   The content of this publication does not necessarily reflect the views
   or policies of the US Department of the Army, the US Department of
   Defense, or the US Department of Health and Human Services or of the
   institutions and companies affiliated with the authors. J.H.K. performed
   this work as an employee of Tunnell Government Services, Inc., and
   G.G.O. and J.P. as employees of MRI Global, both subcontractors to
   Battelle Memorial Institute under its prime contract with NIAID, under
   contract HHSN272200700016I.
NR 37
TC 17
Z9 17
U1 2
U2 17
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 SEP 29
PY 2015
VL 12
IS 12
BP 2111
EP 2120
DI 10.1016/j.celrep.2015.08.038
PG 10
WC Cell Biology
SC Cell Biology
GA CS4CN
UT WOS:000362022600015
PM 26365189
ER

PT J
AU Jensen, JL
   Balbo, A
   Neau, DB
   Chakravarthy, S
   Zhao, H
   Sinha, SC
   Colbert, CL
AF Jensen, Jaime L.
   Balbo, Andrea
   Neau, David B.
   Chakravarthy, Srinivas
   Zhao, Huaying
   Sinha, Sangita C.
   Colbert, Christopher L.
TI Mechanistic Implications of the Unique Structural Features and
   Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma
   Regulator, PupR
SO BIOCHEMISTRY
LA English
DT Article
ID FERRIC CITRATE TRANSPORT; RAY SOLUTION SCATTERING; SMALL-ANGLE
   SCATTERING; TONB-DEPENDENT TRANSPORTERS; CIRCULAR-DICHROISM SPECTRA;
   BACTERIAL-CELL ENVELOPE; ESCHERICHIA-COLI K-12; SIGNAL-TRANSDUCTION;
   CRYSTAL-STRUCTURE; OUTER-MEMBRANE
AB Gram-negative bacteria tightly regulate infracellular levels of iron, an essential nutrient. To ensure this strict control, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here, we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism of this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 angstrom. Size exclusion chromatography, small-angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation all indicate that, in contrast to other ASDs, the PupR-ASD exists as a diner in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. These combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation.
C1 [Jensen, Jaime L.; Sinha, Sangita C.; Colbert, Christopher L.] N Dakota State Univ, Dept Chem & Biochem, Fargo, ND 58108 USA.
   [Balbo, Andrea] Natl Inst Biomed Imaging & Bioengn, Biomed Engn & Phys Sci Shared Resource, NIH, Bethesda, MD 20892 USA.
   [Neau, David B.] Cornell Univ, Dept Chem & Chem Biol, Northeastern Collaborat Access Team, Argonne Natl Lab, Argonne, IL 60439 USA.
   [Chakravarthy, Srinivas] Biophys Collaborat Access Team, Adv Photon Source, Argonne, IL 60439 USA.
   [Zhao, Huaying] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Colbert, CL (reprint author), N Dakota State Univ, Dept Chem & Biochem, Fargo, ND 58108 USA.
EM christopher.colbert@ndsu.edu
RI ID, BioCAT/D-2459-2012; Sinha, Sangita/R-6119-2016
FU NIH NIGMS [1R15 GM113227, P30 GM103332]; NIH NCRR [2P20 RR015566]; NIH
   NINDS [1R03 NS090939]; NSF [MCB-1413525]; NSF ND EPSCoR INSPIRE DDA
   [FAR0025216]
FX This work was funded by the following grants to C.L.C.: NIH NIGMS 1R15
   GM113227, NIH NCRR 2P20 RR015566, and a pilot project grant from NIH
   NIGMS P30 GM103332; and to S.C.S.: NIH NINDS 1R03 NS090939 and NSF
   MCB-1413525. J.L.J. is supported by an NSF ND EPSCoR INSPIRE DDA
   #FAR0025216.
NR 75
TC 1
Z9 1
U1 4
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD SEP 29
PY 2015
VL 54
IS 38
BP 5867
EP 5877
DI 10.1021/acs.biochem.5b00826
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CS7DG
UT WOS:000362243700010
PM 26313375
ER

PT J
AU Menke, A
   Casagrande, S
   Cowie, CC
AF Menke, Andy
   Casagrande, Sarah
   Cowie, Catherine C.
TI Leukocyte telomere length and diabetes status, duration, and control:
   the 1999-2002 National Health and Nutrition Examination Survey
SO BMC ENDOCRINE DISORDERS
LA English
DT Article
DE Telomere; Diabetes mellitus; Aging
ID OXIDATIVE STRESS; CELLS; RISK; ASSOCIATION; BLOOD
AB Background: Studies investigating the association between telomere length and diabetes have been inconsistent, and there are few data available investigating the associations of telomere length with diabetes duration and control. We evaluated the relationship of leukocyte telomere length with diabetes, and the relationship of leukocyte telomere length with diabetes duration and poor glucose control among people with diabetes.
   Methods: We used data from the 1999-2002 National Health and Nutrition Examination Survey, a representative sample of the US civilian non-institutionalized population. In 3921 participants, leukocyte telomere length was measured and diabetes status was determined based on a previous diagnosis, hemoglobin A1c >= 6.5 %, or fasting glucose >= 126 mg/dL.
   Results: The odds ratios (95 % confidence intervals) of diabetes associated with the first, second, and third quartile of leukocyte telomere length, compared to the highest quartile, was 2.09 (1.46-2.98), 1.74 (1.30-2.31), and 1.08 (0.76-1.54), respectively (p-trend < 0.01), in unadjusted models and 0.74 (0.48-1.14), 0.91 (0.61-1.34), and 0.87 (0.59-1.29), respectively (p-trend = 0.20), in multivariable adjusted models. Among participants with diabetes, unadjusted and adjusted leukocyte telomere length was not associated with diabetes duration or glucose control based on an hemoglobin A1c < 7 or < 8 % (all p > 0.05).
   Conclusions: In this study of the US general population, leukocyte telomere length was not associated with diabetes status, diabetes duration, or diabetes control.
C1 [Menke, Andy; Casagrande, Sarah] Social & Sci Syst Inc, Silver Spring, MD 20910 USA.
   [Cowie, Catherine C.] Nat Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA.
RP Menke, A (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA.
EM amenke@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
   [GS10F0381L]
FX This work was supported by a contract from the National Institute of
   Diabetes and Digestive and Kidney Diseases (GS10F0381L). The findings
   and conclusions in this report are those of the authors and do not
   necessarily represent the official position of the National Institute of
   Diabetes and Digestive and Kidney Diseases.
NR 20
TC 5
Z9 5
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6823
J9 BMC ENDOCR DISORD
JI BMC Endocr. Disord.
PD SEP 29
PY 2015
VL 15
AR 52
DI 10.1186/s12902-015-0050-1
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS2XW
UT WOS:000361936300001
PM 26419237
ER

PT J
AU Guertin, KA
   Freedman, ND
   Loftfield, E
   Stolzenberg-Solomon, RZ
   Graubard, BI
   Sinha, R
AF Guertin, K. A.
   Freedman, N. D.
   Loftfield, E.
   Stolzenberg-Solomon, R. Z.
   Graubard, B. I.
   Sinha, R.
TI A prospective study of coffee intake and pancreatic cancer: results from
   the NIH-AARP Diet and Health Study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE pancreas; coffee; caffeine; tobacco; smoking
ID PROSPECTIVE COHORT; DECAFFEINATED COFFEE; POOLED-ANALYSIS; RISK;
   CONSUMPTION; TEA; METAANALYSIS; ASSOCIATION
AB Background: Evidence evaluating the association between type of coffee intake (caffeinated, decaffeinated) and risk of pancreatic cancer is limited.
   Methods: In the US NIH-AARP Diet and Health Study, we used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for coffee intake and risk of pancreatic cancer among 457 366 US adults.
   Results: Over 4 155 256 person-years of follow-up, 1541 incident first primary pancreatic cancers occurred. Following detailed adjustment for tobacco smoking history, risk estimates for coffee drinking were not statistically significant; compared with never drinkers of coffee, the hazard ratios (95% CI) were 1.05 (0.85-1.30), 1.06 (0.86-1.31), 1.03 (0.85-1.25), 1.00 (0.79-1.25), and 1.24 (0.93-1.65) for <1, 1, 2-3, 4-5, and >= 6 cups per day, respectively (P-value for trend 0.46). The observed null association was consistent across all examined strata (sex, smoking status, coffee caffeination, and prevalent diabetes).
   Conclusions: In a prospective study of coffee intake with the largest number of pancreatic cancer cases to date, we did not observe an association between total, caffeinated, or decaffeinated coffee intake and pancreatic cancer.
C1 [Guertin, K. A.; Freedman, N. D.; Loftfield, E.; Stolzenberg-Solomon, R. Z.; Sinha, R.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Graubard, B. I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Guertin, KA (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 9609 Med Ctr Dr,Room 6E326,MSC 9760, Bethesda, MD 20892 USA.
EM kristin.guertin@nih.gov
RI Freedman, Neal/B-9741-2015
OI Freedman, Neal/0000-0003-0074-1098
FU Intramural Research Program of the National Institutes of Health,
   Division of Cancer Epidemiology and Genetics, National Cancer Institute,
   National Institutes of Health, and Department of Health and Human
   Services
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health, Division of Cancer Epidemiology and
   Genetics, National Cancer Institute, National Institutes of Health, and
   Department of Health and Human Services.
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD SEP 29
PY 2015
VL 113
IS 7
BP 1081
EP 1085
DI 10.1038/bjc.2015.235
PG 5
WC Oncology
SC Oncology
GA CS4IM
UT WOS:000362039500012
PM 26402414
ER

PT J
AU Kigozi, SP
   Pindolia, DK
   Smith, DL
   Arinaitwe, E
   Katureebe, A
   Kilama, M
   Nankabirwa, J
   Lindsay, SW
   Staedke, SG
   Dorsey, G
   Kamya, MR
   Tatem, AJ
AF Kigozi, Simon P.
   Pindolia, Deepa K.
   Smith, David L.
   Arinaitwe, Emmanuel
   Katureebe, Agaba
   Kilama, Maxwell
   Nankabirwa, Joaniter
   Lindsay, Steve W.
   Staedke, Sarah G.
   Dorsey, Grant
   Kamya, Moses R.
   Tatem, Andrew J.
TI Associations between urbanicity and malaria at local scales in Uganda
SO MALARIA JOURNAL
LA English
DT Article
DE Urbanization; Plasmodium falciparum; Remote sensing; GIS; Urban malaria
ID SUB-SAHARAN AFRICA; LONG ROAD; URBANIZATION; TRANSMISSION; POPULATION;
   CHALLENGES; ENDEMICITY; DISEASE; HEALTH
AB Background: Sub-Saharan Africa is expected to show the greatest rates of urbanization over the next 50 years. Urbanization has shown a substantial impact in reducing malaria transmission due to multiple factors, including unfavourable habitats for Anopheles mosquitoes, generally healthier human populations, better access to healthcare, and higher housing standards. Statistical relationships have been explored at global and local scales, but generally only examining the effects of urbanization on single malaria metrics. In this study, associations between multiple measures of urbanization and a variety of malaria metrics were estimated at local scales.
   Methods: Cohorts of children and adults from 100 households across each of three contrasting sub-counties of Uganda (Walukuba, Nagongera and Kihihi) were followed for 24 months. Measures of urbanicity included density of surrounding households, vegetation index, satellite-derived night-time lights, land cover, and a composite urbanicity score. Malaria metrics included the household density of mosquitoes (number of female Anopheles mosquitoes captured), parasite prevalence and malaria incidence. Associations between measures of urbanicity and malaria metrics were made using negative binomial and logistic regression models.
   Results: One site (Walukuba) had significantly higher urbanicity measures compared to the two rural sites. In Walukuba, all individual measures of higher urbanicity were significantly associated with a lower household density of mosquitoes. The higher composite urbanicity score in Walukuba was also associated with a lower household density of mosquitoes (incidence rate ratio = 0.28, 95 % CI 0.17-0.48, p < 0.001) and a lower parasite prevalence (odds ratio, OR = 0.44, CI 0.20-0.97, p = 0.04). In one rural site (Kihihi), only a higher density of surrounding households was associated with a lower parasite prevalence (OR = 0.15, CI 0.07-0.34, p < 0.001). And, in only one rural site (Nagongera) was living where NDVI <= 0.45 associated with higher incidence of malaria (IRR = 1.35, CI 1.35-1.70, p = 0.01).
   Conclusions: Urbanicity has been shown previously to lead to a reduction in malaria transmission at large spatial scales. At finer scales, individual household measures of higher urbanicity were associated with lower mosquito densities and parasite prevalence only in the site that was generally characterized as being urban. The approaches outlined here can help better characterize urbanicity at the household level and improve targeting of control interventions.
C1 [Kigozi, Simon P.; Arinaitwe, Emmanuel; Katureebe, Agaba; Kilama, Maxwell; Nankabirwa, Joaniter; Kamya, Moses R.] Infect Dis Res Collaborat, Kampala, Uganda.
   [Pindolia, Deepa K.] Clinton Hlth Access Initiat, Boston, MA USA.
   [Smith, David L.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Smith, David L.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
   [Lindsay, Steve W.] Univ Durham, Sch Biol & Biomed Sci, Durham, England.
   [Staedke, Sarah G.] London Sch Hyg & Trop Med, London WC1, England.
   [Dorsey, Grant] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA.
   [Kamya, Moses R.] Makerere Univ, Coll Hlth Sci, Sch Med, Kampala, Uganda.
   [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
   [Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
RP Kigozi, SP (reprint author), Infect Dis Res Collaborat, Kampala, Uganda.
EM skigozi@yahoo.com
FU National Institutes of Health as part of the International Centers of
   Excellence in Malaria Research (ICMER) [U19AI089674]; RAPIDD of the
   Science and Technology Directorate, Department of Homeland Security;
   Fogarty International Center, National Institutes of Health; Bill and
   Melinda Gates Foundation [OPP1106427, 1032350]; Bill & Melinda Gates
   Foundation [OPP1110495]
FX This study was realized through the help of research Funders,
   cooperative study participants and their families, the Makerere
   University-UCSF Research Collaboration and Infectious Diseases Research
   Collaboration (IDRC) with administrative and technical support, and a
   hard working study team. Funding was provided by the National Institutes
   of Health as part of the International Centers of Excellence in Malaria
   Research (ICMER) (U19AI089674). AJT and DLS acknowledge funding support
   from the RAPIDD of the Science and Technology Directorate, Department of
   Homeland Security, and the Fogarty International Center, National
   Institutes of Health. AJT is also supported by grants from the Bill and
   Melinda Gates Foundation (OPP1106427and # 1032350). DLS acknowledges
   funding from the Bill & Melinda Gates Foundation (# OPP1110495). The
   funders had no role in the study design, data collection and analysis,
   decision to publish or preparation of the manuscript.
NR 24
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD SEP 29
PY 2015
VL 14
AR 374
DI 10.1186/s12936-015-0865-2
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CS7EQ
UT WOS:000362247300001
PM 26415959
ER

PT J
AU Liao, YL
   Tu, KX
   Han, XG
   Hu, LB
   Connell, JW
   Chen, ZF
   Lin, Y
AF Liao, Yunlong
   Tu, Kaixiong
   Han, Xiaogang
   Hu, Liangbing
   Connell, John W.
   Chen, Zhongfang
   Lin, Yi
TI Oxidative Etching of Hexagonal Boron Nitride Toward Nanosheets with
   Defined Edges and Holes
SO SCIENTIFIC REPORTS
LA English
DT Article
ID POROUS GRAPHENE MATERIALS; ENERGY-STORAGE; BULK PREPARATION; NANOMESH;
   NANORIBBONS; NANOTUBES; VAPOR; FABRICATION; GROWTH; OXIDE
AB Lateral surface etching of two-dimensional (2D) nanosheets results in holey 2D nanosheets that have abundant edge atoms. Recent reports on holey graphene showed that holey 2D nanosheets can outperform their intact counterparts in many potential applications such as energy storage, catalysis, sensing, transistors, and molecular transport/separation. From both fundamental and application perspectives, it is desirable to obtain holey 2D nanosheets with defined hole morphology and hole edge structures. This remains a great challenge for graphene and is little explored for other 2D nanomaterials. Here, a facile, controllable, and scalable method is reported to carve geometrically defined pit/hole shapes and edges on hexagonal boron nitride (h-BN) basal plane surfaces via oxidative etching in air using silver nanoparticles as catalysts. The etched h-BN was further purified and exfoliated into nanosheets that inherited the hole/edge structural motifs and, under certain conditions, possess altered optical bandgap properties likely induced by the enriched zigzag edge atoms. This method opens up an exciting approach to further explore the physical and chemical properties of hole-and edge-enriched boron nitride and other 2D nanosheets, paving the way toward applications that can take advantage of their unique structures and performance characteristics.
C1 [Liao, Yunlong; Lin, Yi] NIA, Hampton, VA 23666 USA.
   [Liao, Yunlong; Tu, Kaixiong; Chen, Zhongfang] Univ Puerto Rico, Inst Funct Nanomat, Dept Chem, San Juan, PR 00931 USA.
   [Han, Xiaogang; Hu, Liangbing] Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20742 USA.
   [Connell, John W.] NASA Langley Res Ctr, Adv Mat & Proc Branch, Hampton, VA 23681 USA.
   [Lin, Yi] Coll William & Mary, Dept Appl Sci, Williamsburg, VA 23185 USA.
RP Chen, ZF (reprint author), Univ Puerto Rico, Inst Funct Nanomat, Dept Chem, Rio Piedras Campus, San Juan, PR 00931 USA.
EM zhongfangchen@gmail.com; yi.lin@nianet.org
RI Chen, Zhongfang/A-3397-2008; Hu, Liangbing/N-6660-2013
FU Institute for Functional Nanomaterials (IFN) at University of Puerto
   Rico; National Institute of Aerospace; Internal Research and Development
   (IRAD) program from NASA Langley Research Center; Department of Defense
   [W911NF-12-1-0083]; NASA [NNX10AM80H, NNX13AB22A]
FX The authors thank Dr. W. Cao and Prof. H. Elsayed-Ali at Applied
   Research Center of Old Dominion University for their experimental
   assistance in acquiring HR-TEM images and C. Chamberlain at NASA Langley
   Research Center in conducting TGA experiments. Y. Liao is partially
   supported by the fellowship awarded via Institute for Functional
   Nanomaterials (IFN) at University of Puerto Rico. Y. Lin acknowledges
   the financial support by National Institute of Aerospace and the
   Internal Research and Development (IRAD) program from NASA Langley
   Research Center. Z. Chen acknowledges the support by Department of
   Defense (Grant W911NF-12-1-0083) and NASA (Grant Nos. NNX10AM80H and
   NNX13AB22A).
NR 37
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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 SEP 29
PY 2015
VL 5
AR 14510
DI 10.1038/srep14510
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS2DT
UT WOS:000361878700001
PM 26416484
ER

PT J
AU Goldberger, JJ
   Bonow, RO
   Cuffe, M
   Liu, L
   Rosenberg, Y
   Shah, PK
   Smith, SC
   Subacius, H
AF Goldberger, Jeffrey J.
   Bonow, Robert O.
   Cuffe, Michael
   Liu, Lei
   Rosenberg, Yves
   Shah, Prediman K.
   Smith, Sidney C., Jr.
   Subacius, Haris
CA OBTAIN Investigators
TI Effect of Beta-Blocker Dose on Survival After Acute Myocardial
   Infarction
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE adrenergic beta-antagonists; follow-up studies; registries; survival
   analysis
ID CHRONIC HEART-FAILURE; ACUTE-CORONARY-SYNDROME; RANDOMIZED-TRIALS;
   POSTMYOCARDIAL INFARCTION; CLINICAL-OUTCOMES; INDUCED REDUCTION;
   ELDERLY-PATIENTS; META-REGRESSION; METOPROLOL; MORTALITY
AB BACKGROUND Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy. OBJECTIVES This study evaluated the association of beta-blocker dose with survival after acute MI, hypothesizing that higher dose beta-blocker therapy will be associated with increased survival.
   METHODS A multicenter registry enrolled 7,057 consecutive patients with acute MI. Discharge beta-blocker dose was indexed to the target beta-blocker doses used in randomized clinical trials, grouped as >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target dose. Follow-up vital status was assessed, with the primary endpoint of time-to-death right-censored at 2 years. Multivariable and propensity score analyses were used to account for group differences.
   RESULTS Of 6,682 patients with follow-up (median 2.1 years), 91.5% were discharged on a beta-blocker (mean dose 38.1% of the target dose). Lower mortality was observed with all beta-blocker doses (p < 0.0002) versus no beta-blocker therapy. After multivariable adjustment, hazard ratios for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI]: 0.677 to 1.098), 0.799 (95% CI: 0.635 to 1.005), and 0.963 (95% CI: 0.765 to 1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose groups, respectively. Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome.
   CONCLUSIONS These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous randomized clinical trials compared with lower doses. These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy. (C) 2015 by the American College of Cardiology Foundation.
C1 [Goldberger, Jeffrey J.; Bonow, Robert O.; Subacius, Haris] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA.
   [Cuffe, Michael] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA.
   [Cuffe, Michael] Hosp Corp Amer, Brentwood, TN USA.
   [Liu, Lei] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
   [Rosenberg, Yves] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
   [Shah, Prediman K.] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA.
   [Smith, Sidney C., Jr.] Univ N Carolina, Heart & Vasc Ctr, Chapel Hill, NC USA.
RP Goldberger, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, 676 North St Clair,Arkes 600, Chicago, IL 60611 USA.
EM j-goldberger@northwestern.edu
RI Liu, Lei/B-4968-2009
OI Liu, Lei/0000-0003-1844-338X
FU National Heart, Lung, and Blood Institute of the National Institutes of
   Health [5U01HL080416]
FX This research was supported by grant 5U01HL080416 from the National
   Heart, Lung, and Blood Institute of the National Institutes of Health.
   The views expressed in this manuscript are the authors' and do not
   necessarily reflect those of the National Institutes of Health or the
   Department of Health and Human Services. Dr. Liu is a consultant to
   Celladon, Outcome Research Solutions, and Zensun. All other authors have
   reported that they have no relationships relevant to the contents of
   this paper to disclose.
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U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD SEP 29
PY 2015
VL 66
IS 13
BP 1431
EP 1441
DI 10.1016/j.jacc.2015.07.047
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR6LH
UT WOS:000361457900003
PM 26403339
ER

PT J
AU Tan, IS
   Weiss, CA
   Popham, DL
   Ramamurthi, KS
AF Tan, Irene S.
   Weiss, Cordelia A.
   Popham, David L.
   Ramamurthi, Kumaran S.
TI A Quality-Control Mechanism Removes Unfit Cells from a Population of
   Sporulating Bacteria
SO DEVELOPMENTAL CELL
LA English
DT Article
ID SUBTILIS SPORE COAT; BACILLUS-SUBTILIS; MORPHOGENETIC PROTEIN;
   ESCHERICHIA-COLI; CORTEX FORMATION; CLP PROTEASE; SIGMA-K; ROLES; GENE;
   RESISTANCE
AB Recent discoveries of regulated cell death in bacteria have led to speculation about possible benefits that apoptosis-like pathways may confer to single-celled organisms. However, establishing how these pathways provide increased ecological fitness has remained difficult to determine. Here, we report a pathway in Bacillus subtilis in which regulated cell death maintains the fidelity of sporulation through selective removal of cells that misassemble the spore envelope. The spore envelope, which protects the dormant spore's genome from environmental insults, uses the protein SpoIVA as a scaffold for assembly. We found that disrupting envelope assembly activates a cell death pathway wherein the small protein CmpA acts as an adaptor to the AAA+ ClpXP protease to degrade SpoIVA, thereby halting sporulation and resulting in lysis of defective sporulating cells. We propose that removal of unfit cells from a population of terminally differentiating cells protects against evolutionary deterioration and ultimately loss of the sporulation program.
C1 [Tan, Irene S.; Weiss, Cordelia A.; Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Tan, Irene S.] Johns Hopkins Univ, NIH, Grad Partnership Program, Baltimore, MD 21218 USA.
   [Popham, David L.] Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA.
RP Ramamurthi, KS (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM ramamurthiks@mail.nih.gov
RI Ramamurthi, Kumaran/P-3516-2015; Popham, David/F-8066-2015
OI Popham, David/0000-0002-2614-143X
FU NIH [AI088298]; Intramural Research Program of NIH, National Cancer
   Institute, Center for Cancer Research
FX We thank V. Bliskovsky (Genomics Core facility, NCI) for whole-genome
   sequencing of spontaneous suppressors; P. Setlow, R. Losick, D. Kearns,
   S. Ebmeier, and D. Ziegler (BGSC) for strains; S. Wickner for E. coli
   ClpX antiserum; S. Gottesman, S. Wickner, M. Maurizi, G. Storz, M.
   Lichten, and Y.-S. Lee for discussion; and A. Hitchcock-Camp and C.
   Ellermeier for comments on the manuscript. This work was funded by NIH
   grant AI088298 (D.L.P.) and the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research (K.S.R.).
NR 56
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U2 4
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 SEP 28
PY 2015
VL 34
IS 6
BP 682
EP 693
DI 10.1016/j.devcel.2015.08.009
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA CS2ZT
UT WOS:000361941500009
PM 26387458
ER

PT J
AU Hu, N
   Wang, CY
   Clifford, RJ
   Yang, HH
   Su, H
   Wang, LM
   Wang, Y
   Xu, Y
   Tang, ZZ
   Ding, T
   Zhang, TW
   Goldstein, AM
   Giffen, C
   Lee, MP
   Taylor, PR
AF Hu, Nan
   Wang, Chaoyu
   Clifford, Robert J.
   Yang, Howard H.
   Su, Hua
   Wang, Lemin
   Wang, Yuan
   Xu, Yi
   Tang, Ze-Zhong
   Ding, Ti
   Zhang, Tongwu
   Goldstein, Alisa M.
   Giffen, Carol
   Lee, Maxwell P.
   Taylor, Philip R.
TI Integrative genomics analysis of genes with biallelic loss and its
   relation to the expression of mRNA and micro-RNA in esophageal squamous
   cell carcinoma
SO BMC GENOMICS
LA English
DT Article
DE Esophageal squamous cell carcinoma; Biallelic loss; Gene expression;
   microRNA
ID HIGH-RISK POPULATION; NUMBER NEUTRAL LOSS; HOMOZYGOUS DELETIONS; CANCER
   STATISTICS; CHINA; HETEROZYGOSITY; ADENOCARCINOMA; INACTIVATION;
   METASTASIS; SUBGROUPS
AB Background: Genomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) and copy number (CN) changes in tumors. In the current study we focus on biallelic loss and its relation to expression of mRNA and miRNA in ESCC using results from 500K SNP, mRNA, and miRNA arrays in 30 cases from a high-risk region of China.
   Results: (i) Biallelic loss was uncommon but when it occurred it exhibited a consistent pattern: only 77 genes (<0.5%) showed biallelic loss in at least 10% of ESCC samples, but nearly all of these genes were concentrated on just four chromosomal arms (ie, 42 genes on 3p, 14 genes on 9p, 10 genes on 5q, and seven genes on 4p). (ii) Biallelic loss was associated with lower mRNA expression: 52 of the 77 genes also had RNA expression data, and 41 (79%) showed lower expression levels in cases with biallelic loss compared to those without. (iii) The relation of biallelic loss to miRNA expression was less clear but appeared to favor higher miRNA levels: of 60 miRNA-target gene pairs, 34 pairs (57%) had higher miRNA expression with biallelic loss than without, while 26 pairs (43%) had lower miRNA expression. (iv) Finally, the effect of biallelic loss on the relation between miRNA and mRNA expression was complex. Biallelic loss was most commonly associated with a pattern of elevated miRNA and reduced mRNA (43%), but a pattern of both reduced miRNA and mRNA was also common (35%).
   Conclusion: Our results indicate that biallelic loss in ESCC is uncommon, but when it occurs it is localized to a few specific chromosome regions and is associated with reduced mRNA expression of affected genes. The effect of biallelic loss on miRNA expression and on the relation between miRNA and mRNA expressions was complex.
C1 [Hu, Nan; Wang, Chaoyu; Su, Hua; Wang, Lemin; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, DCEG, Bethesda, MD 20892 USA.
   [Clifford, Robert J.; Yang, Howard H.; Lee, Maxwell P.] Ctr Canc Res, Basic Res Lab, High Dimens Data Anal Grp, Bethesda, MD 20892 USA.
   [Wang, Yuan; Xu, Yi; Tang, Ze-Zhong; Ding, Ti] Shanxi Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China.
   [Zhang, Tongwu] NCI, Lab Translat Genom, DCEG, Bethesda, MD 20892 USA.
   [Giffen, Carol] Information Management Serv Inc, Bethesda, MD 20904 USA.
RP Lee, MP (reprint author), Ctr Canc Res, Basic Res Lab, High Dimens Data Anal Grp, 9609 Med Ctr Dr,Rm 1W586, Bethesda, MD 20892 USA.
EM leemax@mail.nih.gov; ptaylor@mail.nih.gov
RI Zhang, Tongwu/M-4975-2015
FU Intramural Research Program of the NIH, the National Cancer Institute,
   the Division of Cancer Epidemiology and Genetics, and the Center for
   Cancer Research
FX This research was supported by the Intramural Research Program of the
   NIH, the National Cancer Institute, the Division of Cancer Epidemiology
   and Genetics, and the Center for Cancer Research.
NR 30
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U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD SEP 26
PY 2015
VL 16
AR 732
DI 10.1186/s12864-015-1919-0
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CS0YC
UT WOS:000361787100001
PM 26409826
ER

PT J
AU Griggs, J
   Church, G
AF Griggs, Jessica
   Church, George
TI Our superhuman future is just a few edits away
SO NEW SCIENTIST
LA English
DT Editorial Material
C1 [Church, George] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
   [Church, George] NIH, Ctr Causal Consequences Variat, Ctr Excellence Genom Sci, Cambridge, MA USA.
   [Church, George] PersonalGenomes Org, London, England.
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U1 3
U2 5
PU REED BUSINESS INFORMATION LTD
PI SUTTON
PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND
SN 0262-4079
J9 NEW SCI
JI New Sci.
PD SEP 26
PY 2015
VL 227
IS 3040
BP 28
EP 30
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1UW
UT WOS:000361855000014
ER

PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Origin of eukaryotes from within archaea, archaeal eukaryome and bursts
   of gene gain: eukaryogenesis just made easier?
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE endosymbiosis; phagocytosis; cytoskeleton; horizontal gene transfer;
   archaea
ID UBIQUITIN-RELATED DOMAINS; NUCLEAR-PORE-COMPLEX; CELL-DIVISION; PROTEIN
   MODIFIER; BACTERIAL-CELL; PHYLOGENETIC CLASSIFICATION; MICROBIAL
   DIVERSITY; ARGONAUTE PROTEINS; ORTHOLOGOUS GENES; PROVIDES EVIDENCE
AB The origin of eukaryotes is a fundamental, forbidding evolutionary puzzle. Comparative genomic analysis clearly shows that the last eukaryotic common ancestor (LECA) possessed most of the signature complex features of modern eukaryotic cells, in particular the mitochondria, the endomembrane system including the nucleus, an advanced cytoskeleton and the ubiquitin network. Numerous duplications of ancestral genes, e.g. DNA polymerases, RNA polymerases and proteasome subunits, also can be traced back to the LECA. Thus, the LECA was not a primitive organism and its emergence must have resulted from extensive evolution towards cellular complexity. However, the scenario of eukaryogenesis, and in particular the relationship between endosymbiosis and the origin of eukaryotes, is far from being clear. Four recent developments provide new clues to the likely routes of eukaryogenesis. First, evolutionary reconstructions suggest complex ancestors for most of the major groups of archaea, with the subsequent evolution dominated by gene loss. Second, homologues of signature eukaryotic proteins, such as actin and tubulin that form the core of the cytoskeleton or the ubiquitin system, have been detected in diverse archaea. The discovery of this 'dispersed eukaryome' implies that the archaeal ancestor of eukaryotes was a complex cell that might have been capable of a primitive form of phagocytosis and thus conducive to endosymbiont capture. Third, phylogenomic analyses converge on the origin of most eukaryotic genes of archaeal descent from within the archaeal evolutionary tree, specifically, the TACK superphylum. Fourth, evidence has been presented that the origin of the major archaeal phyla involved massive acquisition of bacterial genes. Taken together, these findings make the symbiogenetic scenario for the origin of eukaryotes considerably more plausible and the origin of the organizational complexity of eukaryotic cells more readily explainable than they appeared until recently.
C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Services
FX The author's research is supported by intramural funds of the US
   Department of Health and Human Services (to the National Library of
   Medicine, NIH).
NR 161
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Z9 15
U1 19
U2 78
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD SEP 26
PY 2015
VL 370
IS 1678
AR 20140333
DI 10.1098/rstb.2014.0333
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CQ4CV
UT WOS:000360552800013
PM 26323764
ER

PT J
AU Wang, ZQ
   Yang, BX
   Liu, YS
   Shugart, YY
   Cheng, ZH
   Jin, CH
   Yuan, JM
   Zhu, W
   Wang, GQ
   Zhang, FQ
AF Wang, Zhiqiang
   Yang, Bixiu
   Liu, Yansong
   Shugart, Yin Yao
   Cheng, Zaohuo
   Jin, Chunhui
   Yuan, Jianmin
   Zhu, Wei
   Wang, Guoqiang
   Zhang, Fuquan
TI Further evidence supporting the association of NKAPL with schizophrenia
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Schizophrenia; NKAPL; rs1635
ID GENOME-WIDE ASSOCIATION; HAN CHINESE; COMMON VARIANTS; LOCUS; CELLS
AB Schizophrenia (SZ) is a severe chronic mental disorder with complex genetic mechanisms. Increasing evidence implicate immune system dysfunction in the pathogenesis of SZ. The non-synonymous single nucleotide polymorphism (SNP) rs1635 in NKAPL, was identified by a genome-wide association study (GWAS) for SZ in Han Chinese from north China. A replication study failed to detect the association of rs1635 with SZ in Han Chinese from central south of China, while another one confirmed the positive association in Han Chinese from Taiwan. To further clarify these findings, we conducted a case-control association study of rs1635 in a cohort of Han Chinese from east China, including 1406 SZ cases and 1136 healthy controls. We detected a positive association of rs1635 with SZ, with the major allele (G) of rs1635 conferring a risk for SZ (P=0.033, OR=1.14). Our findings add further evidence for the involvement of NKAPL polymorphisms in the development of SZ. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Wang, Zhiqiang; Yang, Bixiu] Cent S Univ, Key Lab Psychiat & Mental Hlth Hunan Prov, Natl Technol Inst Psychiat, Mental Hlth Inst,Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.
   [Liu, Yansong; Cheng, Zaohuo; Jin, Chunhui; Yuan, Jianmin; Zhu, Wei; Wang, Guoqiang; Zhang, Fuquan] Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China.
   [Shugart, Yin Yao] NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Wang, GQ (reprint author), Wuxi Mental Hlth Ctr, 156 Qianrong Rd, Wuxi 214151, Jiangsu, Peoples R China.
EM wuwangguoqiang@126.com; zfqeee@126.com
FU National Natural Science Foundation of China [81471364]
FX We would sincerely thank the SZ participants, their families and the
   healthy volunteers for their participation, and all the medical staff
   involved in specimen collection. This work was supported by the National
   Natural Science Foundation of China (81471364).
NR 21
TC 2
Z9 2
U1 2
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD SEP 25
PY 2015
VL 605
BP 49
EP 52
DI 10.1016/j.neulet.2015.08.023
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA CT6JB
UT WOS:000362918200010
PM 26297123
ER

PT J
AU de Sousa, RT
   Streck, EL
   Forlenza, OV
   Brunoni, AR
   Zanetti, MV
   Ferreira, GK
   Diniz, BS
   Portela, LV
   Carvalho, AF
   Zarate, CA
   Gattaz, WF
   Machado-Vieira, R
AF de Sousa, Rafael T.
   Streck, Emilio L.
   Forlenza, Orestes V.
   Brunoni, Andre R.
   Zanetti, Marcus V.
   Ferreira, Gabriela K.
   Diniz, Breno S.
   Portela, Luis V.
   Carvalho, Andre F.
   Zarate, Carlos A., Jr.
   Gattaz, Wagner F.
   Machado-Vieira, Rodrigo
TI Regulation of leukocyte tricarboxylic acid cycle in drug-naive Bipolar
   Disorder
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Bipolar disorder; Mitochondria; Bioenergetics; Tricarboxylic acid cycle;
   Pathophysiology; Depression
ID PERIPHERAL-BLOOD LEUKOCYTES; COMPLEX I ACTIVITY;
   SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; SKELETAL-MUSCLE;
   RATING-SCALE; LITHIUM; BRAIN; MANIA; DEHYDROGENASE
AB Several lines of evidence suggest a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA cycle) is fundamental for mitochondrial energy production and produces substrates used in oxidative phosphorylation by the mitochondrial electron transport chain. The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase, and succinate dehydrogenase has never been evaluated in BD. In the present study, these enzymes were assayed from leukocytes of drug-naive BD patients in a major depressive episode (n = 18) and compared to 24 age-matched healthy controls. Drug-naive BD patients did not show differences in activities of citrate synthase (p = 0.79), malate dehydrogenase (p = 0.17), and succinate dehydrogenase (p = 0.35) compared with healthy controls. No correlation between any TCA cycle enzyme activity and severity of depressive symptoms was observed. Overall, these data suggest that the activities of the TCA cycle enzymes are not altered in major depressive episodes of recent-onset BD, which may support the concept of illness staging and neuroprogression in BD. Published by Elsevier Ireland Ltd.
C1 [de Sousa, Rafael T.; Forlenza, Orestes V.; Brunoni, Andre R.; Zanetti, Marcus V.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, Lab Neurosci, BR-05508 Sao Paulo, Brazil.
   [de Sousa, Rafael T.; Zarate, Carlos A., Jr.] NIMH, ETPB, NIH, Bethesda, MD 20892 USA.
   [Streck, Emilio L.; Ferreira, Gabriela K.] Univ Extremo Sul Catarinense, Lab Bioenerget, Programa Posgrad Ciencias Saude, Criciuma, SC, Brazil.
   [Zanetti, Marcus V.] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo, Brazil.
   [Zanetti, Marcus V.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept & Inst Psychiat, Lab Psychiat Neuroimaging, BR-05508 Sao Paulo, Brazil.
   [Diniz, Breno S.] Univ Fed Minas Gerais, Fac Med, Dept Mental Hlth, Belo Horizonte, MG, Brazil.
   [Diniz, Breno S.] Univ Fed Minas Gerais, Natl Inst Sci & Technol Mol Med, Belo Horizonte, MG, Brazil.
   [Portela, Luis V.] Fed Univ Rio Grande Sul UFRGS, ICBS, Dept Biochem, Postgrad Program Biochem, Porto Alegre, RS, Brazil.
   [Carvalho, Andre F.] Univ Fed Ceara, Translat Psychiat Res Grp, Fortaleza, Ceara, Brazil.
   [Carvalho, Andre F.] Univ Fed Ceara, Dept Clin Med, Fac Med, Fortaleza, Ceara, Brazil.
RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Dept & Inst Psychiat, LIM 27, BR-05508 Sao Paulo, Brazil.
EM machadovieirar@gmail.com
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; 
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Diniz,
   Breno/0000-0003-0653-1905; Russowsky Brunoni, Andre/0000-0002-6310-3571
FU Sao Paulo Research Foundation (FAPESP, Brazil) [2009/14891-9];
   Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS); JNK
   Empreendimentos e Incorporacoes
FX We thank Sao Paulo Research Foundation for funding our study (FAPESP,
   Brazil; Grant 2009/14891-9, RM-V); FAPESP had no role in the design of
   the study, collection, analysis of data, and decision to publish. We
   also thank Associacao Beneficente Alzira Denise Hertzog da Silva
   (ABADHS) and JNK Empreendimentos e Incorporacoes support to Laboratory
   of Neurosciences.
NR 30
TC 1
Z9 1
U1 1
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD SEP 25
PY 2015
VL 605
BP 65
EP 68
DI 10.1016/j.neulet.2015.08.022
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA CT6JB
UT WOS:000362918200013
PM 26297865
ER

PT J
AU Gutierrez, L
   House, MJ
   Vasavda, N
   Drasar, E
   Marin, IGGY
   Kulasekararaj, AG
   St Pierre, TG
   Thein, SL
AF Gutierrez, Lucia
   House, Michael J.
   Vasavda, Nisha
   Drasar, Emma
   Gonzalez-Gascon y Marin, Isabel
   Kulasekararaj, Austin G.
   St Pierre, Tim G.
   Thein, Swee L.
TI Tissue Iron Distribution Assessed by MRI in Patients with Iron Loading
   Anemias
SO PLOS ONE
LA English
DT Article
ID SICKLE-CELL-DISEASE; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA;
   BETA-THALASSEMIA MAJOR; BONE-MARROW; MAGNETIC-RESONANCE; SERUM FERRITIN;
   LIVER-BIOPSY; OVERLOAD; STORES; RELAXOMETRY
AB Bone marrow, spleen, liver and kidney proton transverse relaxation rates (R2), together with cardiac R2* from patients with sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNH) and non-transfusion dependent thalassemia (NTDT) have been compared with a control group. Increased liver and bone marrow R2 values for the three groups of patients in comparison with the controls have been found. SCD and PNH patients also present an increased spleen R2 in comparison with the controls. The simultaneous measurement of R2 values for several tissue types by magnetic resonance imaging (MRI) has allowed the identification of iron distribution patterns in diseases associated with iron imbalance. Preferential liver iron loading is found in the highly transfused SCD patients, while the low transfused ones present a preferential iron loading of the spleen. Similar to the highly transfused SCD group, PNH patients preferentially accumulate iron in the liver. A reduced spleen iron accumulation in comparison with the liver and bone marrow loading has been found in NTDT patients, presumably related to the differential increased intestinal iron absorption. The correlation between serum ferritin and tissue R2 is moderate to good for the liver, spleen and bone marrow in SCD and PNH patients. However, serum ferritin does not correlate with NTDT liver R2, spleen R2 or heart R2*. As opposed to serum ferritin measurements, tissue R2 values are a more direct measurement of each tissue's iron loading. This kind of determination will allow a better understanding of the different patterns of tissue iron biodistribution in diseases predisposed to tissue iron accumulation.
C1 [Gutierrez, Lucia] ICMM CSIC, Inst Ciencia Mat Madrid, Madrid, Spain.
   [Gutierrez, Lucia; House, Michael J.; St Pierre, Tim G.] Univ Western Australia, Sch Phys, Crawley, WA, Australia.
   [Vasavda, Nisha; Drasar, Emma; Gonzalez-Gascon y Marin, Isabel; Kulasekararaj, Austin G.; Thein, Swee L.] Kings Coll London, Fac Life Sci & Med, Mol Haematol, London WC2R 2LS, England.
   [Drasar, Emma; Kulasekararaj, Austin G.; Thein, Swee L.] Kings Coll Hosp NHS Fdn Trust, Dept Haematol, London, England.
   [Gonzalez-Gascon y Marin, Isabel] Hosp Infanta Leonor, Dept Haematol, Madrid, Spain.
   [Thein, Swee L.] NHLB, NIH, Sickle Cell Branch, Bethesda, MD 20892 USA.
RP Gutierrez, L (reprint author), ICMM CSIC, Inst Ciencia Mat Madrid, Madrid, Spain.
EM lucia@icmm.csic.es
RI House, Michael/B-6477-2008; Gutierrez, Lucia/A-4305-2008
OI House, Michael/0000-0002-1752-6274; Gutierrez, Lucia/0000-0003-2366-3598
FU AXA Research Fund; Medical Research Council (UK) Development grant
   [G0001249 ID: 62593]
FX LG is the beneficiary of a postdoctoral grant from the AXA Research
   Fund. SLT was funded by an Medical Research Council (UK) Development
   grant (G0001249 ID: 62593). The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 39
TC 0
Z9 0
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 25
PY 2015
VL 10
IS 9
AR e0139220
DI 10.1371/journal.pone.0139220
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1CR
UT WOS:000361800700193
PM 26406992
ER

PT J
AU Stanfill, A
   Hathaway, D
   Cashion, A
   Homayouni, R
   Cowan, P
   Thompson, C
   Madahian, B
   Conley, Y
AF Stanfill, Ansley
   Hathaway, Donna
   Cashion, Ann
   Homayouni, Ramin
   Cowan, Patricia
   Thompson, Carol
   Madahian, Behrouz
   Conley, Yvette
TI A Pilot Study of Demographic and Dopaminergic Genetic Contributions to
   Weight Change in Kidney Transplant Recipients
SO PLOS ONE
LA English
DT Article
ID OBESITY; POLYMORPHISMS; THERAPY; TRIAL; GAIN
AB Kidney transplant recipients often experience a significant amount of weight gain in the first year post-transplantation. While demographic factors such as age, race, and sex have been associated with weight gain in this population, these factors do not explain all of the variability seen. A number of studies have suggested that genetics also plays a critical role in weight changes. Recently, alterations in the activity of the neurotransmitter dopamine have been associated with weight change, and gene expression studies in kidney transplant recipients have supported this association. The purpose of this pilot study is to first examine the feasibility and methodology, and then to examine the associations of age, race, sex, and genotype for 13 SNPs and 3 VNTRs in 9 dopaminergic pathway genes (ANKK1, DRD2, DRD3, DRD4, SLC6A3/DAT1, MAOA, MAOB, COMT, CPE) for associations with percent weight change at 12 months post-transplantation. Seventy kidney transplant recipients had demographic and clinical data collected as a part of a larger observational study. DNA was extracted from repository buffy coat samples taken at the time of transplant, and genotyped using Taqman and PCR based methods. Three SNPs were independently associated with percent weight change: ANKK1 rs1800497 (r = -0.28, p = 0.05), SLC6A3/DAT1 rs6347 (p = 0.046), and CPE rs1946816 (p = 0.028). Stepwise regression modelling confirmed the combined associations of age (p = 0.0021), DRD4 VNTR 4/5 genotype (p = 0.0074), and SLC6A3/DAT1 rs6347 CC genotype (p = 0.0009) and TT genotype (p = 0.0004) with percent weight change in a smaller sample (n = 35) of these kidney transplant recipients that had complete genotyping. These associations indicate that there may be a genetic, and an age component to weight changes post transplantation.
C1 [Stanfill, Ansley; Conley, Yvette] Univ Pittsburgh, Hlth Promot & Dev, Pittsburgh, PA 15260 USA.
   [Hathaway, Donna; Cowan, Patricia] Univ Tennessee, Ctr Hlth Sci, Coll Nursing, Memphis, TN 38163 USA.
   [Cashion, Ann] NINR, NIH, Bethesda, MD 20892 USA.
   [Homayouni, Ramin; Madahian, Behrouz] Univ Memphis, Bioinformat, Memphis, TN 38152 USA.
   [Thompson, Carol] Univ Kentucky, Coll Nursing, Lexington, KY USA.
RP Stanfill, A (reprint author), Univ Pittsburgh, Hlth Promot & Dev, Pittsburgh, PA 15260 USA.
EM Stanfill@pitt.edu
FU National Institute of Nursing Resarch [1F31NR013812, T32 NR009759];
   Southern Nursing Research Society
FX Funding: This work was supported by the National Institute of Nursing
   Resarch grant 1F31NR013812 to AS; by the National Institute of Nursing
   Resarch grant T32 NR009759 to YC; and by the Southern Nursing Research
   Society Dissertation award to AS. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 25
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 25
PY 2015
VL 10
IS 9
AR e0138885
DI 10.1371/journal.pone.0138885
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1CR
UT WOS:000361800700109
PM 26406335
ER

PT J
AU Kakar, S
   Fang, XY
   Lubkowska, L
   Zhou, YN
   Shaw, GX
   Wang, YX
   Jin, DJ
   Kashlev, M
   Ji, XH
AF Kakar, Smita
   Fang, Xianyang
   Lubkowska, Lucyna
   Zhou, Yan Ning
   Shaw, Gary X.
   Wang, Yun-Xing
   Jin, Ding Jun
   Kashlev, Mikhail
   Ji, Xinhua
TI Allosteric Activation of Bacterial Swi2/Snf2 (Switch/Sucrose
   Non-fermentable) Protein RapA by RNA Polymerase BIOCHEMICAL AND
   STRUCTURAL STUDIES
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SMALL-ANGLE SCATTERING; X-RAY-SCATTERING; MOLECULAR-STRUCTURE
   DETERMINATION; REPAIR COUPLING FACTOR; BIOLOGICAL MACROMOLECULES;
   THERMUS-THERMOPHILUS; CRYSTAL-STRUCTURE; HIGH-RESOLUTION; XPLOR-NIH;
   TRANSCRIPTION
AB Members of the Swi2/Snf2 (switch/sucrose non-fermentable) family depend on their ATPase activity to mobilize nucleic acid-protein complexes for gene expression. In bacteria, RapA is an RNA polymerase (RNAP)-associated Swi2/Snf2 protein that mediates RNAP recycling during transcription. It is known that the ATPase activity of RapA is stimulated by its interaction with RNAP. It is not known, however, how the RapA-RNAP interaction activates the enzyme. Previously, we determined the crystal structure of RapA. The structure revealed the dynamic nature of its N-terminal domain (Ntd), which prompted us to elucidate the solution structure and activity of both the full-length protein and its Ntd-truncated mutant (RapA Delta N). Here, we report the ATPase activity of RapA and RapA Delta N in the absence or presence of RNAP and the solution structures of RapA and RapA Delta N either ligand-free or in complex with RNAP. Determined by small-angle x-ray scattering, the solution structures reveal a new conformation of RapA, define the binding mode and binding site of RapA on RNAP, and show that the binding sites of RapA and sigma(70) on the surface of RNAP largely overlap. We conclude that the ATPase activity of RapA is inhibited by its Ntd but stimulated by RNAP in an allosteric fashion and that the conformational changes of RapA and its interaction with RNAP are essential for RNAP recycling. These and previous findings outline the functional cycle of RapA, which increases our understanding of the mechanism and regulation of Swi2/Snf2 proteins in general and of RapA in particular. The new structural information also leads to a hypothetical model of RapA in complex with RNAP immobilized during transcription.
C1 [Ji, Xinhua] NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
   [Fang, Xianyang; Wang, Yun-Xing] NCI, Struct Biophys Lab, NIH, Frederick, MD 21702 USA.
   [Lubkowska, Lucyna; Zhou, Yan Ning; Jin, Ding Jun; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
RP Jin, DJ (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
EM jind@mail.nih.gov; kashlevm@mail.nih.gov; jix@mail.nih.gov
FU United States Department of Energy, Office of Science, Office of Basic
   Energy Sciences [DE-AC02-06CH11357]
FX We thank Drs. Xiaobing Zuo and Randall Winans for assistance with the
   SAXS experiments, Dr. Charles D. Schwieters for helpful discussions of
   Xplor-NIH, and Dr. Genbin Shi for critical reading of the manuscript.
   SAXS was collected at the Advanced Photon Source (APS), Argonne National
   Laboratory. Use of the APS was supported by the United States Department
   of Energy, Office of Science, Office of Basic Energy Sciences under
   Contract DE-AC02-06CH11357 and under Partner User Proposal PUP 22978.
   In-gel digestion and mass spectrometry were performed at the Protein
   Chemistry Laboratory, Frederick National Laboratory for Cancer Research.
NR 47
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U1 1
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 25
PY 2015
VL 290
IS 39
BP 23656
EP 23669
DI 10.1074/jbc.M114.618801
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CS1IF
UT WOS:000361816500016
PM 26272746
ER

PT J
AU Mott, BT
   Eastman, RT
   Guha, R
   Sherlach, KS
   Siriwardana, A
   Shinn, P
   McKnight, C
   Michael, S
   Lacerda-Queiroz, N
   Patel, PR
   Khine, P
   Sun, HM
   Kasbekar, M
   Aghdam, N
   Fontaine, SD
   Liu, DB
   Mierzwa, T
   Mathews-Griner, LA
   Ferrer, M
   Renslo, AR
   Inglese, J
   Yuan, J
   Roepe, PD
   Su, XZ
   Thomas, CJ
AF Mott, Bryan T.
   Eastman, Richard T.
   Guha, Rajarshi
   Sherlach, Katy S.
   Siriwardana, Amila
   Shinn, Paul
   McKnight, Crystal
   Michael, Sam
   Lacerda-Queiroz, Norinne
   Patel, Paresma R.
   Khine, Pwint
   Sun, Hongmao
   Kasbekar, Monica
   Aghdam, Nima
   Fontaine, Shaun D.
   Liu, Dongbo
   Mierzwa, Tim
   Mathews-Griner, Lesley A.
   Ferrer, Marc
   Renslo, Adam R.
   Inglese, James
   Yuan, Jing
   Roepe, Paul D.
   Su, Xin-zhuan
   Thomas, Craig J.
TI High-throughput matrix screening identifies synergistic and antagonistic
   antimalarial drug combinations
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CHLOROQUINE RESISTANCE TRANSPORTER; PLASMODIUM-FALCIPARUM MALARIA;
   ARTEMISININ RESISTANCE; PARASITES; QUANTIFICATION; INHIBITORS;
   MEFLOQUINE; MECHANISM; EFFICACY; TARGETS
AB Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of approved and investigational drugs, tested 13,910 drug pairs, and identified many promising antimalarial drug combinations. The activity of known antimalarial drug regimens was confirmed and a myriad of new classes of positively interacting drug pairings were discovered. Network and clustering analyses reinforced established mechanistic relationships for known drug combinations and identified several novel mechanistic hypotheses. From eleven screens comprising >4,600 combinations per parasite strain (including duplicates) we further investigated interactions between approved antimalarials, calcium homeostasis modulators, and inhibitors of phosphatidylinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR). These studies highlight important targets and pathways and provide promising leads for clinically actionable antimalarial therapy.
C1 [Mott, Bryan T.; Guha, Rajarshi; Shinn, Paul; McKnight, Crystal; Michael, Sam; Patel, Paresma R.; Sun, Hongmao; Kasbekar, Monica; Aghdam, Nima; Liu, Dongbo; Mierzwa, Tim; Mathews-Griner, Lesley A.; Ferrer, Marc; Inglese, James; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20892 USA.
   [Eastman, Richard T.; Lacerda-Queiroz, Norinne; Khine, Pwint; Yuan, Jing; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Sherlach, Katy S.; Siriwardana, Amila; Aghdam, Nima; Roepe, Paul D.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
   [Roepe, Paul D.] Georgetown Univ, Dept Biochem Cellular & Mol Biol, Washington, DC USA.
   [Roepe, Paul D.] Georgetown Univ, Ctr Infect Dis, Washington, DC USA.
   [Fontaine, Shaun D.; Renslo, Adam R.] Univ Calif San Francisco, Dept Pharmaceut Chem Small Mol Discovery, San Francisco, CA 94143 USA.
   [Inglese, James] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Thomas, CJ (reprint author), NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20892 USA.
EM roepep@georgetown.edu; XSU@niaid.nih.gov; craigt@mail.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU Division of Preclinical Innovation, National Center for Advancing
   Translational Sciences; Molecular Libraries Initiative of the National
   Institutes of Health Roadmap for Medical Research; Division of
   Intramural Research at the National Institute of Allergy and Infectious
   Diseases (NIAID) [U54CA143930, RO1 AI111962]
FX The authors thank Ken Chih-Chien Cheng, Ian Goldlust, Ben Munoz, Theresa
   Shapiro and David Sullivan for assistance and helpful discussion during
   the course of this work. This work was supported by the Division of
   Preclinical Innovation, National Center for Advancing Translational
   Sciences, the Molecular Libraries Initiative of the National Institutes
   of Health Roadmap for Medical Research, the Division of Intramural
   Research at the National Institute of Allergy and Infectious Diseases
   (NIAID) and grants # U54CA143930 and RO1 AI111962.
NR 52
TC 10
Z9 10
U1 2
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 25
PY 2015
VL 5
AR 13891
DI 10.1038/srep13891
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0JQ
UT WOS:000361745700001
PM 26403635
ER

PT J
AU Chung, HS
   Piana-Agostinetti, S
   Shaw, DE
   Eaton, WA
AF Chung, Hoi Sung
   Piana-Agostinetti, Stefano
   Shaw, David E.
   Eaton, William A.
TI Structural origin of slow diffusion in protein folding
SO SCIENCE
LA English
DT Article
ID SINGLE-MOLECULE FRET; 3-HELIX BUNDLE PROTEIN; TRANSITION PATH TIMES;
   INTERNAL-FRICTION; REACTION COORDINATE; CHEMICAL-REACTIONS; ENERGY
   LANDSCAPE; CHAIN DYNAMICS; VISCOSITY; KINETICS
AB Experimental, theoretical, and computational studies of small proteins suggest that interresidue contacts not present in the folded structure play little or no role in the self-assembly mechanism. Non-native contacts can, however, influence folding kinetics by introducing additional local minima that slow diffusion over the global free-energy barrier between folded and unfolded states. Here, we combine single-molecule fluorescence with all-atom molecular dynamics simulations to discover the structural origin for the slow diffusion that markedly decreases the folding rate for a designed a-helical protein. Our experimental determination of transition path times and our analysis of the simulations point to non-native salt bridges between helices as the source, which provides a quantitative glimpse of how specific intramolecular interactions influence protein folding rates by altering dynamics and not activation free energies.
C1 [Chung, Hoi Sung; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Piana-Agostinetti, Stefano; Shaw, David E.] DE Shaw Res, New York, NY 10036 USA.
   [Shaw, David E.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
RP Chung, HS (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM chunghoi@niddk.nih.gov; stefano.piana-agostinetti@DEShawResearch.com;
   david.shaw@DEShawResearch.com; eaton@helix.nih.gov
RI Chung, Hoi Sung/C-2624-2009
FU NIDDK
FX We thank R. Best and A. Szabo for many helpful and insightful
   discussions. Work at NIH was supported by the Intramural Research
   Program of the NIDDK. We are also thank J. M. Louis for the preparation,
   dye labeling, and purification of the protein used in this work, with
   technical assistance from A. Aniana.
NR 42
TC 29
Z9 29
U1 20
U2 113
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 SEP 25
PY 2015
VL 349
IS 6255
BP 1504
EP 1510
DI 10.1126/science.aab1369
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR9WA
UT WOS:000361707000039
PM 26404828
ER

PT J
AU Cicmil, N
   Cumming, BG
   Parker, AJ
   Krug, K
AF Cicmil, Nela
   Cumming, Bruce G.
   Parker, Andrew J.
   Krug, Kristine
TI Reward modulates the effect of visual cortical microstimulation on
   perceptual decisions
SO ELIFE
LA English
DT Article
ID SUPERIOR TEMPORAL SULCUS; PARIETAL CORTEX; AREA MT; LATERAL
   INTRAPARIETAL; FUNCTIONAL-PROPERTIES; BINOCULAR DISPARITY; STEREOSCOPIC
   DEPTH; MACAQUE MONKEY; RHESUS-MONKEY; RESPONSE BIAS
AB Effective perceptual decisions rely upon combining sensory information with knowledge of the rewards available for different choices. However, it is not known where reward signals interact with the multiple stages of the perceptual decision-making pathway and by what mechanisms this may occur. We combined electrical microstimulation of functionally specific groups of neurons in visual area V5/MT with performance-contingent reward manipulation, while monkeys performed a visual discrimination task. Microstimulation was less effective in shifting perceptual choices towards the stimulus preferences of the stimulated neurons when available reward was larger. Psychophysical control experiments showed this result was not explained by a selective change in response strategy on microstimulated trials. A bounded accumulation decision model, applied to analyse behavioural performance, revealed that the interaction of expected reward with microstimulation can be explained if expected reward modulates a sensory representation stage of perceptual decision-making, in addition to the better-known effects at the integration stage.
C1 [Cicmil, Nela; Parker, Andrew J.; Krug, Kristine] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England.
   [Cumming, Bruce G.] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
RP Cicmil, N (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Oxford, England.
EM nela.cicmil@dpag.ox.ac.uk
OI Parker, Andrew/0000-0001-5800-0407; Krug, Kristine/0000-0001-7119-9350
FU Wellcome Trust [065511/Z/01/Z, WT101092MA]; Usher Cunningham Studentship
   (DPAG and Exeter College, Oxford); National Institutes of Health (NIH)
   [EY000404]
FX Wellcome Trust 065511/Z/01/Z and WT101092MA Andrew J Parker, Kristine
   Krug; Usher Cunningham Studentship (DPAG and Exeter College, Oxford)
   Graduate Studentship Nela Cicmil; National Institutes of Health (NIH)
   EY000404 Bruce G Cumming
NR 70
TC 3
Z9 3
U1 2
U2 2
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD SEP 24
PY 2015
VL 4
AR e07832
DI 10.7554/eLife.07832
PG 25
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DJ0EJ
UT WOS:000373874300001
PM 26402458
ER

PT J
AU Xie, L
   Bourne, PE
AF Xie, Lei
   Bourne, Philip E.
TI Developing multi-target therapeutics to fine-tune the evolutionary
   dynamics of the cancer ecosystem
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Editorial Material
DE multi-target drug; cancer evolution; non-linear dynamic system;
   polypharmacology; cell-cell communication
ID PROTEIN-PROTEIN INTERACTIONS; MODELS; DRUGS; CELLS; POLYPHARMACOLOGY;
   HETEROGENEITY; STRATEGIES; RESISTANCE; DISCOVERY; DESIGN
C1 [Xie, Lei] CUNY, CUNY Hunter Coll, Dept Comp Sci, New York, NY 10021 USA.
   [Xie, Lei] CUNY, Grad Ctr, New York, NY 10021 USA.
   [Bourne, Philip E.] NIH, Off Director, Bethesda, MD 20892 USA.
RP Xie, L (reprint author), CUNY, CUNY Hunter Coll, Dept Comp Sci, New York, NY 10021 USA.
EM lei.xie@hunter.cuny.edu
FU NLM NIH HHS [R01 LM011986]
NR 40
TC 3
Z9 3
U1 0
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
   SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD SEP 24
PY 2015
VL 6
AR 209
DI 10.3389/fphar.2015.00209
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CX3SV
UT WOS:000365620400002
PM 26441664
ER

PT J
AU Huntsman, HD
   Bat, T
   Cheng, H
   Cash, A
   Cheruku, PS
   Fu, JF
   Keyvanfar, K
   Childs, RW
   Dunbar, CE
   Larochelle, A
AF Huntsman, Heather D.
   Bat, Taha
   Cheng, Hai
   Cash, Ayla
   Cheruku, Patali S.
   Fu, Jian-Fei
   Keyvanfar, Keyvan
   Childs, Richard W.
   Dunbar, Cynthia E.
   Larochelle, Andre
TI Human hematopoietic stem cells from mobilized peripheral blood can be
   purified based on CD49f integrin expression
SO BLOOD
LA English
DT Letter
ID CORD BLOOD; BONE-MARROW
C1 [Huntsman, Heather D.; Bat, Taha; Cheng, Hai; Cash, Ayla; Cheruku, Patali S.; Fu, Jian-Fei; Keyvanfar, Keyvan; Childs, Richard W.; Dunbar, Cynthia E.; Larochelle, Andre] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Cheng, Hai] Xuzhou Med Coll, Dept Hematol, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China.
   [Fu, Jian-Fei] Shanghai Jiao Tong Univ, Shanghai Inst Hematol, Rui Jin Hosp, Shanghai 200030, Peoples R China.
RP Larochelle, A (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA.
EM larochea@nhlbi.nih.gov
NR 8
TC 0
Z9 0
U1 1
U2 2
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 SEP 24
PY 2015
VL 126
IS 13
BP 1631
EP 1633
DI 10.1182/blood-2015-07-660670
PG 3
WC Hematology
SC Hematology
GA CU4EX
UT WOS:000363481000020
PM 26405217
ER

PT J
AU Wolf, G
   Macfarlan, TS
AF Wolf, Gernot
   Macfarlan, Todd S.
TI Revealing the Complexity of Retroviral Repression
SO CELL
LA English
DT Editorial Material
ID EMBRYONIC STEM-CELLS; ENDOGENOUS RETROVIRUSES; ZFP809
AB Retroviral restriction is a complex phenomenon that, despite remarkable recent progress, is far from being well understood. In this Preview, we introduce an insightful study by Yang et al. that represents the first attempt to identify the global determinants of retroviral repression in pluripotent mammalian cells.
C1 [Wolf, Gernot; Macfarlan, Todd S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Macfarlan, TS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM todd.macfarlan@nih.gov
NR 10
TC 0
Z9 0
U1 1
U2 3
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 SEP 24
PY 2015
VL 163
IS 1
BP 30
EP 32
DI 10.1016/j.cell.2015.09.014
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CS1RX
UT WOS:000361846500018
PM 26406368
ER

PT J
AU Day, CP
   Merlino, G
   Van Dyke, T
AF Day, Chi-Ping
   Merlino, Glenn
   Van Dyke, Terry
TI Preclinical Mouse Cancer Models: A Maze of Opportunities and Challenges
SO CELL
LA English
DT Article
ID CELL LUNG-CANCER; ACUTE PROMYELOCYTIC LEUKEMIA; GROWTH-FACTOR RECEPTOR;
   IN-VIVO; TUMOR XENOGRAFTS; DRUG DEVELOPMENT; THERAPEUTIC RESPONSE;
   PANCREATIC-CANCER; CLINICAL-RESPONSE; SURVIVAL BENEFIT
AB Significant advances have been made in developing novel therapeutics for cancer treatment, and targeted therapies have revolutionized the treatment of some cancers. Despite the promise, only about five percent of new cancer drugs are approved, and most fail due to lack of efficacy. The indication is that current preclinical methods are limited in predicting successful outcomes. Such failure exacts enormous cost, both financial and in the quality of human life. This Primer explores the current status, promise, and challenges of preclinical evaluation in advanced mouse cancer models and briefly addresses emerging models for early-stage preclinical development.
C1 [Day, Chi-Ping; Merlino, Glenn] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Van Dyke, Terry] NCI, Ctr Adv Preclin Res, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Merlino, G (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gmerlino@helix.nih.gov; vandyket@mail.nih.gov
FU Intramural NIH HHS [Z01 BC008756-21]
NR 107
TC 25
Z9 26
U1 6
U2 27
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 SEP 24
PY 2015
VL 163
IS 1
BP 39
EP 53
DI 10.1016/j.cell.2015.08.068
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CS1RX
UT WOS:000361846500020
PM 26406370
ER

PT J
AU Stanford, JB
   Brenner, R
   Fetterer, D
   Palmer, L
   Schoendorf, KC
AF Stanford, Joseph B.
   Brenner, Ruth
   Fetterer, David
   Palmer, Leslie
   Schoendorf, Kenneth C.
CA US Natl Children's Study
TI Impact of preconception enrollment on birth enrollment and timing of
   exposure assessment in the initial vanguard cohort of the US National
   Children's Study
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Birth cohort; Children; Epidemiology; National children's study;
   Pregnancy; Prospective studies; Intention
ID UNITED-STATES; CONTRACEPTIVE FAILURE; PROSPECTIVE PREGNANCY;
   RESIDENTIAL-MOBILITY; HEALTH; RECRUITMENT; POPULATION; WOMEN;
   RECOMMENDATIONS; CONCEPTION
AB Background: The initial vanguard cohort of the U.S. National Children's Study was a pregnancy and birth cohort study that sought to enroll some women prior to pregnancy, and to assess exposures early in pregnancy.
   Methods: During the recruitment phase (2009-2010), geographically based sampling was used to recruit women early in pregnancy and women not currently pregnant, not using contraception and heterosexually active. We assessed the following outcomes for women enrolled preconception and early in pregnancy: yield of births; demographic characteristics of births for different enrollment groups; time to pregnancy for preconception women; and the timing of study visits for exposure assessment.
   Results: 1399 women were recruited into the initial vanguard cohort: 429 preconception (198 trying for pregnancy, and 231 not trying) and 970 already pregnant. There were 1135 pregnancies (81 % of women) and 922 newborns enrolled (81 % of pregnancies) through September 2012. Preconception women represented 30.6 % of women enrolled, and contributed 14.5 % of births. Among women who gave birth, and who had enrolled preconception trying for pregnancy, 67.3 % were white non-Hispanic, compared to 50.0 % of preconception women not trying for pregnancy, and 61.5 % of pregnant women. Women enrolled preconception who were trying for pregnancy had higher cumulative probability of pregnancy at one year compared to women not trying (adjusted 86 % versus 56 %). Of 165 women enrolled preconception who became pregnant, 19 % had a study visit within 30 days of conception. By 10.5 weeks after conception, 75 % of women enrolled preconception had completed a pregnancy study visit; for women enrolled pregnant, the 75 % threshold was reached at 28.4 weeks.
   Conclusions: There were demographic differences in births from women enrolled preconception trying for pregnancy, preconception not trying for pregnancy, or during pregnancy. Time to pregnancy was shorter for women actively trying for pregnancy. Most women enrolled preconception did not have exposure assessment within 30 days of conception, but they did have exposure assessment much earlier during pregnancy than women who enrolled during pregnancy.
C1 [Stanford, Joseph B.] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT 84108 USA.
   [Stanford, Joseph B.; Palmer, Leslie] Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA.
   [Brenner, Ruth] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Fetterer, David] ARCBridge Consulting & Training, Herndon, VA USA.
   [Schoendorf, Kenneth C.] Sinai Hosp Baltimore, Greenspring Pediat Associates, Baltimore, MD USA.
RP Stanford, JB (reprint author), Univ Utah, Dept Family & Prevent Med, 375 Chipeta Way, Salt Lake City, UT 84108 USA.
EM joseph.stanford@utah.edu
FU NICHD [HHSN275200503413C, HHSN275201100005C, HHSN275200503396C,
   HHSN275201100014C, HHSN275200603416C, HHSN275201100004C,
   HHSN275200503410C, HHSN275201100009C, HHSN275200503415C,
   HHSN275201100007C, HHSN275201000060U];  [HSN275200503414C]; 
   [HHSN275201100003C];  [HHSN275200503411C];  [HHSN275201100002C]
FX This manuscript was developed by a Writing Team identified by the
   National Children's Study (NCS) Publications Committee for the purpose
   of timely sharing of centrally collected NCS data. The Writing Team
   wishes to acknowledge the input and participation of Shirley Beresford,
   University of Washington, Nigel Paneth, University of Michigan, and Cora
   MacPherson and Katherine Griffin, Social and Scientific Systems, Inc.
   This work was supported in part by NICHD Contracts HSN275200503414C,
   HHSN275201100003C, HHSN275200503411C, HHSN275201100002C,
   HHSN275200503413C, HHSN275201100005C, HHSN275200503396C,
   HHSN275201100014C, HHSN275200603416C, HHSN275201100004C,
   HHSN275200503410C, HHSN275201100009C, HHSN275200503415C,
   HHSN275201100007C, and HHSN275201000060U. The NCS is indebted to the
   many communities and families, whose participation make this study
   possible. The views expressed in this article are the responsibility of
   the authors and do not necessarily represent the position of the
   National Children's Study, the National Institutes of Health, or the
   U.S. Department of Health and Human Services.
NR 50
TC 1
Z9 1
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD SEP 24
PY 2015
VL 15
AR 75
DI 10.1186/s12874-015-0067-1
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CR9YP
UT WOS:000361713700001
PM 26399430
ER

PT J
AU Alonso, WJ
   McCormick, BJJ
   Miller, MA
   Schuck-Paim, C
   Asrar, GR
AF Alonso, Wladimir Jimenez
   McCormick, Benjamin Joseph James
   Miller, Mark A.
   Schuck-Paim, Cynthia
   Asrar, Ghassem R.
TI Beyond crystal balls: crosscutting solutions in global health to prepare
   for an unpredictable future
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Public health; Prediction; Models; Resilience; Health risks
ID EBOLA-VIRUS DISEASE; TICK-BORNE ENCEPHALITIS; CLIMATE-CHANGE;
   PUBLIC-HEALTH; SYSTEMATIC ANALYSIS; MODELING ANALYSIS; INFLUENZA;
   TRANSMISSION; MALARIA; BURDEN
AB Background: Efforts in global heath need to deal not only with current challenges, but also to anticipate new scenarios, which sometimes unfold at lightning speed. Predictive modeling is frequently used to assist planning, but outcomes depend heavily on a subset of critical assumptions, which are mostly hampered by our limited knowledge about the many factors, mechanisms and relationships that determine the dynamics of disease systems, by a lack of data to parameterize and validate models, and by uncertainties about future scenarios.
   Discussion: We propose a shift from a focus on the prediction of individual disease patterns to the identification and mitigation of broader fragilities in public health systems. Modeling capabilities should be used to perform "stress tests" on how interrelated fragilities respond when faced with a range of possible or plausible threats of different nature and intensity. This system should be able to reveal crosscutting solutions with the potential to address not only one threat, but multiple areas of vulnerability to future health risks.
   Summary: Actionable knowledge not based on a narrow subset of threats and conditions can better guide policy, build societal resilience and ensure effective prevention in an uncertain world.
C1 [Alonso, Wladimir Jimenez; McCormick, Benjamin Joseph James; Miller, Mark A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Alonso, Wladimir Jimenez; Schuck-Paim, Cynthia] Origem Sci, Sao Paulo, SP, Brazil.
   [Asrar, Ghassem R.] Univ Maryland, Joint Global Change Res Inst, College Pk, MD 20740 USA.
RP McCormick, BJJ (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM ben.mccormick@nih.gov
FU Fogarty International Centre, National Institutes of Health
FX This work was funded by the Fogarty International Centre, National
   Institutes of Health.
NR 68
TC 1
Z9 1
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD SEP 24
PY 2015
VL 15
AR 955
DI 10.1186/s12889-015-2285-1
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CS1AI
UT WOS:000361793500003
PM 26400682
ER

PT J
AU Resnik, DB
   McCann, DJ
AF Resnik, David B.
   McCann, David J.
TI Deception by Research Participants
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CLINICAL-TRIALS
C1 [Resnik, David B.] NIEHS, NIH, Bethesda, MD 20892 USA.
   [McCann, David J.] NIDA, NIH, Bethesda, MD 20892 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Bethesda, MD 20892 USA.
NR 5
TC 2
Z9 2
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD SEP 24
PY 2015
VL 373
IS 13
BP 1192
EP 1193
DI 10.1056/NEJMp1506985
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR8WP
UT WOS:000361635200004
PM 26398069
ER

PT J
AU Diamond, MP
   Legro, RS
   Coutifaris, C
   Alvero, R
   Robinson, RD
   Casson, P
   Christman, GM
   Ager, J
   Huang, H
   Hansen, KR
   Baker, V
   Usadi, R
   Seungdamrong, A
   Bates, GW
   Rosen, RM
   Haisenleder, D
   Krawetz, SA
   Barnhart, K
   Trussell, JC
   Ohl, D
   Jin, Y
   Santoro, N
   Eisenberg, E
   Zhang, H
AF Diamond, M. P.
   Legro, R. S.
   Coutifaris, C.
   Alvero, R.
   Robinson, R. D.
   Casson, P.
   Christman, G. M.
   Ager, J.
   Huang, H.
   Hansen, K. R.
   Baker, V.
   Usadi, R.
   Seungdamrong, A.
   Bates, G. W.
   Rosen, R. M.
   Haisenleder, D.
   Krawetz, S. A.
   Barnhart, K.
   Trussell, J. C.
   Ohl, D.
   Jin, Y.
   Santoro, N.
   Eisenberg, E.
   Zhang, H.
CA NICHD Reprod Med Network
TI Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ASSISTED REPRODUCTIVE TECHNOLOGY; MULTIPLE INTRAUTERINE GESTATIONS;
   RANDOMIZED CONTROLLED-TRIAL; STIMULATION AMIGOS TRIAL; OVARIAN
   STIMULATION; AROMATASE INHIBITORS; FERTILITY TREATMENTS; OVULATION
   INDUCTION; UNITED-STATES; CITRATE
AB BACKGROUND
   The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates.
   METHODS
   We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies.
   RESULTS
   After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P = 0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P = 0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P = 0.15) or clomiphene alone (8 of 85, 9%; P = 0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P = 0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications.
   CONCLUSIONS
   In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.)
C1 [Diamond, M. P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA 30912 USA.
   [Diamond, M. P.; Ager, J.; Krawetz, S. A.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
   [Legro, R. S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA.
   [Coutifaris, C.; Barnhart, K.] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
   [Alvero, R.; Santoro, N.] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA.
   [Robinson, R. D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
   [Casson, P.] Univ Vermont, Dept Obstet & Gynecol, Burlington, VT 05405 USA.
   [Christman, G. M.; Ohl, D.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
   [Huang, H.; Jin, Y.; Zhang, H.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA.
   [Hansen, K. R.] Univ Oklahoma, Coll Med, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA.
   [Baker, V.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
   [Usadi, R.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
   [Seungdamrong, A.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
   [Bates, G. W.] Univ Alabama Birmingham, Birmingham, AL 35487 USA.
   [Rosen, R. M.] Univ Calif San Francisco, Dept Reprod Endocrinol & Infertil, San Francisco, CA 94143 USA.
   [Haisenleder, D.] Univ Virginia, Ctr Res Reprod, Ligand Core Lab, Charlottesville, VA USA.
   [Trussell, J. C.] Upstate Univ Hosp, Syracuse, NY USA.
   [Eisenberg, E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Fertil & Infertil Branch, Rockville, MD USA.
RP Diamond, MP (reprint author), Georgia Regents Univ, Dept Obstet & Gynecol, 1120 15th St,Rm BA-7313, Augusta, GA 30912 USA.
EM michael.diamond@gru.edu
OI Diamond, Michael/0000-0001-6353-4489
FU National Institutes of Health
FX Funded by the National Institutes of Health and others
NR 25
TC 20
Z9 22
U1 2
U2 8
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 SEP 24
PY 2015
VL 373
IS 13
BP 1230
EP 1240
DI 10.1056/NEJMoa1414827
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR8WP
UT WOS:000361635200008
PM 26398071
ER

PT J
AU Zhao, X
   Parpart, S
   Takai, A
   Roessler, S
   Budhu, A
   Yu, Z
   Blank, M
   Zhang, YE
   Jia, HL
   Ye, QH
   Qin, LX
   Tang, ZY
   Thorgeirsson, SS
   Wang, XW
AF Zhao, X.
   Parpart, S.
   Takai, A.
   Roessler, S.
   Budhu, A.
   Yu, Z.
   Blank, M.
   Zhang, Y. E.
   Jia, H-L
   Ye, Q-H
   Qin, L-X
   Tang, Z-Y
   Thorgeirsson, S. S.
   Wang, X. W.
TI Integrative genomics identifies YY1AP1 as an oncogenic driver in
   EpCAM(+) AFP(+) hepatocellular carcinoma
SO ONCOGENE
LA English
DT Article
ID CANCER STEM-CELLS; H2B UBIQUITYLATION; SOMATIC MUTATIONS; H3
   METHYLATION; BREAST-CANCER; NUDE-MICE; TUMOR; PREDICTION; SURVIVAL;
   GENES
AB Identification of key drivers and new therapeutic targets is important given the poor prognosis for hepatocellular carcinoma (HCC) patients, particularly those ineligible for surgical resection or liver transplant. However, the approach to identify such driver genes is facing significant challenges due to the genomically heterogenous nature of HCC. Here we tested whether the integrative genomic profiling of a well-defined HCC subset that is classified by an extreme EpCAM(+) AFP(+) gene expression signature and associated with poor prognosis, all attributes of a stem cell-like phenotype, could uncover survival-related driver genes in HCC. Following transcriptomic analysis of the well-defined HCC cases, a Gene Set Enrichment Analysis coupled with genomic copy number alteration assessment revealed that YY1-associated protein 1 (YY1AP1) is a critical oncoprotein specifically activated in EpCAM(+) AFP+ HCC. YY1AP1 silencing eliminates oncogene addiction by altering the chromatin landscape and triggering massive apoptosis in vitro and tumor suppression in vivo. YY1AP1 expression promotes HCC proliferation and is required for the maintenance of stem cell features. We revealed that YY1AP1 cooperates with YY1 to alter the chromatin landscape and activate transcription of stemness regulators. Thus YY1AP1 may serve as a key molecular target for EpCAM(+) AFP(+) HCC subtype. Our results demonstrate the feasibility and power of a new strategy by utilizing well-defined patient samples and integrative genomics to uncover critical pathways linked to HCC subtypes with prognostic impact.
C1 [Zhao, X.; Parpart, S.; Takai, A.; Roessler, S.; Budhu, A.; Yu, Z.; Wang, X. W.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Blank, M.; Zhang, Y. E.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Jia, H-L; Ye, Q-H; Qin, L-X; Tang, Z-Y] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China.
   [Thorgeirsson, S. S.] NCI, Lab Expt Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Liver Carcinogenesis Sect, Ctr Canc Res, Bldg 37,Room 3044A,37 Convent Dr, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009; Zhang, Ying/G-3657-2015
OI Zhang, Ying/0000-0003-2753-7601
FU Intramural Research Grants of the Center for Cancer Research; US
   National Cancer Institute [Z01 BC 010313, Z01 BC 010877, Z01 BC 010876]
FX We thank Dr Curtis Harris for critical reading of the manuscript, Dr
   Zheng-Gang Liu for advice on apoptosis study, Dominic Esposito at the
   Advanced Technology Program of SAIC-Frederick, Inc., for the help in
   designing the Tet-C2 inducible construct and Liver Tissue Cell
   Distribution System (LTCDS) at the University of Minnesota (Minneapolis,
   MN, USA) for generous donation of normal liver specimens. We also thank
   Karen Yarrick for the bibliographic assistance. This work was supported
   by the Intramural Research Grants of the Center for Cancer Research and
   the US National Cancer Institute Z01 BC 010313, Z01 BC 010877 and Z01 BC
   010876.
NR 44
TC 4
Z9 4
U1 1
U2 7
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 SEP 24
PY 2015
VL 34
IS 39
BP 5095
EP 5104
DI 10.1038/onc.2014.438
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA CR9RC
UT WOS:000361693300009
PM 25597408
ER

PT J
AU Jiaox, X
   Khan, SY
   Irum, B
   Khan, AO
   Wang, QW
   Kabir, F
   Khan, AA
   Husnain, T
   Akram, J
   Riazuddin, S
   Hejtmancik, JF
   Riazuddin, SA
AF Jiaox, Xiaodong
   Khan, Shahid Y.
   Irum, Bushra
   Khan, Arif O.
   Wang, Qiwei
   Kabir, Firoz
   Khan, Asma A.
   Husnain, Tayyab
   Akram, Javed
   Riazuddin, Sheikh
   Hejtmancik, J. Fielding
   Riazuddin, S. Amer
TI Missense Mutations in CRYAB Are Liable for Recessive Congenital
   Cataracts
SO PLOS ONE
LA English
DT Article
ID B-CRYSTALLIN MUTATION; CONSANGUINEOUS PAKISTANI FAMILIES; POSTERIOR
   POLAR CATARACT; NONSENSE MUTATION; NUCLEAR CATARACT; CHINESE FAMILY;
   GENE CAUSES; LOCUS; CARDIOMYOPATHY; BLINDNESS
AB Purpose
   This study was initiated to identify causal mutations responsible for autosomal recessive congenital cataracts in consanguineous familial cases.
   Methods
   Affected individuals underwent a detailed ophthalmological and clinical examination, and slit-lamp photographs were ascertained for affected individuals who have not yet been operated for the removal of the cataractous lens. Blood samples were obtained, and genomic DNA was extracted from white blood cells. A genome-wide scan was completed with short tandem repeat (STR) markers, and the logarithm of odds (LOD) scores were calculated. Protein coding exons of CRYAB were sequenced, bi-directionally. Evolutionary conservation was investigated by aligning CRYAB orthologues, and the expression of Cryab in embryonic and postnatal mice lens was investigated with TaqMan probe.
   Results
   The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis suggested a potential region on chromosome 11q23 harboring CRYAB. DNA sequencing identified a missense variation: c.34C> T (p.R12C) in CRYAB that segregated with the disease phenotype in the family. Subsequent interrogation of our entire cohort of familial cases identified a second familial case localized to chromosome 11q23 harboring a c.31C> T (p.R11C) mutation. In silico analyses suggested that the mutations identified in familial cases, p.R11C and p.R12C will not be tolerated by the three-dimensional structure of CRYAB. Real-time PCR analysis identified the expression of Cryab in mouse lens as early as embryonic day 15 (E15) that increased significantly until postnatal day 6 (P6) with steady level of expression thereafter.
   Conclusion
   Here, we report two novel missense mutations, p.R11C and p.R12C, in CRYAB associated with autosomal recessive congenital nuclear cataracts.
C1 [Jiaox, Xiaodong; Wang, Qiwei; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
   [Khan, Shahid Y.; Irum, Bushra; Kabir, Firoz; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Irum, Bushra; Khan, Asma A.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
   [Khan, Arif O.] King Khalid Eye Specialist Hosp, Riyadh 12329, Saudi Arabia.
   [Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore 54550, Pakistan.
   [Akram, Javed; Riazuddin, Sheikh] Shaheed Zulfiqar Ali Bhutto Med Univ, Natl Ctr Genet Dis, Islamabad, Pakistan.
RP Riazuddin, SA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
EM riazuddin@jhmi.edu
FU National Eye Institute [1R01EY022714]; Knight Templar Eye Foundation;
   King Khaled Eye Specialist Hospital-Johns Hopkins University; National
   Academy of Sciences, Washington DC USA; Higher Education Commission,
   Islamabad Pakistan
FX This study was supported in part by the National Eye Institute, Grant
   1R01EY022714 (SAR), Knight Templar Eye Foundation Grant (SAR), King
   Khaled Eye Specialist Hospital-Johns Hopkins University collaboration
   grant (SAR), the National Academy of Sciences, Washington DC USA and the
   Higher Education Commission, Islamabad Pakistan.
NR 41
TC 4
Z9 4
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 24
PY 2015
VL 10
IS 9
AR e0137973
DI 10.1371/journal.pone.0137973
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1BS
UT WOS:000361798100015
PM 26402864
ER

PT J
AU Barry, CE
AF Barry, Clifton E., III
TI Major Global Killer Tamed by Hydrogen
SO ACS CENTRAL SCIENCE
LA English
DT Editorial Material
ID MYCOBACTERIUM-TUBERCULOSIS
C1 [Barry, Clifton E., III] NIAID, NIH, Bethesda, MD 20892 USA.
   [Barry, Clifton E., III] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
RP Barry, CE (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@niaid.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2374-7943
EI 2374-7951
J9 ACS CENTRAL SCI
JI ACS Central Sci.
PD SEP 23
PY 2015
VL 1
IS 6
BP 286
EP 288
DI 10.1021/acscentsci.5b00293
PG 3
WC Chemistry, Multidisciplinary
SC Chemistry
GA CX8QR
UT WOS:000365969200004
ER

PT J
AU Ray, U
   Cinque, P
   Gerevini, S
   Longo, V
   Lazzarin, A
   Schippling, S
   Martin, R
   Buck, CB
   Pastrana, DV
AF Ray, Upasana
   Cinque, Paola
   Gerevini, Simonetta
   Longo, Valeria
   Lazzarin, Adriano
   Schippling, Sven
   Martin, Roland
   Buck, Christopher B.
   Pastrana, Diana V.
TI JC polyomavirus mutants escape antibody-mediated neutralization
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CAPSID PROTEIN VP1;
   MULTIPLE-SCLEROSIS; RISK STRATIFICATION; BK POLYOMAVIRUS;
   VIRUS-INFECTION; CELL-LINE; INTERLEUKIN-7; ESTABLISHMENT; GENOTYPES
AB JC polyomavirus (JCV) persistently infects the urinary tract of most adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease, progressive multifocal leukoencephalopathy (PML). JCV strains found in the cerebrospinal fluid of PML patients contain distinctive mutations in surface loops of the major capsid protein, VP1. We hypothesized that VP1 mutations might allow the virus to evade antibody-mediated neutralization. Consistent with this hypothesis, neutralization serology revealed that plasma samples from PML patients neutralized wild-type JCV strains but failed to neutralize patient-cognate PML-mutant JCV strains. This contrasted with serological results for healthy individuals, most of whom robustly cross-neutralized all tested JCV variants. Mice administered a JCV virus-like particle (VLP) vaccine initially showed neutralizing "blind spots" (akin to those observed in PML patients) that closed after booster immunization. A PML patient administered an experimental JCV VLP vaccine likewise showed markedly increased neutralizing titer against her cognate PML-mutant JCV. The results indicate that deficient humoral immunity is a common aspect of PML pathogenesis and that vaccination may overcome this humoral deficiency. Thus, vaccination with JCV VLPs might prevent the development of PML.
C1 [Ray, Upasana; Buck, Christopher B.; Pastrana, Diana V.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Cinque, Paola; Longo, Valeria; Lazzarin, Adriano] Ist Sci San Raffaele, Dept Infect Dis, I-20132 Milan, Italy.
   [Gerevini, Simonetta] Ist Sci San Raffaele, Head & Neck Dept, Neuroradiol Unit, I-20132 Milan, Italy.
   [Lazzarin, Adriano] San Raffaele Univ, I-20132 Milan, Italy.
   [Schippling, Sven; Martin, Roland] Univ Zurich, Univ Zurich Hosp, Neuroimmunol & Multiple Sclerosis Res Sect, Dept Neurol, CH-8091 Zurich, Switzerland.
RP Buck, CB (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM buckc@mail.nih.gov; pastrand@mail.nih.gov
FU Intramural Research Program of NIH; Center for Cancer Research; ISS
   grant (AIDS Research Program) [40H.83]; ISS grant (Italian Ministry of
   Health)
FX The work was funded in part by the Intramural Research Program of the
   NIH with support from the Center for Cancer Research and by ISS grant
   40H.83 (AIDS Research Program, Italian Ministry of Health).
NR 49
TC 13
Z9 15
U1 1
U2 1
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 SEP 23
PY 2015
VL 7
IS 306
AR 306ra151
DI 10.1126/scitranslmed.aab1720
PG 7
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CW8EP
UT WOS:000365232600005
PM 26400912
ER

PT J
AU Qureshi, ZU
   Millum, J
   Blencowe, H
   Kelley, M
   Fottrell, E
   Lawn, JE
   Costello, A
   Colbourn, T
AF Qureshi, Zeshan U.
   Millum, Joseph
   Blencowe, Hannah
   Kelley, Maureen
   Fottrell, Edward
   Lawn, Joy E.
   Costello, Anthony
   Colbourn, Tim
TI Stillbirth should be given greater priority on the global health agenda
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Editorial Material
ID VERBAL AUTOPSY; SYSTEMATIC ANALYSIS; NEONATAL DEATH; MORTALITY;
   INTERVENTIONS; DEPRESSION; PREGNANCY; OUTCOMES; ANXIETY; BABIES
C1 [Qureshi, Zeshan U.; Fottrell, Edward; Costello, Anthony; Colbourn, Tim] UCL, Inst Global Hlth, London, England.
   [Millum, Joseph] NIH, Clin Ctr Dept Bioeth, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Blencowe, Hannah; Lawn, Joy E.] London Sch Hyg & Trop Med, Maternal Adolescent Reprod & Child Hlth Ctr, London WC1, England.
   [Kelley, Maureen] Univ Oxford, Nuffield Dept Populat Hlth, Ethox Ctr, Oxford, England.
RP Qureshi, ZU (reprint author), UCL, Inst Global Hlth, London, England.
EM zeshan.u.qureshi@gmail.com
NR 40
TC 1
Z9 1
U1 2
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD SEP 23
PY 2015
VL 351
AR h4620
DI 10.1136/bmj.h4620
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS3FL
UT WOS:000361957200003
PM 26400645
ER

PT J
AU Drozd, VM
   Saenko, VA
   Brenner, AV
   Drozdovitch, V
   Pashkevich, VI
   Kudelsky, AV
   Demidchik, YE
   Branovan, I
   Shiglik, N
   Rogounovitch, TI
   Yamashita, S
   Biko, J
   Reiners, C
AF Drozd, Valentina M.
   Saenko, Vladimir A.
   Brenner, Alina V.
   Drozdovitch, Vladimir
   Pashkevich, Vasilii I.
   Kudelsky, Anatoliy V.
   Demidchik, Yuri E.
   Branovan, Igor
   Shiglik, Nikolay
   Rogounovitch, Tatiana I.
   Yamashita, Shunichi
   Biko, Johannes
   Reiners, Christoph
TI Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus
   after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?
SO PLOS ONE
LA English
DT Article
ID POWER-STATION ACCIDENT; IODINE NUTRITION; SKIN HEMANGIOMA; POOLED
   ANALYSIS; RISK; CHILDREN; RADIATION; EXPOSURE; AREAS; RADIOTHERAPY
AB One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (I-131) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the I-131-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.
C1 [Drozd, Valentina M.; Biko, Johannes; Reiners, Christoph] Int Fund Help Patients Radiat Induced Thyroid Can, Minsk, Byelarus.
   [Drozd, Valentina M.] Belarusian Med Acad Postgrad Educ, Dept Endocrinol, Minsk, Byelarus.
   [Saenko, Vladimir A.; Yamashita, Shunichi] Nagasaki Univ, Atom Bomb Dis Inst, Dept Radiat Mol Epidemiol, Nagasaki 852, Japan.
   [Brenner, Alina V.; Drozdovitch, Vladimir] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
   [Pashkevich, Vasilii I.; Kudelsky, Anatoliy V.] Natl Acad Sci, Inst Nat Management, Lab Hydrogeol & Hydroecol, Minsk, Byelarus.
   [Demidchik, Yuri E.] Belarusian Med Acad Postgrad Educ, Dept Oncol, Minsk, Byelarus.
   [Branovan, Igor; Shiglik, Nikolay] Project Chernobyl, Brooklyn, NY USA.
   [Rogounovitch, Tatiana I.] Nagasaki Univ, Atom Bomb Dis Inst, Dept Global Hlth Med & Welf, Nagasaki 852, Japan.
   [Yamashita, Shunichi] Nagasaki Univ, Atom Bomb Dis Inst, Dept Radiat Med Sci, Nagasaki 852, Japan.
   [Biko, Johannes; Reiners, Christoph] Univ Wurzburg, Clin & Polyclin Nucl Med, D-97070 Wurzburg, Germany.
RP Saenko, VA (reprint author), Nagasaki Univ, Atom Bomb Dis Inst, Dept Radiat Mol Epidemiol, Nagasaki 852, Japan.
EM saenko@nagasaki-u.ac.jp
OI Yamashita, Shunichi/0000-0001-6399-6261
FU Japan Society for the Promotion of Science [25257508, 26670460]
FX This work was supported in part by research grants 25257508 and 26670460
   from the Japan Society for the Promotion of Science
   (https://www.jsps.go.jp/english/) to SY. This work has received no other
   funding. The funder had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 65
TC 2
Z9 4
U1 12
U2 27
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 SEP 23
PY 2015
VL 10
IS 9
AR e0137226
DI 10.1371/journal.pone.0137226
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1BM
UT WOS:000361797500024
PM 26397978
ER

PT J
AU Hsu, CH
   Nguyen, C
   Yan, CH
   Ries, RE
   Chen, QR
   Hu, Y
   Ostronoff, F
   Stirewalt, DL
   Komatsoulis, G
   Levy, S
   Meerzaman, D
   Meshinchi, S
AF Hsu, Chih-Hao
   Cu Nguyen
   Yan, Chunhua
   Ries, Rhonda E.
   Chen, Qing-Rong
   Hu, Ying
   Ostronoff, Fabiana
   Stirewalt, Derek L.
   Komatsoulis, George
   Levy, Shawn
   Meerzaman, Daoud
   Meshinchi, Soheil
TI Transcriptome Profiling of Pediatric Core Binding Factor AML
SO PLOS ONE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; RNA-SEQ; FUSION
   GENES; DIFFERENTIAL EXPRESSION; MITOTIC CHROMOSOMES; SEQUENCING DATA;
   CBF-BETA; HOX; CANCER
AB The t(8; 21) and Inv(16) translocations disrupt the normal function of core binding factors alpha (CBFA) and beta (CBFB), respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML) patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq) to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8; 21) (N = 17), Inv(16) (N = 14), and normal karyotype (NK, N = 33) were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21) and 474 genes in Inv(16) were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10(-30)) are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs) differentially expressed across subtypes, with 337 t(8;21)-specific and 407 Inv(16)-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5x10(-51) and p = 1.8x10(-54) for the two subsets). In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six patients. Clustering of differentially expressed genes indicated that the homeobox (HOX) gene family, including two transcription factors (MEIS1 and NKX2-3) were down-regulated in CBF compared to NK samples. This finding supports existing data that the dysregulation of HOX genes play a central role in biology CBF-AML hematopoiesis. These data provide comprehensive transcriptome profiling of CBF-AML and delineate genes and pathways that are differentially expressed, providing insights into the shared biology as well as differences in the two CBF subsets.
C1 [Hsu, Chih-Hao; Cu Nguyen; Yan, Chunhua; Chen, Qing-Rong; Hu, Ying; Komatsoulis, George; Meerzaman, Daoud] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20850 USA.
   [Ries, Rhonda E.; Ostronoff, Fabiana; Stirewalt, Derek L.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Levy, Shawn] Hudson Alpha Inst Biotechnol, Huntsville, AL USA.
RP Meshinchi, S (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
EM smeshinc@fredhutch.org
FU National Cancer Institute [NCI 5 R01 CA114563-08]; Scientific Leadership
   NIH National Clinical Trials Network (NCTN) [U10CA180886]
FX This work was funded by a grant from the National Cancer Institute, NCI
   5 R01 CA114563-08 (www.nih.gov) and a Scientific Leadership NIH National
   Clinical Trials Network (NCTN) Grant (U10CA180886).
NR 55
TC 3
Z9 3
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 23
PY 2015
VL 10
IS 9
AR e0138782
DI 10.1371/journal.pone.0138782
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1BM
UT WOS:000361797500106
PM 26397705
ER

PT J
AU Zhang, ZY
   Chan, AKY
   Ding, XJ
   Qin, ZY
   Hong, CS
   Chen, LC
   Zhang, X
   Zhao, FP
   Wang, Y
   Wang, Y
   Zhou, LF
   Zhuang, ZP
   Ng, HK
   Yan, H
   Yao, Y
   Maro, Y
AF Zhang, Zhen-Yu
   Chan, Aden Ka-Yin
   Ding, Xiao-Jie
   Qin, Zhi-Yong
   Hong, Christopher S.
   Chen, Ling-Chao
   Zhang, Xin
   Zhao, Fang-Ping
   Wang, Yin
   Wang, Yang
   Zhou, Liang-Fu
   Zhuang, Zhengping
   Ng, Ho-Keung
   Yan, Hai
   Yao, Yu
   Maro, Ying
TI TERT promoter mutations contribute to IDH mutations in predicting
   differential responses to adjuvant therapies in WHO grade II and III
   diffuse gliomas
SO ONCOTARGET
LA English
DT Article
DE TERT promoter; IDH; gliomas; radiation therapy; chemotherapy
ID ADULT MALIGNANT GLIOMAS; BRAIN-TUMOR GROUP; OLIGODENDROGLIAL TUMORS;
   NERVOUS-SYSTEM; GLIOBLASTOMAS; ASTROCYTOMAS; SURVIVAL; CLASSIFICATION;
   TEMOZOLOMIDE; PROCARBAZINE
AB IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have favorable prognosis compared to wild-type tumors. However, whether IDH mutations in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter mutations may be promising biomarkers in glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant therapies to explore their impact on the sensitivity of tumors to genotoxic therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p < 0.001) were independent prognostic factors for PFS and OS in patients receiving genotoxic therapies while TERT promoter mutations were not. In univariate analysis, IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic therapies were administered after surgery. Importantly, we also found that TERT promoter mutations further stratify IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to adjuvant therapies. Taken together, TERT promoter mutations may predict enhanced sensitivity to genotoxic therapies in IDH wild-type WHO grade II and III diffuse gliomas and may justify intensified treatment in this subgroup.
C1 [Zhang, Zhen-Yu; Ding, Xiao-Jie; Qin, Zhi-Yong; Chen, Ling-Chao; Zhang, Xin; Wang, Yang; Zhou, Liang-Fu; Yao, Yu; Maro, Ying] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200433, Peoples R China.
   [Chan, Aden Ka-Yin; Ng, Ho-Keung] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China.
   [Hong, Christopher S.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
   [Zhao, Fang-Ping] Genetron Hlth Inc, Beijing, Peoples R China.
   [Wang, Yin] Fudan Univ, Huashan Hosp, Dept Neuropathol, Shanghai 200433, Peoples R China.
   [Yan, Hai] Duke Univ, Med Ctr, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr,Pediat Brain, Durham, NC 27710 USA.
RP Yao, Y (reprint author), Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200433, Peoples R China.
EM hkng@cuhk.edu.hk; hai.yan@duke.edu; yu_yao@fudan.edu.cn
RI Ng, Ho Keung/I-3952-2015; Chan, Aden Ka-yin/I-2535-2015
OI Chan, Aden Ka-yin/0000-0001-9176-963X
FU Research Special Fund For Public Welfare Industry of Health [201402008];
   Natural Science Foundation [81172412]; National Key Clinical Specialist
   Construction Programs of China; Intramural Research Program of the
   National Institute of Neurological Disorders and Stroke at the National
   Institutes of Health (Bethesda, MD, USA)
FX This work was supported by the following grants: the Research Special
   Fund For Public Welfare Industry of Health (No. 201402008), Natural
   Science Foundation Grant 81172412, National Key Clinical Specialist
   Construction Programs of China, and the Intramural Research Program of
   the National Institute of Neurological Disorders and Stroke at the
   National Institutes of Health (Bethesda, MD, USA).
NR 29
TC 4
Z9 5
U1 0
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD SEP 22
PY 2015
VL 6
IS 28
BP 24871
EP 24883
DI 10.18632/oncotarget.4549
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CT9TS
UT WOS:000363160100028
PM 26314843
ER

PT J
AU Gaiser, MR
   Daily, K
   Hoffmann, J
   Brune, M
   Enk, A
   Brownell, I
AF Gaiser, Maria Rita
   Daily, Kenneth
   Hoffmann, Jochen
   Brune, Maik
   Enk, Alexander
   Brownell, Isaac
TI Evaluating blood levels of neuron specific enolase, chromogranin A, and
   circulating tumor cells as Merkel cell carcinoma biomarkers
SO ONCOTARGET
LA English
DT Article
DE Merkel cell carcinoma; neuron specific enolase; chromogranin A;
   circulating tumor cells; EpCAM
ID CONSENSUS STAGING SYSTEM; CANCER-PATIENTS; ADHESION MOLECULE;
   BREAST-CANCER; NEUROENDOCRINE NEOPLASMS; PERIPHERAL-BLOOD;
   PROSTATE-CANCER; SERUM MARKER; DISEASE; SURVIVAL
AB Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Although used to monitor MCC patients, the clinical utility of neuron-specific enolase (NSE) and chromogranin A (ChrA) blood levels is untested. EpCAM-positive circulating tumor cells (CTC) reflect disease status in several epithelial tumors. Here we investigate the use of NSE and ChrA blood levels and CTC counts as biomarkers for MCC disease behavior.
   Methods: NSE and ChrA blood levels from 60 patients with MCC were retrospectively analyzed; 30 patients were additionally screened for CTC. Biomarker values were correlated to clinical parameters.
   Results: Despite routine use by some physicians, NSE and ChrA blood levels did not correlate with progression free survival, disease specific survival, or MCC recurrence. We found CTC in 97% of tested MCC patients. CTC counts were elevated in patients with active disease, suggesting their potential use in monitoring MCC.
   Conclusion: NSE and ChrA levels were not effective in predicting outcomes or detecting recurrences of MCC. In contrast, CTC counts have potential utility as a biomarker for MCC disease behavior.
C1 [Gaiser, Maria Rita; Hoffmann, Jochen; Enk, Alexander] Heidelberg Univ, Dept Dermatol, Heidelberg, Germany.
   [Daily, Kenneth; Brownell, Isaac] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Brune, Maik] Heidelberg Univ, Dept Internal Med & Clin Chem 1, Heidelberg, Germany.
RP Gaiser, MR (reprint author), Heidelberg Univ, Dept Dermatol, Heidelberg, Germany.
EM maria-gaiser@gmx.de
OI Daily, Kenneth/0000-0001-5729-7376
FU Olympia-Morata-Program of the University of Heidelberg; National
   Institutes of Health Intramural Research Program, Center of Cancer
   Research, National Cancer Institute
FX This work was supported by the Olympia-Morata-Program of the University
   of Heidelberg to MRG, and the National Institutes of Health Intramural
   Research Program, Center of Cancer Research, National Cancer Institute
   to IB. The opinions expressed are those of the authors and do not
   necessarily represent those of the National Institutes of Health or the
   National Cancer Institute.
NR 56
TC 3
Z9 3
U1 0
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD SEP 22
PY 2015
VL 6
IS 28
BP 26472
EP 26482
DI 10.18632/oncotarget.4500
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CT9TS
UT WOS:000363160100144
PM 26299616
ER

PT J
AU Nightingale, SL
AF Nightingale, Stuart L.
TI FDA Expanded Access Programs for Experimental Medicines
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 NIH, Consultant Publ Hlth Policy & Regulatory Affairs, Chevy Chase, MD 20815 USA.
RP Nightingale, SL (reprint author), NIH, Consultant Publ Hlth Policy & Regulatory Affairs, Chevy Chase, MD 20815 USA.
EM stuart.nightingale@comcast.net
NR 3
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD SEP 22
PY 2015
VL 314
IS 12
BP 1296
EP 1296
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS5IE
UT WOS:000362110700025
PM 26393859
ER

PT J
AU Wilson, LE
   Kim, S
   Xu, ZL
   Harlid, S
   Sandler, DP
   Taylor, JA
AF Wilson, Lauren E.
   Kim, Sangmi
   Xu, Zongli
   Harlid, Sophia
   Sandler, Dale P.
   Taylor, Jack A.
TI Non-Steroidal Anti-Inflammatory Drug Use and Genomic DNA Methylation in
   Blood
SO PLOS ONE
LA English
DT Article
ID BREAST-CANCER; EXPRESSION; TISSUES; SISTER; GENES; CELLS
AB Background
   Non-steroidal anti-inflammatory drug (NSAID) use is associated with decreased risk of some cancers. NSAID use modulates the epigenetic profile of normal colonic epithelium and may reduce risk of colon cancer through this pathway; however, the effect of NSAID use on the DNA methylation profile of other tissues including whole blood has not yet been examined.
   Findings
   Using the Sister Study cohort, we examined the association between NSAID usage and whole genome methylation patterns in blood DNA. Blood DNA methylation status across 27,589 CpG sites was evaluated for 871 women using the Illumina Infinium HumanMethylation27 Beadchip, and in a non-overlapping replication sample of 187 women at 485,512 CpG sites using the Infinium HumanMethylation450 Beadchip. We identified a number of CpG sites that were differentially methylated in regular, long-term users of NSAIDs in the discovery group, but none of these sites were statistically significant in our replication group.
   Conclusions
   We found no replicable methylation differences in blood related to NSAID usage. If NSAID use does effect blood DNA methylation patterns, differences are likely small.
C1 [Wilson, Lauren E.; Xu, Zongli; Harlid, Sophia; Sandler, Dale P.; Taylor, Jack A.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
   [Kim, Sangmi] Georgia Regents Univ, Ctr Canc, Dept Med, Hematol Oncol Sect, Augusta, GA USA.
   [Kim, Sangmi] Med Coll Georgia, Augusta, GA 30912 USA.
RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM taylor@niehs.nih.gov
OI Harlid, Sophia/0000-0001-8540-6891; xu, zongli/0000-0002-9034-8902;
   taylor, jack/0000-0001-5303-6398; Sandler, Dale/0000-0002-6776-0018;
   Wilson, Lauren/0000-0002-5953-2293
FU National Institute of Environmental Health Sciences, NIH [Z01 ES044005,
   Z01 ES044032, Z01 ES049033]
FX This research was supported by the Intramural Research Program of the
   National Institute of Environmental Health Sciences, NIH (Z01 ES044005,
   Z01 ES044032, and Z01 ES049033).
NR 23
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 22
PY 2015
VL 10
IS 9
AR e0138920
DI 10.1371/journal.pone.0138920
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0ZW
UT WOS:000361792100115
PM 26393518
ER

PT J
AU Burke, LE
   Ma, J
   Azar, KMJ
   Bennett, GG
   Peterson, ED
   Zheng, Y
   Riley, W
   Stephens, J
   Shah, SH
   Suffoletto, B
   Turan, TN
   Spring, B
   Steinberger, J
   Quinn, CC
AF Burke, Lora E.
   Ma, Jun
   Azar, Kristen M. J.
   Bennett, Gary G.
   Peterson, Eric D.
   Zheng, Yaguang
   Riley, William
   Stephens, Janna
   Shah, Svati H.
   Suffoletto, Brian
   Turan, Tanya N.
   Spring, Bonnie
   Steinberger, Julia
   Quinn, Charlene C.
TI Current Science on Consumer Use of Mobile Health for Cardiovascular
   Disease Prevention A Scientific Statement From the American Heart
   Association
SO CIRCULATION
LA English
DT Editorial Material
DE AHA Scientific Statements; cardiovascular diseases; consumer health
   information; electronic mail; lifestyle; mobile health; prevention and
   control
ID RANDOMIZED CONTROLLED-TRIAL; HOME BLOOD-PRESSURE; LIFE-STYLE
   INTERVENTION; SHORT-MESSAGE SERVICE; SMOKING-CESSATION PROGRAM; TYPE-2
   DIABETIC-PATIENTS; SELF-MANAGEMENT EDUCATION; WEIGHT-LOSS INTERVENTIONS;
   PHYSICAL-ACTIVITY; YOUNG-ADULTS
C1 [Burke, Lora E.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   [Bennett, Gary G.] Duke Univ, Durham, NC 27706 USA.
   [Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
   [Quinn, Charlene C.] Univ Maryland, Sch Med, College Pk, MD USA.
   [Riley, William] NIH, Washington, DC USA.
   [Shah, Svati H.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
   [Spring, Bonnie] Northwestern Univ, Evanston, IL 60208 USA.
   [Steinberger, Julia] Univ Minnesota, Minneapolis, MN 55455 USA.
   [Stephens, Janna] Johns Hopkins, Baltimore, MD USA.
   [Turan, Tanya N.] Med Univ S Carolina, Columbia, SC USA.
   [Zheng, Yaguang] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15260 USA.
RP Burke, LE (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA.
RI Stephens, Janna/F-7383-2016; 
OI Turan, Tanya/0000-0001-5399-8845
NR 245
TC 46
Z9 46
U1 8
U2 19
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 SEP 22
PY 2015
VL 132
IS 12
BP 1157
EP 1213
DI 10.1161/CIR.0000000000000232
PG 57
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CR6VG
UT WOS:000361485400011
PM 26271892
ER

PT J
AU Pronobis, MI
   Rusan, NM
   Peifer, M
AF Pronobis, Mira I.
   Rusan, Nasser M.
   Peifer, Mark
TI A novel GSK3-regulated APC: Axin interaction regulates Wnt signaling by
   driving a catalytic cycle of efficient beta catenin destruction
SO ELIFE
LA English
DT Article
ID ADENOMATOUS POLYPOSIS-COLI; TUMOR-SUPPRESSOR; PROTEIN INTERACTIONS;
   NEGATIVE REGULATOR; SOMATIC MUTATIONS; CANCER CELLS; DIX DOMAIN;
   PHOSPHORYLATION; COMPLEX; DROSOPHILA
AB APC, a key negative regulator of Wnt signaling in development and oncogenesis, acts in the destruction complex with the scaffold Axin and the kinases GSK3 and CK1 to target beta catenin for destruction. Despite 20 years of research, APC's mechanistic function remains mysterious. We used FRAP, super-resolution microscopy, functional tests in mammalian cells and flies, and other approaches to define APC's mechanistic role in the active destruction complex when Wnt signaling is off. Our data suggest APC plays two roles: (1) APC promotes efficient Axin multimerization through one known and one novel APC: Axin interaction site, and (2) GSK3 acts through APC motifs R2 and B to regulate APC: Axin interactions, promoting high-throughput of beta catenin to destruction. We propose a new dynamic model of how the destruction complex regulates Wnt signaling and how this goes wrong in cancer, providing insights into how this multiprotein signaling complex is assembled and functions via multivalent interactions.
C1 [Pronobis, Mira I.; Peifer, Mark] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC USA.
   [Rusan, Nasser M.] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA.
   [Peifer, Mark] Univ N Carolina, Dept Biol, Chapel Hill, NC USA.
   [Peifer, Mark] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Peifer, M (reprint author), Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC USA.
EM peifer@unc.edu
RI Rusan, Nasser/P-3511-2016
FU National Institute of General Medical Sciences (NIGMS) [R01 GM47857];
   Howard Hughes Medical Institute (HHMI) HHMI International Student
   Research Fellowship; National Heart, Lung, and Blood Institute (NHBLI)
   [1ZIAHL006126]
FX National Institute of General Medical Sciences (NIGMS) R01 GM47857 Mark
   Peifer; Howard Hughes Medical Institute (HHMI) HHMI International
   Student Research Fellowship (no grant number) Mira I Pronobis; National
   Heart, Lung, and Blood Institute (NHBLI) 1ZIAHL006126 Nasser M Rusan;
   The funders had no role in study design, data collection and
   interpretation, or the decision to submit the work for publication.
NR 54
TC 13
Z9 13
U1 2
U2 10
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD SEP 22
PY 2015
VL 4
AR e08022
DI 10.7554/eLife.08022
PG 31
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CR8PR
UT WOS:000361616700001
PM 26393419
ER

PT J
AU Abdulla, S
   Ashley, EA
   Bassat, Q
   Bethell, D
   Bjorkman, A
   Borrmann, S
   D'Alessandro, U
   Dahal, P
   Day, NP
   Diakite, M
   Djimde, AA
   Dondorp, AM
   Duong, S
   Edstein, MD
   Fairhurst, RM
   Faiz, MA
   Falade, C
   Flegg, JA
   Fogg, C
   Gonzalez, R
   Greenwood, B
   Guerin, PJ
   Guthmann, JP
   Hamed, K
   Hien, TT
   Htut, Y
   Juma, E
   Lim, P
   Martensson, A
   Mayxay, M
   Mokuolu, OA
   Moreira, C
   Newton, P
   Noedl, H
   Nosten, F
   Ogutu, BR
   Onyamboko, MA
   Owusu-Agyei, S
   Phyo, AP
   Premji, Z
   Price, RN
   Pukrittayakamee, S
   Ramharter, M
   Sagara, I
   Se, Y
   Suon, S
   Stepniewska, K
   Ward, SA
   White, NJ
   Winstanley, PA
AF Abdulla, Salim
   Ashley, Elizabeth A.
   Bassat, Quique
   Bethell, Delia
   Bjorkman, Anders
   Borrmann, Steffen
   D'Alessandro, Umberto
   Dahal, Prabin
   Day, Nicholas P.
   Diakite, Mahamadou
   Djimde, Abdoulaye A.
   Dondorp, Arjen M.
   Duong, Socheat
   Edstein, Michael D.
   Fairhurst, Rick M.
   Faiz, M. Abul
   Falade, Catherine
   Flegg, Jennifer A.
   Fogg, Carole
   Gonzalez, Raquel
   Greenwood, Brian
   Guerin, Philippe J.
   Guthmann, Jean-Paul
   Hamed, Kamal
   Tran Tinh Hien
   Htut, Ye
   Juma, Elizabeth
   Lim, Pharath
   Martensson, Andreas
   Mayxay, Mayfong
   Mokuolu, Olugbenga A.
   Moreira, Clarissa
   Newton, Paul
   Noedl, Harald
   Nosten, Francois
   Ogutu, Bernhards R.
   Onyamboko, Marie A.
   Owusu-Agyei, Seth
   Phyo, Aung Pyae
   Premji, Zul
   Price, Ric N.
   Pukrittayakamee, Sasithon
   Ramharter, Michael
   Sagara, Issaka
   Se, Youry
   Suon, Seila
   Stepniewska, Kasia
   Ward, Stephen A.
   White, Nicholas J.
   Winstanley, Peter A.
CA WWARN Parasite Clearance Study Grp
TI Baseline data of parasite clearance in patients with falciparum malaria
   treated with an artemisinin derivative: an individual patient data
   meta-analysis
SO MALARIA JOURNAL
LA English
DT Article
DE Malaria; Parasite clearance; Artemisinin resistance; Drug resistance;
   Plasmodium falciparum
ID RESISTANT PLASMODIUM-FALCIPARUM; ARTEMETHER-LUMEFANTRINE; UNCOMPLICATED
   MALARIA; WESTERN CAMBODIA; ORAL ARTESUNATE; AFRICAN INFANTS;
   SOUTHEAST-ASIA; NO EVIDENCE; CHILDREN; EFFICACY
AB Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up.
   Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive.
   Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 > 5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007.
   Conclusions: Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
C1 [Abdulla, Salim] Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
   [Ashley, Elizabeth A.; Dahal, Prabin; Day, Nicholas P.; Dondorp, Arjen M.; Guerin, Philippe J.; Tran Tinh Hien; Mayxay, Mayfong; Moreira, Clarissa; Newton, Paul; Nosten, Francois; Onyamboko, Marie A.; Price, Ric N.; Stepniewska, Kasia; White, Nicholas J.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.
   [Ashley, Elizabeth A.; Day, Nicholas P.; Dondorp, Arjen M.; White, Nicholas J.] Mahidol Univ, Mahidol Oxford Trop Med Res Unit MORU, Fac Trop Med, Bangkok 10700, Thailand.
   [Bassat, Quique] Univ Barcelona, Ctr Invest Saude Manhica Manhica Mozamb & ISGloba, Barcelona Ctr Int Hlth Res CRESIB, Hosp Clin, Barcelona, Spain.
   [Bethell, Delia] AFRIMS, Dept Immunol & Med, Bangkok, Thailand.
   [Bjorkman, Anders] Karolinska Inst, Dept Microbiol Tumour & Cell Biol, Malaria Res, Stockholm, Sweden.
   [Borrmann, Steffen] Kenya Govt Med Res Ctr, Wellcome Trust Res Programme, Kilifi, Kenya.
   [Borrmann, Steffen] Univ Magdeburg, Sch Med, D-39106 Magdeburg, Germany.
   [D'Alessandro, Umberto] Inst Trop Med, Unit Malariol, B-2000 Antwerp, Belgium.
   [D'Alessandro, Umberto] MRC Unit, Fajara, Gambia.
   [Dahal, Prabin; Guerin, Philippe J.; Moreira, Clarissa; Price, Ric N.; Stepniewska, Kasia] WorldWide Antimalarial Resistance Network WWARN, Oxford, England.
   [Diakite, Mahamadou] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali.
   [Duong, Socheat] Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
   [Fairhurst, Rick M.; Lim, Pharath] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
   [Faiz, M. Abul] Malaria Res Grp MRG & Dev Care Fdn, Dhaka, Bangladesh.
   [Falade, Catherine] Univ Ibadan, Coll Med, Ibadan, Nigeria.
   [Flegg, Jennifer A.] Monash Univ, Sch Math Sci, Clayton, Vic 3800, Australia.
   [Fogg, Carole] Univ Portsmouth, Portsmouth, Hants, England.
   [Gonzalez, Raquel] Ctr Invest Saude Manhica Manhica Mozamb, Barcelona, Spain.
   [Gonzalez, Raquel] CRESIB, Barcelona, Spain.
   [Greenwood, Brian] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England.
   [Guthmann, Jean-Paul] Epicentre, Paris, France.
   [Hamed, Kamal] Novartis Pharmaceut, E Hanover, NJ USA.
   [Tran Tinh Hien] OUCRU, Wellcome Trust Major Overseas Programme MOP, Ho Chi Minh City, Vietnam.
   [Htut, Ye] Dept Med Res, Lower Myanmar, Yangon, Myanmar.
   [Juma, Elizabeth] Kenya Govt Med Res Ctr, Nairobi, Kenya.
   [Lim, Pharath] US & Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
   [Martensson, Andreas] Karolinska Inst, Dept Microbiol Cell & Tumour Biol, Dept Publ Hlth Sci, Malaria Res, Stockholm, Sweden.
   [Martensson, Andreas] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden.
   [Mayxay, Mayfong; Newton, Paul] Mahosot Hosp, Lao Oxford Mahosot Hosp, Wellcome Trust Res Unit LOMWRU, Viangchan, Laos.
   [Mayxay, Mayfong] Univ Hlth Sci, Fac Postgrad Studies, Viangchan, Laos.
   [Mokuolu, Olugbenga A.] Univ Ilorin, Dept Paediat & Child Hlth, Ilorin, Nigeria.
   [Noedl, Harald] Med Univ Vienna, Inst Specif Prophylaxis & Trop Med, Vienna, Austria.
   [Nosten, Francois; Phyo, Aung Pyae] Mahidol Univ, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Fac Trop Med, Bangkok 10700, Thailand.
   [Ogutu, Bernhards R.] Kenya Govt Med Res Ctr, US Army Med Res Unit, Kisumu, Kenya.
   [Onyamboko, Marie A.] Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO.
   [Owusu-Agyei, Seth] Kintampo Hlth Res Ctr, Kintampo, Ghana.
   [Premji, Zul] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
   [Price, Ric N.] Menzies Sch Hlth Res, Global & Trop Hlth Div, Darwin, NT, Australia.
   [Price, Ric N.] Charles Darwin Univ, Darwin, NT 0909, Australia.
   [Pukrittayakamee, Sasithon] Mahidol Univ, Fac Trop Med, Bangkok 10700, Thailand.
   [Ramharter, Michael] Med Univ Vienna, Div Infect Dis & Trop Med, Dept Med 1, Vienna, Austria.
   [Ramharter, Michael] Univ Tubingen, Inst Tropenmed, Tubingen, Germany.
   [Ramharter, Michael] Ctr Rech Med Lambarene, Lambarene, Gabon.
   [Sagara, Issaka] Univ Bamako, Fac Med Pharm & Odontostomatol, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali.
   [Se, Youry] AFRIMS, Phnom Penh, Cambodia.
   [Suon, Seila] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
   [Ward, Stephen A.] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England.
   [Winstanley, Peter A.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
RP Abdulla, S (reprint author), Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
EM sabdulla@ihi.or.tz; liz@tropmedres.ac; quique.bassat@isglobal.org;
   deliabethell@btinternet.com; anders.bjorkman@ki.se;
   sborrmann@kilifi.kemri-wellcome.org; udalessandro@mrc.gm;
   prabin.dahal@wwarn.org; nickd@tropmedres.ac; mdiakite@icermali.org;
   adjimde@icermali.org; arjen@tropmedres.ac; d_socheat@yahoo.com;
   Mike.Edstein@defence.gov.au; rfairhurst@niaid.nih.gov;
   drmafaiz@gmail.com; lillyfunke@yahoo.com; jennifer.flegg@monash.edu;
   carole.fogg@port.ac.uk; raquel.gonzalez@cresib.cat;
   brian.greenwood@lshtm.ac.uk; philippe.guerin@wwarn.org;
   jp.guthmann@invs.sante.fr; kamal.hamed@novartis.com; hientt@oucru.org;
   dr.y.htut@gmail.com; jumaelizabeth@yahoo.com; limp@niaid.nih.gov;
   andreas.martensson@ki.se; mayfong@tropmedres.ac; oamokuolu@yahoo.com;
   clarissa.moreira@wwarn.org; paul@tropmedres.ac;
   harald.noedl@meduniwien.ac.at; francois@tropmedres.ac;
   bernhards.ogutu@usamru-k.org; akatshimarie@yahoo.fr;
   owusu-agyei@kintampo-hrc.org; aungpyaephyo@shoklo-unit.com;
   zulpremji688@gmail.com; ric.price@wwarn.org; yon@tropmedres.ac;
   michael.ramharter@meduniwien.ac.at; isagara@mrtcbko.org;
   suon_seila012@yahoo.com; kasia.stepniewska@wwarn.org;
   saward@liverpool.ac.uk; nickwdt@tropmedres.ac;
   P.Winstanley@warwick.ac.uk
RI Ward, Steve/G-6003-2015; 
OI Guerin, Philippe/0000-0002-6008-2963; Ward, Steve/0000-0003-2331-3192;
   Price, Richard/0000-0003-2000-2874; Flegg, Jennifer/0000-0002-8809-726X;
   Dahal, Prabin/0000-0002-2158-846X
FU Bill and Melinda Gates Foundation; NIAID, NIH
FX We thank the patients and staff who participated in the clinical trials
   at all sites. WWARN is funded by a Bill and Melinda Gates Foundation
   grant. The funder did not participate in developing the protocol or
   writing the paper. This study was supported in part by the Intramural
   Research Program of the NIAID, NIH. All clinical studies were approved
   by the respective ethics committees or institutional review boards of
   each collaborative entity and host country of conduct. All subjects
   provided informed consent before study participation, and parents or
   legal guardians provided informed consent on behalf of their children.
   Disclaimer: The opinions expressed are those of the authors and do not
   necessarily reflect those of the Australian Defence Organisation or any
   extant policy.
NR 45
TC 0
Z9 0
U1 2
U2 27
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD SEP 22
PY 2015
VL 14
AR 359
DI 10.1186/s12936-015-0874-1
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CR6AW
UT WOS:000361426500001
ER

PT J
AU Hauptmann, J
   Schraivogel, D
   Bruckmann, A
   Manickavel, S
   Jakob, L
   Eichner, N
   Pfaff, J
   Urban, M
   Sprunck, S
   Hafner, M
   Tuschl, T
   Deutzmann, R
   Meister, G
AF Hauptmann, Judith
   Schraivogel, Daniel
   Bruckmann, Astrid
   Manickavel, Sudhir
   Jakob, Leonhard
   Eichner, Norbert
   Pfaff, Janina
   Urban, Marc
   Sprunck, Stefanie
   Hafner, Markus
   Tuschl, Thomas
   Deutzmann, Rainer
   Meister, Gunter
TI Biochemical isolation of Argonaute protein complexes by Ago-APP
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE Argonaute; small RNAs; microRNAs; GW proteins; RNAi
ID MICRORNA TARGETS; GENE-EXPRESSION; RNA CLEAVAGE; BINDING;
   IDENTIFICATION; REPRESSION; RECOGNITION; ARABIDOPSIS; DISSECTION; FAMILY
AB During microRNA (miRNA)-guided gene silencing, Argonaute (Ago) proteins interact with a member of the TNRC6/GW protein family. Here we used a short GW protein-derived peptide fused to GST and demonstrate that it binds to Ago proteins with high affinity. This allows for the simultaneous isolation of all Ago protein complexes expressed in diverse species to identify associated proteins, small RNAs, or target mRNAs. We refer to our method as "Ago protein Affinity Purification by Peptides" (Ago-APP). Furthermore, expression of this peptide competes for endogenous TNRC6 proteins, leading to global inhibition of miRNA function in mammalian cells.
C1 [Hauptmann, Judith; Schraivogel, Daniel; Bruckmann, Astrid; Jakob, Leonhard; Eichner, Norbert; Pfaff, Janina; Deutzmann, Rainer; Meister, Gunter] Univ Regensburg, Lab RNA Biol, Biochem Ctr Regensburg, D-93053 Regensburg, Germany.
   [Manickavel, Sudhir; Hafner, Markus] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Urban, Marc; Sprunck, Stefanie] Univ Regensburg, Biochem Ctr Regensburg, Cell Biol & Plant Biochem, D-93053 Regensburg, Germany.
   [Tuschl, Thomas] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10065 USA.
RP Meister, G (reprint author), Univ Regensburg, Lab RNA Biol, Biochem Ctr Regensburg, D-93053 Regensburg, Germany.
EM gunter.meister@vkl.uni-regensburg.de
OI Hafner, Markus/0000-0002-4336-6518; Schraivogel,
   Daniel/0000-0002-5734-6980
FU Deutsche Forschungsgemeinschaft [SFB 960]; European Research Council
   [242792]; Bavarian Genome Research Network (BayGene); German Cancer Aid;
   Bavarian Systems-Biology Network (BioSysNet)
FX We thank S. Ammon, C. Friederich, and E. Hochmuth for technical
   assistance and Julius Durr and Klaus Grasser for plant material. Our
   research is supported by grants from the Deutsche Forschungsgemeinschaft
   (SFB 960, FOR2127); the European Research Council (Grant 242792 "sRNAs,"
   Initial Training Network RNATrain); the Bavarian Genome Research Network
   (BayGene); the German Cancer Aid and the Bavarian Systems-Biology
   Network (BioSysNet).
NR 40
TC 4
Z9 4
U1 3
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 22
PY 2015
VL 112
IS 38
BP 11841
EP 11845
DI 10.1073/pnas.1506116112
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR7JH
UT WOS:000361525100045
PM 26351695
ER

PT J
AU Perera, L
   Freudenthal, BD
   Beard, WA
   Shock, DD
   Pedersen, LG
   Wilson, SH
AF Perera, Lalith
   Freudenthal, Bret D.
   Beard, William A.
   Shock, David D.
   Pedersen, Lee G.
   Wilson, Samuel H.
TI Requirement for transient metal ions revealed through computational
   analysis for DNA polymerase going in reverse
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE DNA polymerase; pyrophosphorolysis; QM/MM; DNA repair; reaction
   mechanism
ID STATE KINETIC-ANALYSIS; ACTIVE-SITE; ELECTROSTATIC POTENTIALS;
   MECHANISM; BETA; NUCLEOTIDE; PYROPHOSPHOROLYSIS; TRANSCRIPTASE;
   UNBLOCKING; INSERTION
AB DNA polymerases facilitate faithful insertion of nucleotides, a central reaction occurring during DNA replication and repair. DNA synthesis (forward reaction) is "balanced," as dictated by the chemical equilibrium by the reverse reaction of pyrophosphorolysis. Two closely spaced divalent metal ions (catalytic and nucleotide-binding metals) provide the scaffold for these reactions. The catalytic metal lowers the pK(a) of O3' of the growing primer terminus, and the nucleotide-binding metal facilitates substrate binding. Recent time-lapse crystallographic studies of DNA polymerases have identified an additional metal ion (product metal) associated with pyrophosphate formation, leading to the suggestion of its possible involvement in the reverse reaction. Here, we establish a rationale for a role of the product metal using quantum mechanical/molecular mechanical calculations of the reverse reaction in the confines of the DNA polymerase beta active site. Additionally, site-directed mutagenesis identifies essential residues and metal-binding sites necessary for pyrophosphorolysis. The results indicate that the catalytic metal site must be occupied by a magnesium ion for pyrophosphorolysis to occur. Critically, the product metal site is occupied by a magnesium ion early in the pyrophosphorolysis reaction path but must be removed later. The proposed dynamic nature of the active site metal ions is consistent with crystallographic structures. The transition barrier for pyrophosphorolysis was estimated to be significantly higher than that for the forward reaction, consistent with kinetic activity measurements of the respective reactions. These observations provide a framework to understand how ions and active site changes could modulate the internal chemical equilibrium of a reaction that is central to genome stability.
C1 [Perera, Lalith; Freudenthal, Bret D.; Beard, William A.; Shock, David D.; Pedersen, Lee G.; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   [Pedersen, Lee G.] Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA.
RP Perera, L (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM pereral2@niehs.nih.gov
FU 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 the National
   Institutes of Health Grant U19CA105010.
NR 43
TC 6
Z9 6
U1 0
U2 11
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 SEP 22
PY 2015
VL 112
IS 38
BP E5228
EP E5236
DI 10.1073/pnas.1511207112
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR7JH
UT WOS:000361525100005
PM 26351676
ER

PT J
AU Gotoh, S
   Negishi, M
AF Gotoh, Saki
   Negishi, Masahiko
TI Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by
   scaffolding PP2C to induce hepatic gluconeogenesis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID COA REDUCTASE INHIBITORS; CROSS-TALK; GLUCOSE; METABOLISM; GENES; MOUSE;
   CAR
AB Statin therapy is known to increase blood glucose levels in humans. Statins utilize pregnane X receptor (PXR) and serum/glucocorticoid regulated kinase 2 (SGK2) to activate phosphoenolpyruvate carboxykinase 1 (PEPCK1) and glucose-6-phosphatase (G6Pase) genes, thereby increasing glucose production in human liver cells. Here, the novel statin/PXR/SGK2-mediated signaling pathway has now been characterized for hepatic gluconeogenesis. Statin-activated PXR scaffolds the protein phosphatase 2C (PP2C) and SGK2 to stimulate PP2C to dephosphorylate SGK2 at threonine 193. Non-phosphorylated SGK2 co-activates PXR-mediated trans-activation of promoters of gluconeogenic genes in human liver cells, thereby enhancing gluconeogenesis. This gluconeogenic statin-PXR-SGK2 signal is not present in mice, in which statin treatment suppresses hepatic gluconeogenesis. These findings provide the basis for statin-associated side effects such as an increased risk for Type 2 diabetes.
C1 [Gotoh, Saki; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
FU Intramural Research Program of the NIH [Z01ES71005-01]; NIEHS
FX We thank the NIEHS DNA sequencing core. This work was supported by the
   Intramural Research Program (Z01ES71005-01) of the NIH and NIEHS.
NR 18
TC 12
Z9 12
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 22
PY 2015
VL 5
AR 14076
DI 10.1038/srep14076
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR7GD
UT WOS:000361515500001
PM 26392083
ER

PT J
AU Giacomin, PR
   Moy, RH
   Noti, M
   Osborne, LC
   Siracusa, MC
   Alenghat, T
   Liu, BG
   McCorkell, KA
   Troy, AE
   Rak, GD
   Hu, YL
   May, MJ
   Ma, HL
   Fouser, LA
   Sonnenberg, GF
   Artis, D
AF Giacomin, Paul R.
   Moy, Ryan H.
   Noti, Mario
   Osborne, Lisa C.
   Siracusa, Mark C.
   Alenghat, Theresa
   Liu, Bigang
   McCorkell, Kelly A.
   Troy, Amy E.
   Rak, Gregory D.
   Hu, Yinling
   May, Michael J.
   Ma, Hak-Ling
   Fouser, Lynette A.
   Sonnenberg, Gregory F.
   Artis, David
TI Epithelial-intrinsic IKK alpha expression regulates group 3 innate
   lymphoid cell responses and antibacterial immunity
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID NF-KAPPA-B; THYMIC STROMAL LYMPHOPOIETIN; CHRONIC INTESTINAL
   INFLAMMATION; LYMPHOTOXIN-BETA-RECEPTOR; CD4(+) T-CELLS; COMMENSAL
   BACTERIA; CITROBACTER-RODENTIUM; DENDRITIC CELLS; BOWEL-DISEASE;
   ALLERGIC INFLAMMATION
AB Innate lymphoid cells (ILCs) are critical for maintaining epithelial barrier integrity at mucosal surfaces; however, the tissue-specific factors that regulate ILC responses remain poorly characterized. Using mice with intestinal epithelial cell (IEC)-specific deletions in either inhibitor of kappa B kinase (IKK)alpha or IKK beta, two critical regulators of NF kappa B activation, we demonstrate that IEC-intrinsic IKK alpha expression selectively regulates group 3 ILC (ILC3)-dependent antibacterial immunity in the intestine. Although IKK beta(Delta IEC) mice efficiently controlled Citrobacter rodentium infection, IKK alpha(Delta IEC) mice exhibited severe intestinal inflammation, increased bacterial dissemination to peripheral organs, and increased host mortality. Consistent with weakened innate immunity to C. rodentium, IKK alpha(Delta IEC) mice displayed impaired IL-22 production by ROR gamma t(+) ILC3s, and therapeutic delivery of rIL-22 or transfer of sort-purified IL-22-competent ILCs from control mice could protect IKK alpha(Delta IEC) mice from C. rodentium-induced morbidity. Defective ILC3 responses in IKK alpha(Delta IEC) mice were associated with overproduction of thymic stromal lymphopoietin (TSLP) by IECs, which negatively regulated IL-22 production by ILC3s and impaired innate immunity to C. rodentium. IEC-intrinsic IKK alpha expression was similarly critical for regulation of intestinal inflammation after chemically induced intestinal damage and colitis. Collectively, these data identify a previously unrecognized role for epithelial cell-intrinsic IKK alpha expression and TSLP in regulating ILC3 responses required to maintain intestinal barrier immunity.
C1 [Giacomin, Paul R.; Moy, Ryan H.; Noti, Mario; Osborne, Lisa C.; Siracusa, Mark C.; Alenghat, Theresa; Troy, Amy E.; Rak, Gregory D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [McCorkell, Kelly A.; May, Michael J.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
   [Osborne, Lisa C.; Sonnenberg, Gregory F.; Artis, David] Cornell Univ, Weill Cornell Med Coll, Jill Roberts Inst Res Inflammatory Bowel Dis, New York, NY 10021 USA.
   [Liu, Bigang] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX 78957 USA.
   [Hu, Yinling] NCI, Ctr Canc Res, Canc & Inflammat Program, Lab Expt Immunol, Frederick, MD 21701 USA.
   [Ma, Hak-Ling; Fouser, Lynette A.] Pfizer Biotherapeut Res & Dev, Inflammat & Immunol, Cambridge, MA 02140 USA.
RP Artis, D (reprint author), Cornell Univ, Weill Cornell Med Coll, Jill Roberts Inst Res Inflammatory Bowel Dis, New York, NY 10021 USA.
EM dartis@med.cornell.edu
OI May, Michael/0000-0002-2485-3716
FU National Cancer Institute Comprehensive Cancer Center Support Grant
   [2-P30CA016520]; National Institutes of Health (NIH) [AI061570,
   AI074878, AI087990, AI095466, AI095608, AI102942, AI106697, AI097333,
   T32-RR007063, K08-DK093784, F32-AI72943]; NIH [DP50D012116]; Burroughs
   Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award;
   Crohn's and Colitis Foundation of America grant; Australian National
   Health and Medical Research Council Overseas Biomedical Fellowship
   [613718]; Swiss National Science Foundation [PBBEP3_130438,
   PA00P3_136468]; Irvington Institute Postdoctoral Fellowship of the
   Cancer Research Institute
FX We thank members of the Artis laboratory for discussions and critical
   reading of manuscript drafts, the Matthew J. Ryan Veterinary Hospital
   Pathology Laboratory and the Abramson Cancer Center Flow Cytometry and
   Cell Sorting Resource Laboratory (partially supported by National Cancer
   Institute Comprehensive Cancer Center Support Grant [#2-P30CA016520])
   for technical advice and support, and K. Lam and A. Root (Pfizer) for
   purification of IL-22 diagnostic Abs. We thank M.R. Comeau (Amgen) for
   provision of TSLP-related reagents and mice.; Research in the Artis
   laboratory is supported by National Institutes of Health (NIH) grants
   AI061570, AI074878, AI087990, AI095466, AI095608, AI102942, AI106697,
   and AI097333 to D. Artis, T32-RR007063 and K08-DK093784 to T. Alenghat,
   and F32-AI72943 to A.E. Troy. This research is also supported by NIH
   grant DP50D012116 to G.F. Sonnenberg, the Burroughs Wellcome Fund
   Investigator in Pathogenesis of Infectious Disease Award to D. Artis,
   Crohn's and Colitis Foundation of America grant to D. Artis, the
   Australian National Health and Medical Research Council Overseas
   Biomedical Fellowship 613718 to P.R. Giacomin, the Swiss National
   Science Foundation grants PBBEP3_130438 and PA00P3_136468 to M. Noti,
   and the Irvington Institute Postdoctoral Fellowship of the Cancer
   Research Institute to L.C. Osborne.
NR 106
TC 9
Z9 9
U1 2
U2 13
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD SEP 21
PY 2015
VL 212
IS 10
BP 1513
EP 1528
DI 10.1084/jem.20141831
PG 16
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CW6VB
UT WOS:000365135200007
PM 26371187
ER

PT J
AU Kreins, AY
   Ciancanelli, MJ
   Okada, S
   Kong, XF
   Ramirez-Alejo, N
   Kilic, SS
   El Baghdadi, J
   Nonoyama, S
   Mahdaviani, SA
   Ailal, F
   Bousfiha, A
   Mansouri, D
   Nievas, E
   Ma, CS
   Rao, G
   Bernasconi, A
   Kuehn, HS
   Niemela, J
   Stoddard, J
   Deveau, P
   Cobat, A
   El Azbaoui, S
   Sabri, A
   Lim, CK
   Sundin, M
   Avery, DT
   Halwani, R
   Grant, AV
   Boisson, B
   Bogunovic, D
   Itan, Y
   Moncada-Velez, M
   Martinez-Barricarte, R
   Migaud, M
   Deswarte, C
   Alsina, L
   Kotlarz, D
   Klein, C
   Muller-Fleckenstein, I
   Fleckenstein, B
   Cormier-Daire, V
   Rose-John, S
   Picard, C
   Hammarstrom, L
   Puel, A
   Al-Muhsen, S
   Abel, L
   Chaussabel, D
   Rosenzweig, SD
   Minegishi, Y
   Tangye, SG
   Bustamante, J
   Casanova, JL
   Boisson-Dupuis, S
AF Kreins, Alexandra Y.
   Ciancanelli, Michael J.
   Okada, Satoshi
   Kong, Xiao-Fei
   Ramirez-Alejo, Noe
   Kilic, Sara Sebnem
   El Baghdadi, Jamila
   Nonoyama, Shigeaki
   Mahdaviani, Seyed Alireza
   Ailal, Fatima
   Bousfiha, Aziz
   Mansouri, Davood
   Nievas, Elma
   Ma, Cindy S.
   Rao, Geetha
   Bernasconi, Andrea
   Kuehn, Hye Sun
   Niemela, Julie
   Stoddard, Jennifer
   Deveau, Paul
   Cobat, Aurelie
   El Azbaoui, Safa
   Sabri, Ayoub
   Lim, Che Kang
   Sundin, Mikael
   Avery, Danielle T.
   Halwani, Rabih
   Grant, Audrey V.
   Boisson, Bertrand
   Bogunovic, Dusan
   Itan, Yuval
   Moncada-Velez, Marcela
   Martinez-Barricarte, Ruben
   Migaud, Melanie
   Deswarte, Caroline
   Alsina, Laia
   Kotlarz, Daniel
   Klein, Christoph
   Muller-Fleckenstein, Ingrid
   Fleckenstein, Bernhard
   Cormier-Daire, Valerie
   Rose-John, Stefan
   Picard, Capucine
   Hammarstrom, Lennart
   Puel, Anne
   Al-Muhsen, Saleh
   Abel, Laurent
   Chaussabel, Damien
   Rosenzweig, Sergio D.
   Minegishi, Yoshiyuki
   Tangye, Stuart G.
   Bustamante, Jacinta
   Casanova, Jean-Laurent
   Boisson-Dupuis, Stephanie
TI Human TYK2 deficiency: Mycobacterial and viral infections without
   hyper-IgE syndrome
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; PROTEIN-TYROSINE KINASE; T-CELL
   MEMORY; RECEPTOR BETA-1 DEFICIENCY; HUMAN STAT1 DEFICIENCY;
   INBORN-ERRORS; IFN-GAMMA; INTERFERON-ALPHA/BETA; CLINICAL-FEATURES;
   SIGNAL TRANSDUCER
AB Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-alpha/beta, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-gamma, IL-28/29 (IFN-lambda), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-alpha/beta. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
C1 [Kreins, Alexandra Y.; Ciancanelli, Michael J.; Okada, Satoshi; Kong, Xiao-Fei; Ramirez-Alejo, Noe; Boisson, Bertrand; Bogunovic, Dusan; Itan, Yuval; Moncada-Velez, Marcela; Martinez-Barricarte, Ruben; Picard, Capucine; Abel, Laurent; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
   [Kreins, Alexandra Y.] Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA.
   [Kilic, Sara Sebnem] Uludag Univ, Fac Med, Dept Pediat Immunol, TR-16059 Gorukle, Bursa, Turkey.
   [El Baghdadi, Jamila; El Azbaoui, Safa; Sabri, Ayoub] Mil Hosp Mohamed V, Genet Unit, Rabat 10100, Morocco.
   [Nonoyama, Shigeaki] Natl Def Med Coll, Dept Pediat, Tokorozawa, Saitama 3590042, Japan.
   [Mahdaviani, Seyed Alireza] Shahid Beheshti Univ Med Sci, Pediat Resp Dis Res Ctr, Tehran 141556153, Iran.
   [Mansouri, Davood] Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, Natl Res Inst TB & Lung Dis, Dept Clin Immunol & Infect Dis, Tehran 141556153, Iran.
   [Ailal, Fatima; Bousfiha, Aziz] King Hassan II Univ, CHU Ibn Rochd, Dept Pediat, Clin Immunol Unit, Casablanca 20000, Morocco.
   [Nievas, Elma] Pediat Hosp A Fleming OSEP, Immunol Unit, RA-5500 Mendoza, Argentina.
   [Ma, Cindy S.; Rao, Geetha; Avery, Danielle T.; Tangye, Stuart G.] St Vincents Hosp, Garvan Inst Med Res, Immunol Program, Darlinghurst, NSW 2010, Australia.
   [Ma, Cindy S.; Tangye, Stuart G.] Univ New S Wales, St Vincents Clin Sch, Darlinghurst, NSW 2010, Australia.
   [Bernasconi, Andrea] Garrahan Hosp, Immunol & Rheumatol Serv, RA-1408 Buenos Aires, DF, Argentina.
   [Kuehn, Hye Sun; Niemela, Julie; Stoddard, Jennifer; Rosenzweig, Sergio D.] NIAID, NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
   [Rosenzweig, Sergio D.] NIAID, NIH, Primary Immunodeficiency Clin, Bethesda, MD 20892 USA.
   [Deveau, Paul; Cobat, Aurelie; Grant, Audrey V.; Migaud, Melanie; Deswarte, Caroline; Picard, Capucine; Puel, Anne; Abel, Laurent; Bustamante, Jacinta; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie] Necker Enfants Malad Hosp, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, F-75015 Paris, France.
   [Deveau, Paul; Cobat, Aurelie; Grant, Audrey V.; Migaud, Melanie; Deswarte, Caroline; Picard, Capucine; Puel, Anne; Abel, Laurent; Bustamante, Jacinta; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie] Univ Paris 05, Imagine Inst, F-75006 Paris, France.
   [El Azbaoui, Safa; Sabri, Ayoub] Ibn Tofail Univ, Fac Sci Kenitra, Mexico City 14000, DF, Mexico.
   [Lim, Che Kang; Hammarstrom, Lennart] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Lab Med,Div Clin Immunol, S-14152 Stockholm, Sweden.
   [Lim, Che Kang] Singapore Gen Hosp, Dept Clin Res, Singapore 169856, Singapore.
   [Sundin, Mikael] Astrid Lindgrens Childrens Hosp, Pediat Hematol Immunol, S-14186 Stockholm, Sweden.
   [Sundin, Mikael] Karolinska Inst, S-14186 Stockholm, Sweden.
   [Halwani, Rabih; Al-Muhsen, Saleh] King Saud Univ, Coll Med, Asthma Res Chair, Riyadh 12372, Saudi Arabia.
   [Halwani, Rabih; Al-Muhsen, Saleh] King Saud Univ, Coll Med, Prince Naif Ctr Immunol Res, Dept Pediat, Riyadh 12372, Saudi Arabia.
   [Moncada-Velez, Marcela] Univ Antioquia UdeA, Inst Biol, Grp Primary Immunodeficiencies, Medellin 1226, Colombia.
   [Alsina, Laia] Baylor Inst Immunol Res, Dallas, TX 75204 USA.
   [Alsina, Laia] Baylor Res Inst, Dallas, TX 75204 USA.
   [Alsina, Laia] Univ Barcelona, Hosp St Joan Deu, Allergy & Clin Immunol Dept, Barcelona 08950, Spain.
   [Kotlarz, Daniel; Klein, Christoph] Univ Munich, Dr von Hauner Childrens Hosp, Dept Pediat, D-80337 Munich, Germany.
   [Muller-Fleckenstein, Ingrid; Fleckenstein, Bernhard] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany.
   [Cormier-Daire, Valerie] Univ Paris 05, Sorbonne Paris Cite, Necker Enfants Malad Hosp, INSERM U1163,Imagine Inst,Dept Genet, F-75015 Paris, France.
   [Rose-John, Stefan] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany.
   [Picard, Capucine; Bustamante, Jacinta] Necker Enfants Malad Hosp, AP HP, Ctr Study Primary Immunodeficiencies, F-75015 Paris, France.
   [Chaussabel, Damien] Sidra Med & Res Ctr, Dept Syst Biol, Doha, Qatar.
   [Minegishi, Yoshiyuki] Tokyo Med & Dent Univ, Grad Sch, Dept Immune Regulat, Bunkyo Ku, Tokyo 1138510, Japan.
   [Casanova, Jean-Laurent] Necker Enfants Malad Hosp, Pediat Immunol & Hematol Unit, F-75015 Paris, France.
   [Casanova, Jean-Laurent] Howard Hughes Med Inst, New York, NY 10065 USA.
RP Boisson-Dupuis, S (reprint author), Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
EM stbo603@rockefeller.edu
RI Okada, Satoshi/B-8901-2011; Rose-John, Stefan/A-7998-2010; Sundin,
   Mikael/E-5942-2013; 
OI Okada, Satoshi/0000-0002-4622-5657; Rose-John,
   Stefan/0000-0002-7519-3279; Ciancanelli, Michael/0000-0002-4623-852X;
   mahdaviani, alireza/0000-0001-6224-4797; Sundin,
   Mikael/0000-0002-9871-0961; mansouri, davood/0000-0002-0564-8282;
   Chaussabel, Damien/0000-0002-6131-7242
FU French National Agency for Research (ANR); EU-grant HOMITB
   [HEALTH-F3-2008-200732]; European Research Council (ERC)
   [ERC-2010-AdG-268777]; Bill and Melinda Gates Foundation; St. Giles
   Foundation; Jeffrey Modell Foundation; Talecris Biotherapeutics;
   National Center for Research Resources; National Institutes of Health
   [8UL1TR000043]; National Institute of Allergy and Infectious Diseases
   (NIAID) [5R01AI089970, 5R37AI095983, 5U01AI088685]; Rockefeller
   University; Fondation Medicale Medische Stichting Mathilde E.
   Horlait-Dapsens; Helmsley Fellowship for Basic and Translational
   Research on Disorders of the Digestive System; NIAID [1K99AI106942];
   Stony Wold-Herbert Fund; European Molecular Biology Organization (EMBO);
   National Health and Medical Research Council of Australia; Deutsche
   Forschungsgemeinschaft (DFG), Bonn [SFB841, C1, SFB877, A1]; Cluster of
   Excellence "Inflammation at interfaces"; National Center for Advancing
   Sciences (NCATS)
FX The Laboratory of Human Genetics of Infectious Diseases was supported in
   part by grants from the French National Agency for Research (ANR), the
   EU-grant HOMITB (HEALTH-F3-2008-200732), the European Research Council
   (ERC; ERC-2010-AdG-268777), the Bill and Melinda Gates Foundation, the
   St. Giles Foundation, the Jeffrey Modell Foundation and Talecris
   Biotherapeutics, the National Center for Research Resources and the
   National Center for Advancing Sciences (NCATS), National Institutes of
   Health grant 8UL1TR000043, the National Institute of Allergy and
   Infectious Diseases (NIAID) grants 5R01AI089970, 5R37AI095983, and
   5U01AI088685, and The Rockefeller University. A.Y. Kreins was supported
   by Fondation Medicale Medische Stichting Mathilde E. Horlait-Dapsens, D.
   Bogunovic by the Helmsley Fellowship for Basic and Translational
   Research on Disorders of the Digestive System and NIAID grant
   1K99AI106942, X.-F. Kong by the Stony Wold-Herbert Fund, and R.
   Martinez-Barricarte by the European Molecular Biology Organization
   (EMBO). C.S. Ma and S.G. Tangye are supported by fellowships and grants
   from the National Health and Medical Research Council of Australia. The
   work of S. Rose-John was supported by the Deutsche
   Forschungsgemeinschaft (DFG), Bonn (SFB841, project C1; SFB877, project
   A1), and by the Cluster of Excellence "Inflammation at interfaces."
NR 104
TC 23
Z9 24
U1 5
U2 9
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD SEP 21
PY 2015
VL 212
IS 10
BP 1641
EP 1662
DI 10.1084/jem.20140280
PG 22
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CW6VB
UT WOS:000365135200014
PM 26304966
ER

PT J
AU Kolhatkar, NS
   Brahmandam, A
   Thouvenel, CD
   Becker-Herman, S
   Jacobs, HM
   Schwartz, MA
   Allenspach, EJ
   Khim, S
   Panigrahi, AK
   Prak, ETL
   Thrasher, AJ
   Notarangelo, LD
   Candotti, F
   Torgerson, TR
   Sanz, I
   Rawlings, DJ
AF Kolhatkar, Nikita S.
   Brahmandam, Archana
   Thouvenel, Christopher D.
   Becker-Herman, Shirly
   Jacobs, Holly M.
   Schwartz, Marc A.
   Allenspach, Eric J.
   Khim, Socheath
   Panigrahi, Anil K.
   Prak, Eline T. Luning
   Thrasher, Adrian J.
   Notarangelo, Luigi D.
   Candotti, Fabio
   Torgerson, Troy R.
   Sanz, Ignacio
   Rawlings, David J.
TI Altered BCR and TLR signals promote enhanced positive selection of
   autoreactive transitional B cells in Wiskott-Aldrich syndrome
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TOLL-LIKE RECEPTORS; CD4(+) T-CELLS;
   AUTOANTIBODY PRODUCTION; AUTOIMMUNE-DISEASE; TRANSGENIC MICE; MARGINAL
   ZONE; TOLERANCE; BAFF; DIFFERENTIATION
AB Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder frequently associated with systemic autoimmunity, including autoantibody-mediated cytopenias. WAS protein (WASp)-deficient B cells have increased B cell receptor (BCR) and Toll-like receptor (TLR) signaling, suggesting that these pathways might impact establishment of the mature, naive BCR repertoire. To directly investigate this possibility, we evaluated naive B cell specificity and composition in WASp-deficient mice and WAS subjects (n = 12). High-throughput sequencing and single-cell cloning analysis of the BCR repertoire revealed altered heavy chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and human naive B cells. Although negative selection mechanisms including deletion, anergy, and receptor editing were relatively unperturbed, WASp-deficient transitional B cells showed enhanced proliferation in vivo mediated by antigen-and Myd88-dependent signals. Finally, using both BCR sequencing and cell surface analysis with a monoclonal antibody recognizing an intrinsically autoreactive heavy chain, we show enrichment in self-reactive cells specifically at the transitional to naive mature B cell stage in WAS subjects. Our combined data support a model wherein modest alterations in B cell-intrinsic, BCR, and TLR signals in WAS, and likely other autoimmune disorders, are sufficient to alter B cell tolerance via positive selection of self-reactive transitional B cells.
C1 [Kolhatkar, Nikita S.; Schwartz, Marc A.; Rawlings, David J.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
   [Brahmandam, Archana; Thouvenel, Christopher D.; Becker-Herman, Shirly; Jacobs, Holly M.; Allenspach, Eric J.; Khim, Socheath; Torgerson, Troy R.; Rawlings, David J.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
   [Brahmandam, Archana; Thouvenel, Christopher D.; Becker-Herman, Shirly; Jacobs, Holly M.; Khim, Socheath; Torgerson, Troy R.; Rawlings, David J.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA 98101 USA.
   [Panigrahi, Anil K.; Prak, Eline T. Luning] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Thrasher, Adrian J.] UCL, Inst Child Hlth, Sect Mol & Cellular Immunol, Mol Immunol Unit,Ctr Immunodeficiency, London WC1N 1EH, England.
   [Notarangelo, Luigi D.] Childrens Hosp Boston, Dept Immunol, Boston, MA USA.
   [Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Sanz, Ignacio] Emory Univ, Lowance Ctr Human Immunol, Atlanta, GA 30322 USA.
   [Sanz, Ignacio] Emory Univ, Dept Med, Div Rheumatol, Atlanta, GA 30322 USA.
RP Rawlings, DJ (reprint author), Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
EM drawling@u.washington.edu
RI Notarangelo, Luigi/F-9718-2016; 
OI Notarangelo, Luigi/0000-0002-8335-0262; Allenspach,
   Eric/0000-0001-7346-5835
FU National Heart, Lung, and Blood Institute; National Institute of
   Diabetes and Digestive and Kidney Diseases; National Institute of
   Allergy and Infectious Diseases of the NIH [R01HL075453, R01AI084457,
   R01AI071163, DP3DK097672, 5P01HL059561, UO1 DK070430]; Wiskott-Aldrich
   Foundation; Benaroya Family Gift Fund; ACR REF/Ephraim P. Engleman
   Endowed Resident Research Preceptorship; Cancer Research Institute
   Pre-doctoral Training Grant
FX This work was supported by the National Heart, Lung, and Blood
   Institute, National Institute of Diabetes and Digestive and Kidney
   Diseases, and National Institute of Allergy and Infectious Diseases of
   the NIH under award numbers R01HL075453, R01AI084457, R01AI071163, and
   DP3DK097672 (all to D.J. Rawlings); 5P01HL059561 (to L.D. Notarangelo);
   and UO1 DK070430 (to E.T. Luning Prak). The content is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the NIH. Additional support was provided by the
   Wiskott-Aldrich Foundation and Benaroya Family Gift Fund (to D.J.
   Rawlings), an ACR REF/Ephraim P. Engleman Endowed Resident Research
   Preceptorship (to E.J. Allenspach), and a Cancer Research Institute
   Pre-doctoral Training Grant (to N.S. Kolhatkar and M.A. Schwartz).
NR 58
TC 9
Z9 9
U1 2
U2 5
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD SEP 21
PY 2015
VL 212
IS 10
BP 1663
EP 1677
DI 10.1084/jem.20150585
PG 15
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CW6VB
UT WOS:000365135200015
PM 26371186
ER

PT J
AU Chong, WP
   van Panhuys, N
   Chen, J
   Silver, PB
   Jittayasothorn, Y
   Mattapallil, MJ
   Germain, RN
   Caspi, RR
AF Chong, Wai Po
   van Panhuys, Nicholas
   Chen, Jun
   Silver, Phyllis B.
   Jittayasothorn, Yingyos
   Mattapallil, Mary J.
   Germain, Ronald N.
   Caspi, Rachel R.
TI NK-DC crosstalk controls the autopathogenic Th17 response through an
   innate IFN-gamma-IL-27 axis
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID NATURAL-KILLER-CELLS; EXPERIMENTAL AUTOIMMUNE UVEITIS; REGULATORY
   T-CELLS; IFN-GAMMA; DENDRITIC CELLS; INTERFERON-GAMMA; OCULAR
   AUTOIMMUNITY; MULTIPLE-SCLEROSIS; EFFECTOR RESPONSE; DEFICIENT MICE
AB IFN-gamma is a pathogenic cytokine involved in inflammation. Paradoxically, its deficiency exacerbates experimental autoimmune encephalomyelitis, uveitis, and arthritis. Here, we demonstrate using IFN-gamma(-/-) mice repleted with IFN-gamma(+/+) NK cells that innate production of IFN-gamma from NK cells is necessary and sufficient to trigger an endogenous regulatory circuit that limits autoimmunity. After immunization, DCs recruited IFN-gamma-producing NK cells to the draining lymph node and interacted with them in a CXCR3-dependent fashion. The interaction caused DCs to produce IL-27, which in turn enhanced IFN-gamma production by NK cells, forming a self-amplifying positive feedback loop. IL-10, produced by the interacting cells themselves, was able to limit this process. The NK-DC-dependent IL-27 inhibited development of the adaptive pathogenic IL-17 response and induced IL-10-producing Tr1-like cells, which ameliorated disease in an IL-10-dependent manner. Our data reveal that an early NK-DC interaction controls the adaptive Th17 response and limits tissue-specific autoimmunity through an innate IFN-gamma-IL-27 axis.
C1 [Chong, Wai Po; Chen, Jun; Silver, Phyllis B.; Jittayasothorn, Yingyos; Mattapallil, Mary J.; Caspi, Rachel R.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
   [van Panhuys, Nicholas; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
   [Chen, Jun] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
RP Caspi, RR (reprint author), NEI, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA.
EM waipoc@mail.nih.gov; rcaspi@helix.nih.gov
RI van Panhuys, Nicholas/E-1812-2011
FU Intramural Research Programs of the National Eye Institute; National
   Institute of Allergy and Infectious Diseases, National Institutes of
   Health
FX This work was supported by the Intramural Research Programs of the
   National Eye Institute and the National Institute of Allergy and
   Infectious Diseases, National Institutes of Health.
NR 49
TC 6
Z9 7
U1 2
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD SEP 21
PY 2015
VL 212
IS 10
BP 1739
EP 1752
DI 10.1084/jem.20141678
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CW6VB
UT WOS:000365135200020
PM 26347474
ER

PT J
AU Sattin, S
   Tao, JH
   Vettoretti, G
   Moroni, E
   Pennati, M
   Lopergolo, A
   Morelli, L
   Bugatti, A
   Zuehlke, A
   Moses, M
   Prince, T
   Kijima, T
   Beebe, K
   Rusnati, M
   Neckers, L
   Zaffaroni, N
   Agard, DA
   Bernardi, A
   Colombo, G
AF Sattin, Sara
   Tao, Jiahui
   Vettoretti, Gerolamo
   Moroni, Elisabetta
   Pennati, Marzia
   Lopergolo, Alessia
   Morelli, Laura
   Bugatti, Antonella
   Zuehlke, Abbey
   Moses, Mike
   Prince, Thomas
   Kijima, Toshiki
   Beebe, Kristin
   Rusnati, Marco
   Neckers, Len
   Zaffaroni, Nadia
   Agard, David A.
   Bernardi, Anna
   Colombo, Giorgio
TI Activation of Hsp90 Enzymatic Activity and Conformational Dynamics
   through Rationally Designed Allosteric Ligands
SO CHEMISTRY-A EUROPEAN JOURNAL
LA English
DT Article
DE allostery; drug design; functional dynamics; glycoconjugates; Hsp90
ID MOLECULAR CHAPERONE HSP90; SHOCK-PROTEIN 90; ESCHERICHIA-COLI; DRUG
   DISCOVERY; ATP HYDROLYSIS; INHIBITORS; BINDING; SCAFFOLD; REVEALS;
   CANCER
AB Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP-regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP-competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2-phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 angstrom from the active site. Specifically, analysis of protein responses to first-generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules' effects on Hsp90 enzymatic, conformational, co-chaperone and client-binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary.
C1 [Sattin, Sara; Morelli, Laura; Bernardi, Anna] Univ Milan, Dipartimento Chim, I-20133 Milan, Italy.
   [Tao, Jiahui; Agard, David A.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Tao, Jiahui; Agard, David A.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Vettoretti, Gerolamo; Moroni, Elisabetta; Colombo, Giorgio] CNR, Ist Chim Riconoscimento Mol, I-20131 Milan, Italy.
   [Pennati, Marzia; Lopergolo, Alessia; Zaffaroni, Nadia] Fdn IRCCS Ist Nazl Tumori, Mol Pharmacol Unit, Dept Expt Oncol & Mol Med, I-20133 Milan, Italy.
   [Bugatti, Antonella; Rusnati, Marco] Univ Brescia, Dept Mol & Translat Med, I-25123 Brescia, Italy.
   [Zuehlke, Abbey; Moses, Mike; Prince, Thomas; Kijima, Toshiki; Beebe, Kristin; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Colombo, G (reprint author), CNR, Ist Chim Riconoscimento Mol, Via Mario Bianco 9, I-20131 Milan, Italy.
EM giorgio.colombo@icrm.cnr.it
RI Colombo, Giorgio/A-2730-2012; Tao, Jiahui/K-5488-2016; Sattin,
   Sara/L-2234-2016; Bernardi, Anna/A-1167-2012; Zaffaroni,
   Nadia/J-8178-2016; 
OI Colombo, Giorgio/0000-0002-1318-668X; Sattin, Sara/0000-0002-5558-3915;
   Bernardi, Anna/0000-0002-1258-2007; Zaffaroni,
   Nadia/0000-0002-4669-0890; Zuehlke, Abbey/0000-0003-0432-8823; RUSNATI,
   Marco/0000-0001-9968-5908; Pennati, Marzia/0000-0002-6181-2681
FU Fondazione Cariplo [2011.1800]; AIRC (Associazione Italiana Ricerca sul
   Cancro) [IG 15420]; Universita' degli Studi di Milano
FX We acknowledge funding from Fondazione Cariplo through grant 2011.1800,
   "Premio Fondazione Cariplo per la Ricerca di Frontiera". G.C.
   acknowledges funding from the AIRC (Associazione Italiana Ricerca sul
   Cancro) grant IG 15420; Universita' degli Studi di Milano is
   acknowledged for a grant to S.S. (Assegno di ricerca tipo A).
NR 58
TC 6
Z9 6
U1 4
U2 17
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0947-6539
EI 1521-3765
J9 CHEM-EUR J
JI Chem.-Eur. J.
PD SEP 21
PY 2015
VL 21
IS 39
BP 13598
EP 13608
DI 10.1002/chem.201502211
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA CR2VZ
UT WOS:000361190200019
PM 26286886
ER

PT J
AU Wenger, C
   Salvador, R
   Basser, PJ
   Miranda, PC
AF Wenger, Cornelia
   Salvador, Ricardo
   Basser, Peter J.
   Miranda, Pedro C.
TI The electric field distribution in the brain during TTFields therapy and
   its dependence on tissue dielectric properties and anatomy: a
   computational study
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE tumor treating fields; realistic human head model; anisotropic
   conductivity tensor; sensitivity analysis; finite element model
ID ELEMENT HEAD MODEL; WHITE-MATTER; ANISOTROPIC CONDUCTIVITY; RECURRENT
   GLIOBLASTOMA; CURRENT STIMULATION; TREATMENT MODALITY; CEREBRAL CORTEX;
   NOVOTTF-100A; FREQUENCY; IMPEDANCE
AB Tumor treating fields (TTFields) are a non-invasive, anti-mitotic and approved treatment for recurrent glioblastoma multiforme (GBM) patients. In vitro studies have shown that inhibition of cell division in glioma is achieved when the applied alternating electric field has a frequency in the range of 200 kHz and an amplitude of 1-3 V cm(-1). Our aim is to calculate the electric field distribution in the brain during TTFields therapy and to investigate the dependence of these predictions on the heterogeneous, anisotropic dielectric properties used in the computational model.
   A realistic head model was developed by segmenting MR images and by incorporating anisotropic conductivity values for the brain tissues. The finite element method (FEM) was used to solve for the electric potential within a volume mesh that consisted of the head tissues, a virtual lesion with an active tumour shell surrounding a necrotic core, and the transducer arrays.
   The induced electric field distribution is highly non-uniform. Average field strength values are slightly higher in the tumour when incorporating anisotropy, by about 10% or less. A sensitivity analysis with respect to the conductivity and permittivity of head tissues shows a variation in field strength of less than 42% in brain parenchyma and in the tumour, for values within the ranges reported in the literature. Comparing results to a previously developed head model suggests significant inter-subject variability.
   This modelling study predicts that during treatment with TTFields the electric field in the tumour exceeds 1 V cm(-1), independent of modelling assumptions. In the future, computational models may be useful to optimize delivery of TTFields.
C1 [Wenger, Cornelia; Salvador, Ricardo; Miranda, Pedro C.] Univ Lisbon, Fac Ciencias, Inst Biophys & Biomed Engn, P-1749016 Lisbon, Portugal.
   [Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA.
RP Wenger, C (reprint author), Univ Lisbon, Fac Ciencias, Inst Biophys & Biomed Engn, P-1749016 Lisbon, Portugal.
EM cwenger@fc.ul.pt; rnsalvador@fc.ul.pt; pjbasser@helix.nih.gov;
   pcmiranda@fc.ul.pt
RI Miranda, Pedro/A-5643-2013; Salvador, Ricardo/K-2301-2015; 
OI Miranda, Pedro/0000-0002-6793-8111; Salvador,
   Ricardo/0000-0003-1235-6533; Wenger, Cornelia/0000-0001-7889-9093
FU Novocure; Intramural Research Program (IRP) of the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development, NIH;
   Foundation for Science and Technology (FCT), Portugal
FX CW was supported by Novocure. PJB was supported by the Intramural
   Research Program (IRP) of the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development, NIH. PCM and RS were supported in
   part by the Foundation for Science and Technology (FCT), Portugal.
NR 52
TC 7
Z9 7
U1 2
U2 13
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 SEP 21
PY 2015
VL 60
IS 18
BP 7339
EP 7357
DI 10.1088/0031-9155/60/18/7339
PG 19
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA CR1ZL
UT WOS:000361124000019
PM 26350296
ER

PT J
AU Minard-Colin, V
   Brugieres, L
   Reiter, A
   Cairo, MS
   Gross, TG
   Woessmann, W
   Burkhardt, B
   Sandlund, JT
   Williams, D
   Pillon, M
   Horibe, K
   Auperin, A
   Le Deley, MC
   Zimmerman, M
   Perkins, SL
   Raphael, M
   Lamant, L
   Klapper, W
   Mussolin, L
   Poirel, HA
   Macintyre, E
   Damm-Welk, C
   Rosolen, A
   Patte, C
AF Minard-Colin, Veronique
   Brugieres, Laurence
   Reiter, Alfred
   Cairo, Mitchell S.
   Gross, Thomas G.
   Woessmann, Wilhelm
   Burkhardt, Birgit
   Sandlund, John T.
   Williams, Denise
   Pillon, Marta
   Horibe, Keizo
   Auperin, Anne
   Le Deley, Marie-Cecile
   Zimmerman, Martin
   Perkins, Sherrie L.
   Raphael, Martine
   Lamant, Laurence
   Klapper, Wolfram
   Mussolin, Lara
   Poirel, Helene A.
   Macintyre, Elizabeth
   Damm-Welk, Christine
   Rosolen, Angelo
   Patte, Catherine
TI Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through
   Effective Collaboration, Current Knowledge, and Challenges Ahead
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID LARGE-CELL LYMPHOMA; ACUTE-LYMPHOBLASTIC-LEUKEMIA;
   PEDIATRIC-ONCOLOGY-GROUP; MINIMAL DISSEMINATED DISEASE;
   FRANKFURT-MUNSTER GROUP; HIGH-DOSE METHOTREXATE; AIEOP LNH-92 PROTOCOL;
   ALK-POSITIVE ALCL; PHASE-III TRIAL; ADVANCED-STAGE
AB Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse. (C) 2015 by American Society of Clinical Oncology
C1 [Minard-Colin, Veronique; Brugieres, Laurence; Auperin, Anne; Le Deley, Marie-Cecile; Patte, Catherine] Inst Gustave Roussy, Villejuif, France.
   [Raphael, Martine] Univ Paris 11, CNRS, UMR 8126, Paris, France.
   [Macintyre, Elizabeth] Univ Paris Descartes Sorbonne Cite, Inst Necker Enfants Malad, Inst Natl Rech Med U1151, Paris, France.
   [Macintyre, Elizabeth] Hop Necker Enfants Malad, AP HP, Paris, France.
   [Lamant, Laurence] Inst Univ Canc Toulouse Oncopole, Toulouse, France.
   [Lamant, Laurence] Univ Toulouse 3, F-31062 Toulouse, France.
   [Woessmann, Wilhelm; Damm-Welk, Christine] Univ Giessen, D-35390 Giessen, Germany.
   [Burkhardt, Birgit] Children Univ Hosp, Munster, Germany.
   [Zimmerman, Martin] Hannover Med Sch, D-30623 Hannover, Germany.
   [Klapper, Wolfram] Univ Kiel, Kiel, Germany.
   [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA.
   [Gross, Thomas G.] NCI, Bethesda, MD 20892 USA.
   [Sandlund, John T.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
   [Sandlund, John T.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Memphis, TN USA.
   [Perkins, Sherrie L.] Univ Utah Hlth Sci, Salt Lake City, UT USA.
   [Williams, Denise] Cambridge Univ Hosp Fdn Trust, Cambridge, England.
   [Pillon, Marta; Rosolen, Angelo] Univ Padua, Padua, Italy.
   [Mussolin, Lara] Fdn Cittadella Speranza, Ist Ric Pediat, Padua, Italy.
   [Mussolin, Lara] Univ Padua, Padua, Italy.
   [Horibe, Keizo] Natl Hosp Org, Nagoya Med Ctr, Nagoya, Aichi, Japan.
   [Poirel, Helene A.] Catholic Univ Louvain, Clin Univ St Luc, Ctr Human Genet, B-1200 Brussels, Belgium.
RP Patte, C (reprint author), Gustave Roussy, Dept Pediat Oncol, 114 Rue Paul Vaillant, F-94800 Villejuif, France.
EM catherine.patte@gustaveroussy.fr
RI Klapper, Wolfram/S-6314-2016
NR 99
TC 16
Z9 16
U1 4
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 2963
EP U54
DI 10.1200/JCO.2014.59.5827
PG 14
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800004
PM 26304908
ER

PT J
AU Isakoff, MS
   Bielack, SS
   Meltzer, P
   Gorlick, R
AF Isakoff, Michael S.
   Bielack, Stefan S.
   Meltzer, Paul
   Gorlick, Richard
TI Osteosarcoma: Current Treatment and a Collaborative Pathway to Success
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID CHILDRENS-ONCOLOGY-GROUP; HIGH-DOSE METHOTREXATE; PHASE-II TRIAL;
   HIGH-GRADE OSTEOSARCOMA; REFRACTORY SOLID TUMORS; PRECLINICAL TESTING
   PROGRAM; OSTEOGENIC-SARCOMA; ADJUVANT CHEMOTHERAPY; PREOPERATIVE
   CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY
AB Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor. (C) 2015 by American Society of Clinical Oncology
C1 [Isakoff, Michael S.; Bielack, Stefan S.; Meltzer, Paul; Gorlick, Richard] Ctr Canc & Blood Disorders, Connecticut Childrens Med Ctr, Michael S Isakoff, Hartford, CT USA.
   [Isakoff, Michael S.] Connecticut Childrens Med Ctr, Ctr Canc & Blood Disorders, Hartford, CT USA.
   [Bielack, Stefan S.] Olgahospital, Klinikum Stuttgart, Stuttgart, Germany.
   [Meltzer, Paul] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
RP Gorlick, R (reprint author), Childrens Hosp Montefiore, Pediat Hematol Oncol, 3415 Bainbridge Ave,Rosenthal Pavil,Room 300, Bronx, NY 10467 USA.
EM RGorlick@montefiore.org
FU Deutsche Forschungsgemeinschaft (DFG) [BI 1045/1-1, BI 1045/1-2];
   Deutsche Krebshilfe (DKH) [50-2723-Bi2]; European Union under project
   European Network for Cancer Research in Children and Adolescents
   [HEALTH-F2-2011-261474]
FX Supported by the Deutsche Forschungsgemeinschaft (DFG Reference Nos. BI
   1045/1-1 and BI 1045/1-2; S.S.B.), Deutsche Krebshilfe (DKH Reference
   No. 50-2723-Bi2; S.S.B.), and the European Union's Seventh Framework
   Programme (Grant No. FP7/2007-2013; S.S.B.) under project European
   Network for Cancer Research in Children and Adolescents, Grant Agreement
   HEALTH-F2-2011-261474.
NR 59
TC 59
Z9 64
U1 6
U2 18
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 3029
EP U127
DI 10.1200/JCO.2014.59.4895
PG 8
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800010
PM 26304877
ER

PT J
AU Pappo, AS
   Furman, WL
   Schultz, KA
   Ferrari, A
   Helman, L
   Krailo, MD
AF Pappo, Alberto S.
   Furman, Wayne L.
   Schultz, Kris A.
   Ferrari, Andrea
   Helman, Lee
   Krailo, Mark D.
TI Rare Tumors in Children: Progress Through Collaboration
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID GASTROINTESTINAL STROMAL TUMORS; PLEUROPULMONARY BLASTOMA REGISTRY;
   PEDIATRIC-LIVER-TUMOR; ITALIAN TREP PROJECT; SUCCINATE-DEHYDROGENASE;
   DICER1 MUTATIONS; ONCOLOGY-GROUP; CHILDHOOD HEPATOBLASTOMA;
   INTERNATIONAL SOCIETY; INFUSION DOXORUBICIN
AB Rare pediatric tumors account for approximately 10% of all childhood cancers, which in themselves are a rare entity. The diverse histologies and clinical behaviors of rare pediatric tumors pose challenges to the investigation of their biologic and clinical features. National and international cooperative groups such as the Rare Tumor Committee of the Children's Oncology Group, Rare Tumors in Pediatric Age Project, and European Cooperative Study Group for Pediatric Rare Tumors have developed several initiatives to advance knowledge about rare pediatric cancers. However, these programs have been only partially effective, necessitating the development of alternative mechanisms to study these challenging diseases. In this article, we review the current national and international collaborative strategies to study rare pediatric cancers and alternative methods under exploration to enhance those efforts, such as independent registries and disease-specific, National Cancer Institute-sponsored clinics. (C) 2015 by American Society of Clinical Oncology
C1 [Pappo, Alberto S.; Furman, Wayne L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
   [Schultz, Kris A.] Childrens Hosp Minnesota, Minneapolis, MN USA.
   [Ferrari, Andrea] Inst Nazl Tumori, Milan, Italy.
   [Helman, Lee] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Krailo, Mark D.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
RP Pappo, AS (reprint author), St Jude Childrens Res Hosp, Dept Oncol, MS 260,262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM alberto.pappo@stjude.org
OI Ferrari, Andrea/0000-0002-4724-0517
FU NCI NIH HHS [U10 CA098543, U10 CA180899]
NR 57
TC 4
Z9 4
U1 2
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 3047
EP U150
DI 10.1200/JCO.2014.59.3632
PG 10
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800012
PM 26304909
ER

PT J
AU Rodriguez-Galindo, C
   Friedrich, P
   Alcasabas, P
   Antillon, F
   Banavali, S
   Castillo, L
   Israels, T
   Jeha, S
   Harif, M
   Sullivan, MJ
   Quah, TC
   Patte, C
   Pui, CH
   Barr, R
   Gross, T
AF Rodriguez-Galindo, Carlos
   Friedrich, Paola
   Alcasabas, Patricia
   Antillon, Federico
   Banavali, Shripad
   Castillo, Luis
   Israels, Trijn
   Jeha, Sima
   Harif, Mhammed
   Sullivan, Michael J.
   Thuan Chong Quah
   Patte, Catherine
   Pui, Ching-Hon
   Barr, Ronald
   Gross, Thomas
TI Toward the Cure of All Children With Cancer Through Collaborative
   Efforts: Pediatric Oncology As a Global Challenge
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; RESOURCE-STRATIFIED GUIDELINES; ENDEMIC
   BURKITT-LYMPHOMA; MIDDLE-INCOME COUNTRIES; CHILDHOOD-CANCER;
   CLINICAL-TRIALS; GRADUATED-INTENSITY; ESSENTIAL DRUGS; AFRICA;
   MANAGEMENT
AB Advances in the treatment of childhood cancers have resulted in part from the development of national and international collaborative initiatives that have defined biologic determinants and generated risk-adapted therapies that maximize cure while minimizing acute and long-term effects. Currently, more than 80% of children with cancer who are treated with modern multidisciplinary treatments in developed countries are cured; however, of the approximately 160,000 children and adolescents who are diagnosed with cancer every year worldwide, 80% live in low- and middle-income countries (LMICs), where access to quality care is limited and chances of cure are low. In addition, the disease burden is not fully known because of the lack of population-based cancer registries in low-resource countries. Regional and ethnic variations in the incidence of the different childhood cancers suggest unique interactions between genetic and environmental factors that could provide opportunities for etiologic research. Regional collaborative initiatives have been developed in Central and South America and the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives integrate regional capacity building, education of health care providers, implementation of intensity-graduated treatments, and establishment of research programs that are adjusted to local capacity and local needs. Together, the existing consortia and regional networks operating in LMICs have the potential to reach out to almost 60% of all children with cancer worldwide. In summary, childhood cancer burden has been shifted toward LMICs and, for that reason, global initiatives directed at pediatric cancer care and control are needed. Regional networks aiming to build capacity while incorporating research on epidemiology, health services, and outcomes should be supported. (C) 2015 by American Society of Clinical Oncology
C1 [Rodriguez-Galindo, Carlos; Friedrich, Paola] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
   [Rodriguez-Galindo, Carlos; Friedrich, Paola] Harvard Univ, Sch Med, Boston, MA USA.
   [Alcasabas, Patricia] Philippines Gen Hosp, Manila, Philippines.
   [Antillon, Federico] Unidad Nacl Oncol Pediat, Guatemala City, Guatemala.
   [Antillon, Federico] Francisco Marroquin Med Sch, Guatemala City, Guatemala.
   [Banavali, Shripad] Tata Mem Hosp, Bombay 400012, Maharashtra, India.
   [Castillo, Luis] Hosp Pereira Rossell, Montevideo, Uruguay.
   [Israels, Trijn] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
   [Jeha, Sima; Pui, Ching-Hon] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
   [Harif, Mhammed] Ctr Hosp Univ Mohammed VI, Marrakech, Morocco.
   [Sullivan, Michael J.] Royal Childrens Hosp, Melbourne, Vic, Australia.
   [Thuan Chong Quah] Natl Univ Hlth Syst, Singapore, Singapore.
   [Patte, Catherine] Inst Gustave Roussy, Villejuif, France.
   [Barr, Ronald] McMaster Univ, Hamilton, ON, Canada.
   [Barr, Ronald] McMaster Childrens Hosp, Hamilton, ON, Canada.
   [Gross, Thomas] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA.
RP Rodriguez-Galindo, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D3-133, Boston, MA 02215 USA.
EM carlos_rodriguez-galindo@dfci.harvard.edu
NR 62
TC 16
Z9 16
U1 5
U2 11
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 3065
EP U175
DI 10.1200/JCO.2014.60.6376
PG 12
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800014
PM 26304881
ER

PT J
AU Carre, A
   Louzada, RAN
   Fortunato, RS
   Ameziane-El-Hassani, R
   Morand, S
   Ogryzko, V
   de Carvalho, DP
   Grasberger, H
   Leto, TL
   Dupuy, C
AF Carre, Aurore
   Louzada, Ruy A. N.
   Fortunato, Rodrigo S.
   Ameziane-El-Hassani, Rabii
   Morand, Stanislas
   Ogryzko, Vasily
   de Carvalho, Denise Pires
   Grasberger, Helmut
   Leto, Thomas L.
   Dupuy, Corinne
TI When an Intramolecular Disulfide Bridge Governs the Interaction of DUOX2
   with Its Partner DUOXA2
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID DUAL OXIDASE; CONGENITAL HYPOTHYROIDISM; NADPH OXIDASE; MATURATION
   FACTOR; PLASMA-MEMBRANE; MUTATIONS; GENE; DUAL-OXIDASE-2; EXPRESSION;
   PROTEINS
AB Aims: The dual oxidase 2 (DUOX2) protein belongs to the NADPH oxidase (NOX) family. As H2O2 generator, it plays a key role in both thyroid hormone biosynthesis and innate immunity. DUOX2 forms with its maturation factor, DUOX activator 2 (DUOXA2), a stable complex at the cell surface that is crucial for the H2O2-generating activity, but the nature of their interaction is unknown. The contribution of some cysteine residues located in the N-terminal ectodomain of DUOX2 in a surface protein-protein interaction is suggested. We have investigated the involvement of different cysteine residues in the formation of covalent bonds that could be of critical importance for the function of the complex. Results: We report the identification and the characterization of an intramolecular disulfide bond between cys-124 of the N-terminal ectodomain and cys-1162 of an extracellular loop of DUOX2, which has important functional implications in both export and activity of DUOX2. This intramolecular bridge provides structural support for the formation of interdisulfide bridges between the N-terminal domain of DUOX2 and the two extracellular loops of its partner, DUOXA2. Innovation: Both stability and function of the maturation factor, DUOXA2, are dependent on the oxidative folding of DUOX2, indicating that DUOX2 displays a chaperone-like function with respect to its partner. Conclusions: The oxidative folding of DUOX2 that takes place in the endoplasmic reticulum (ER) appears to be a key event in the trafficking of the DUOX2/DUOXA2 complex as it promotes an appropriate conformation of the N-terminal region, which is propitious to subsequent covalent interactions with the maturation factor, DUOXA2. Antioxid. Redox Signal. 23, 724-733.
C1 [Carre, Aurore; Louzada, Ruy A. N.; Ameziane-El-Hassani, Rabii; Dupuy, Corinne] Univ Paris 11, Orsay, France.
   [Carre, Aurore; Ameziane-El-Hassani, Rabii; Dupuy, Corinne] UMR 8200 CNRS, Villejuif, France.
   [Carre, Aurore; Ameziane-El-Hassani, Rabii; Dupuy, Corinne] Inst Gustave Roussy, F-94805 Villejuif, France.
   [Louzada, Ruy A. N.; Fortunato, Rodrigo S.; de Carvalho, Denise Pires] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Fisiol Endocrina Doris Rosenthal, BR-21941 Rio De Janeiro, Brazil.
   [Morand, Stanislas; Leto, Thomas L.] NIAID, Lab Host Def, NIH, Rockville, MD USA.
   [Ogryzko, Vasily] UMR 8126 CNRS, Villejuif, France.
   [Grasberger, Helmut] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
RP Dupuy, C (reprint author), Inst Gustave Roussy, UMR CNRS 8200, 114 Rue Edouard Vaillant, F-94805 Villejuif, France.
EM corinne.dupuy@gustaveroussy.fr
RI Ogryzko, Vasily/M-6665-2015; Carvalho, Denise/H-6306-2012; 
OI Ogryzko, Vasily/0000-0002-8548-1389; Carvalho,
   Denise/0000-0001-6933-6424; Louzada, Ruy Andrade/0000-0003-1789-4234;
   Fortunato, Rodrigo/0000-0003-3497-8173
FU Institut National du Cancer (INCa, France); CAPES-COFECUB; Intramural
   Research Program of the National Institute of Allergy and Infectious
   Diseases, NIH; INCA
FX The authors are indebted to Monique Talbot for her excellent assistance
   in immunohistochemistry and Emilie Cochet for her excellent assistance
   in proteomic. A.C. was supported by the Institut National du Cancer
   (INCa, France), and R.A.N.L. was supported by CAPES-COFECUB. S.M. and
   T.L.L were supported by funds from the Intramural Research Program of
   the National Institute of Allergy and Infectious Diseases, NIH. This
   work was supported by a grant from INCA.
NR 20
TC 3
Z9 3
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD SEP 20
PY 2015
VL 23
IS 9
BP 724
EP 733
DI 10.1089/ars.2015.6265
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CR5ML
UT WOS:000361387100003
PM 25761904
ER

PT J
AU Kunz, LM
   Normand, SLT
   Sedrakyan, A
AF Kunz, Lauren M.
   Normand, Sharon-Lise T.
   Sedrakyan, Art
TI Meta-analysis of rate ratios with differential follow-up by treatment
   arm: inferring comparative effectiveness of medical devices
SO STATISTICS IN MEDICINE
LA English
DT Article
DE aggregated data; bayesian; comparative effectiveness
ID CARDIAC-RESYNCHRONIZATION THERAPY; HEART-FAILURE; NETWORK METAANALYSIS;
   SURVIVAL; DEFIBRILLATION; STATISTICS; OUTCOMES
AB Modeling events requires accounting for differential follow-up duration, especially when combining randomized and observational studies. Although events occur at any point over a follow-up period and censoring occurs throughout, most applied researchers use odds ratios as association measures, assuming follow-up duration is similar across treatment groups. We derive the bias of the rate ratio when incorrectly assuming equal follow-up duration in the single study binary treatment setting. Simulations illustrate bias, efficiency, and coverage and demonstrate that bias and coverage worsen rapidly as the ratio of follow-up duration between arms moves away from one. Combining study rate ratios with hierarchical Poisson regression models, we examine bias and coverage for the overall rate ratio via simulation in three cases: when average arm-specific follow-up duration is available for all studies, some studies, and no study. In the null case, bias and coverage are poor when the study average follow-up is used and improve even if some arm-specific follow-up information is available. As the rate ratio gets further from the null, bias and coverage remain poor. We investigate the effectiveness of cardiac resynchronization therapy devices compared with those with cardioverter-defibrillator capacity where three of eight studies report arm-specific follow-up duration. Copyright (c) 2015John Wiley & Sons, Ltd.
C1 [Kunz, Lauren M.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
   [Kunz, Lauren M.; Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
   [Sedrakyan, Art] Cornell Univ, Weill Cornell Med Coll, New York, NY 10065 USA.
   [Sedrakyan, Art] New York Presbyterian Hosp, New York, NY 10065 USA.
RP Kunz, LM (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM lauren.kunz@nih.gov
FU Research Participation Program, Center for Devices and Radiological
   Health; FDA;  [HHSF223201110172C]
FX The authors thank Jennifer Moon, Ph.D. for performing the data
   abstraction. The authors thank Francesca Dominici, Ph.D. and Miguel
   Hernan, M.D., Dr.P.H. for the input and suggestions that improved the
   paper. This material is based upon work supported by the Research
   Participation Program, Center for Devices and Radiological Health,
   administered by the Oak Ridge Institute for Science and Education
   through an inter-agency agreement between the US Department of Energy
   and the US Food and Drug Administration (FDA), as well as Contract No.
   HHSF223201110172C and the Critical Path Initiative (Development of
   Innovative Methodologies for Medical Devices), both from the FDA. The
   authors also thank Danica Marinac-Dabic, M.D., Ph.D. for her valuable
   assistance with this manuscript.
NR 20
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U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD SEP 20
PY 2015
VL 34
IS 21
BP 2913
EP 2925
DI 10.1002/sim.6530
PG 13
WC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Medicine, Research &
   Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Research & Experimental
   Medicine; Mathematics
GA CO0MS
UT WOS:000358846400003
PM 26011521
ER

PT J
AU Wurtz, RH
AF Wurtz, Robert H.
TI Using perturbations to identify the brain circuits underlying active
   vision
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE brain-circuits; behaviour; monkeys; lesions; inactivations; optogenetics
ID SACCADIC EYE-MOVEMENTS; MONKEY SUPERIOR COLLICULUS; CORTICAL AREA MT;
   STRIATE CORTEX; COROLLARY DISCHARGE; RECEPTIVE FIELDS; NEURAL FUNCTION;
   AWAKE MONKEYS; OCULOMOTOR; LESIONS
AB The visual and oculomotor systems in the brain have been studied extensively in the primate. Together, they can be regarded as a single brain system that underlies active vision-the normal vision that begins with visual processing in the retina and extends through the brain to the generation of eye movement by the brainstem. The system is probably one of the most thoroughly studied brain systems in the primate, and it offers an ideal opportunity to evaluate the advantages and disadvantages of the series of perturbation techniques that have been used to study it. The perturbations have been critical in moving from correlations between neuronal activity and behaviour closer to a causal relation between neuronal activity and behaviour. The same perturbation techniques have also been used to tease out neuronal circuits that are related to active vision that in turn are driving behaviour. The evolution of perturbation techniques includes ablation of both cortical and subcortical targets, punctate chemical lesions, reversible inactivations, electrical stimulation, and finally the expanding optogenetic techniques. The evolution of perturbation techniques has supported progressively stronger conclusions about what neuronal circuits in the brain underlie active vision and how the circuits themselves might be organized.
C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM bob@lsr.nei.nih.gov
FU Intramural Research Program, National Eye Institute, NIH
FX This study was funded by Intramural Research Program, National Eye
   Institute, NIH.
NR 44
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U2 6
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD SEP 19
PY 2015
VL 370
IS 1677
AR 20140205
DI 10.1098/rstb.2014.0205
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CQ4CP
UT WOS:000360552100004
PM 26240420
ER

PT J
AU Tu, JJ
   Ng, SH
   Luk, ACS
   Liao, JY
   Jiang, XH
   Feng, B
   Mak, KKL
   Rennert, OM
   Chan, WY
   Lee, TL
AF Tu, Jiajie
   Ng, Shuk Han
   Luk, Alfred Chun Shui
   Liao, Jinyue
   Jiang, Xiaohua
   Feng, Bo
   Mak, Kingston King Lun
   Rennert, Owen M.
   Chan, Wai-Yee
   Lee, Tin-Lap
TI MicroRNA-29b/Tet1 regulatory axis epigenetically modulates mesendoderm
   differentiation in mouse embryonic stem cells
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DNA METHYLATION; MIR-29; 5-HYDROXYMETHYLCYTOSINE; TET1; TARGETS;
   5-METHYLCYTOSINE; SPECIFICATION; EXPRESSION; MYOGENESIS; CONVERSION
AB Ten eleven translocation ( Tet) family- mediated DNA oxidation on 5- methylcytosine ( 5mC) to 5hydroxymethylcytosine ( 5hmC) represents a novel epigenetic modification that regulates dynamic gene expression during embryonic stem cells ( ESCs) differentiation. Through the role of Tet on 5hmC regulation in stem cell development is relatively defined, how the Tet family is regulated and impacts on ESCs lineage development remains elusive. In this study, we show non- coding RNA regulation on Tet family may contribute to epigenetic regulation during ESCs differentiation, which is suggested by microRNA- 29b ( miR- 29b) binding sites on the Tet1 3 ' untranslated region ( 3' UTR). We demonstrate miR- 29b increases sharply after embyoid body ( EB) formation, which causes Tet1 repression and reduction of cellular 5hmC level during ESCs differentiation. Importantly, we show this miR- 29b/ Tet1 regulatory axis promotes themesendoderm lineage formation both in vitro and in vivo by inducing the Nodal signaling pathway and repressing the key target of the active demethylation pathway, Tdg. Taken together, our findings underscore the contribution of small non- coding RNA mediated regulation on DNA demethylation dynamics and the differential expressions of key mesendoderm regulators during ESCs lineage specification. MiR- 29b could potentially be applied to enrich production of mesoderm and endoderm derivatives and be further differentiated into desired organ- specific cells.
C1 [Tu, Jiajie; Ng, Shuk Han; Luk, Alfred Chun Shui; Liao, Jinyue; Chan, Wai-Yee; Lee, Tin-Lap] Chinese Univ Hong Kong, Sch Biomed Sci, Reprod Dev & Endocrinol Program, Shatin, Hong Kong, Peoples R China.
   [Tu, Jiajie; Ng, Shuk Han; Luk, Alfred Chun Shui; Liao, Jinyue; Chan, Wai-Yee; Lee, Tin-Lap] Chinese Univ Hong Kong, Shandong Univ CUHK SDU Joint Lab Reprod Genet, Shatin, Hong Kong, Peoples R China.
   [Jiang, Xiaohua; Feng, Bo; Mak, Kingston King Lun] Chinese Univ Hong Kong, Sch Biomed Sci, Stem Cell & Regenerat Program, Shatin, Hong Kong, Peoples R China.
   [Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Lee, TL (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Reprod Dev & Endocrinol Program, Shatin, Hong Kong, Peoples R China.
EM leetl@cuhk.edu.hk
RI Lee, Tin-Lap/A-7853-2009; Feng, Bo/D-7831-2014
OI Lee, Tin-Lap/0000-0002-6654-0988; 
FU General Research Fund from Hong Kong Research Grant Council [469713];
   Direct Research Fund from the Faculty of Medicine, The Chinese
   University of Hong Kong [MD12465]; School of Biomedical Sciences,
   Faculty of Medicine, The Chinese University of Hong Kong [4620504]
FX General Research Fund from Hong Kong Research Grant Council [469713];
   Direct Research Fund from the Faculty of Medicine, The Chinese
   University of Hong Kong [MD12465] and School of Biomedical Sciences,
   Faculty of Medicine, The Chinese University of Hong Kong [4620504].
NR 44
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U1 3
U2 14
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 SEP 18
PY 2015
VL 43
IS 16
BP 7805
EP 7822
DI 10.1093/nar/gkv653
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CS4WW
UT WOS:000362077900019
PM 26130713
ER

PT J
AU Das, S
   Rundell, MS
   Mirza, AH
   Pingle, MR
   Shigyo, K
   Garrison, AR
   Paragas, J
   Smith, SK
   Olson, VA
   Larone, DH
   Spitzer, ED
   Barany, F
   Golightly, LM
AF Das, Sanchita
   Rundell, Mark S.
   Mirza, Aashiq H.
   Pingle, Maneesh R.
   Shigyo, Kristi
   Garrison, Aura R.
   Paragas, Jason
   Smith, Scott K.
   Olson, Victoria A.
   Larone, Davise H.
   Spitzer, Eric D.
   Barany, Francis
   Golightly, Linnie M.
TI A Multiplex PCR/LDR Assay for the Simultaneous Identification of
   Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and
   Variola Virus
SO PLOS ONE
LA English
DT Article
ID LIGASE DETECTION REACTION; REVERSE-TRANSCRIPTASE PCR;
   POLYMERASE-CHAIN-REACTION; EBOLA-VIRUS; BIOTERRORISM AGENTS;
   SMALLPOX-VIRUS; DIAGNOSIS; DISEASE; DNA; OUTBREAK
AB CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).
C1 [Das, Sanchita; Shigyo, Kristi; Golightly, Linnie M.] Cornell Univ, Dept Med, Div Infect Dis, Weill Med Coll, New York, NY 10021 USA.
   [Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Larone, Davise H.; Barany, Francis; Golightly, Linnie M.] Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY 10021 USA.
   [Garrison, Aura R.] US Army Med Res Inst Infect Dis, Frederick, MD USA.
   [Paragas, Jason] NIAID, Integrated Res Facil, Div Clin Res, NIH, Ft Detrick, MD USA.
   [Smith, Scott K.; Olson, Victoria A.] Ctr Dis Control & Prevent, Poxvirus Team, Poxvirus & Rabies Branch,Natl Ctr Emerging Zoonot, Div High Consequence Pathogens & Pathol, Atlanta, GA USA.
   [Larone, Davise H.] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA.
   [Spitzer, Eric D.] SUNY Stony Brook, Dept Pathol, Med Ctr, Stony Brook, NY 11794 USA.
RP Golightly, LM (reprint author), Cornell Univ, Dept Med, Div Infect Dis, Weill Med Coll, New York, NY 10021 USA.
EM lgolight@med.cornell.edu
FU National Institute of Allergy and Infectious Diseases of the National
   Institute of Health [UC1-AI062579]
FX This work was supported by contract UC1-AI062579 awarded to FB by the
   National Institute of Allergy and Infectious Diseases of the National
   Institute of Health (http://www.niaid.nih.gov/Pages/default.aspx). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript. At no time during
   the study did they receive salary support, other funds, or research
   materials from Beckman Coulter or Coferon Inc. to support the study, nor
   do either of these entities have any commercial rights or interest in
   developing a product from the current study.
NR 57
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U1 1
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 18
PY 2015
VL 10
IS 9
AR e0138484
DI 10.1371/journal.pone.0138484
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0ZE
UT WOS:000361790200113
PM 26381398
ER

PT J
AU Negrete, A
   Shiloach, J
AF Negrete, Alejandro
   Shiloach, Joseph
TI Constitutive expression of the sRNA GadY decreases acetate production
   and improves E-coli growth
SO MICROBIAL CELL FACTORIES
LA English
DT Article
DE Acid resistance; sRNA; GadY; Glutamate decarboxylase; Acetate
ID GLUTAMATE-DECARBOXYLASE GENES; DEPENDENT ACID RESISTANCE;
   TRANSCRIPTIONAL ACTIVATOR; NONCODING RNAS; STRESS; PROTEIN; PH;
   FERMENTATION; REGULATORS; SYSTEM
AB Background: Escherichia coli responds to acid stress by applying various physiological, metabolic, and proton-consuming mechanisms depending on the growth media composition, cell density, growth phase, pH, and aerobic or anaerobic growth conditions. It was reported that at mild acidic conditions (pH 5.8), the Hfq-associated sRNA GadY is activated. It was also reported that the two decarboxylase systems-the lysine decarboxylase system (LDS) and the glutamate decarboxylase system (GDS)-are activated to maintain intracellular balance of protons. The purpose of this study was to establish the role of GadY in high density growth of E. coli and to evaluate the possibility of using this small RNA to create an acid-resistant strain suitable for industrial applications.
   Results: Parental E. coli K-12 and constitutively expressing GadY strains were grown to high cell densities in a bioreactor at pH 7.0 and pH 6.0. At pH 7.0, both strains grew to similar cell densities of 43 OD, but the constitutively expressing GadY strain produced around 6 g/L acetate compared with 10 g/L by the parental strain. At pH 6.0, the parental strain grew to an OD of 20 and produced 10 g/L of acetate while the GadY strain grew to an average OD of 31 and produced 4 g/L acetate. After analyzing 17 genes associated with acid stress, it was found that at pH 7.0 LDS was expressed in the early exponential phase and GDS was expressed in the late exponential phase in both strains. However, at pH. 6.0, GDS was expressed in the late exponential phase only in the parental strain and not in the constitutively expressing GadY strain, while there was no difference in the LDS expression pattern; it was expressed in the early exponential phase in both strains. This indicates that GadY affects GDS expression at low pH since the GDS was not detected in the GadY strain at pH 6.0.
   Conclusions: The constitutive expression of GadY improves E. coli growth at pH 6.0 by deactivating the expression of the GDS in the late exponential growth phase. The expression of GadY also decreases acetate production regardless of pH, which decreases the inhibitory effect of this acid on bacterial growth.
C1 [Negrete, Alejandro; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bldg 14A Room 173, Bethesda, MD 20892 USA.
EM JosephS@niddk.nih.gov
FU Intramural program at the National Institute of Diabetes and Digestive
   and Kidney Diseases, National Institutes of Health
FX Funding was provided by the Intramural program at the National Institute
   of Diabetes and Digestive and Kidney Diseases, National Institutes of
   Health. The authors would like to thank Dr. Gisela Storz for providing
   the GadY constitutively expressing strain and Mrs. D. Livnat for helping
   editing the manuscript.
NR 37
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U1 4
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2859
J9 MICROB CELL FACT
JI Microb. Cell. Fact.
PD SEP 18
PY 2015
VL 14
AR 148
DI 10.1186/s12934-015-0334-1
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA CR6GG
UT WOS:000361442300001
PM 26383169
ER

PT J
AU Katzelnick, LC
   Fonville, JM
   Gromowski, GD
   Arriaga, JB
   Green, A
   James, SL
   Lau, L
   Montoya, M
   Wang, CL
   VanBlargan, LA
   Russell, CA
   Thu, HM
   Pierson, TC
   Buchy, P
   Aaskov, JG
   Munoz-Jordan, JL
   Vasilakis, N
   Gibbons, RV
   Tesh, RB
   Osterhaus, ADME
   Fouchier, RAM
   Durbin, A
   Simmons, CP
   Holmes, EC
   Harris, E
   Whitehead, SS
   Smith, DJ
AF Katzelnick, Leah C.
   Fonville, Judith M.
   Gromowski, Gregory D.
   Arriaga, Jose Bustos
   Green, Angela
   James, Sarah L.
   Lau, Louis
   Montoya, Magelda
   Wang, Chunling
   VanBlargan, Laura A.
   Russell, Colin A.
   Thu, Hlaing Myat
   Pierson, Theodore C.
   Buchy, Philippe
   Aaskov, John G.
   Munoz-Jordan, Jorge L.
   Vasilakis, Nikos
   Gibbons, Robert V.
   Tesh, Robert B.
   Osterhaus, Albert D. M. E.
   Fouchier, Ron A. M.
   Durbin, Anna
   Simmons, Cameron P.
   Holmes, Edward C.
   Harris, Eva
   Whitehead, Stephen S.
   Smith, Derek J.
TI Dengue viruses cluster antigenically but not as discrete serotypes
SO SCIENCE
LA English
DT Article
ID REDUCTION NEUTRALIZATION TEST; HEMORRHAGIC-FEVER; INFLUENZA-VIRUS;
   ANTIBODY-LEVELS; INFECTION; EVOLUTION; THAILAND; VACCINE;
   IDENTIFICATION; FLAVIVIRUSES
AB The four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution. We characterized antigenic diversity in the DENV types by antigenic maps constructed from neutralizing antibody titers obtained from African green monkeys and after human vaccination and natural infections. Genetically, geographically, and temporally, diverse DENV isolates clustered loosely by type, but we found that many are as similar antigenically to a virus of a different type as to some viruses of the same type. Primary infection antisera did not neutralize all viruses of the same DENV type any better than other types did up to 2 years after infection and did not show improved neutralization to homologous type isolates. That the canonical DENV types are not antigenically homogeneous has implications for vaccination and research on the dynamics of immunity, disease, and the evolution of DENV.
C1 [Katzelnick, Leah C.; Fonville, Judith M.; James, Sarah L.; Smith, Derek J.] Univ Cambridge, Dept Zool, Ctr Pathogen Evolut, Cambridge CB2 3EJ, England.
   [Katzelnick, Leah C.; Fonville, Judith M.; James, Sarah L.; Smith, Derek J.] World Hlth Org WHO Collaborating Ctr Modeling Evo, Cambridge CB2 3EJ, England.
   [Katzelnick, Leah C.; Gromowski, Gregory D.; Arriaga, Jose Bustos; VanBlargan, Laura A.; Pierson, Theodore C.; Whitehead, Stephen S.] NIAID, NIH, Bethesda, MD 20892 USA.
   [Katzelnick, Leah C.; Green, Angela; Lau, Louis; Montoya, Magelda; Wang, Chunling; Harris, Eva] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA.
   [Fonville, Judith M.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.; Smith, Derek J.] Erasmus MC, Dept Virosci, NL-3015 GE Rotterdam, Netherlands.
   [Russell, Colin A.] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.
   [Thu, Hlaing Myat] Dept Med Res, Yangon, Myanmar.
   [Buchy, Philippe] Reseau Int Inst Pasteur, Inst Pasteur Cambodia, Phnom Penh 12201, Cambodia.
   [Aaskov, John G.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
   [Aaskov, John G.] Australian Army Malaria Inst, Brisbane, Qld 4051, Australia.
   [Munoz-Jordan, Jorge L.] Ctr Dis Control & Prevent, Dengue Branch, Div Vector Borne Dis, San Juan, PR 00971 USA.
   [Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
   [Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA.
   [Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA.
   [Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA.
   [Gibbons, Robert V.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand.
   [Durbin, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA.
   [Simmons, Cameron P.] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
   [Simmons, Cameron P.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX3 7LJ, England.
   [Simmons, Cameron P.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
   [Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Charles Perkins Ctr, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.
   [Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
RP Smith, DJ (reprint author), Univ Cambridge, Dept Zool, Ctr Pathogen Evolut, Downing St, Cambridge CB2 3EJ, England.
EM djs200@cam.ac.uk
RI Fouchier, Ron/A-1911-2014; 
OI Fouchier, Ron/0000-0001-8095-2869; Simmons, Cameron
   P./0000-0002-9039-7392; Holmes, Edward/0000-0001-9596-3552
FU Intramural Research Program of the U.S. NIH; National Institute of
   Allergy and Infectious Diseases (NIAID); European Union (EU) [223498,
   278976]; Human Frontier Science Program (HFSP) program grant
   [P0050/2008]; NIH Director's Pioneer Award [DP1-OD000490-01]; FIRST
   program from the Bill and Melinda Gates Foundation; Instituto Carlos
   Slim de la Salud; NIAID-NIH Centers of Excellence for Influenza Research
   and Surveillance [HHSN266200700010C, HHSN272201400008C]; Gates Cambridge
   Scholarship; NIH Oxford Cambridge Scholars Program; Medical Research
   Council Fellowship [MR/K021885/1]; Junior Research Fellowship from
   Homerton College Cambridge; National Health and Medical Research Council
   Australia Fellowship; NIH [HHSN272201000040I/HHSN27200004/D04]; GSK
   Pharma; GSK Vaccines; Merck
FX We express our gratitude to the members of the Dengue Antigenic
   Cartography Consortium, named in the supplementary materials, for their
   advice and contributions to the Consortium to date. We thank D. Burke,
   N. Lewis, E. Selkov, E. Skepner, A. Mosterin, R. Mogling, S. Wilks, T.
   Kotarba, and V. Duong for their technical expertise. M. Melendrez, J.
   Hang, R. Jarman, S. M. Cave, S. G. Widen, T. G. Wood, and V. Duong
   assisted with virus sequencing. C. Firestone and M. Galvez assisted with
   neutralization assay titrations. This research was supported in part by
   the Intramural Research Program of the U.S. NIH, National Institute of
   Allergy and Infectious Diseases (NIAID), European Union (EU) FP7
   programs EMPERIE (223498) and ANTIGONE (278976), Human Frontier Science
   Program (HFSP) program grant P0050/2008, the NIH Director's Pioneer
   Award DP1-OD000490-01, the FIRST program from the Bill and Melinda Gates
   Foundation, and the Instituto Carlos Slim de la Salud (E.H.). The
   antigenic cartography toolkit was in part supported by NIAID-NIH Centers
   of Excellence for Influenza Research and Surveillance contracts
   HHSN266200700010C and HHSN272201400008C for use on influenza virus.
   L.C.K. was supported by the Gates Cambridge Scholarship and the NIH
   Oxford Cambridge Scholars Program. J.M.F. was supported by a Medical
   Research Council Fellowship (MR/K021885/1) and a Junior Research
   Fellowship from Homerton College Cambridge. E.C.H. was supported by an
   National Health and Medical Research Council Australia Fellowship. N.V.
   and R.B.T were supported by NIH contract
   HHSN272201000040I/HHSN27200004/D04. The viruses and sera used in this
   study are covered by standard material transfer agreements at the home
   institutions of S.S.W., C.P.S., E.H., P.B., J.G.A., J.L.M.J., N.V., and
   R.B.T. A.D.M.E.O. is a professor and director of Artemis One Health
   Utrecht, The Netherlands; Chief Scientific Officer Viroclinics
   Biosciences BV, the Netherlands; and a Board Member of Protein Sciences
   USA. P.B. performed this work while at the Institut Pasteur in Cambodia,
   but since June 2015, is with GlaxoSmithKline vaccines in Singapore, and
   has stock options with GSK. C.P.S. is a paid consultant to GSK Pharma,
   GSK Vaccines, and Merck and has received a grant and consulting payments
   to his institution from Sanofi Pasteur. The sequences used in this study
   are available from GenBank (http://www.ncbi.nlm.nih.gov/genbank/) and
   are listed in table S1. Files used for genetic analyses are available as
   supplementary data files. The NIH monovalent DENV vaccines trials
   (ClinicalTrials.gov identifiers: NCT00473135 NCT00920517, NCT00831012,
   NCT00831012) were performed under an investigational new drug
   application reviewed by the U.S. Food and Drug Administration and
   approved by the Institutional Review Board at the University of Vermont
   and Johns Hopkins University. Informed consent was obtained in
   accordance federal and international regulations (21CFR50, ICHE6). The
   Pediatric Dengue Cohort Study in Managua, Nicaragua, was approved by the
   Institutional Review Boards of the Nicaraguan Ministry of Health and the
   University of California, Berkeley. Parents or legal guardians of all
   subjects provided written informed consent, and subjects 6 years of age
   and older provided assent.
NR 41
TC 18
Z9 18
U1 4
U2 23
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 SEP 18
PY 2015
VL 349
IS 6254
BP 1338
EP 1343
DI 10.1126/science.aac5017
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5CR
UT WOS:000361357700049
PM 26383952
ER

PT J
AU Olson, MA
   Lee, MS
   Kissner, TL
   Alam, S
   Waugh, DS
   Saikh, KU
AF Olson, Mark A.
   Lee, Michael S.
   Kissner, Teri L.
   Alam, Shahabuddin
   Waugh, David S.
   Saikh, Kamal U.
TI Discovery of small molecule inhibitors of MyD88-dependent signaling
   pathways using a computational screen
SO SCIENTIFIC REPORTS
LA English
DT Article
ID TOLL/INTERLEUKIN-1 RECEPTOR DOMAINS; STAPHYLOCOCCAL-ENTEROTOXIN-B;
   TOLL-LIKE RECEPTORS; MHC CLASS-II; TIR-DOMAIN; CRYSTAL-STRUCTURE;
   ESCHERICHIA-COLI; STRUCTURAL BASIS; PROTEIN DOCKING; MYD88
AB In this study, we used high-throughput computational screening to discover drug-like inhibitors of the host MyD88 protein-protein signaling interaction implicated in the potentially lethal immune response associated with Staphylococcal enterotoxins. We built a protein-protein dimeric docking model of the Toll-interleukin receptor (TIR)-domain of MyD88 and identified a binding site for docking small molecules. Computational screening of 5 million drug-like compounds led to testing of 30 small molecules; one of these molecules inhibits the TIR-TIR domain interaction and attenuates pro-inflammatory cytokine production in human primary cell cultures. Compounds chemically similar to this hit from the PubChem database were observed to be more potent with improved drug-like properties. Most of these 2nd generation compounds inhibit Staphylococcal enterotoxin B (SEB)-induced TNF-alpha, IFN-gamma, IL-6, and IL-1 beta production at 2-10 mu M in human primary cells. Biochemical analysis and a cell-based reporter assay revealed that the most promising compound, T6167923, disrupts MyD88 homodimeric formation, which is critical for its signaling function. Furthermore, we observed that administration of a single dose of T6167923 completely protects mice from lethal SEB-induced toxic shock. In summary, our in silico approach has identified anti-inflammatory inhibitors against in vitro and in vivo toxin exposure with promise to treat other MyD88-related proinflammatory diseases.
C1 [Olson, Mark A.; Lee, Michael S.] US Army Med Res Inst Infect Dis, Dept Biochem & Cell Biol, Frederick, MD 21702 USA.
   [Kissner, Teri L.; Alam, Shahabuddin; Saikh, Kamal U.] US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Dept Immunol, Frederick, MD 21702 USA.
   [Waugh, David S.] NCI, Ctr Macromol Crystallog, Frederick, MD 21702 USA.
   [Lee, Michael S.] US Army Res Lab, Computat Sci Div, Aberdeen Proving Ground, MD 21005 USA.
RP Olson, MA (reprint author), US Army Med Res Inst Infect Dis, Dept Biochem & Cell Biol, Frederick, MD 21702 USA.
EM molson@compbiophys.org; kamal.u.saikh.civ@mail.mil
FU United States Defense Threat Reduction Agency [CBM.THROX.03.10.RD.006]
FX This work was supported by the United States Defense Threat Reduction
   Agency to K. U. S. (grant CBM.THROX.03.10.RD.006). We gratefully
   acknowledge Sreejith Raran-Kurussi and Joseph E. Tropea for their help
   in the expression and purification of TIR domain protein of MyD88 used
   in this study. We thank Prof. Julius Rebek Jr., Dr. Mitra Rebek, Dr.
   Darius Ajami and Dr. Robert G. Ulrich for helpful discussions during the
   course of this work. We also thank David Fetterer for statistical
   analysis and Lorraine Farinick for preparing the figures. We are also
   grateful to the investigators at Addgene for providing plasmids
   originally published in Proc. Natl. Acad. Sci. 2006, 103(29): 10961-6.
   Computational time was provided by the U. S. Army Research Laboratory
   DoD Supercomputing Resource Center.
NR 50
TC 2
Z9 2
U1 4
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 18
PY 2015
VL 5
AR 14246
DI 10.1038/srep14246
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5HF
UT WOS:000361371000002
PM 26381092
ER

PT J
AU Li, CL
   Golebiowski, FM
   Onishi, Y
   Samara, NL
   Sugasawa, K
   Yang, W
AF Li, Chia-Lung
   Golebiowski, Filip M.
   Onishi, Yuki
   Samara, Nadine L.
   Sugasawa, Kaoru
   Yang, Wei
TI Tripartite DNA Lesion Recognition and Verification by XPC, TFIIH, and
   XPA in Nucleotide Excision Repair
SO MOLECULAR CELL
LA English
DT Article
ID TRANSCRIPTION FACTOR TFIIH; DAMAGE RECOGNITION; STRUCTURAL BASIS;
   MAMMALIAN-CELLS; PROMOTER ESCAPE; HELICASE XPD; COMPLEX; PROTEIN;
   STRAND; MECHANISM
AB Transcription factor IIH (TFIIH) is essential for both transcription and nucleotide excision repair (NER). DNA lesions are initially detected by NER factors XPC and XPE or stalled RNA polymerases, but only bulky lesions are preferentially repaired by NER. To elucidate substrate specificity in NER, we have prepared homogeneous human ten-subunit TFIIH and its seven-subunit core (Core7) without the CAK module and show that bulky lesions in DNA inhibit the ATPase and helicase activities of both XPB and XPD in Core7 to promote NER, whereas non-genuine NER substrates have no such effect. Moreover, the NER factor XPA activates unwinding of normal DNA by Core7, but inhibits the Core7 helicase activity in the presence of bulky lesions. Finally, the CAK module inhibits DNA binding by TFIIH and thereby enhances XPC-dependent specific recruitment of TFIIH. Our results support a tripartite lesion verification mechanism involving XPC, TFIIH, and XPA for efficient NER.
C1 [Li, Chia-Lung; Golebiowski, Filip M.; Samara, Nadine L.; Yang, Wei] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
   [Onishi, Yuki; Sugasawa, Kaoru] Kobe Univ, Org Adv Sci & Technol, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan.
   [Onishi, Yuki; Sugasawa, Kaoru] Kobe Univ, Grad Sch Sci, Dept Biol, Kobe, Hyogo 6578501, Japan.
RP Yang, W (reprint author), NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
EM wei.yang@nih.gov
FU NIH [DK075037-06]; JSPS; MEXT, Japan
FX We thank Dr. Mikalai Lapkouski for help with negative staining electron
   microscopy; Lindsay Wise for purified XPA protein; and Drs. Bob Craigie,
   Dan Leahy, and Marty Gellert for critical reading of the manuscript.
   This work is funded by NIH intramural program (DK075037-06), and
   Grants-in-Aid for Scientific Research from JSPS and MEXT, Japan.
NR 62
TC 17
Z9 18
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD SEP 17
PY 2015
VL 59
IS 6
BP 1025
EP 1034
DI 10.1016/j.molcel.2015.08.012
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CW7GQ
UT WOS:000365166500014
PM 26384665
ER

PT J
AU Duan, LL
   Rai, G
   Roggero, C
   Zhang, QJ
   Wei, Q
   Ma, SH
   Zhou, YY
   Santoyo, J
   Martinez, ED
   Xiao, GH
   Raj, GV
   Jadhav, A
   Simeonov, A
   Maloney, DJ
   Rizo, J
   Hsieh, JT
   Liu, ZP
AF Duan, Lingling
   Rai, Ganesha
   Roggero, Carlos
   Zhang, Qing-Jun
   Wei, Qun
   Ma, Shi Hong
   Zhou, Yunyun
   Santoyo, John
   Martinez, Elisabeth D.
   Xiao, Guanghua
   Raj, Ganesh V.
   Jadhav, Ajit
   Simeonov, Anton
   Maloney, David J.
   Rizo, Josep
   Hsieh, Jer-Tsong
   Liu, Zhi-Ping
TI KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by
   Suppressing the Expression of AR and BMYB-Regulated Genes
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID ANDROGEN RECEPTOR; LYSINE DEMETHYLASE; JMJD2 FAMILY; CANCER-CELLS;
   IDENTIFICATION; MOLECULE; VIEW
AB Histone lysine demethylase KDM4/JMJD2s are over-expressed in many human tumors including prostate cancer (PCa). KDM4s are co-activators of androgen receptor (AR) and are thus potential therapeutic targets. Yet to date few KDM4 inhibitors that have anti-prostate tumor activity in vivo have been developed. Here, we report the anti-tumor growth effect and molecular mechanisms of three novel KDM4 inhibitors (A1, I9, and B3). These inhibitors repressed the transcription of both AR and BMYB-regulated genes. Compound B3 is highly selective for a variety of cancer cell lines including PC3 cells that lack AR. B3 inhibited the in vivo growth of tumors derived from PC3 cells and ex vivo human PCa explants. We identified a novel mechanism by which KDM4B activates the transcription of Polo-like kinase 1 (PLK1). B3 blocked the binding of KDM4B to the PLK1 promoter. Our studies suggest a potential mechanism-based therapeutic strategy for PCa and tumors with elevated KDM4B/PLK1 expression.
C1 [Duan, Lingling; Zhang, Qing-Jun; Wei, Qun; Liu, Zhi-Ping] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Duan, Lingling; Zhang, Qing-Jun; Wei, Qun; Liu, Zhi-Ping] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Rai, Ganesha; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
   [Roggero, Carlos; Rizo, Josep] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
   [Roggero, Carlos; Rizo, Josep] Univ Texas SW Med Ctr Dallas, Dept Biochem & Pharmacol, Dallas, TX 75390 USA.
   [Ma, Shi Hong; Santoyo, John; Raj, Ganesh V.; Hsieh, Jer-Tsong] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
   [Zhou, Yunyun; Xiao, Guanghua] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Martinez, Elisabeth D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
RP Liu, ZP (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
EM zhi-ping.liu@utsouthwestern.edu
FU NIHRO1; Welch Foundation; CPRIT-MIRA [RP120717-P1, RP120717-P3,
   RP120717-C1]; intramural research program of National Center for
   Advancing Translational Sciences; Molecular Libraries Program of the NIH
   Common Fund [U54MH084681]
FX We thank Yilun Sun, Elizabeth Hernandez, and Leah Gandee for excellent
   technical assistance. Supported by NIHRO1 (Z.P.L. and E.D.M.), the Welch
   Foundation (E.D.M), CPRIT-MIRA RP120717-P1 (Z.P.L.), CPRIT-MIRA
   RP120717-P3 (J.R.), and CPRIT-MIRA RP120717-C1 (J.T.H). G.R., A.J.,
   A.S., and D.J.M. were supported by the intramural research program of
   the National Center for Advancing Translational Sciences and the
   Molecular Libraries Program of the NIH Common Fund (U54MH084681).
NR 40
TC 5
Z9 5
U1 1
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
EI 1879-1301
J9 CHEM BIOL
JI Chem. Biol.
PD SEP 17
PY 2015
VL 22
IS 9
BP 1185
EP 1196
DI 10.1016/j.chembiol.2015.08.007
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CV1JT
UT WOS:000364012100004
PM 26364928
ER

PT J
AU Hiraki, M
   Hwang, SY
   Cao, SG
   Ramadhar, TR
   Byun, S
   Yoon, KW
   Lee, JH
   Chu, K
   Gurkar, AU
   Kolev, V
   Zhang, JM
   Namba, T
   Murphy, ME
   Newman, DJ
   Mandinova, A
   Clardy, J
   Lee, SW
AF Hiraki, Masatsugu
   Hwang, So-Young
   Cao, Shugeng
   Ramadhar, Timothy R.
   Byun, Sanguine
   Yoon, Kyoung Wan
   Lee, Jung Hyun
   Chu, Kiki
   Gurkar, Aditi U.
   Kolev, Vihren
   Zhang, Jianming
   Namba, Takushi
   Murphy, Maureen E.
   Newman, David J.
   Mandinova, Anna
   Clardy, Jon
   Lee, Sam W.
TI Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through
   the p53-Hsp40 Regulatory Axis
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR P53; CANCER-CELLS; BREAST-CANCER; COMPLEX; STRESS;
   TARGET; IDENTIFICATION; TRANSCRIPTION; INHIBITION; EXPRESSION
AB TP53 is the most frequently mutated gene in human cancer, and small-molecule reactivation of mutant p53 function represents an important anticancer strategy. A cell-based, high-throughput small-molecule screen identified chetomin (CTM) as a mutant p53 R175H reactivator. CTM enabled p53 to transac-tivate target genes, restored MDM2 negative regulation, and selectively inhibited the growth of cancer cells harboring mutant p53 R175H in vitro and in vivo. We found that CTM binds to Hsp40 and increases the binding capacity of Hsp40 to the p53 R175H mutant protein, causing a potential conformational change to a wild-type-like p53. Thus, CTM acts as a specific reactivator of the p53 R175H mutant form through Hsp40. These results provide new insights into the mechanism of reactivation of this specific p53 mutant.
C1 [Hiraki, Masatsugu; Hwang, So-Young; Byun, Sanguine; Yoon, Kyoung Wan; Lee, Jung Hyun; Chu, Kiki; Gurkar, Aditi U.; Kolev, Vihren; Zhang, Jianming; Namba, Takushi; Mandinova, Anna; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
   [Hiraki, Masatsugu; Hwang, So-Young; Byun, Sanguine; Yoon, Kyoung Wan; Lee, Jung Hyun; Chu, Kiki; Gurkar, Aditi U.; Kolev, Vihren; Zhang, Jianming; Namba, Takushi; Mandinova, Anna; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   [Cao, Shugeng] Univ Hawaii, Dept Pharmaceut Sci, Daniel K Inouye Coll Pharm, Hilo, HI 96720 USA.
   [Cao, Shugeng; Ramadhar, Timothy R.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Murphy, Maureen E.] Wistar Inst Anat & Biol, Program Mol & Cellular Oncogenesis, Philadelphia, PA 19104 USA.
   [Newman, David J.] Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
   [Mandinova, Anna; Lee, Sam W.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
RP Clardy, J (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM jon_clardy@hms.harvard.edu; swlee@mgh.harvard.edu
OI Ramadhar, Timothy/0000-0002-7063-5445
FU postdoctoral fellowships for research abroad from the Japan Society for
   the Promotion of Science; research fellowship for research abroad from
   the Uehara Memorial Foundation; F32 postdoctoral fellowship from the NIH
   [GM108415]; NIH [CA142805, CA149477, CA80058, GM086258]; FAS Division of
   Science, Research Computing group at Harvard University
FX We thank Z. Yuan for MEF cells, X. Chen and J. Manfredi for mutant p53
   plasmids and tet-inducible cell lines, J. Manfredi for p53 binding site
   of PUMA promoter plasmid, M. Taipale and S. Lindquist for materials and
   help on some heat-shock protein activity experiments, H. Li and S. J.
   Lee for help on Biacore studies, and W. Gu for in vitro gel-shift
   experiments. M. H. and T.N. were supported by postdoctoral fellowships
   for research abroad from the Japan Society for the Promotion of Science.
   M. H. was also supported by a research fellowship for research abroad
   from the Uehara Memorial Foundation. T.R.R. was supported by an F32
   postdoctoral fellowship from the NIH (GM108415). The research was
   supported by NIH grants CA142805, CA149477, CA80058, and GM086258.
   Quantum-chemical calculations were run on the Odyssey cluster supported
   by the FAS Division of Science, Research Computing group at Harvard
   University.
NR 46
TC 7
Z9 7
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
EI 1879-1301
J9 CHEM BIOL
JI Chem. Biol.
PD SEP 17
PY 2015
VL 22
IS 9
BP 1206
EP 1216
DI 10.1016/j.chembiol.2015.07.016
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CV1JT
UT WOS:000364012100006
PM 26320861
ER

PT J
AU Schleicher, RI
   Reichenbach, F
   Kraft, P
   Kumar, A
   Lescan, M
   Todt, F
   Gobel, K
   Hilgendorf, I
   Geisler, T
   Bauer, A
   Olbrich, M
   Schaller, M
   Wesselborg, S
   O'Reilly, L
   Meuth, SG
   Schulze-Osthoff, K
   Gawaz, M
   Li, XR
   Kleinschnitz, C
   Edlich, F
   Langer, HF
AF Schleicher, Rebecca I.
   Reichenbach, Frank
   Kraft, Peter
   Kumar, Anil
   Lescan, Mario
   Todt, Franziska
   Goebel, Kerstin
   Hilgendorf, Ingo
   Geisler, Tobias
   Bauer, Axel
   Olbrich, Marcus
   Schaller, Martin
   Wesselborg, Sebastian
   O'Reilly, Lorraine
   Meuth, Sven G.
   Schulze-Osthoff, Klaus
   Gawaz, Meinrad
   Li, Xuri
   Kleinschnitz, Christoph
   Edlich, Frank
   Langer, Harald F.
TI Platelets induce apoptosis via membrane-bound FasL
SO BLOOD
LA English
DT Article
ID LIGAND-INDUCED APOPTOSIS; ACUTE ISCHEMIC-STROKE; CYTOCHROME-C RELEASE;
   BRAIN-BARRIER DAMAGE; BCL-2 PROTEIN FAMILY; CELL-DEATH; T-CELLS;
   ACTIVATED PLATELETS; ARTERIAL THROMBOSIS; ADHESION MECHANISMS
AB After tissue injury, both wound sealing and apoptosis contribute to restoration of tissue integrity and functionality. Although the role of platelets (PLTs) for wound closure and induction of regenerative processes is well established, the knowledge about their contribution to apoptosis is incomplete. Here, we show that PLTs present the death receptor Fas ligand (FasL) on their surface after activation. Activated PLTs as well as the isolated membrane fraction of activated PLTs but not of resting PLTs induced apoptosis in a dose-dependent manner in primary murine neuronal cells, human neuroblastoma cells, and mouse embryonic fibroblasts. Membrane protein from PLTs lacking membrane bound FasL (FasL(Delta m/Delta m)) failed to induce apoptosis. Bax/Bak-mediated mitochondrial apoptosis signaling in target cells was not required for PLT-induced cell death, but increased the apoptotic response to PLT-induced Fas signaling. In vivo, PLT depletion significantly reduced apoptosis in a stroke model and an inflammation-independent model of N-methyl-D-aspartic acid-induced retinal apoptosis. Furthermore, experiments using PLT-specific PF4Cre(+) FasL(fl/fl) mice demonstrated a role of PLT-derived FasL for tissue apoptosis. Because apoptosis secondary to injury prevents inflammation, our findings describe a novel mechanism on how PLTs contribute to tissue homeostasis.
C1 [Schleicher, Rebecca I.; Olbrich, Marcus; Langer, Harald F.] Univ Tubingen, Univ Hosp, Dept Cardiovasc Med, Sect Cardioimmunol, D-72076 Tubingen, Germany.
   [Schleicher, Rebecca I.; Geisler, Tobias; Bauer, Axel; Olbrich, Marcus; Gawaz, Meinrad; Langer, Harald F.] Univ Tubingen, Univ Hosp, Dept Cardiovasc Med, D-72076 Tubingen, Germany.
   [Reichenbach, Frank; Todt, Franziska; Edlich, Frank] Univ Freiburg, Ctr Biochem & Mol Cell Res ZBMZ, Inst Biochem & Mol Biol, D-79106 Freiburg, Germany.
   [Reichenbach, Frank] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany.
   [Kraft, Peter; Kleinschnitz, Christoph] Univ Hosp Wuerzburg, Dept Neurol, Wurzburg, Germany.
   [Kumar, Anil] NEI, Bethesda, MD 20892 USA.
   [Lescan, Mario] Univ Tubingen, Univ Hosp, Dept Cardiovasc Surg, D-72076 Tubingen, Germany.
   [Goebel, Kerstin; Meuth, Sven G.] Univ Munster, Dept Neurol, Munster, Germany.
   [Goebel, Kerstin; Meuth, Sven G.] Univ Munster, Inst Physiol Neuropathophysiol, Munster, Germany.
   [Hilgendorf, Ingo] Univ Freiburg, Ctr Heart, Dept Cardiol & Angiol 1, D-79106 Freiburg, Germany.
   [Schaller, Martin] Univ Tubingen, Univ Hosp, Dept Dermatol, D-72076 Tubingen, Germany.
   [Wesselborg, Sebastian] Univ Dusseldorf, Inst Mol Med, Dusseldorf, Germany.
   [O'Reilly, Lorraine] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
   [Schulze-Osthoff, Klaus] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany.
   [Schulze-Osthoff, Klaus] German Canc Consortium, Heidelberg, Germany.
   [Schulze-Osthoff, Klaus] German Canc Res Ctr, Heidelberg, Germany.
   [Li, Xuri] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
   [Edlich, Frank] Univ Freiburg, Ctr Biol Signaling Studies, D-79106 Freiburg, Germany.
RP Langer, HF (reprint author), Univ Tubingen, Sect Cardioimmunol, Otfried Mueller Str 10, D-72076 Tubingen, Germany.
EM frank.edlich@biochemie.uni-freiburg.de;
   harald.langer@med.uni-tuebingen.de
RI Schulze-Osthoff, Klaus/N-9025-2013
OI Schulze-Osthoff, Klaus/0000-0003-1443-2720
FU Volkswagen Foundation (Lichtenberg program); German Heart Foundation;
   Wilhelm Sander Foundation; German Research Council (Deutsche
   Forschungsgemeinschaft) [KFO 274-PLTs]; Emmy Noether program of the
   Deutsche Forschungsgemeinschaft; Else Kroener Fresenius Foundation;
   Excellence Initiative of the German Research Foundation (Spemann
   Graduate School) [GSC-4]; National Health and Medical Research Council
   (Australia); National Health and Medical Research Council; Victorian
   State Government (OIS)
FX This study was supported by the Volkswagen Foundation (Lichtenberg
   program), the German Heart Foundation, and Wilhelm Sander Foundation
   (H.F.L.). M.G. and H.F.L. are members of the Tuebingen Platelet
   Investigative Consortium funded by the German Research Council (Deutsche
   Forschungsgemeinschaft, KFO 274-PLTs: Basic mechanisms and clinical
   implications). F.R., F.T., and F.E. are supported by the Emmy Noether
   program of the Deutsche Forschungsgemeinschaft, the Else Kroener
   Fresenius Foundation, and the Excellence Initiative of the German
   Research Foundation (GSC-4, Spemann Graduate School). L.O. is supported
   by a National Health and Medical Research Council (Australia) project
   grant, National Health and Medical Research Council infrastructure
   grant, and the Victorian State Government (OIS grant).
NR 67
TC 5
Z9 5
U1 1
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD SEP 17
PY 2015
VL 126
IS 12
BP 1483
EP 1493
DI 10.1182/blood-2013-12-544445
PG 11
WC Hematology
SC Hematology
GA CU4ET
UT WOS:000363480500014
PM 26232171
ER

PT J
AU Wakabayashi, KT
   Ren, SE
   Kiyatkin, EA
AF Wakabayashi, Ken T.
   Ren, Suelynn E.
   Kiyatkin, Eugene A.
TI Methylenedioxypyrovalerone (MDPV) mimics cocaine in its physiological
   and behavioral effects but induces distinct changes in NAc glucose
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE electrochemistry and electrochemical processes; brain thermorecording;
   extracellular glucose concentration; vascular tone; metabolism
ID CEREBRAL-BLOOD-FLOW; FREELY MOVING RATS; INTRAVENOUS COCAINE; BRAIN
   TEMPERATURE; IN-VIVO; 3,4-METHYLENEDIOXYPYROVALERONE MDPV; BATH SALTS;
   CARDIOVASCULAR-RESPONSES; EXTRACELLULAR GLUTAMATE; LOCOMOTOR-ACTIVITY
AB Methylenedioxypyrovalerone (MDPV) is generally considered to be a more potent cocaine like psychostimulant, as it shares a similar pharmacological profile with cocaine and induces similar physiological and locomotor responses. Recently, we showed that intravenous cocaine induces rapid rise in nucleus accumbens (NAc) glucose and established its relation to neural activation triggered by the peripheral drug actions. This study was conducted to find out whether MDPV, at a behaviorally equivalent dose, shares a similar pattern of NAc glucose dynamics. Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine. By analyzing Skin Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction: a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose. While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose. These results imply that cocaine-users may be more susceptible to addiction than MDPV-users due to the presence of an interoceptive signal (i.e., sensory cue), which may result in earlier and more direct reward detection. Additionally, while health complications arising from acute cocaine use are typically cardiovascular related, MDPV may be more dangerous to the brain due to uncompensated cerebral vasoconstriction.
C1 [Wakabayashi, Ken T.; Ren, Suelynn E.; Kiyatkin, Eugene A.] NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU NIH [1ZIADA000566-05]
FX These studies were supported by Intramural Research Program, NIH
   (1ZIADA000566-05, EK).
NR 58
TC 3
Z9 3
U1 6
U2 8
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
   SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD SEP 17
PY 2015
VL 9
AR 324
DI 10.3389/fnins.2015.00324
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA CS6SM
UT WOS:000362212000001
PM 26441499
ER

PT J
AU Lammers, KM
   Chieppa, M
   Liu, L
   Liu, S
   Omatsu, T
   Janka-Junttila, M
   Casolaro, V
   Reinecker, HC
   Parent, CA
   Fasano, A
AF Lammers, Karen M.
   Chieppa, Marcello
   Liu, Lunhua
   Liu, Song
   Omatsu, Tatsushi
   Janka-Junttila, Mirkka
   Casolaro, Vincenzo
   Reinecker, Hans-Christian
   Parent, Carole A.
   Fasano, Alessio
TI Gliadin Induces Neutrophil Migration via Engagement of the Formyl
   Peptide Receptor, FPR1
SO PLOS ONE
LA English
DT Article
ID MUCOSAL GRANULOCYTE ACTIVATION; CELIAC-DISEASE; INTESTINAL PERMEABILITY;
   BARRIER FUNCTION; GUT PERMEABILITY; CONTROLLED-TRIAL; GENE-EXPRESSION;
   GLUTEN; ZONULIN; CHEMOTAXIS
AB Background
   Gliadin, the immunogenic component within gluten and trigger of celiac disease, is known to induce the production of Interleukin-8, a potent neutrophil-activating and chemoattractant chemokine. We sought to study the involvement of neutrophils in the early immunological changes following gliadin exposure.
   Methods
   Utilizing immunofluorescence microscopy and flow cytometry, the redistribution of major tight junction protein, Zonula occludens (ZO)-1, and neutrophil recruitment were assessed in duodenal tissues of gliadin-gavaged C57BL/6 wild-type and Lys-GFP reporter mice, respectively. Intravital microscopy with Lys-GFP mice allowed monitoring of neutrophil recruitment in response to luminal gliadin exposure in real time. In vitro chemotaxis assays were used to study murine and human neutrophil chemotaxis to gliadin, synthetic alpha-gliadin peptides and the neutrophil chemoattractant, fMet-Leu-Phe, in the presence or absence of a specific inhibitor of the fMet-Leu-Phe receptor-1 (FPR1), cyclosporine H. An irrelevant protein, zein, served as a control.
   Results
   Redistribution of ZO-1 and an influx of CD11b(+)Lys6G(+) cells in the lamina propria of the small intestine were observed upon oral gavage of gliadin. In vivo intravital microscopy revealed a slowing down of GFP(+) cells within the vessels and influx in the mucosal tissue within 2 hours after challenge. In vitro chemotaxis assays showed that gliadin strongly induced neutrophil migration, similar to fMet-Leu-Phe. We identified thirteen synthetic gliadin peptide motifs that induced cell migration. Blocking of FPR1 completely abrogated the fMet-Leu-Phe-, gliadin- and synthetic peptide-induced migration.
   Conclusions
   Gliadin possesses neutrophil chemoattractant properties similar to the classical neutrophil chemoattractant, fMet-Leu-Phe, and likewise uses FPR1 in the process.
C1 [Lammers, Karen M.; Fasano, Alessio] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA.
   [Chieppa, Marcello] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Liu, Lunhua; Janka-Junttila, Mirkka; Parent, Carole A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Liu, Song; Omatsu, Tatsushi; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
RP Lammers, KM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA.
EM klammers@mgh.harvard.edu
RI Casolaro, Vincenzo/E-9144-2010; 
OI Casolaro, Vincenzo/0000-0001-9810-0488; Chieppa,
   Marcello/0000-0001-9819-0823
FU National Institutes of Health [DK-078699, DK-48373, DK068181, AI113333,
   DK033506, DK043351, MFAG 10684]; Center for Cancer Research, NCI, NIH;
   Associazione Italiana per la Ricerca sul Cancro
FX This research was supported in part by the National Institutes of Health
   Grants DK-078699 and DK-48373 to AF, DK068181, AI113333, DK033506 and
   DK043351 to HCR, MFAG 10684 (AIRC) to MC, and the Intramural Research
   Program of the Center for Cancer Research, NCI, NIH to CAP. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 41
TC 2
Z9 2
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 17
PY 2015
VL 10
IS 9
AR e0138338
DI 10.1371/journal.pone.0138338
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0RH
UT WOS:000361769400084
PM 26378785
ER

PT J
AU Maggio, S
   Takeda, K
   Stark, F
   Meierovics, AI
   Yabe, I
   Cowley, SC
AF Maggio, Savannah
   Takeda, Kazuyo
   Stark, Felicity
   Meierovics, Anda I.
   Yabe, Idalia
   Cowley, Siobhan C.
TI Control of Francisella tularensis Intracellular Growth by Pulmonary
   Epithelial Cells
SO PLOS ONE
LA English
DT Article
ID SYNTHASE GENE-EXPRESSION; NITRIC-OXIDE; REACTIVE NITROGEN; IFN-GAMMA; II
   CELLS; MURINE MACROPHAGES; IN-VITRO; SCHU S4; LUNG; ACTIVATION
AB The virulence of F. tularensis is often associated with its ability to grow in macrophages, although recent studies show that Francisella proliferates in multiple host cell types, including pulmonary epithelial cells. Thus far little is known about the requirements for killing of F. tularensis in the non-macrophage host cell types that support replication of this organism. Here we sought to address this question through the use of a murine lung epithelial cell line (TC-1 cells). Our data show that combinations of the cytokines IFN-gamma, TNF, and IL-17A activated murine pulmonary epithelial cells to inhibit the intracellular growth of the F. tularensis Live Vaccine Strain (LVS) and the highly virulent F. tularensis Schu S4 strain. Although paired combinations of IFN-gamma, TNF, and IL-17A all significantly controlled LVS growth, simultaneous treatment with all three cytokines had the greatest effect on LVS growth inhibition. In contrast, Schu S4 was more resistant to cytokine-induced growth effects, exhibiting significant growth inhibition only in response to all three cytokines. Since one of the main antimicrobial mechanisms of activated macrophages is the release of reactive nitrogen intermediates (RNI) via the activity of iNOS, we investigated the role of RNI and iNOS in Francisella growth control by pulmonary epithelial cells. NOS2 gene expression was significantly up-regulated in infected, cytokine-treated pulmonary epithelial cells in a manner that correlated with LVS and Schu S4 growth control. Treatment of LVS-infected cells with an iNOS inhibitor significantly reversed LVS killing in cytokine-treated cultures. Further, we found that mouse pulmonary epithelial cells produced iNOS during in vivo respiratory LVS infection. Overall, these data demonstrate that lung epithelial cells produce iNOS both in vitro and in vivo, and can inhibit Francisella intracellular growth via reactive nitrogen intermediates.
C1 [Maggio, Savannah; Meierovics, Anda I.; Cowley, Siobhan C.] US FDA, Lab Mucosal Pathogens & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
   [Takeda, Kazuyo] US FDA, Microscopy & Imaging Core Facil, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
   [Stark, Felicity] Natl Res Council Canada, Human Hlth Therapeut Portfolio, Ottawa, ON K1A 0R6, Canada.
   [Yabe, Idalia] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Cowley, SC (reprint author), US FDA, Lab Mucosal Pathogens & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM siobhan.cowley@fda.hhs.gov
FU FDA Medical Countermeasures Initiative
FX This work was supported by the FDA Medical Countermeasures Initiative.
   The funder had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 33
TC 0
Z9 0
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 17
PY 2015
VL 10
IS 9
AR e0138565
DI 10.1371/journal.pone.0138565
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0RH
UT WOS:000361769400110
PM 26379269
ER

PT J
AU Walitt, B
   Nahin, RL
   Katz, RS
   Bergman, MJ
   Wolfe, F
AF Walitt, Brian
   Nahin, Richard L.
   Katz, Robert S.
   Bergman, Martin J.
   Wolfe, Frederick
TI The Prevalence and Characteristics of Fibromyalgia in the 2012 National
   Health Interview Survey
SO PLOS ONE
LA English
DT Article
ID CHRONIC WIDESPREAD PAIN; FUNCTIONAL SOMATIC SYNDROMES; POLYSYMPTOMATIC
   DISTRESS; RHEUMATOID-ARTHRITIS; PHARMACEUTICAL-INDUSTRY; SOMATOFORM
   DISORDERS; GENERAL-POPULATION; BODILY DISTRESS; SYMPTOMS; DISEASE
AB Background
   Most knowledge of fibromyalgia comes from the clinical setting, where healthcare-seeking behavior and selection issues influence study results. The characteristics of fibromyalgia in the general population have not been studied in detail.
   Methods
   We developed and tested surrogate study specific criteria for fibromyalgia in rheumatology practices using variables from the US National Health Interview Survey (NHIS) and the modification (for surveys) of the 2010 American College of Rheumatology (ACR) preliminary fibromyalgia criteria. The surrogate criteria were applied to the 2012 NHIS and identified persons who satisfied criteria from symptom data. The NHIS weighted sample of 8446 persons represents 225.7 million US adults.
   Results
   Fibromyalgia was identified in 1.75%(95% CI 1.42, 2.07), or 3.94 million persons. However, 73% of identified cases self-reported a physician's diagnosis other than fibromyalgia. Identified cases had high levels of self-reported pain, non-pain symptoms, comorbidity, psychological distress, medical costs, Social Security and work disability. Caseness was associated with gender, education, ethnicity, citizenship and unhealthy behaviors. Demographics, behaviors, and comorbidity were predictive of case status. Examination of the surrogate polysymptomatic distress scale (PSD) of the 2010 ACR criteria found fibromyalgia symptoms extending through the full length of the scale.
   Conclusions
   Persons identified with criteria-based fibromyalgia have severe symptoms, butmost (73%) have not received a clinical diagnosis of fibromyalgia. The association of fibromyalgia-like symptoms over the full length of the PSD scale with physiological as well as mental stressors suggests PSD may be a universal response variable rather than one restricted to fibromyalgia.
C1 [Walitt, Brian; Nahin, Richard L.] NIH, Natl Ctr Complementary & Integrat Hlth, Bethesda, MD 20892 USA.
   [Katz, Robert S.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
   [Bergman, Martin J.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
   [Wolfe, Frederick] Natl Data Bank Rheumat Dis, Wichita, KS USA.
RP Walitt, B (reprint author), NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA.
EM brian.walitt@nih.gov
NR 59
TC 18
Z9 18
U1 4
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 17
PY 2015
VL 10
IS 9
AR e0138024
DI 10.1371/journal.pone.0138024
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0RH
UT WOS:000361769400044
PM 26379048
ER

PT J
AU Zhang, JL
   Yan, B
   Spath, SS
   Qun, H
   Cornelius, S
   Guan, D
   Shao, JF
   Hagiwara, K
   Van Waes, C
   Chen, Z
   Su, XL
   Bi, YY
AF Zhang, Jialing
   Yan, Bin
   Spath, Stephan Stanislaw
   Qun, Hu
   Cornelius, Shaleeka
   Guan, Daogang
   Shao, Jiaofang
   Hagiwara, Koichi
   Van Waes, Carter
   Chen, Zhong
   Su, Xiulan
   Bi, Yongyi
TI Integrated transcriptional profiling and genomic analyses reveal RPN2
   and HMGB1 as promising biomarkers in colorectal cancer
SO CELL AND BIOSCIENCE
LA English
DT Article
DE Colorectal cancer; Gene signature; Genomic alterations; Transcription
   factor; Gene regulation
ID COPY NUMBER ALTERATIONS; GROUP BOX 1; ISLAND METHYLATOR PHENOTYPE; II
   COLON-CANCER; NF-KAPPA-B; STAGE-II; MICROSATELLITE-INSTABILITY;
   PROGNOSTIC-FACTORS; GENE-EXPRESSION; CARCINOMA
AB Colorectal cancer (CRC) is a heterogeneous disease that is associated with a gradual accumulation of genetic and epigenetic alterations. Among all CRC stages, stage II tumors are highly heterogeneous with a high relapse rate in about 20-25 % of stage II CRC patients following surgery. Thus, a comprehensive analysis of gene signatures to identify aggressive and metastatic phenotypes in stage II CRC is desired for a more accurate disease classification and outcome prediction. By utilizing a Cancer Array, containing 440 oncogenes and tumor suppressors to profile mRNA expression, we identified a larger number of differentially expressed genes in poorly differentiated stage II colorectal adenocarcinoma tissues, compared to their matched normal tissues. Ontology and Ingenuity Pathway Analysis (IPA) indicated that these genes are involved in functional mechanisms associated with several transcription factors. Genomic alterations of these genes were also investigated through The Cancer Genome Atlas (TCGA) database, utilizing 195 published CRC specimens. The percentage of genomic alterations in these genes was ranked based on their mRNA expression, copy number variations and mutations. This data was further combined with published microarray studies from a large set of CRC tumors classified based on prognostic features. This led to the identification of eight candidate genes including RPN2, HMGB1, AARS, IGFBP3, STAT1, HYOU1, NQO1 and PEA15 that were associated with the progressive phenotype. In particular, RPN2 and HMGB1 displayed a higher genomic alteration frequency in CRC, compared to eight other major solid cancers. Immunohistochemistry was performed on additional 78 stage I-IV CRC samples, where RPN2 protein immunostaining exhibited a significant association with stage III/IV tumors, distant metastasis, and poor differentiation, indicating that RPN2 expression is associated with poor prognosis. Further, our study revealed significant transcriptional regulatory mechanisms, networks and gene signatures, underlying CRC malignant progression and phenotype warranting future clinical investigations.
C1 [Zhang, Jialing; Bi, Yongyi] Wuhan Univ, Sch Publ Hlth, Wuhan 430072, Peoples R China.
   [Zhang, Jialing; Su, Xiulan] Inner Mongolia Med Univ, Affiliated Hosp, Clin Med Res Ctr, Hohhot, Peoples R China.
   [Zhang, Jialing; Cornelius, Shaleeka; Van Waes, Carter; Chen, Zhong] NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
   [Yan, Bin] Chinese Acad Sci, Shenzhen Inst Adv Technol, Lab Food Safety & Environm Technol, Shenzhen, Peoples R China.
   [Spath, Stephan Stanislaw] Karolinska Inst, Pediat Endocrinol Unit, Dept Womens & Childrens Hlth, Stockholm, Sweden.
   [Spath, Stephan Stanislaw] Univ Hosp, Stockholm, Sweden.
   [Qun, Hu] Inner Mongolia Med Univ, Affiliated Hosp, Dept Oncol, Hohhot, Peoples R China.
   [Guan, Daogang] Hong Kong Baptist Univ, Dept Biol, Hong Kong, Hong Kong, Peoples R China.
   [Shao, Jiaofang] Nanjing Med Univ, Sch Basic Med Sci, Dept Bioinformat, Nanjing, Jiangsu, Peoples R China.
   [Hagiwara, Koichi] Jichi Med Univ, Saitama Med Ctr, Dept Resp Med, Saitama, Japan.
RP Chen, Z (reprint author), NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
EM chenz@nidcd.nih.gov; xlsu@hotmail.com; yongyib@yahoo.com.cn
OI Guan, Daogang/0000-0003-1414-0189
FU National Natural Science Foundation of China (China) [81160253]; Natural
   Science Foundation of Inner Mongolia (China) [2011MS1158]; NIDCD
   [ZIA-DC-00016]; Natural Science Foundation of Inner Mongolia
FX This work was supported by the National Natural Science Foundation of
   China (Grant no. 81160253, China) and Natural Science Foundation of
   Inner Mongolia (Grant no. 2011MS1158, China). JLZ was supported by
   Natural Science Foundation of Inner Mongolia. ZC and CVW are supported
   by NIDCD intramural project ZIA-DC-00016. We thank Dr. Jiro Kato at
   NIH/NHLBI and Han Si at NIH/NEI for critical reading of the manuscript
   and for valuable discussions.
NR 58
TC 0
Z9 0
U1 3
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD SEP 17
PY 2015
VL 5
AR 53
DI 10.1186/s13578-015-0043-9
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CR6LK
UT WOS:000361458200001
PM 26388988
ER

PT J
AU Lee, DE
   Yue, XY
   Ibrahim, WG
   Lentz, MR
   Peterson, KL
   Jagoda, EM
   Kassiou, M
   Maric, D
   Reid, WC
   Hammoud, DA
AF Lee, Dianne E.
   Yue, Xuyi
   Ibrahim, Wael G.
   Lentz, Margaret R.
   Peterson, Kristin L.
   Jagoda, Elaine M.
   Kassiou, Michael
   Maric, Dragan
   Reid, William C.
   Hammoud, Dima A.
TI Lack of neuroinflammation in the HIV-1 transgenic rat: an [F-18]-DPA714
   PET imaging study
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE HIV; Transgenic rat; Positron emission tomography; Neuroinflammation
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN 18 KDA; TRANSLOCATOR PROTEIN;
   IN-VIVO; MICROGLIAL ACTIVATION; NEUROCOGNITIVE DISORDERS; BRAIN;
   EXPRESSION; DISEASE; LIGAND
AB Background: HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems.
   Methods: Dynamic [F-18]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages.
   Results: [F-18]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [F-18]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA-lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different.
   Conclusion: Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [F-18]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat.
C1 [Lee, Dianne E.; Ibrahim, Wael G.; Lentz, Margaret R.; Peterson, Kristin L.; Reid, William C.; Hammoud, Dima A.] NIH, Ctr Infect Dis Imaging CIDI, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA.
   [Yue, Xuyi] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
   [Jagoda, Elaine M.] NCI, MIP, Bethesda, MD 20892 USA.
   [Kassiou, Michael] Univ Sydney, Dept Chem, Sydney, NSW 2006, Australia.
   [Maric, Dragan] NINDS, DIR, NIH, Bethesda, MD 20892 USA.
RP Hammoud, DA (reprint author), NIH, Ctr Infect Dis Imaging CIDI, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Room 1C368, Bethesda, MD 20814 USA.
EM hammoudd@cc.nih.gov
FU Center of Infectious Disease Imaging (CIDI), Radiology and Imaging
   Sciences (RIS), Clinical Center, National Institutes of Health
   (Intramural Program)
FX This work was supported by the Center of Infectious Disease Imaging
   (CIDI), Radiology and Imaging Sciences (RIS), Clinical Center, National
   Institutes of Health (Intramural Program).
NR 70
TC 2
Z9 2
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD SEP 17
PY 2015
VL 12
AR 171
DI 10.1186/s12974-015-0390-9
PG 11
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA CR4DE
UT WOS:000361281200006
PM 26377670
ER

PT J
AU Johnson, J
   Ascierto, ML
   Mittal, S
   Newsome, D
   Kang, L
   Briggs, M
   Tanner, K
   Marincola, FM
   Berens, ME
   Woude, GFV
   Xie, Q
AF Johnson, Jennifer
   Ascierto, Maria Libera
   Mittal, Sandeep
   Newsome, David
   Kang, Liang
   Briggs, Michael
   Tanner, Kirk
   Marincola, Francesco M.
   Berens, Michael E.
   Woude, George F. Vande
   Xie, Qian
TI Genomic profiling of a Hepatocyte growth factor-dependent signature for
   MET-targeted therapy in glioblastoma
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Predictive signature; Hepatocyte growth Factor; MET; Glioblastoma;
   Targeted therapy
ID ACQUIRED-RESISTANCE; MALIGNANT GLIOMAS; INHIBITORS; EGFR; ERLOTINIB;
   INVASION; AMPLIFICATION; MECHANISMS; MUTATIONS; GEFITINIB
AB Background: Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable patients for treatment. Because endogenous HGF overexpression often causes autocrine MET activation, and also indicates sensitivity to MET inhibitors, we investigated whether it drives the expression of distinct genes which could serve as a signature indicating vulnerability to MET-targeted therapy in GBM.
   Methods: Interrogation of genomic data from TCGA GBM (Student's t test, GBM patients with high and low HGF expression, p <= 0.00001) referenced against patient-derived xenograft (PDX) models (Student's t test, sensitive vs. insensitive models, p <= 0.005) was used to identify the HGF-dependent signature. Genomic analysis of GBM xenograft models using both human and mouse gene expression microarrays (Student's t test, treated vs. vehicle tumors, p <= 0.01) were performed to elucidate the tumor and microenvironment cross talk. A PDX model with EGFR(amp) was tested for MET activation as a mechanism of erlotinib resistance.
   Results: We identified a group of 20 genes highly associated with HGF overexpression in GBM and were up-or down-regulated only in tumors sensitive to MET inhibitor. The MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall impede tumor growth by inhibiting cell cycle progression. EGFRamp tumors undergo erlotinib resistance responded to a combination of MET and EGFR inhibitors.
   Conclusions: Combining TCGA primary tumor datasets (human) and xenograft tumor model datasets (human tumor grown in mice) using therapeutic efficacy as an endpoint may serve as a useful approach to discover and develop molecular signatures as therapeutic biomarkers for targeted therapy. The HGF dependent signature may serve as a candidate predictive signature for patient enrollment in clinical trials using MET inhibitors. Human and mouse microarrays maybe used to dissect the tumor-host interactions. Targeting MET in EGFRamp GBM may delay the acquired resistance developed during treatment with erlotinib.
C1 [Johnson, Jennifer; Kang, Liang; Xie, Qian] Van Andel Res Inst, Mol Oncol Lab, Mol Oncogenesis & Targeted Therapy, Grand Rapids, MI 49503 USA.
   [Johnson, Jennifer; Kang, Liang; Woude, George F. Vande] Van Andel Res Inst, Mol Oncol Lab, Grand Rapids, MI USA.
   [Ascierto, Maria Libera; Marincola, Francesco M.] Trans Nat Inst Hlth Ctr Human Immunol, Dept Transfus Med, Infect Dis & Immunogenet Sect, Ctr Clin,NIH, Bethesda, MD USA.
   [Ascierto, Maria Libera] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
   [Mittal, Sandeep] Wayne State Univ, Karmanos Canc Inst, Dept Neurosurg & Oncol, Detroit, MI USA.
   [Newsome, David; Tanner, Kirk] Vertex Pharmaceut Inc, Boston, MA USA.
   [Briggs, Michael] Woodland Pharmaceut, Shrewsbury, MA USA.
   [Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar.
   [Berens, Michael E.] Translat Genom Res Inst, Phoenix, AZ USA.
RP Xie, Q (reprint author), Van Andel Res Inst, Mol Oncol Lab, Mol Oncogenesis & Targeted Therapy, 333 Bostwick AVE NE, Grand Rapids, MI 49503 USA.
EM qian.xie@vai.org
FU American Brain Tumor Association; Steven M. Coffman Charitable Fund; Van
   Andel Institute; NIH/NCI [R01 CA123451, U01CA168397]; Fund for Medical
   Research and Education; Strategic Research Initiative Grant; Ben and
   Catherine Ivy Foundation; Wayne State University School of Medicine;
   Karmanos Cancer Institute
FX We thank Drs. Jann Sarkaria (Mayo Clinic) for providing GBM PDX models
   for this study; Drs. Ena Wang (Department of Transfusion Medicine,
   Clinical Center, NIH) and Kyle Furge (Van Andel Research Institute) for
   suggestions and instructions on microarray and bio-informatics analysis.
   We thank David Nadziejka for technical editing of the manuscript. This
   work was supported by the American Brain Tumor Association Discovery
   Grant 2013 and the Steven M. Coffman Charitable Fund (QX), Van Andel
   Institute (GVW and QX); NIH/NCI R01 CA123451, Fund for Medical Research
   and Education, Wayne State University School of Medicine, Strategic
   Research Initiative Grant, Karmanos Cancer Institute (SM); NIH/NCI
   U01CA168397 and the Ben and Catherine Ivy Foundation (MEB).
NR 34
TC 1
Z9 1
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD SEP 17
PY 2015
VL 13
AR 306
DI 10.1186/s12967-015-0667-x
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CR5CD
UT WOS:000361356100003
PM 26381735
ER

PT J
AU Akinyemiju, TF
   Pisu, M
   Waterbor, JW
   Altekruse, SF
AF Akinyemiju, Tomi F.
   Pisu, Maria
   Waterbor, John W.
   Altekruse, Sean F.
TI Socioeconomic status and incidence of breast cancer by hormone receptor
   subtype
SO SPRINGERPLUS
LA English
DT Article
DE Breast cancer; Socio-economic status; Disparities; Triple-negative;
   Cancer
ID AFRICAN-AMERICAN WOMEN; REPRODUCTIVE FACTORS; FEEDING DURATION;
   INCIDENCE RATES; RISK; CALIFORNIA; HEALTH; COHORT; RACE/ETHNICITY;
   DISPARITIES
AB Recent developments in genetics and molecular biology have classified breast cancer into subtypes based on tumor markers of estrogen (ER), progesterone (PR) and human epidermal growth Factor-2 receptors (Her-2), with the basal-like (ER-, PR-, Her2-) subtype commonly referred to as "triple negative" breast cancer (TNBC) being the most aggressive. Prior studies have provided evidence that higher socio-economic status (SES) is associated with increased breast cancer risk, likely due to hormone related risk factors such as parity and hormonal contraceptive use. However, it is unclear if the relationship between SES and overall breast cancer incidence exists within each subtype, and if this association varies by race/ethnicity. Analysis was based on data obtained from the SEER database linked to 2008-2012 American Community Survey data, and restricted to women diagnosed with breast cancer in 2010. The NCI SES census tract SES index based on measures of income, poverty, unemployment, occupational class, education and house value, was examined and categorized into quintiles. Age-adjusted incidence rate ratios were calculated comparing the lowest to the highest SES groups by subtype, separately for each race/ethnic group. We identified 47,586 women with breast cancer diagnosed in 2010. The majority was diagnosed with Her2-/HR+ tumors (73 %), while 12 % had triple negative tumors (TNBC). There was a significant trend of higher incidence with increasing SES for Her2-/HR+ (IRR Highest vs. Lowest SES: 1.32, 95 % CI 1.27-1.39; p value trend: 0.01) and Her2+/HR+ tumors (IRR Highest vs. Lowest SES: 1.46, 95 % CI 1.27-1.68; p value trend: 0.01) among White cases. There was no association between SES and incidence of HR-subtypes (Her2+/HR-or TNBC). Similar associations were observed among Black, Hispanic and Asian or Pacific Islander cases. The positive association between SES and breast cancer incidence is primarily driven by hormone receptor positive tumors. To the extent that neighborhood SES is a proxy for individual SES, future studies are still needed to identify etiologic risk factors for other breast cancer subtypes.
C1 [Akinyemiju, Tomi F.; Waterbor, John W.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35233 USA.
   [Pisu, Maria] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA.
   [Akinyemiju, Tomi F.; Pisu, Maria; Waterbor, John W.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
   [Altekruse, Sean F.] NCI, Canc Stat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Akinyemiju, TF (reprint author), Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35233 USA.
EM tomiakin@uab.edu
FU NCI NIH HHS [U54 CA118948]
NR 53
TC 9
Z9 9
U1 3
U2 14
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-1801
J9 SPRINGERPLUS
JI SpringerPlus
PD SEP 17
PY 2015
VL 4
AR 508
DI 10.1186/s40064-015-1282-2
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR4KJ
UT WOS:000361300600010
PM 26405628
ER

PT J
AU Brown, JD
   Saeed, M
   Do, L
   Braz, J
   Basbaum, AI
   Iadarola, MJ
   Wilson, DM
   Dillon, WP
AF Brown, Jacob D.
   Saeed, Maythem
   Do, Loi
   Braz, Joao
   Basbaum, Allan I.
   Iadarola, Michael J.
   Wilson, David M.
   Dillon, William P.
TI CT-guided injection of a TRPV1 agonist around dorsal root ganglia
   decreases pain transmission in swine
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PRIMARY AFFERENT NEURONS; SENSORY NEURONS; INTRATHECAL RESINIFERATOXIN;
   VANILLOID RECEPTOR-1; MODEL; MANAGEMENT; CAPSAICIN; ABLATION; RAT;
   INFLAMMATION
AB One approach to analgesia is to block pain at the site of origin or along the peripheral pathway by selectively ablating pain-transmitting neurons or nerve terminals directly. The heat/capsaicin receptor (TRPV1) expressed by nociceptive neurons is a compelling target for selective interventional analgesia because it leaves somatosensory and proprioceptive neurons intact. Resiniferatoxin (RTX), like capsaicin, is a TRPV1 agonist but has greater potency. We combine RTX-mediated inactivation with the precision of computed tomography (CT)-guided delivery to ablate peripheral pain fibers in swine. Under CT guidance, RTX was delivered unilaterally around the lumbar dorsal root ganglia (DRG), and vehicle only was administered to the contralateral side. During a 4-week observation period, animals demonstrated delayed or absent withdrawal responses to infrared laser heat stimuli delivered to sensory dermatomes corresponding to DRG receiving RTX treatment. Motor function was unimpaired as assessed by disability scoring and gait analysis. In treated DRG, TRPV1 mRNA expression was reduced, as were nociceptive neuronal perikarya in ganglia and their nerve terminals in the ipsilateral dorsal horn. CT guidance to precisely deliver RTX to sites of peripheral pain transmission in swine may be an approach that could be tailored to block an array of clinical pain conditions in patients.
C1 [Brown, Jacob D.; Saeed, Maythem; Do, Loi; Wilson, David M.; Dillon, William P.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94117 USA.
   [Braz, Joao; Basbaum, Allan I.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94117 USA.
   [Basbaum, Allan I.] NIH, Ctr Clin, Dept Perioperat Med, Bethesda, MD 20892 USA.
RP Dillon, WP (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94117 USA.
EM william.dillon@ucsf.edu
FU Radiological Society of North America, Research and Education
   Foundation: Resident Research Grant [RR1411]; Seed Grant from Department
   of Radiology and Biomedical Imaging, University of California, San
   Francisco [14 -03]; NIH [R01 CA166766, DA29204]; NIH T32 Post-doctoral
   Training Grant;  [NS14627]
FX This project was supported by grant funds from the Radiological Society
   of North America, Research and Education Foundation: RR1411 Resident
   Research Grant and Seed Grant #14 -03 from the Department of Radiology
   and Biomedical Imaging, University of California, San Francisco, awarded
   to J.D.B. and W.P.D., and salary support for J.D.B. through the NIH T32
   Post-doctoral Training Grant administered through the UCSF Department of
   Radiology. The contribution of A.I.B. and J.B. was supported by NIH
   DA29204 and NS14627. D.M.W. receives salary support through NIH R01
   CA166766.
NR 40
TC 2
Z9 2
U1 1
U2 3
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 SEP 16
PY 2015
VL 7
IS 305
AR 305ra145
DI 10.1126/scitranslmed.aac6589
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CW8EH
UT WOS:000365231800005
PM 26378245
ER

PT J
AU van der Brug, MP
   Singleton, A
   Gasser, T
   Lewis, PA
AF van der Brug, Marcel P.
   Singleton, Andrew
   Gasser, Thomas
   Lewis, Patrick A.
TI Parkinson's disease: From human genetics to clinical trials
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID CHAPERONE-MEDIATED AUTOPHAGY; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE;
   GLUCOCEREBROSIDASE MUTATIONS; ACTIVATE PARKIN; LRRK2; UBIQUITIN;
   NEURODEGENERATION; DEFICIENCY; PINK1
AB Combining genetic insights into the pathogenesis of Parkinson's disease (PD) with findings from animal and cellular models of this disorder has advanced our understanding of the pathways that lead to the characteristic degeneration of dopaminergic neurons in the brain's nigrostriatal pathway. This has fueled an increase in candidate compounds designed to modulate these pathways and to alter the processes underlying neuronal death in this disorder. Using mitochondrial quality control and the macroautophagy/lysosomal pathways as examples, we discuss the pipeline from a comprehensive genetic architecture for PD through to clinical trials for drugs targeting pathways linked to neurodegeneration in PD. We also identify opportunities and pitfalls on the road to a clinically effective disease-modifying treatment for this disease.
C1 [van der Brug, Marcel P.] Genentech Inc, Dept Diagnost Discovery, San Francisco, CA 94080 USA.
   [Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Gasser, Thomas] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
   [Gasser, Thomas] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany.
   [Lewis, Patrick A.] Univ Reading, Sch Pharm, Reading RG6 6AP, Berks, England.
   [Lewis, Patrick A.] Univ Reading, Ctr Integrated Neurosci & Neurodynam, Reading RG6 6AP, Berks, England.
   [Lewis, Patrick A.] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
RP Lewis, PA (reprint author), Univ Reading, Sch Pharm, Reading RG6 6AP, Berks, England.
EM p.a.lewis@reading.ac.uk
RI Singleton, Andrew/C-3010-2009; 
OI Lewis, Patrick/0000-0003-4537-0489
FU Wellcome Trust/Medical Research Council (MRC) Joint Call in
   Neurode-generation award [WT089698]; MRC grant [MR/L010933/1];  [F1002]
FX P.A.L. is a Parkinson's UK research fellow (grant F1002). This work was
   supported in part by the Wellcome Trust/Medical Research Council (MRC)
   Joint Call in Neurode-generation award (WT089698) to the UK Parkinson's
   Disease Consortium (UKPDC) whose members include University College,
   London Institute of Neurology, the University of Sheffield and the MRC
   Protein Phosphorylation Unit at the University of Dundee, and MRC grant
   MR/L010933/1.
NR 67
TC 10
Z9 10
U1 4
U2 16
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 SEP 16
PY 2015
VL 7
IS 305
AR 305ps20
DI 10.1126/scitranslmed.aaa8280
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CW8EH
UT WOS:000365231800003
PM 26378242
ER

PT J
AU Wu, XH
   Zou, QH
   Hu, J
   Tang, WJ
   Mao, Y
   Gao, L
   Zhu, JH
   Jin, Y
   Wu, X
   Lu, L
   Zhang, YJ
   Zhang, Y
   Dai, ZJ
   Gao, JH
   Weng, XC
   Zhou, LF
   Northoff, G
   Giacino, JT
   He, Y
   Yang, YH
AF Wu, Xuehai
   Zou, Qihong
   Hu, Jin
   Tang, Weijun
   Mao, Ying
   Gao, Liang
   Zhu, Jianhong
   Jin, Yi
   Wu, Xin
   Lu, Lu
   Zhang, Yaojun
   Zhang, Yao
   Dai, Zhengjia
   Gao, Jia-Hong
   Weng, Xuchu
   Zhou, Liangfu
   Northoff, Georg
   Giacino, Joseph T.
   He, Yong
   Yang, Yihong
TI Intrinsic Functional Connectivity Patterns Predict Consciousness Level
   and Recovery Outcome in Acquired Brain Injury
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE acquired brain injury; hub; posterior cingulate cortex/precuneus;
   prediction; recovery outcome; resting state fMRI
ID DEFAULT MODE NETWORK; POSTERIOR CINGULATE CORTEX; RESTING-STATE;
   VEGETATIVE STATE; ALZHEIMERS-DISEASE; COGNITIVE CONTROL; COMATOSE
   PATIENTS; PRACTICAL SCALE; CORTICAL HUBS; GLOBAL SIGNAL
AB For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI.
C1 [Wu, Xuehai; Hu, Jin; Mao, Ying; Zhu, Jianhong; Jin, Yi; Wu, Xin; Zhou, Liangfu] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200040, Peoples R China.
   [Tang, Weijun] Fudan Univ, Huashan Hosp, Dept Radiol, Shanghai 200040, Peoples R China.
   [Zou, Qihong; Gao, Jia-Hong] Peking Univ, Ctr MRI Res, Beijing 100871, Peoples R China.
   [Zou, Qihong; Gao, Jia-Hong] Peking Univ, Beijing City Key Lab Med Phys & Engn, Beijing 100871, Peoples R China.
   [Gao, Liang] Shanghai 10 Hosp, Dept Neurosurg, Shanghai 200072, Peoples R China.
   [Lu, Lu; Zhang, Yaojun; Zhang, Yao] Huajia Hosp, Dept Neurosurg, Shanghai 200433, Peoples R China.
   [Dai, Zhengjia; He, Yong] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
   [Dai, Zhengjia; He, Yong] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China.
   [Dai, Zhengjia; He, Yong] Beijing Normal Univ, Ctr Collaborat & Innovat Brain & Learning Sci, Beijing 100875, Peoples R China.
   [Gao, Jia-Hong] Peking Univ, McGovern Inst Brain Res, Beijing 100871, Peoples R China.
   [Weng, Xuchu] Hangzhou Normal Univ, Ctr Cognit & Brain Disorders, Hangzhou 310015, Zhejiang, Peoples R China.
   [Weng, Xuchu] Hangzhou Normal Univ, Affiliated Hosp, Hangzhou 310015, Zhejiang, Peoples R China.
   [Northoff, Georg] Univ Ottawa, Inst Mental Hlth Res, Ottawa, ON K1Z 7K4, Canada.
   [Giacino, Joseph T.] Spaulding Rehabil Hosp, Boston, MA 02129 USA.
   [Giacino, Joseph T.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02129 USA.
   [Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
RP Zhou, LF (reprint author), Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200040, Peoples R China.
EM lfzhouc@126.com; yihongyang@mail.nih.gov
FU National Strategic Basic Research Program ("973") of China
   [2015CB856400, 2012CB720700, 2010CB945500, 2012CB966300, 2009CB941100];
   Natural Science Foundation of China [81201142, 81225012, 91432115];
   National Science and Technology 863 Program [2015AA020501]; Shanghai
   Natural Science Foundation [08411952000, 10ZR1405400]; Canadian
   Institutes of Health Research (CIHR); EJLB Foundation-CIHR; Michael
   Smith Foundation; Human Development Research Foundation; Intramural
   Research Program of the National Institute on Drug Abuse, National
   Institutes of Health
FX This work was supported by the National Strategic Basic Research Program
   ("973") of China Grants 2015CB856400, 2012CB720700, 2010CB945500,
   2012CB966300, and 2009CB941100; Natural Science Foundation of China
   Grants 81201142, 81225012, and 91432115; National Science and Technology
   863 Program 2015AA020501; Shanghai Natural Science Foundation Grants
   08411952000 and 10ZR1405400; the Canadian Institutes of Health Research
   (CIHR), EJLB Foundation-CIHR, the Michael Smith Foundation, and the
   Human Development Research Foundation. Y.Y. was supported by the
   Intramural Research Program of the National Institute on Drug Abuse,
   National Institutes of Health. We thank Drs. Gang Chen and Thomas Ross
   for providing help with statistical analyses; Drs. Yu-Feng Zang, Xi-Nian
   Zuo, and Zhifeng Kou for their insightful discussion; and Ms. Julia K.
   Brynildsen for linguistic editing of the manuscript.
NR 65
TC 2
Z9 2
U1 3
U2 8
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 SEP 16
PY 2015
VL 35
IS 37
BP 12932
EP 12946
DI 10.1523/JNEUROSCI.0415-15.2015
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA CU6RC
UT WOS:000363659500027
PM 26377477
ER

PT J
AU d'Ettorre, G
   Ceccarelli, G
   Giustini, N
   Serafino, S
   Calantone, N
   De Girolamo, G
   Bianchi, L
   Bellelli, V
   Ascoli-Bartoli, T
   Marcellini, S
   Turriziani, O
   Brenchley, JM
   Vullo, V
AF d'Ettorre, Gabriella
   Ceccarelli, Giancarlo
   Giustini, Noemi
   Serafino, Sara
   Calantone, Nina
   De Girolamo, Gabriella
   Bianchi, Luigi
   Bellelli, Valeria
   Ascoli-Bartoli, Tommaso
   Marcellini, Sonia
   Turriziani, Ombretta
   Brenchley, Jason M.
   Vullo, Vincenzo
TI Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected
   Individuals: Results of the "Probio-HIV" Clinical Trial
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MUCOSAL IMMUNE RECONSTITUTION; REGULATORY
   T-CELLS; MICROBIAL TRANSLOCATION; DOUBLE-BLIND; IN-VIVO; ACTIVATION;
   THERAPY; COAGULATION; DECLINE
AB Background
   HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation.
   Methods
   In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma.
   Results
   We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls.
   Conclusions
   Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis.
C1 [d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Giustini, Noemi; Serafino, Sara; De Girolamo, Gabriella; Bianchi, Luigi; Bellelli, Valeria; Ascoli-Bartoli, Tommaso; Marcellini, Sonia; Vullo, Vincenzo] Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, I-00185 Rome, Italy.
   [Turriziani, Ombretta] Univ Roma La Sapienza, Dept Virol, I-00185 Rome, Italy.
   [Calantone, Nina; Brenchley, Jason M.] NIAID, Program Barrier Immun & Repair, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Ceccarelli, G (reprint author), Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
EM giancarlo.ceccarelli@uniroma1.it
RI Ceccarelli, Giancarlo/K-6454-2016; d'Ettorre, Gabriella/K-4511-2016; 
OI Ceccarelli, Giancarlo/0000-0001-5921-3180; d'Ettorre,
   Gabriella/0000-0002-3571-5677
FU Division of Intramural Research / National Institute of Allergy and
   Infectious Diseases (NIAID) / National Institutes of Health (NIH)
FX Funding for this study (NC) was provided in part by the Division of
   Intramural Research / National Institute of Allergy and Infectious
   Diseases (NIAID) / National Institutes of Health (NIH).
NR 34
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U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 16
PY 2015
VL 10
IS 9
AR e0137200
DI 10.1371/journal.pone.0137200
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8NH
UT WOS:000361610200032
PM 26376436
ER

PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Why the Central Dogma: on the nature of the great biological exclusion
   principle
SO BIOLOGY DIRECT
LA English
DT Editorial Material
DE Central Dogma; Digital information; Analogous information; Translation;
   Aminoacyl-tRNA synthetases
ID EVOLUTION; SEQUENCE
AB The Central Dogma of molecular biology posits that transfer of information from proteins back to nucleic acids does not occur in biological systems. I argue that the impossibility of reverse translation is indeed a major, physical exclusion principle that emerges due to the transition from the digital information carriers, nucleic acids, to analog information carriers, proteins, which involves irreversible suppression of the digital information.
   Reviewers: This article was reviewed by Itai Yanai, Martin Lercher and Frank Eisenhaber.
C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU Intramural NIH HHS
NR 15
TC 1
Z9 1
U1 6
U2 44
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD SEP 16
PY 2015
VL 10
AR 52
DI 10.1186/s13062-015-0084-3
PG 5
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CR4EQ
UT WOS:000361285000002
PM 26377089
ER

PT J
AU Ross, J
   Kuzin, A
   Brody, T
   Odenwald, WF
AF Ross, Jermaine
   Kuzin, Alexander
   Brody, Thomas
   Odenwald, Ward F.
TI cis-regulatory analysis of the Drosophila pdm locus reveals a diversity
   of neural enhancers
SO BMC GENOMICS
LA English
DT Article
DE Nubbin; pdm-2; cis-regulation; Neurogenesis; Drosophila; Enhancers
ID POU DOMAIN GENES; DEVELOPMENTAL ENHANCERS; MOLECULAR EVOLUTION; CENTRAL
   COMPLEX; EXPRESSION; CNS; IDENTIFICATION; SPECIFICATION; MELANOGASTER;
   HUNCHBACK
AB Background: One of the major challenges in developmental biology is to understand the regulatory events that generate neuronal diversity. During Drosophila embryonic neural lineage development, cellular temporal identity is established in part by a transcription factor (TF) regulatory network that mediates a cascade of cellular identity decisions. Two of the regulators essential to this network are the POU-domain TFs Nubbin and Pdm-2, encoded by adjacent genes collectively known as pdm. The focus of this study is the discovery and characterization of cis-regulatory DNA that governs their expression.
   Results: Phylogenetic footprinting analysis of a 125 kb genomic region that spans the pdm locus identified 116 conserved sequence clusters. To determine which of these regions function as cis-regulatory enhancers that regulate the dynamics of pdm gene expression, we tested each for in vivo enhancer activity during embryonic development and postembryonic neurogenesis. Our screen revealed 77 unique enhancers positioned throughout the noncoding region of the pdm locus. Many of these activated neural-specific gene expression during different developmental stages and many drove expression in overlapping patterns. Sequence comparisons of functionally related enhancers that activate overlapping expression patterns revealed that they share conserved elements that can be predictive of enhancer behavior. To facilitate data accessibility, the results of our analysis are catalogued in cisPatterns, an online database of the structure and function of these and other Drosophila enhancers.
   Conclusions: These studies reveal a diversity of modular enhancers that most likely regulate pdm gene expression during embryonic and adult development, highlighting a high level of temporal and spatial expression specificity. In addition, we discovered clusters of functionally related enhancers throughout the pdm locus. A subset of these enhancers share conserved elements including sequences that correspond to known TF DNA binding sites. Although comparative analysis of the nubbin and pdm-2 encoding sequences indicate that these two genes most likely arose from a duplication event, we found only partial evidence of sequence duplication between their enhancers, suggesting that after the putative duplication their cis-regulatory DNA diverged at a higher rate than their coding sequences.
C1 [Ross, Jermaine; Kuzin, Alexander; Brody, Thomas; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
RP Ross, J (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM rossje@ninds.nih.gov; odenwaldw@ninds.nih.gov
FU Intramural Research Program of the NIH, NINDS
FX We are grateful to Chi-Hon lee, Anne Hart, and Gilad Barnea for helpful
   discussions and advice during the project. We also would like to
   acknowledge the editorial expertise and assistance of Judith Brody. This
   work was completed as a partial requirement for a doctoral degree from
   the Brown University-NIH cooperative Ph.D. program. This research was
   supported by the Intramural Research Program of the NIH, NINDS.
NR 59
TC 0
Z9 0
U1 1
U2 5
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 SEP 16
PY 2015
VL 16
AR 700
DI 10.1186/s12864-015-1897-2
PG 20
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CR5BF
UT WOS:000361353300002
PM 26377945
ER

PT J
AU Llewellyn, D
   Miura, K
   Fay, MP
   Williams, AR
   Murungi, LM
   Shi, J
   Hodgson, SH
   Douglas, AD
   Osier, FH
   Fairhurst, RM
   Diakite, M
   Pleass, RJ
   Long, CA
   Draper, SJ
AF Llewellyn, David
   Miura, Kazutoyo
   Fay, Michael P.
   Williams, Andrew R.
   Murungi, Linda M.
   Shi, Jianguo
   Hodgson, Susanne H.
   Douglas, Alexander D.
   Osier, Faith H.
   Fairhurst, Rick M.
   Diakite, Mahamadou
   Pleass, Richard J.
   Long, Carole A.
   Draper, Simon J.
TI Standardization of the antibody-dependent respiratory burst assay with
   human neutrophils and Plasmodium falciparum malaria
SO SCIENTIFIC REPORTS
LA English
DT Article
ID GAMMA RECEPTOR-IIA; FC-GAMMA; CD32 POLYMORPHISM; CEREBRAL MALARIA;
   PARASITE GROWTH; BLOOD STAGES; IN-VITRO; STAGE; PHAGOCYTOSIS; PROTECTION
AB The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration, and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors, and indexing responses against a standard positive control of pooled hyperimmune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials, and requires only 6 mu L of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naive individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity, and provides an important standardized cell-based assay in the field.
C1 [Llewellyn, David; Williams, Andrew R.; Murungi, Linda M.; Hodgson, Susanne H.; Douglas, Alexander D.; Draper, Simon J.] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
   [Miura, Kazutoyo; Fairhurst, Rick M.; Long, Carole A.] NIAID, NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
   [Fay, Michael P.] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA.
   [Murungi, Linda M.; Osier, Faith H.] KEMRI Ctr Geog Med Res, Kilifi, Kenya.
   [Shi, Jianguo; Pleass, Richard J.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
   [Diakite, Mahamadou] Univ Bamako, Fac Med Pharm & Odonto Stomatol, Malaria Res & Training Ctr, Bamako, Mali.
RP Llewellyn, D (reprint author), Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England.
EM dlle7934@uni.sydney.edu.au
RI Douglas, Alexander/E-7040-2012; 
OI Douglas, Alexander/0000-0002-5410-7562; Pleass,
   Richard/0000-0001-7438-8296; Williams, Andrew/0000-0002-8231-282X;
   Draper, Simon/0000-0002-9415-1357
FU UK Medical Research Council (MRC) [G1000527]; European Community
   [242095]; Intramural Program of the National Institute of Allergy and
   Infectious Diseases; EMVDA (European Malaria Vaccine Development
   Association) [VAC036, VAC039]; Rhodes Trust; UK MRC [G1000527]; UK
   Department for International Development (DFID) under the MRC/DFID
   Concordat agreement [G1000527]
FX We thank J. Furze, A. Spencer, D. Worth and the Flow Cytometry Core
   Facility (Jenner Institute, University of Oxford); E. Johnson
   (Bioimaging Facility, Sir William Dunn School of Pathology, University
   of Oxford); K. Marsh (KEMRI-Wellcome, Kilifi, Kenya); and S. Younis and
   E. Remarque (Biomedical Primate Research Centre, the Netherlands) for
   their assistance. This study is published with the permission of the
   Director of KEMRI. This work was supported by the UK Medical Research
   Council (MRC) [grant number G1000527]; and by the European Community's
   Seventh Framework Programme (FP7/2007-2013) under grant agreement No
   242095 - EVIMalaR. Work on the Mali cohort and statistical analysis was
   supported by the Intramural Program of the National Institute of Allergy
   and Infectious Diseases. We also thank A. Hill, C. Duncan, S. Elias, P.
   Choudhary and the clinical trials team at the Centre for Clinical
   Vaccinology and Tropical Medicine, University of Oxford, as well as the
   EMVDA (European Malaria Vaccine Development Association) for funding the
   VAC036 and VAC039 clinical trials. DL is supported by the Rhodes Trust.
   SHH is a Wellcome Trust clinical research fellow [097940/Z/11/Z]. ADD
   held a Wellcome Trust Research Training Fellowship [089455/2/09/Z]. SJD
   is a Jenner Investigator, Lister Institute Research Prize Fellow and a
   UK MRC Career Development Fellow [grant number G1000527; this Fellowship
   is jointly funded by the UK MRC and the UK Department for International
   Development (DFID) under the MRC/DFID Concordat agreement].
NR 57
TC 6
Z9 6
U1 0
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 SEP 16
PY 2015
VL 5
AR 14081
DI 10.1038/srep14081
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR4HZ
UT WOS:000361294100001
PM 26373337
ER

PT J
AU Koelle, K
   Rasmussen, DA
AF Koelle, Katia
   Rasmussen, David A.
TI The effects of a deleterious mutation load on patterns of influenza
   A/H3N2's antigenic evolution in humans
SO ELIFE
LA English
DT Article
ID A H3N2 VIRUSES; BENEFICIAL MUTATIONS; ASEXUAL EVOLUTION; EPOCHAL
   EVOLUTION; GLOBAL CIRCULATION; GENETIC EVOLUTION; HUMAN-POPULATIONS;
   MULLERS RATCHET; VIRAL LOAD; SELECTION
AB Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.
C1 [Koelle, Katia; Rasmussen, David A.] Duke Univ, Dept Biol, Durham, NC 27706 USA.
   [Koelle, Katia] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Rasmussen, David A.] Eidgenoss TH Zurich, Dept Biosyst Sci & Engn, Basel, Switzerland.
RP Koelle, K (reprint author), Duke Univ, Dept Biol, Durham, NC 27706 USA.
EM katia.koelle@duke.edu
FU James S. McDonnell Foundation (JSMF); National Institute of General
   Medical Sciences (NIGMS) [U54-GM111274]; U.S. Department of Homeland
   Security RAPIDD program of the Science and Technology Directorate
FX James S. McDonnell Foundation (JSMF) Katia Koelle, David A Rasmussen;
   National Institute of General Medical Sciences (NIGMS) U54-GM111274
   Katia Koelle; U.S. Department of Homeland Security RAPIDD program of the
   Science and Technology Directorate Katia Koelle; The funders had no role
   in study design, data collection and interpretation, or the decision to
   submit the work for publication.
NR 81
TC 7
Z9 7
U1 1
U2 2
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD SEP 15
PY 2015
VL 4
AR e07361
DI 10.7554/eLife.07361
PG 31
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9UZ
UT WOS:000373849500001
PM 26371556
ER

PT J
AU Fauci, AS
   Morens, DM
   Marston, HD
AF Fauci, Anthony S.
   Morens, David M.
   Marston, Hilary D.
TI Vaccination and the Lasker Awards Enduring Legacies
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID POLIOMYELITIS
C1 [Fauci, Anthony S.; Morens, David M.; Marston, Hilary D.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, NIH, 31 Ctr Dr,MSC 2520,Bldg 31,Room 7A-03, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 7
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 SEP 15
PY 2015
VL 314
IS 11
BP 1119
EP 1120
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR4EL
UT WOS:000361284500014
PM 26372572
ER

PT J
AU Uchida, Y
   James, JM
   Suto, F
   Mukouyama, YS
AF Uchida, Yutaka
   James, Jennifer M.
   Suto, Fumikazu
   Mukouyama, Yoh-suke
TI Class 3 semaphorins negatively regulate dermal lymphatic network
   formation
SO BIOLOGY OPEN
LA English
DT Article
DE SEMA3s; NRP2; Dermal lymphangiogenesis; LEC sprouting; LEC growth
ID NEUROPILIN-2 MUTANT MICE; ARTERIAL DIFFERENTIATION; ENDOTHELIAL-CELLS;
   VALVE FORMATION; SENSORY NERVES; METASTASIS; EXPRESSION; MIGRATION;
   GROWTH; GENE
AB The development of a patterned lymphatic vascular network is essential for proper lymphatic functions during organ development and homeostasis. Here we report that class 3 semaphorins (SEMA3s), SEMA3F and SEMA3G negatively regulate lymphatic endothelial cell (LEC) growth and sprouting to control dermal lymphatic network formation. Neuropilin2 (NRP2) functions as a receptor for SEMA3F and SEMA3G, as well as vascular endothelial growth factor C (VEGFC). In culture, Both SEMA3F and SEMA3G inhibit VEGFC-mediated sprouting and proliferation of human dermal LECs. In the developing mouse skin, Sema3f is expressed in the epidermis and Sema3g expression is restricted to arteries, whereas their receptor Nrp2 is preferentially expressed by lymphatic vessels. Both Sema3f; Sema3g double mutants and Nrp2 mutants exhibit increased LEC growth in the skin. In contrast, Sema3f; Sema3g double mutants display increased lymphatic branching, while Nrp2 mutants exhibit reduced lymphatic branching. A targeted mutation in PlexinA1 or PlexinA2, signal transducers forming a receptor complex with NRP2 for SEMA3s, exhibits an increase in LEC growth and lymphatic branching as observed in Sema3f; Sema3g double mutants. Our results provide the first evidence that SEMA3F and SEMA3G function as a negative regulator for dermal lymphangiogenesis in vivo. The reciprocal phenotype in lymphatic branching between Sema3f; Sema3g double mutants and Nrp2 mutants suggest a complex NRP2 function that regulates LEC behavior both positively and negatively, through a binding with VEGFC or SEMA3s.
C1 [Uchida, Yutaka; James, Jennifer M.; Mukouyama, Yoh-suke] NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Suto, Fumikazu] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Ultrastruct Res, Tokyo 1878502, Japan.
RP Mukouyama, YS (reprint author), NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bldg 10-6C103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mukoyamay@mail.nih.gov
FU Intramural Research Program of the National Heart, Lung, and Blood
   Institute, National Institutes of Health [HL005702-07]
FX This work was supported by the Intramural Research Program of the
   National Heart, Lung, and Blood Institute, National Institutes of Health
   [HL005702-07 to Y.-s.M.].
NR 45
TC 4
Z9 5
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 2046-6390
J9 BIOL OPEN
JI Biol. Open
PD SEP 15
PY 2015
VL 4
IS 9
BP 1194
EP 1205
DI 10.1242/bio.012302
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CW5ZS
UT WOS:000365076600013
PM 26319580
ER

PT J
AU Geerlings, MI
   Sigurdsson, S
   Eiriksdottir, G
   Garcia, ME
   Harris, TB
   Gudnason, V
   Launer, LJ
AF Geerlings, Mirjam I.
   Sigurdsson, Sigurdur
   Eiriksdottir, Gudny
   Garcia, Melissa E.
   Harris, Tamara B.
   Gudnason, Vilmundur
   Launer, Lenore J.
TI Salivary cortisol, brain volumes, and cognition in community-dwelling
   elderly without dementia
SO NEUROLOGY
LA English
DT Article
ID LATE-LIFE DEPRESSION; PITUITARY-ADRENOCORTICAL AXIS; HIPPOCAMPAL
   ATROPHY; AGES-REYKJAVIK; GERIATRIC DEPRESSION; ALZHEIMERS-DISEASE; MAJOR
   DEPRESSION; ALLOSTATIC LOAD; RISK; METAANALYSIS
AB Objective:We investigated the associations of morning and evening salivary cortisol levels with regional brain volumes and cognitive functioning in community-dwelling older persons without dementia.Method:From the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,244 persons without dementia (age 76 5 years, 58% women) who had 1.5T brain MRI, assessment of cognitive functioning, and saliva collected at home 45 minutes after awakening and at night. Linear regression analysis was used to estimate the cross-sectional relationship among cortisol levels, brain volumes, and cognitive functioning, adjusting for covariates.Results:Higher evening cortisol was associated with smaller total brain volume (highest vs lowest tertile -16.0 mL; 95% confidence interval -19.7 to -12.2 mL, adjusted for age, sex, education, intracranial volume, smoking, steroid use, white matter lesions, and brain infarcts on MRI). The smaller volumes were observed in all brain regions, but were significantly smaller in gray matter than in white matter regions. Poorer cognitive functioning across all domains was also associated with higher evening cortisol. Higher levels of morning cortisol were associated with slightly greater normal white matter volume and better processing speed and executive functioning, but not with gray matter volume or with memory performance.Conclusions:In older persons, evening and morning cortisol levels may be differentially associated with tissue volume in gray and white matter structures and cognitive function. Understanding these differential associations may aid in developing strategies to reduce the effects of hypothalamic-pituitary-adrenal axis dysfunction on late-life cognitive impairment. Neurology (R) 2015;85:976-983
C1 [Geerlings, Mirjam I.; Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
   [Geerlings, Mirjam I.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
   [Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Gudnason, Vilmundur] Icelandic Heart Assoc, Kopavogur, Iceland.
   [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
RP Launer, LJ (reprint author), NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
EM launerl@nia.nih.gov
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
FU NIH [N01-AG-12100]; NIA Intramural Research Program; Hjartavernd (the
   Icelandic Heart Association); Althingi (the Icelandic Parliament);
   Netherlands Organization for Scientific Research (NWO) [917-66-311];
   University Medical Center Utrecht, the Netherlands
FX Supported by NIH (N01-AG-12100), NIA Intramural Research Program,
   Hjartavernd (the Icelandic Heart Association), and Althingi (the
   Icelandic Parliament). Dr. M.I. Geerlings was supported by a grant from
   the Netherlands Organization for Scientific Research (NWO: project no.
   917-66-311) and a grant (Internationalisation program) from the
   University Medical Center Utrecht, the Netherlands.
NR 38
TC 3
Z9 3
U1 3
U2 8
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 SEP 15
PY 2015
VL 85
IS 11
BP 976
EP 983
DI 10.1212/WNL.0000000000001931
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CW1AB
UT WOS:000364720500009
PM 26291281
ER

PT J
AU Zhang, SL
   Zhou, LL
   Hong, B
   van den Heuvel, APJ
   Prabhu, VV
   Warfel, NA
   Kline, CLB
   Dicker, DT
   Kopelovich, L
   El-Deiry, WS
AF Zhang, Shengliang
   Zhou, Lanlan
   Hong, Bo
   van den Heuvel, A. Pieter J.
   Prabhu, Varun V.
   Warfel, Noel A.
   Kline, Christina Leah B.
   Dicker, David T.
   Kopelovich, Levy
   El-Deiry, Wafik S.
TI Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor
   Effects against Colorectal Cancer via p73 Activation and Degradation of
   Mutant p53
SO CANCER RESEARCH
LA English
DT Article
ID IN-VITRO; CELLS; MDM2; CHEMOSENSITIVITY; UBIQUITINATION; STABILIZATION;
   INHIBITION; MUTATIONS; BINDING; RESCUE
AB The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression, and chemo-or radiotherapy resistance. Thus, targeting mutant p53 to restore a wild-type p53 signaling pathway provides an attractive strategy for cancer therapy. We demonstrate that small-molecule NSC59984 not only restores wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. NSC59984 restores wild-type p53 signaling via p73 activation, specifically in mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984 induces p73-dependent cell death in cancer cells with minimal genotoxicity and without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in vivo. We hypothesize that specific targeting of mutant p53 may be essential for anticancer strategies that involve the stimulation of p73 in order to efficiently restore tumor suppression. Taken together, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by targeting GOF-mutant p53 and stimulates p73 to restore the p53 pathway signaling. (C) 2015 AACR.
C1 [Zhang, Shengliang; Zhou, Lanlan; Hong, Bo; van den Heuvel, A. Pieter J.; Prabhu, Varun V.; Warfel, Noel A.; Kline, Christina Leah B.; Dicker, David T.; El-Deiry, Wafik S.] Penn State Hershey Canc Inst, Hershey, PA USA.
   [Zhang, Shengliang; Zhou, Lanlan; Prabhu, Varun V.; Kline, Christina Leah B.; Dicker, David T.; El-Deiry, Wafik S.] Fox Chase Canc Ctr, Lab Translat Oncol & Expt Canc Therapeut, Dept Med Oncol, Philadelphia, PA 19111 USA.
   [Zhang, Shengliang; Zhou, Lanlan; Prabhu, Varun V.; Kline, Christina Leah B.; Dicker, David T.; El-Deiry, Wafik S.] Fox Chase Canc Ctr, Mol Therapeut Program, Philadelphia, PA 19111 USA.
   [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP El-Deiry, WS (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave,Room P2035, Philadelphia, PA 19111 USA.
EM wafik.eldeiry@gmail.com
FU NIH [N01-CN43302-WA-17, N01-CN43302-WA-27]
FX The work was supported, in part, by NIH grants (N01-CN43302-WA-17 and
   N01-CN43302-WA-27) to W.S. El-Deiry. W.S. El-Deiry is an American Cancer
   Society Research Professor.
NR 31
TC 16
Z9 16
U1 1
U2 11
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 SEP 15
PY 2015
VL 75
IS 18
BP 3842
EP 3852
DI 10.1158/0008-5472.CAN-13-1079
PG 11
WC Oncology
SC Oncology
GA CU2EJ
UT WOS:000363335800019
PM 26294215
ER

PT J
AU Mehta, A
   Zhang, LS
   Boufraqech, M
   Liu-Chittenden, Y
   Zhang, YQ
   Patel, D
   Davis, S
   Rosenberg, A
   Ylaya, K
   Aufforth, R
   Li, ZY
   Shen, M
   Kebebew, E
AF Mehta, Amit
   Zhang, Lisa
   Boufraqech, Myriem
   Liu-Chittenden, Yi
   Zhang, Yaqin
   Patel, Dhaval
   Davis, Sean
   Rosenberg, Avi
   Ylaya, Kris
   Aufforth, Rachel
   Li, Zhuyin
   Shen, Min
   Kebebew, Electron
TI Inhibition of Survivin with YM155 Induces Durable Tumor Response in
   Anaplastic Thyroid Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; SMALL-MOLECULE SUPPRESSOR; PHASE-II; HIGH EFFICACY;
   CARCINOMA; CLASPIN; DOCETAXEL; AUTOPHAGY; LYMPHOMA; DRUGS
AB Purpose:<bold> </bold>Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy without any effective therapy. The aim of this study is to use a high-throughput drug library screening to identify a novel therapeutic agent that targets dysregulated genes/pathways in ATC.
   Experimental Design: <bold> </bold>We performed quantitative high-throughput screening (qHTS) in ATC cell lines using a compound library of 3,282 drugs. Dysregulated genes in ATC were analyzed using genome-wide expression analysis and immunohistochemistry in human ATC tissue samples and ATC cell lines. In vitro and in vivo studies were performed for determining drug activity, effectiveness of targeting, and the mechanism of action.
   Results:<bold> </bold>qHTS identified 100 active compounds in three ATC cell lines. One of the most active agents was the first-in-class survivin inhibitor YM155. Genome-wide expression analysis and immunohistochemistry showed overexpression of survivin in human ATC tissue samples, and survivin was highly expressed in all ATC cell lines tested. YM155 significantly inhibited ATC cellular proliferation. Mechanistically, YM155 inhibited survivin expression in ATC cells. Furthermore, YM155 treatment reduced claspin expression, which was associated with S-phase arrest in ATC cells. In vivo, YM155 significantly inhibited growth and metastases and prolonged survival.
   Conclusions:<bold> </bold>Our data show that YM155 is a promising anticancer agent for ATC and that its target, survivin, is overexpressed in ATC. Our findings support the use of YM155 in clinical trials as a therapeutic option in advanced and metastatic ATC. (C) 2015 AACR.
C1 [Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Liu-Chittenden, Yi; Patel, Dhaval; Aufforth, Rachel; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Mehta, Amit] Geisel Sch Med Dartmouth, Hanover, NH USA.
   [Zhang, Yaqin; Li, Zhuyin; Shen, Min] NIH, Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
   [Davis, Sean] NCI, Canc Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Rosenberg, Avi; Ylaya, Kris] NCI, Lab Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Room 4-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Boufraqech, Myriem/E-4823-2016; 
OI Liu-Chittenden, Yi/0000-0001-6357-5360; Rosenberg,
   Avi/0000-0003-2356-950X; Patel, Dhaval/0000-0002-5744-568X
FU Intramural Research Program of the Center for Cancer Research, National
   Cancer Institute, NIH; NIH
FX This research was supported by the Intramural Research Program of the
   Center for Cancer Research, National Cancer Institute, NIH and by the
   NIH. Medical Research Scholars Program, a public private partnership
   supported jointly by the NIH; and by the generous contributions to the
   Foundation for NIH from Pfizer, the Doris Duke Charitable Foundation,
   Alexandria Real Estate Equities, Inc.; Mr. and Mrs Joel S. Marcus, the
   Howard Hughes Medical Institute, and other private donors. For a
   complete list of donors, please visit the Foundation website at
   hap://fnih.org/workieducation-training-0/medical-research scholars
   program.
NR 34
TC 9
Z9 9
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 15
PY 2015
VL 21
IS 18
BP 4123
EP 4132
DI 10.1158/1078-0432.CCR-14-3251
PG 10
WC Oncology
SC Oncology
GA CU2CN
UT WOS:000363329900013
PM 25944801
ER

PT J
AU Tang, SW
   Bilke, S
   Cao, L
   Murai, J
   Sousa, FG
   Yamade, M
   Rajapakse, V
   Varma, S
   Helman, LJ
   Khan, J
   Meltzer, PS
   Pommier, Y
AF Tang, Sai-Wen
   Bilke, Sven
   Cao, Liang
   Murai, Junko
   Sousa, Fabricio G.
   Yamade, Mihoko
   Rajapakse, Vinodh
   Varma, Sudhir
   Helman, Lee J.
   Khan, Javed
   Meltzer, Paul S.
   Pommier, Yves
TI SLFN11 is a Transcriptional Target of EWS-FLI1 and a Determinant of Drug
   Response in Ewing Sarcoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID FACTOR-BINDING PROFILES; OPEN-ACCESS DATABASE; CELLS IN-VITRO;
   ECTEINASCIDIN 743; PROSTATE-CANCER; GENE-EXPRESSION; BMN 673; FAMILY;
   GROWTH; INHIBITION
AB Purpose:<bold> </bold>SLFN11 was identified as a critical determinant of response to DNA-targeted therapies by analyzing gene expression and drug sensitivity of NCI-60 and CCLE datasets. However, how SLFN11 is regulated in cancer cells remained unknown. Ewing sarcoma, which is characterized by the chimeric transcription factor EWS-FLI1, has notably high SLFN11 expression, leading us to investigate whether EWS-FLI1 drives SLFN11 expression and the role of SLFN11 in the drug response of Ewing sarcoma cells.
   Experimental Design:<bold> </bold>Binding sites of EWS-FLI1 on the SLFN11 promoter were analyzed by chromatin immunoprecipitation sequencing and promoter-luciferase reporter analyses. The relationship between SLFN11 and EWS-FLI1 were further examined in EWS-FLI1-knockdown or -overexpressing cells and in clinical tumor samples.
   Results:<bold> </bold>EWS-FLI1 binds near the transcription start site of SLFN11 promoter and acts as a positive regulator of SLFN11 expression in Ewing sarcoma cells. EWS-FLI1-mediated SLFN11 expression is responsible for high sensitivity of Ewing sarcoma to camptothecin and combinations of PARP inhibitors with temozolomide. Importantly, Ewing sarcoma patients with higher SLFN11 expression showed better tumor-free survival rate. The correlated expression between SLFN11 and FLI1 extends to leukemia, pediatric, colon, breast, and prostate cancers. In addition, expression of other ETS members correlates with SLFN11 in NCI-60 and CCLE datasets, and molecular experiments demonstrate that ETS1 acts as a positive regulator for SLFN11 expression in breast cancer cells.
   Conclusions: Our results imply the emerging relevance of SLFN11 as an ETS transcription factor response gene and for therapeutic response to topoisomerase I inhibitors and temozolomide-PARP inhibitor combinations in ETS-activated cancers. (C) 2015 AACR.
C1 [Tang, Sai-Wen; Murai, Junko; Sousa, Fabricio G.; Yamade, Mihoko; Rajapakse, Vinodh; Varma, Sudhir; Pommier, Yves] NCI, Mol Pharmacol Lab, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
   [Bilke, Sven; Cao, Liang; Khan, Javed; Meltzer, Paul S.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Sousa, Fabricio G.] Univ Fed Mato Grosso do Sul, CETROGEN, PPGFARM, Campo Grande, Brazil.
   [Helman, Lee J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, NIH, 37 Convent Dr,Room 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
RI Khan, Javed/P-9157-2014; Sousa, Fabricio/O-8878-2015
OI Khan, Javed/0000-0002-5858-0488; Sousa, Fabricio/0000-0003-0444-754X
FU Center for Cancer Research Intramural NCI program [Z01 BC 006150]
FX This work was supported by the Center for Cancer Research Intramural NCI
   program (Z01 BC 006150).
NR 47
TC 12
Z9 12
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 15
PY 2015
VL 21
IS 18
BP 4184
EP 4193
DI 10.1158/1078-0432.CCR-14-2112
PG 10
WC Oncology
SC Oncology
GA CU2CN
UT WOS:000363329900019
PM 25779942
ER

PT J
AU Hirbe, AC
   Dahiya, S
   Miller, CA
   Li, TD
   Fulton, RS
   Zhang, XC
   McDonald, S
   DeSchryver, K
   Duncavage, EJ
   Walrath, J
   Reilly, KM
   Abel, HJ
   Pekmezci, M
   Perry, A
   Ley, TJ
   Gutmann, DH
AF Hirbe, Angela C.
   Dahiya, Sonika
   Miller, Christopher A.
   Li, Tiandao
   Fulton, Robert S.
   Zhang, Xiaochun
   McDonald, Sandra
   DeSchryver, Katherine
   Duncavage, Eric J.
   Walrath, Jessica
   Reilly, Karlyne M.
   Abel, Haley J.
   Pekmezci, Melike
   Perry, Arie
   Ley, Timothy J.
   Gutmann, David H.
TI Whole Exome Sequencing Reveals the Order of Genetic Changes during
   Malignant Transforma177: and Metastasis in a Single Patient with
   NF1-plexiform Neurofibroma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NERVE SHEATH TUMORS; SPINDLE-CELL NEOPLASMS; ATAXIA TYPE 5; CANCER
   GENOMICS; SCHWANN-CELLS; MOUSE MODEL; TYPE-1; NF1; SPECTRIN; EXPRESSION
AB Purpose:<bold> </bold>Malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in individuals with neurofibromatosis type 1 (NF1), where they likely arise from benign plexiform neurofibroma precursors. While previous studies have used a variety of discovery approaches to discover genes associated with MPNST pathogenesis, it is currently unclear what molecular events are associated with the evolution of MPNST from plexiform neurofibroma.
   Experimental Design:<bold> </bold>Whole-exome sequencing was performed on biopsy materials representing plexiform neurofibroma (n = 3), MPNST, and metastasis from a single individual with NF1 over a 14-year period. Additional validation cases were used to assess candidate genes involved in malignant progression, while a murine MPNST model was used for functional analysis.
   Results: There was an increasing proportion of cells with a somatic NF1 gene mutation as the tumors progressed from benign to malignant, suggesting a clonal process in MPNST development. Copy number variations, including loss of one copy of the TP53 gene, were identified in the primary tumor and the metastatic lesion, but not in benign precursor lesions. A limited number of genes with nonsynonymous somatic mutations (beta(III)-spectrin and ZNF208) were discovered, several of which were validated in additional primary and metastatic MPNST samples. Finally, increased beta III-spectrin expression was observed in the majority of MPNSTs, and shRNA-mediated knockdown reduced murine MPNST growth in vivo.
   Conclusions: Collectively, the ability to track the molecular evolution of MPNST in a single individual with NF1 offers new insights into the sequence of genetic events important for disease pathogenesis and progression for future mechanistic study. (C) 2015 AACR.
C1 [Hirbe, Angela C.] Washington Univ, Sch Med, Div Med Oncol, Dept Med, St Louis, MO 63110 USA.
   [Dahiya, Sonika; Zhang, Xiaochun; McDonald, Sandra; DeSchryver, Katherine; Duncavage, Eric J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Miller, Christopher A.; Li, Tiandao; Fulton, Robert S.; Ley, Timothy J.] Washington Univ, Dept Genet, Genome Inst, St Louis, MO 63110 USA.
   [Walrath, Jessica; Reilly, Karlyne M.] NCI, Rare Tumors Initiat, Bethesda, MD 20892 USA.
   [Walrath, Jessica; Reilly, Karlyne M.] Div Stat Genom, St Louis, MO USA.
   [Abel, Haley J.] UCSF Sch Med, Dept Pathol, San Francisco, CA USA.
   [Pekmezci, Melike; Perry, Arie] UCSF Sch Med, Neurol Surg, San Francisco, CA USA.
   [Perry, Arie; Gutmann, David H.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
RP Gutmann, DH (reprint author), Washington Univ, Sch Med, 660 S Euclid Ave,Campus Box 8111, St Louis, MO 63110 USA.
EM gutmannd@neuro.wustl.edu
RI Li, Tiandao/F-4039-2012
OI Li, Tiandao/0000-0003-1650-0555
FU NIH [P50 CA094056]; Neuroscience Blueprint Core [NIH P30 NS057105]; 
   [T32 HL007088]
FX This work was partly funded by a generous gift from Schnuck Markets Inc.
   (to D.H. Gutmann). A.C. Hirbe was supported on the T32 HL007088. BLI was
   performed at the Washington University Molecular Imaging Center,
   supported by NIH P50 CA094056. Lentivirus was generated by the
   Washington University Hope Center Viral Vectors Core, which is supported
   by a Neuroscience Blueprint Core grant NIH P30 NS057105.
NR 63
TC 7
Z9 7
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 15
PY 2015
VL 21
IS 18
BP 4201
EP 4211
DI 10.1158/1078-0432.CCR-14-3049
PG 11
WC Oncology
SC Oncology
GA CU2CN
UT WOS:000363329900021
PM 25925892
ER

PT J
AU Villanueva, H
   Visbal, AP
   Obeid, NF
   Ta, AQ
   Faruki, AA
   Wu, MF
   Hilsenbeck, SG
   Shaw, CA
   Yu, P
   Plummer, NW
   Birnbaumer, L
   Lewis, MT
AF Villanueva, Hugo
   Visbal, Adriana P.
   Obeid, Nadine F.
   Ta, Andrew Q.
   Faruki, Adeel A.
   Wu, Meng-Fen
   Hilsenbeck, Susan G.
   Shaw, Chad A.
   Yu, Peng
   Plummer, Nicholas W.
   Birnbaumer, Lutz
   Lewis, Michael T.
TI An essential role for G alpha(i2) in Smoothened-stimulated epithelial
   cell proliferation in the mammary gland
SO SCIENCE SIGNALING
LA English
DT Article
ID HEDGEHOG SIGNALING PATHWAY; HETEROTRIMERIC G-PROTEINS; BREAST-CANCER;
   ACTIVATION; MUTATIONS; MICE; MORPHOGENESIS; MECHANISMS; EXPRESSION;
   NEOPLASIA
AB Hedgehog (Hh) signaling is critical for organogenesis, tissue homeostasis, and stem cell maintenance. The gene encoding Smoothened (SMO), the primary effector of Hh signaling, is expressed aberrantly in human breast cancer, as well as in other cancers. In mice that express a constitutively active form of SMO that does not require Hh stimulation in mammary glands, the cells near the transgenic cells proliferate and participate in hyperplasia formation. Although SMO is a seven-transmembrane receptor like G protein-coupled receptors (GPCRs), SMO-mediated activation of the Gli family of transcription factors is not known to involve G proteins. However, data from Drosophila and mammalian cell lines indicate that SMO functions as a GPCR that couples to heterotrimeric G proteins of the pertussis toxin (PTX)-sensitive G alpha(i) class. Using genetically modified mice, we demonstrated that SMO signaling through G proteins occurred in the mammary gland in vivo. SMO-induced stimulation of proliferation was PTX-sensitive and required G alpha(i2), but not G alpha(i1), G alpha(i3), or activation of Gli1 or Gli2. Our findings show that activated SMO functions as a GPCR to stimulate proliferation in vivo, a finding that may have clinical importance because most SMO-targeted agents have been selected based largely on their ability to block Gli-mediated transcription.
C1 [Villanueva, Hugo; Visbal, Adriana P.; Lewis, Michael T.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Villanueva, Hugo; Visbal, Adriana P.; Obeid, Nadine F.; Ta, Andrew Q.; Faruki, Adeel A.; Wu, Meng-Fen; Hilsenbeck, Susan G.; Lewis, Michael T.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
   [Hilsenbeck, Susan G.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   [Shaw, Chad A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Yu, Peng] Texas A&M Univ, TEES AgriLife Ctr Bioinformat & Genom Syst Engn, Dept Elect & Comp Engn, College Stn, TX 77843 USA.
   [Plummer, Nicholas W.; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   [Lewis, Michael T.] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA.
RP Lewis, MT (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
EM mtlewis@bcm.edu
FU Genomic and RNA Profiling Core at Baylor College of Medicine; NIH
   National Cancer Institute [P30CA125123]; Intramural Research Program of
   the NIH [Z01-ES-101643]; NIH [R01CA127857, U54-CA149196, 1F31CA159774,
   CA125123]
FX This project was supported in part by the Genomic and RNA Profiling Core
   at Baylor College of Medicine with funding from the NIH National Cancer
   Institute (grant P30CA125123) and the expert assistance of L. D. White.
   The research presented in this article was supported in part by the
   Intramural Research Program of the NIH (Z01-ES-101643 to L.B.) and NIH
   grants R01CA127857 and U54-CA149196 (to M.T.L.), 1F31CA159774 (to H.V.),
   and CA125123 (Dan L. Duncan Cancer Center Shared Resources).
NR 41
TC 3
Z9 3
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD SEP 15
PY 2015
VL 8
IS 394
AR ra92
DI 10.1126/scisignal.aaa7355
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CU1YB
UT WOS:000363317200002
PM 26373672
ER

PT J
AU Verma, SK
   Calero-Bernal, R
   Lovallo, MJ
   Sweeny, AR
   Grigg, ME
   Dubey, JP
AF Verma, S. K.
   Calero-Bernal, R.
   Lovallo, M. J.
   Sweeny, A. R.
   Grigg, M. E.
   Dubey, J. P.
TI Detection of Sarcocystis spp. infection in bobcats (Lynx rufus)
SO VETERINARY PARASITOLOGY
LA English
DT Article
DE Bobcat (Lynx rufus); S. neurona; S. fells; S. dasypi; Sarcocysts;
   PCR-DNA sequencing
ID ARMADILLOS DASYPUS-NOVEMCINCTUS; 9-BANDED ARMADILLO; NEURONA;
   PREVALENCE; ENCEPHALOMYELITIS; CAT
AB The protozoan Sarcocystis neurona is an important cause of severe clinical disease of horses (called equine protozoal myeloencephalitis, EPM), marine mammals, companion animals, and several species of wildlife animals in the Americas. The Virginia opossum (Didelphis virginiana) is its definitive host in the USA and other animals act as intermediate or aberrant hosts. Samples of tongue and heart from 35 bobcats hunted for fur and food from Mississippi State, USA in February, 2014 were used for the present study. Muscles were examined for Sarcocystis infection by microscopic examination of either unfixed muscle squash preparations or pepsin digests, by histopathology of fixed samples, and by molecular methods. Sarcotystis-like bradyzoites were found in digests of 14 hearts and 10 tongues of 35 bobcats. In histological sections, sarcocysts were found in 26 of 35 bobcats; all appeared relatively thin-walled similar to S. felis sarcocysts under light microscope at 1000x magnification. S. neurona-like sarcocysts having thickened villar tips were seen in unstained muscle squash of tongue of two bobcats and PCR-DNA sequencing identified them definitively as S. neurona-like parasites. DNA extracted from bradyzoites obtained from tongue and heart muscle digests was analyzed by PCR-DNA sequencing at the ITS1 locus. Results indicated the presence of S. neurona-like parasite in 26 of 35 samples. ITS1 sequences identical to S. dasypi were identified in 3 bobcats, 2 of which were also co-infected with S. neurona-like parasite. The high prevalence of sarcocysts in bobcat tissues suggested an efficient sylvatic cycle of Sarcocystis spp. in the remote regions of Mississippi State with the bobcat as a relevant intermediate host. Published by Elsevier B.V.
C1 [Verma, S. K.; Calero-Bernal, R.; Dubey, J. P.] ARS, USDA, Beltsville Agr Res Ctr, Anim Parasit Dis Lab, Beltsville, MD 20705 USA.
   [Lovallo, M. J.] Penn Game Commiss, Game Mammals Sect, Bur Wildlife Management, Harrisburg, PA 17110 USA.
   [Sweeny, A. R.; Grigg, M. E.] NIAID, Mol Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Dubey, JP (reprint author), ARS, USDA, Beltsville Agr Res Ctr, Anim Parasit Dis Lab, Bldg 1001, Beltsville, MD 20705 USA.
EM Jitender.Dubey@ars.usda.gov
FU Department of Employment and Innovation of the Regional Government of
   Extremadura (Spain) [PO12010]; European Social Fund; Intramural Research
   Program of the NIH and NIAID
FX R. Calero-Bernal is a postdoctoral fellow (Ref. PO12010) funded by the
   Department of Employment and Innovation of the Regional Government of
   Extremadura (Spain) and the European Social Fund. This study was
   financially support in part by the Intramural Research Program of the
   NIH and NIAID. M.E.G. is a scholar of the Canadian Institute for
   Advanced Research Integrated Microbial Biodiversity Program.
NR 20
TC 1
Z9 1
U1 2
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4017
EI 1873-2550
J9 VET PARASITOL
JI Vet. Parasitol.
PD SEP 15
PY 2015
VL 212
IS 3-4
BP 422
EP 426
DI 10.1016/j.vetpar.2015.06.007
PG 5
WC Parasitology; Veterinary Sciences
SC Parasitology; Veterinary Sciences
GA CU2LQ
UT WOS:000363355400056
PM 26138150
ER

PT J
AU Pozios, I
   Corona-Villalobos, C
   Sorensen, LL
   Bravo, PE
   Canepa, M
   Pisanello, C
   Pinheiro, A
   Dimaano, VL
   Luo, HC
   Dardari, Z
   Zhou, X
   Kamel, I
   Zimmerman, SL
   Bluemke, DA
   Abraham, MR
   Abraham, TP
AF Pozios, Iraklis
   Corona-Villalobos, Celia
   Sorensen, Lars L.
   Bravo, Paco E.
   Canepa, Marco
   Pisanello, Chiara
   Pinheiro, Aurelio
   Dimaano, Veronica L.
   Luo, Hongchang
   Dardari, Zeina
   Zhou, Xun
   Kamel, Ihab
   Zimmerman, Stefan L.
   Bluemke, David A.
   Abraham, M. Roselle
   Abraham, Theodore P.
TI Comparison of Outcomes in Patients With Nonobstructive,
   Labile-Obstructive, and Chronically Obstructive Hypertrophic
   Cardiomyopathy
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID OUTFLOW TRACT OBSTRUCTION; CARDIOVASCULAR MAGNETIC-RESONANCE;
   IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; POSITRON-EMISSION-TOMOGRAPHY;
   SUDDEN-DEATH; AMERICAN-SOCIETY; DELAYED ENHANCEMENT; OF-CARDIOLOGY;
   ECHOCARDIOGRAPHY; RECOMMENDATIONS
AB Patients with nonobstructive hypertrophic cardiomyopathy (HC) are considered low risk, generally not requiring aggressive intervention. However, nonobstructive and labile-obstructive HC have been traditionally classified together, and it is unknown if these 2 subgroups have distinct risk profiles. We compared cardiovascular outcomes in 293 patients HC (96 nonobstructive, 114 labile-obstructive, and 83 obstructive) referred for exercise echocardiography and magnetic resonance imaging and followed for 3.3 +/- 3.6 years. A subgroup (34 nonobstructive, 28 labile-obstructive, 21 obstructive) underwent positron emission tomography. The mean number of sudden cardiac death risk factors was similar among groups (nonobstructive: 1.4 vs labile-obstructive: 1.2 vs obstructive: 1.4 risk factors, p = 0.2). Prevalence of late gadolinium enhancement (LGE) was similar across groups but more non-obstructive patients had late gadolinium enhancement >= 20% of myocardial mass (23 [30%] vs 19 [18%] labile-obstructive and 8 [11%] obstructive, p = 0.01]. Fewer labile-obstructive patients had regional positron emission tomography perfusion abnormalities (12 [46%] vs nonobstructive 30 [81%] and obstructive 17 [85%], p = 0.003]. During follow-up, 60 events were recorded (36 ventricular tachycardia/ventricular fibrillation, including 30 defibrillator discharges, 12 heart failure worsening, and 2 deaths). Nonobstructive patients were at greater risk of VT/VF at follow-up, compared to labile obstructive (hazed ratio 0.18, 95% confidence interval 0.04 to 0.84, p = 0.03) and the risk persisted after adjusting for age, gender, syncope, family history of sudden cardiac death, abnormal blood pressure response, and septum >= 3 cm (p = 0.04). Appropriate defibrillator discharges were more frequent in nonobstructive (8 [18%]) compared to labile-obstructive (0 [0%], p = 0.02) patients. In conclusion, nonobstructive hemodynamics is associated with more pronounced fibrosis and ischemia than labile-obstructive and is an independent predictor of VT/VF in HC. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Pozios, Iraklis; Sorensen, Lars L.; Canepa, Marco; Pisanello, Chiara; Pinheiro, Aurelio; Dimaano, Veronica L.; Luo, Hongchang; Dardari, Zeina; Zhou, Xun; Abraham, M. Roselle; Abraham, Theodore P.] Johns Hopkins HCM Ctr Excellence, Baltimore, MD 21287 USA.
   [Corona-Villalobos, Celia; Bravo, Paco E.; Kamel, Ihab; Zimmerman, Stefan L.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
   [Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Abraham, TP (reprint author), Johns Hopkins HCM Ctr Excellence, Baltimore, MD 21287 USA.
EM tabraha3@jhmi.edu
OI Dardari, Zeina/0000-0001-6026-3329; Bluemke, David/0000-0002-8323-8086
FU Dr. Lawrence and Sheila Pakula Foundation; Hypertrophic Cardiomyopathy
   Association
FX The authors thank the sonographers/technologists and nurses of the Johns
   Hopkins Echocardiography and CMR laboratories for their contributions.
   The authors appreciate support from the Dr. Lawrence and Sheila Pakula
   Foundation and the Hypertrophic Cardiomyopathy Association.
NR 30
TC 2
Z9 2
U1 1
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 15
PY 2015
VL 116
IS 6
BP 938
EP 944
DI 10.1016/j.amjcard.2015.06.018
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8ZU
UT WOS:000361643800018
PM 26239580
ER

PT J
AU Lazo-Fernandez, Y
   Aguilera, G
   Pham, TD
   Park, AY
   Beierwaltes, WH
   Sutliff, RL
   Verlander, JW
   Pacak, K
   Osunkoya, AO
   Ellis, CL
   Kim, YH
   Shipley, GL
   Wynne, BM
   Hoover, RS
   Sen, SK
   Plotsky, PM
   Wall, SM
AF Lazo-Fernandez, Yoskaly
   Aguilera, Greti
   Pham, Truyen D.
   Park, Annie Y.
   Beierwaltes, William H.
   Sutliff, Roy L.
   Verlander, Jill W.
   Pacak, Karel
   Osunkoya, Adeboye O.
   Ellis, Carla L.
   Kim, Young Hee
   Shipley, Gregory L.
   Wynne, Brandi M.
   Hoover, Robert S.
   Sen, Shurjo K.
   Plotsky, Paul M.
   Wall, Susan M.
TI Pendrin localizes to the adrenal medulla and modulates catecholamine
   release
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE pendrin; chloride; epinephrine; norepinephrine; dopamine
ID CORTICAL COLLECTING DUCT; INTERCALATED CELLS; MOUSE KIDNEY; BICARBONATE
   SECRETION; ANION-EXCHANGER; PLASMA-RENIN; NULL MICE; RAT; SLC26A4;
   HYPERTENSION
AB Pendrin (Slc26a4) is a Cl-/HCO3-exchanger expressed in renal intercalated cells and mediates renal Cl-absorption. With pendrin gene ablation, blood pressure and vascular volume fall, which increases plasma renin concentration. However, serum aldosterone does not significantly increase in pendrin-null mice, suggesting that pendrin regulates adrenal zona glomerulosa aldosterone production. Therefore, we examined pendrin expression in the adrenal gland using PCR, immunoblots, and immunohistochemistry. Pendrin protein was detected in adrenal lysates from wild-type but not pendrin-null mice. However, immunohistochemistry and qPCR of microdissected adrenal zones showed that pendrin was expressed in the adrenal medulla, rather than in cortex. Within the adrenal medulla, pendrin localizes to both epinephrine-and norepinephrine-producing chromaffin cells. Therefore, we examined plasma catecholamine concentration and blood pressure in wild-type and pendrin-null mice under basal conditions and then after 5 and 20 min of immobilization stress. Under basal conditions, blood pressure was lower in the mutant than in the wild-type mice, although epinephrine and norepinephrine concentrations were similar. Catecholamine concentration and blood pressure increased markedly in both groups with stress. With 20 min of immobilization stress, epinephrine and norepinephrine concentrations increased more in pendrin-null than in wild-type mice, although stress produced a similar increase in blood pressure in both groups. We conclude that pendrin is expressed in the adrenal medulla, where it blunts stress-induced catecholamine release.
C1 [Lazo-Fernandez, Yoskaly; Pham, Truyen D.; Park, Annie Y.; Sutliff, Roy L.; Kim, Young Hee; Wynne, Brandi M.; Hoover, Robert S.; Wall, Susan M.] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA.
   [Aguilera, Greti] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD USA.
   [Beierwaltes, William H.] Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA.
   [Beierwaltes, William H.] Wayne State Sch Med, Detroit, MI USA.
   [Sutliff, Roy L.; Hoover, Robert S.] Atlanta Vet Affairs Hosp, Atlanta, GA USA.
   [Verlander, Jill W.] Univ Florida, Dept Med, Gainesville, FL USA.
   [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
   [Osunkoya, Adeboye O.; Ellis, Carla L.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
   [Shipley, Gregory L.] Univ Texas Med Sch Houston, Dept Integrat Biol & Pharmacol, Houston, TX USA.
   [Sen, Shurjo K.] Cardiovasc Dis Sect, Bethesda, MD USA.
   [Sen, Shurjo K.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Plotsky, Paul M.] Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA.
   [Hoover, Robert S.; Wall, Susan M.] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA.
RP Wall, SM (reprint author), Emory Univ, Sch Med, Div Renal, WMB Rm 338,1639 Pierce Dr NE, Atlanta, GA 30322 USA.
EM smwall@emory.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
   [DK-46493, DK-085097, T32 DK-07656]; National Institute of Child Health
   and Human Development, Intramural Research Program
FX This study was supported by National Institute of Diabetes and Digestive
   and Kidney Diseases grants DK-46493 (to S. M. Wall), DK-085097 (to R. S.
   Hoover), and T32 DK-07656 (to Y. Lazo-Fernandez, B. M. Wynne,. and A. Y.
   Park). This work was also supported by the National Institute of Child
   Health and Human Development, Intramural Research Program (G. Aguilera
   and K. Pacak).
NR 44
TC 7
Z9 7
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD SEP 15
PY 2015
VL 309
IS 6
BP E534
EP E545
DI 10.1152/ajpendo.00035.2015
PG 12
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA CS1II
UT WOS:000361817000004
PM 26173457
ER

PT J
AU Griffith, DE
   Adjemian, J
   Brown-Elliott, BA
   Philley, JV
   Prevots, DR
   Gaston, C
   Olivier, KN
   Wallace, RJ
AF Griffith, David E.
   Adjemian, Jennifer
   Brown-Elliott, Barbara A.
   Philley, Julie V.
   Prevots, D. Rebecca
   Gaston, Christopher
   Olivier, Kenneth N.
   Wallace, Richard J., Jr.
TI Semiquantitative Culture Analysis during Therapy for Mycobacterium avium
   Complex Lung Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE Mycobacterium avium complex; mycobacterial cultures; mycobacterial
   therapy
ID QUALITY-OF-LIFE; CYSTIC-FIBROSIS; BRONCHIECTASIS; TUBERCULOSIS;
   REGIMENS; AZITHROMYCIN; DIAGNOSIS; PULMONARY; IMPROVES
AB Rationale: Microbiologically based criteria such as sputum culture conversion to negative have traditionally been used to define treatment. success for mycobacterial diseases. There are, however, limited data regarding whether nontuberculous mycobacterial sputum culture conversion or semiquantitative culture analysis correlates with subjective or nonmicrobiologic objective indices of treatment response.
   Objectives: To determine whether a semiquantitative mycobacterial culture scale correlated with clinical disease status and was predictive of long-term sputum mycobacterial culture conversion to negative in a cohort of patients with nodular/bronchiectatic Mycobacterium avium complex lung disease undergoing therapy.
   Methods: One hundred and eighty patients undergoing standard macrolide-based therapy for M. avium complex lung disease were monitored at standard frequent intervals with symptomatic, radiographic, and microbiologic data collected, including semiquantitative mycobacterial culture analysis. Analyses were used to evaluate clinical and microbiologic predictors of long-term sputum conversion to culture negative.
   Measurements and Main Results: After 12 months of therapy, 148 (82%) patients had sputum conversion to culture negative. Baseline semiquantitative sputum culture scores did not differ between patients with sputum conversion and those without. The change in sputum culture semiquantitative score from baseline to Month 3 was highly predictive of subsequent sputum long-term conversion status indicative of treatment success, as was improvement in cough, and especially early radiographic improvement.
   Conclusions: Early semiquantitative sputum agar plate culture results can be used to predict symptomatic and radiographic improvement as well as long-term sputum culture conversion to negative in this population. We suggest that semiquantitative sputum culture scores can be a useful tool for evaluating new nontuberculous mycobacterial lung disease therapies.
C1 [Griffith, David E.; Brown-Elliott, Barbara A.; Philley, Julie V.; Gaston, Christopher; Wallace, Richard J., Jr.] Univ Texas Hlth Ctr Tyler, Tyler, TX USA.
   [Adjemian, Jennifer; Prevots, D. Rebecca] NIAID, NIH, Bethesda, MD 20892 USA.
   [Adjemian, Jennifer] US Publ Hlth Serv Commissioned Corp, Rockville, MD USA.
   [Olivier, Kenneth N.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Griffith, DE (reprint author), 11937 US Highway 271, Tyler, TX 75708 USA.
EM david.griffith@uthct.edu
FU University of Texas Health Science Center, Tyler; Amon Carter
   Foundation; Moncrief Foundation; Division of Intramural Research,
   National Institute of Allergy and Infectious Diseases
FX Supported in part by institutional funds from the University of Texas
   Health Science Center, Tyler, the Amon Carter Foundation (R.J.W.), the
   Moncrief Foundation (D.E.G.), and the Division of Intramural Research,
   National Institute of Allergy and Infectious Diseases (J.A. and D.R.P.).
NR 22
TC 9
Z9 9
U1 1
U2 1
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD SEP 15
PY 2015
VL 192
IS 6
BP 754
EP 760
DI 10.1164/rccm.201503-0444OC
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CR5YN
UT WOS:000361420400018
PM 26068042
ER

PT J
AU Fang, ZZ
   Tosh, DK
   Tanaka, N
   Wang, H
   Krausz, KW
   O'Connor, R
   Jacobson, KA
   Gonzalez, FJ
AF Fang, Zhong-Ze
   Tosh, Dilip K.
   Tanaka, Naoki
   Wang, Haina
   Krausz, Kristopher W.
   O'Connor, Robert
   Jacobson, Kenneth A.
   Gonzalez, Frank J.
TI Metabolic mapping of A(3) adenosine receptor agonist MRS5980
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE A(3) adenosine receptor (AR); MRS5980; Metabolomics; Electrophilies
ID PPAR-ALPHA; BIOACTIVATION; INHIBITOR; PHOSPHATIDYLCHOLINE;
   HEPATOTOXICITY; KETOCONAZOLE; ACTIVATION; NOSCAPINE; CYP3A4; PAIN
AB (1S,2R,3S,4R,5S)-4-(2-((5-Chlorothiophen-2-ypethyny1)-6-(methylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide (MRS5980) is an A(3)AR selective agonist containing multiple receptor affinity- and selectivity-enhancing modifications and a therapeutic candidate drug for many inflammatory diseases. Metabolism-related poor pharmacokinetic behavior and toxicities are a major reason for drug R&D failure. Metabolomics with UPLC-MS was employed to profile the metabolism of MRS5980 and MRS5980-induced disruption of endogenous compounds. Recombinant drug-metabolizing enzymes screening experiment were used to determine the enzymes involved in MRS5980 metabolism. Analysis of lipid metabolism-related genes was performed to investigate the reason for MRS5980-induced lipid metabolic disorders. Unsupervised principal components analysis separated the control and MRS5980 treatment groups in feces, urine, and liver samples, but not in bile and serum. The major ions mainly contributing to the separation of feces and urine were oxidized MRS5980, glutathione (GSH) conjugates and cysteine conjugate (degradation product of the GSH conjugates) of MRS5980. The major ions contributing to the group separation of liver samples were phosphatidylcholines. In vitro incubation experiments showed the involvement of CYP3A enzymes in the oxidative metabolism of MRS5980 and direct GSH reactivity of MRS5980. The electrophilic attack by MRS5980 is a minor pathway and did not alter GSH levels in liver or liver histology, and thus may be of minor clinical consequence. Gene expression analysis further showed decreased expression of PC biosynthetic genes choline kinase a and b, which further accelerated conversion of lysophosphatidylcholine to phosphatidylcholines through increasing the expression of lysophosphatidylcholine acyltransferase 3. These data will be useful to guide rational design of drugs targeting A(3)AR, considering efficacy, metabolic elimination, and electrophilic reactivity. Published by Elsevier Inc.
C1 [Fang, Zhong-Ze; Tanaka, Naoki; Wang, Haina; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Tosh, Dilip K.; O'Connor, Robert; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Fang, Zhong-Ze] Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin 300070, Peoples R China.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov; gonzalef@mail.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural Research Programs of the Center for Cancer Research; National
   Cancer Institute; National Institute of Diabetes and Digestive and
   Kidney Diseases, National Institutes of Health; National Natural Science
   Foundation of China [81202586]; Tianjin Project of Thousand Youth
   Talents
FX This study was funded by the Intramural Research Programs of the Center
   for Cancer Research, National Cancer Institute and the National
   Institute of Diabetes and Digestive and Kidney Diseases, National
   Institutes of Health, the National Natural Science Foundation of China
   (No. 81202586), and Tianjin Project of Thousand Youth Talents.
NR 27
TC 2
Z9 2
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD SEP 15
PY 2015
VL 97
IS 2
BP 215
EP 223
DI 10.1016/j.bcp.2015.07.007
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CR9AD
UT WOS:000361644700009
PM 26212548
ER

PT J
AU Nussinov, R
   Tsai, CJ
AF Nussinov, Ruth
   Tsai, Chung-Jung
TI The Role of Allostery in the Termination of Second Messenger Signaling
SO BIOPHYSICAL JOURNAL
LA English
DT News Item
ID MASS-SPECTROMETRY
C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
EM nussinor@helix.nih.gov
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; NCI NIH HHS
   [HHSN261200800001E]; PHS HHS [HHSN261200800001E]
NR 9
TC 0
Z9 0
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD SEP 15
PY 2015
VL 109
IS 6
BP 1080
EP 1081
DI 10.1016/j.bpj.2015.07.007
PG 2
WC Biophysics
SC Biophysics
GA CR7XM
UT WOS:000361565400003
PM 26248688
ER

PT J
AU Guven-Maiorov, E
   Keskin, O
   Gursoy, A
   Nussinov, R
AF Guven-Maiorov, Emine
   Keskin, Ozlem
   Gursoy, Attila
   Nussinov, Ruth
TI A Structural View of Negative Regulation of the Toll-like
   Receptor-Mediated Inflammatory Pathway
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; KAPPA-B ACTIVATION; SIGNALING PATHWAYS; I
   INTERFERON; SEQUESTOSOME 1/P62; ADAPTER PROTEIN; MOLECULAR-BASIS;
   HUMAN-DISEASE; CELL ADAPTER; A20
AB Even though the Toll-like receptor (TLR) pathway is integral to inflammatory defense mechanisms, its excessive signaling may be devastating. Cells have acquired a cascade of strategies to regulate TLR signaling by targeting protein-protein interactions, or ubiquitin chains, but the details of the inhibition mechanisms are still unclear. Here, we provide the structural basis for the regulation of TLR signaling by constructing architectures of protein-protein interactions. Structural data suggest that 1) Toll/IL-1R (TIR) domain-containing regulators (BCAP, SIGIRR, and ST2) interfere with TIR domain signalosome formation; 2) major deubiquitinases such as A20, CYLD, and DUBA prevent association of TRAF6 and TRAF3 with their partners, in addition to removing K63-linked ubiquitin chains that serve as a docking platform for downstream effectors; 3) alternative downstream pathways of TLRs also restrict signaling by competing to bind common partners through shared binding sites. We also performed in silico mutagenesis analysis to characterize the effects of oncogenic mutations on the negative regulators and to observe the cellular outcome (whether there is/is not inflammation). Missense mutations that fall on interfaces and nonsense/frameshift mutations that result in truncated negative regulators disrupt the interactions with the targets, thereby enabling constitutive activation of the nuclear factor-kappa B, and contributing to chronic inflammation, autoimmune diseases, and oncogenesis.
C1 [Guven-Maiorov, Emine; Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey.
   [Guven-Maiorov, Emine; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey.
   [Gursoy, Attila] Koc Univ, Dept Comp Engn, Istanbul, Turkey.
   [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
EM okeskin@ku.edu.tr; nussinor@helix.nih.gov
RI Gursoy, Attila/E-9565-2015; 
OI Gursoy, Attila/0000-0002-2297-2113; Guven Maiorov,
   Emine/0000-0002-7388-9811
FU Federal funds from the National Cancer Institute, National Institutes of
   Health [HHSN261200800001E]; Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research
FX This project has been funded in whole or in part with Federal funds from
   the National Cancer Institute, National Institutes of Health, under
   contract No. HHSN261200800001E. The content of this publication does not
   necessarily reflect the views or policies of the Department of Health
   and Human Services, nor does mention of trade names, commercial
   products, or organizations imply endorsement by the U.S. Government.
   This research was supported (in part) by the Intramural Research Program
   of the NIH, National Cancer Institute, Center for Cancer Research. A.G.
   and O.K. are members of the Science Academy, Turkey.
NR 75
TC 6
Z9 6
U1 3
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD SEP 15
PY 2015
VL 109
IS 6
BP 1214
EP 1226
DI 10.1016/j.bpj.2015.06.048
PG 13
WC Biophysics
SC Biophysics
GA CR7XM
UT WOS:000361565400017
PM 26276688
ER

PT J
AU Muratcioglu, S
   Presman, DM
   Pooley, JR
   Grontved, L
   Hager, GL
   Nussinov, R
   Keskin, O
   Gursoy, A
AF Muratcioglu, Serena
   Presman, Diego M.
   Pooley, John R.
   Grontved, Lars
   Hager, Gordon L.
   Nussinov, Ruth
   Keskin, Ozlem
   Gursoy, Attila
TI Structural Modeling of GR Interactions with the SWI/SNF Chromatin
   Remodeling Complex and C/EBP
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; MEDIATES CRITICAL INTERACTIONS;
   GLUCOCORTICOID-RECEPTOR; STRUCTURE PREDICTION; NUCLEAR RECEPTORS; LIVING
   CELLS; TRANSCRIPTIONAL ACTIVATORS; GENE-TRANSCRIPTION; FORCE-FIELD; WEB
   SERVER
AB The glucocorticoid receptor (GR) is a steroid-hormone-activated transcription factor that modulates gene expression. Transcriptional regulation by the GR requires dynamic receptor binding to specific target sites located across the genome. This binding remodels the chromatin structure to allow interaction with other transcription factors. Thus, chromatin remodeling is an essential component of GR-mediated transcriptional regulation, and understanding the interactions between these molecules at the structural level provides insights into the mechanisms of how GR and chromatin remodeling cooperate to regulate gene expression. This study suggests models for the assembly of the SWI/SNF-A (SWItch/Sucrose-NonFermentable) complex and its interaction with the GR. We used the PRISM algorithm (PRotein Interactions by Structural Matching) to predict the three-dimensional complex structures of the target proteins. The structural models indicate that BAF57 and/or BAF250 mediate the interaction between the GR and the SWI/SNF-A complex, corroborating experimental data. They further suggest that a BAF60a/BAF155 and/or BAF60a/BAF170 interaction is critical for association between the core and variant subunits. Further, we model the interaction between GR and CCAAT-enhancer-binding proteins (C/EBPs), since the GR can regulate gene expression indirectly by interacting with other transcription factors like C/EBPs. We observe that GR can bind to bZip domains of the C/EBPa homodimer as both a monomer and dimer of the DNA-binding domain. In silico mutagenesis of the predicted interface residues confirm the importance of these residues in binding. In vivo analysis of the computationally suggested mutations reveals that double mutations of the leucine residues (L317D+L335D) may disrupt the interaction between GR and C/EBPa. Determination of the complex structures of the GR is of fundamental relevance to understanding its interactions and functions, since the function of a protein or a complex is dictated by its structure. In addition, it may help us estimate the effects of mutations on GR interactions and signaling.
C1 [Muratcioglu, Serena; Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey.
   [Presman, Diego M.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
   [Muratcioglu, Serena; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey.
   [Gursoy, Attila] Koc Univ, Dept Comp Engn, Istanbul, Turkey.
   [Pooley, John R.] Univ Bristol, Henry Wellcome Labs Integrated Neurosci & Endocri, Bristol, Avon, England.
   [Grontved, Lars] Univ Southern Denmark, Dept Biochem & Mol Biol, Odense M, Denmark.
   [Nussinov, Ruth] Leidos Biomedical Res Inc, Canc & Inflammat Program, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
RP Keskin, O (reprint author), Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey.
EM okeskin@ku.edu.tr; agursoy@ku.edu.tr
RI Gursoy, Attila/E-9565-2015; 
OI Gursoy, Attila/0000-0002-2297-2113; Presman, Diego/0000-0003-4515-8058;
   Grontved, Lars/0000-0002-6735-8483
FU National Cancer Institute, NIH [HHSN261200800001E]; Intramural Research
   Program of the NIH, National Cancer Institute, Center for Cancer
   Research
FX This project was funded in whole or in part with federal funds from the
   National Cancer Institute, NIH, under contract number HHSN261200800001E.
   The content of this publication does not necessarily reflect the views
   or policies of the Department of Health and Human Services, nor does
   mention of trade names, commercial products, or organizations imply
   endorsement by the U.S. Government. This research was supported (in
   part) by the Intramural Research Program of the NIH, National Cancer
   Institute, Center for Cancer Research.
NR 73
TC 5
Z9 5
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD SEP 15
PY 2015
VL 109
IS 6
BP 1227
EP 1239
DI 10.1016/j.bpj.2015.06.044
PG 13
WC Biophysics
SC Biophysics
GA CR7XM
UT WOS:000361565400018
PM 26278180
ER

PT J
AU Henry, ER
   Mozzarelli, A
   Viappiani, C
   Abbruzzetti, S
   Bettati, S
   Ronda, L
   Bruno, S
   Eaton, WA
AF Henry, Eric R.
   Mozzarelli, Andrea
   Viappiani, Cristiano
   Abbruzzetti, Stefania
   Bettati, Stefano
   Ronda, Luca
   Bruno, Stefano
   Eaton, William A.
TI Experiments on Hemoglobin in Single Crystals and Silica Gels Distinguish
   among Allosteric Models
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID T-STATE HEMOGLOBIN; COOPERATIVE OXYGEN-BINDING; TERTIARY
   STRUCTURAL-CHANGE; RESONANCE RAMAN; HEME REACTIVITY; LIGAND-BINDING;
   BETA-SUBUNITS; MECHANISM; PROTEINS; CHANGEUX
AB Trapping quaternary structures of hemoglobin in single crystals or by encapsulation in silica gels has provided a demanding set of data to test statistical mechanical models of allostery. In this work, we compare the results of those experiments with predictions of the four major allosteric models for hemoglobin: the quaternary two-state model of Monod, Wyman, and Changeux; the tertiary two-state model of Henry et al., which is the simplest extension of the Monod-Wyman-Changeux model to include pre-equilibria of tertiary as well as quaternary conformations; the structure-based model of Szabo and Karplus; and the modification of the latter model by Lee and Karplus. We show that only the tertiary two-state model can provide a near quantitative explanation of the single-crystal and gel experimental results.
C1 [Henry, Eric R.; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Mozzarelli, Andrea; Bruno, Stefano] CNR, Inst Biophys, I-56100 Pisa, Italy.
   [Mozzarelli, Andrea] Univ Parma, Dept Pharm, I-43100 Parma, Italy.
   [Viappiani, Cristiano] Univ Parma, Dept Phys & Earth Sci, I-43100 Parma, Italy.
   [Viappiani, Cristiano; Abbruzzetti, Stefania] CNR, NEST, Nanosci Inst, I-56100 Pisa, Italy.
   [Abbruzzetti, Stefania] Univ Parma, Dept Life Sci, I-43100 Parma, Italy.
   [Bettati, Stefano; Ronda, Luca] Univ Parma, Dept Neurosci, I-43100 Parma, Italy.
RP Eaton, WA (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM eaton@helix.nih.gov
RI abbruzzetti, stefania/M-8640-2015; Bruno, Stefano/A-4582-2011; 
OI abbruzzetti, stefania/0000-0001-7685-8554; Viappiani,
   Cristiano/0000-0001-7470-4770; Ronda, Luca/0000-0002-5389-2669; Bruno,
   Stefano/0000-0002-7890-2472; Mozzarelli, Andrea/0000-0003-3762-0062
FU Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases, National Institutes of Health; National
   Institute of Biostructures and Biosystems, Rome, Italy; Italian National
   Research Council
FX This work was supported by the Intramural Research Program of the
   National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health (C.V., S.A., W.A.E., and E.R.H.), by the
   National Institute of Biostructures and Biosystems, Rome, Italy (A.M.,
   L.R., S.B., and S.B.) and by the Italian National Research Council
   (A.M., S.B., S.A., and C.V.).
NR 62
TC 4
Z9 4
U1 5
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD SEP 15
PY 2015
VL 109
IS 6
BP 1264
EP 1272
DI 10.1016/j.bpj.2015.04.037
PG 9
WC Biophysics
SC Biophysics
GA CR7XM
UT WOS:000361565400021
PM 26038112
ER

PT J
AU Goncearenco, A
   Shaytan, AK
   Shoemaker, BA
   Panchenko, AR
AF Goncearenco, Alexander
   Shaytan, Alexey K.
   Shoemaker, Benjamin A.
   Panchenko, Anna R.
TI Structural Perspectives on the Evolutionary Expansion of Unique
   Protein-Protein Binding Sites
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID DATA-BANK; INTERACTION NETWORKS; INTERFACE EVOLUTION; DOMAIN
   INTERACTIONS; INTERACTOME; COMPLEXES; DATABASE; BIOINFORMATICS;
   CONSERVATION; ADAPTATION
AB Structures of protein complexes provide atomistic insights into protein interactions. Human proteins represent a quarter of all structures in the Protein Data Bank; however, available protein complexes cover less than 10% of the human proteome. Although it is theoretically possible to infer interactions in human proteins based on structures of homologous protein complexes, it is still unclear to what extent protein interactions and binding sites are conserved, and whether protein complexes from remotely related species can be used to infer interactions and binding sites. We considered biological units of protein complexes and clustered protein-protein binding sites into similarity groups based on their structure and sequence, which allowed us to identify unique binding sites. We showed that the growth rate of the number of unique binding sites in the Protein Data Bank was much slower than the growth rate of the number of structural complexes. Next, we investigated the evolutionary roots of unique binding sites and identified the major phyletic branches with the largest expansion in the number of novel binding sites. We found that many binding sites could be traced to the universal common ancestor of all cellular organisms, whereas relatively few binding sites emerged at the major evolutionary branching points. We analyzed the physicochemical properties of unique binding sites and found that the most ancient sites were the largest in size, involved many salt bridges, and were the most compact and least planar. In contrast, binding sites that appeared more recently in the evolution of eukaryotes were characterized by a larger fraction of polar and aromatic residues, and were less compact and more planar, possibly due to their more transient nature and roles in signaling processes.
C1 [Goncearenco, Alexander; Shaytan, Alexey K.; Shoemaker, Benjamin A.; Panchenko, Anna R.] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA.
RP Panchenko, AR (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA.
EM panch@ncbi.nlm.nih.gov
RI Shaytan, Alexey/D-7306-2012; Goncearenco, Alexander/M-3946-2015
OI Shaytan, Alexey/0000-0003-0312-938X; Goncearenco,
   Alexander/0000-0002-9738-7146
FU Intramural Research Program of the National Library of Medicine,
   National Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Library of Medicine, National Institutes of Health.
NR 68
TC 2
Z9 2
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD SEP 15
PY 2015
VL 109
IS 6
BP 1295
EP 1306
DI 10.1016/j.bpj.2015.06.056
PG 12
WC Biophysics
SC Biophysics
GA CR7XM
UT WOS:000361565400024
PM 26213149
ER

PT J
AU Jiang, QQ
   Paramasivam, M
   Aressy, B
   Wu, JM
   Bellani, M
   Tong, W
   Seidman, MM
   Greenberg, RA
AF Jiang, Qinqin
   Paramasivam, Manikandan
   Aressy, Bernadette
   Wu, Junmin
   Bellani, Marina
   Tong, Wei
   Seidman, Michael M.
   Greenberg, Roger A.
TI MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links
SO GENES & DEVELOPMENT
LA English
DT Article
DE MERIT40; BRCA2; DNA2; ubiquitination; interstrand cross-link repair
ID ELECTROPHORESIS COMET ASSAY; REPLICATION FORK REVERSAL; FANCONI-ANEMIA
   SUBTYPE; DOUBLE-STRAND BREAKS; DAMAGE RESPONSE; HOMOLOGOUS
   RECOMBINATION; GENOMIC STABILITY; OVARIAN-CANCER; HUMAN-CELLS;
   ADP-RIBOSYLATION
AB MERIT40 is an essential component of the RAP80 ubiquitin recognition complex that targets BRCA1 to DNA damage sites. Although this complex is required for BRCA1 foci formation, its physiologic role in DNA repair has remained enigmatic, as has its relationship to canonical DNA repair mechanisms. Surprisingly, we found that Merit40(-/-) mice displayed marked hypersensitivity to DNA interstrand cross-links (ICLs) but not whole-body irradiation. MERIT40 was rapidly recruited to ICL lesions prior to FANCD2, and Merit40-null cells exhibited delayed ICL unhooking coupled with reduced end resection and homologous recombination at ICL damage. Interestingly, Merit40 mutation exacerbated ICL-induced chromosome instability in the context of concomitant Brca2 deficiency but not in conjunction with Fancd2 mutation. These findings implicate MERIT40 in the earliest stages of ICL repair and define specific functional interactions between RAP80 complex-dependent ubiquitin recognition and the Fanconi anemia (FA)-BRCA ICL repair network.
C1 [Jiang, Qinqin; Aressy, Bernadette; Wu, Junmin; Greenberg, Roger A.] Univ Penn, Perelman Sch Med, Basser Res Ctr BRCA, Abramson Family Canc Res Inst,Dept Canc Biol, Philadelphia, PA 19104 USA.
   [Jiang, Qinqin; Aressy, Bernadette; Wu, Junmin; Greenberg, Roger A.] Univ Penn, Perelman Sch Med, Basser Res Ctr BRCA, Abramson Family Canc Res Inst,Dept Pathol, Philadelphia, PA 19104 USA.
   [Paramasivam, Manikandan; Bellani, Marina; Seidman, Michael M.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
   [Tong, Wei] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA.
RP Greenberg, RA (reprint author), Univ Penn, Perelman Sch Med, Basser Res Ctr BRCA, Abramson Family Canc Res Inst,Dept Canc Biol, Philadelphia, PA 19104 USA.
EM rogergr@mail.med.upenn.edu
FU National Institutes of Health [GM101149, CA138835, CA17494]; Abramson
   Family Cancer Research Institute; Basser Research Center for BRCA;
   Intramural Research Program of the National Institutes of Health
   National Institute on Aging [ZO1 AG000746-08]
FX We thank A. D'Andrea (Dana-Farber Cancer Institute) for providing
   FancD2-null mice, J. Chen (M.D. Anderson Cancer Center) for
   Rap80<SUP>+/+</SUP> and Rap80<SUP>-/-</SUP> cell lines, E. Brown
   (University of Pennsylvania) for Cre-ERT2 mice, and R. Ragland
   (University of Pennsylvania) for advice on replication restart
   experiments. This work was supported by National Institutes of Health
   grants GM101149, CA138835, and CA17494 to R.A.G., who is also supported
   by funds from the Abramson Family Cancer Research Institute and Basser
   Research Center for BRCA. This research was supported in part by the
   Intramural Research Program of the National Institutes of Health
   National Institute on Aging (ZO1 AG000746-08).
NR 69
TC 4
Z9 4
U1 1
U2 8
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD SEP 15
PY 2015
VL 29
IS 18
BP 1955
EP 1968
DI 10.1101/gad.264192.115
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA CS0KY
UT WOS:000361749200007
PM 26338419
ER

PT J
AU Noubiap, JJN
   Aka, PV
   Nanfack, AJ
   Agyingi, LA
   Ngai, JN
   Nyambi, PN
AF Noubiap, Jean Jacques N.
   Aka, Peter V.
   Nanfack, Aubin J.
   Agyingi, Lucy A.
   Ngai, Johnson N.
   Nyambi, Phillipe N.
TI Hepatitis B and C Co-Infections in Some HIV-Positive Populations in
   Cameroon, West Central Africa: Analysis of Samples Collected Over More
   Than a Decade
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; EQUATORIAL
   RAIN-FORESTS; NEW-YORK-CITY; NATURAL-HISTORY; RURAL VILLAGES;
   HOMOSEXUAL-MEN; RISK-FACTORS; INFECTION; PREVALENCE
AB As people infected with the human immunodeficiency virus (HIV) in Sub-Saharan Africa live longer due to availability of antiretroviral treatment (ART), so is the rise of associated infections with their burdens on patients. But reliable data on the prevalence of co-infection with hepatitis B (HBV) or C (HCV) still remains sparse and many individuals with HIV do not know their co-infection status. This study attempted to estimate the seroprevalence and identify risk factors associated with hepatitis B and/or C co-infections in HIV-infected individuals from five Regions of Cameroon by screening 531 HIV infected subjects for the presence of HBV surface antigen (HBsAg) and antibodies to HCV (HCV-Ab). A Screening and a confirmatory Enzyme linked immunosorbent assay were used to detect presence of markers of infection. CD4 count levels were also examined. The results indicate that of the 531 participants, 68% were females and 32% males. Mean CD4 count was similar to 400 cells/mu l. Seroprevalence rates for HBsAg and HCV-Ab were 23.7%, and 7.2%, respectively. Associations assessed using logistic regression revealed that HBsAg but not HCV-Ab positivity was linked to age, lower CD4 count and residing in an urban rather than in a rural setting. This high prevalence of co-infection with HBV raises the urgent need to systematically screen all newly diagnosed HIV cases for co-infection in Cameroon and other regions of sub-Saharan Africa where HIV accounts for the majority of the global infection, so as to improve management strategies for HBV infection and ART implementation.
C1 [Noubiap, Jean Jacques N.; Agyingi, Lucy A.; Ngai, Johnson N.] Med Diagnost Ctr, Serol Unit, Yaounde, Cameroon.
   [Aka, Peter V.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Nanfack, Aubin J.; Nyambi, Phillipe N.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Nanfack, Aubin J.] Univ Roma Tor Vergata, Dept Immunol & Appl Biotechnol, Fac Med & Surg, Rome, Italy.
   [Agyingi, Lucy A.] Univ Dschang, Fac Sci, Dschang, Cameroon.
   [Nyambi, Phillipe N.] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA.
RP Nyambi, PN (reprint author), NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
EM phillipe.nyambi@nyumc.org
FU National Institutes of Health from the National Cancer Institute
   [CA153726]; National Institute of Allergy and Infectious Diseases
   [AI083142]
FX This study was supported by the National Institutes of Health grant
   CA153726 from the National Cancer Institute (http://www.cancer.gov/) and
   grant AI083142 from the National Institute of Allergy and Infectious
   Diseases (http://www.niaid.nih.gov/) (PNN). The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 41
TC 4
Z9 4
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 15
PY 2015
VL 10
IS 9
AR e0137375
DI 10.1371/journal.pone.0137375
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8LR
UT WOS:000361604400017
PM 26371878
ER

PT J
AU Sibley, CH
   Lane, KD
AF Sibley, Carol Hopkins
   Lane, Kristin D.
TI Fusion of field studies and the laboratory solves a puzzle in
   antimalarial resistance
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Editorial Material
ID PLASMODIUM-FALCIPARUM MALARIA; FRENCH-GUIANA; CHLOROQUINE RESISTANCE;
   DRUG-RESISTANCE; MUTATIONS; SURVEILLANCE; EVOLUTION; MALAWI; PFCRT
C1 [Sibley, Carol Hopkins] Univ Washington, Dept Genome Sci, WorldWide Antimalarial Resistance Network, Seattle, WA 98195 USA.
   [Lane, Kristin D.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20852 USA.
RP Sibley, CH (reprint author), Univ Washington, Dept Genome Sci, WorldWide Antimalarial Resistance Network, Seattle, WA 98195 USA.
EM carol.sibley@wwarn.org
NR 26
TC 1
Z9 1
U1 1
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 15
PY 2015
VL 112
IS 37
BP 11432
EP 11433
DI 10.1073/pnas.1514403112
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5OW
UT WOS:000361393700025
PM 26333834
ER

PT J
AU Venditti, V
   Schwieters, CD
   Grishaev, A
   Clore, GM
AF Venditti, Vincenzo
   Schwieters, Charles D.
   Grishaev, Alexander
   Clore, G. Marius
TI Dynamic equilibrium between closed and partially closed states of the
   bacterial Enzyme I unveiled by solution NMR and X-ray scattering
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE multidomain protein dynamics; dipolar couplings; X-ray scattering;
   conformational states; ligand binding
ID SUGAR PHOSPHOTRANSFERASE SYSTEM; N-TERMINAL DOMAIN; PROTEIN-PROTEIN
   COMPLEXES; RESIDUAL DIPOLAR COUPLINGS; ESCHERICHIA-COLI;
   ALPHA-KETOGLUTARATE; CRYSTAL-STRUCTURE; HPR; MINIMIZATION; INHIBITION
AB Enzyme I (EI) is the first component in the bacterial phosphotransferase system, a signal transduction pathway in which phosphoryl transfer through a series of bimolecular protein-protein interactions is coupled to sugar transport across the membrane. EI is a multidomain, 128-kDa homodimer that has been shown to exist in two conformational states related to one another by two large (50-90 degrees) rigid body domain reorientations. The open conformation of apo EI allows phosphoryl transfer from His189 located in the N-terminal domain a/ beta (EIN alpha/beta) subdomain to the downstream protein partner bound to the EIN alpha subdomain. The closed conformation, observed in a trapped phosphoryl transfer intermediate, brings the EIN alpha/beta subdomain into close proximity to the C-terminal dimerization domain (EIC), thereby permitting in-line phosphoryl transfer from phosphoenolpyruvate (PEP) bound to EIC to His189. Here, we investigate the solution conformation of a complex of an active site mutant of EI (H189A) with PEP. Simulated annealing refinement driven simultaneously by solution small angle X-ray scattering and NMR residual dipolar coupling data demonstrates unambiguously that the EI(H189A)-PEP complex exists in a dynamic equilibrium between two approximately equally populated conformational states, one corresponding to the closed structure and the other to a partially closed species. The latter likely represents an intermediate in the open-to-closed transition.
C1 [Venditti, Vincenzo; Grishaev, Alexander; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Venditti, Vincenzo] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
   [Schwieters, Charles D.] NIH, Divis Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
FU National Institute for Diabetes and Digestive and Kidney Diseases at the
   National Institutes of Health; Center for Information Technology at the
   National Institutes of Health; AIDS Targeted Antiviral Program of the
   Office of the Director of the National Institutes of Health
FX We thank Drs. Lixin Fan (National Cancer Institute) and Xiaobing Zuo
   (Argonne National Laboratory) for their support at the SAXS beamline.
   This work was supported by the Intramural Programs of the National
   Institute for Diabetes and Digestive and Kidney Diseases (G.M.C.) and
   the Center for Information Technology (C.D.S.) at the National
   Institutes of Health, and by the AIDS Targeted Antiviral Program of the
   Office of the Director of the National Institutes of Health (G.M.C.).
NR 36
TC 5
Z9 5
U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 15
PY 2015
VL 112
IS 37
BP 11565
EP 11570
DI 10.1073/pnas.1515366112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5OW
UT WOS:000361393700048
PM 26305976
ER

PT J
AU Dimitrov, DS
   Jiang, SB
   Ying, TL
   Tseng, CTK
   Zhang, LQ
   Yuen, KY
AF Dimitrov, Dimiter S.
   Jiang, Shibo
   Ying, Tianlei
   Tseng, Chien-Te K.
   Zhang, Linqi
   Yuen, Kwok-yung
TI No evidence for a superior platform to develop therapeutic antibodies
   rapidly in response to MERS-CoV and other emerging viruses
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Letter
C1 [Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21702 USA.
   [Jiang, Shibo; Ying, Tianlei] Fudan Univ, Key Lab Med Mol Virol, Minist Educ & Hlth, Shanghai Med Coll, Shanghai 20032, Peoples R China.
   [Jiang, Shibo; Ying, Tianlei] Fudan Univ, Inst Med Microbiol, Shanghai 20032, Peoples R China.
   [Tseng, Chien-Te K.] Univ Texas Med Branch, Dept Microbiol, Galveston, TX 77555 USA.
   [Tseng, Chien-Te K.] Univ Texas Med Branch, Dept Immunol, Galveston, TX 77555 USA.
   [Zhang, Linqi] Tsinghua Univ, Comprehens AIDS Res Ctr, Res Ctr Publ Hlth, Sch Med, Beijing 100084, Peoples R China.
   [Yuen, Kwok-yung] Univ Hong Kong, State Key Lab Emerging Infect Dis, Dept Microbiol, Res Ctr Infect & Immunol,Carol Yu Ctr Infect, Hong Kong, Hong Kong, Peoples R China.
RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM dimiter.dimitrov@nih.gov; shibojiang@fudan.edu.cn
NR 5
TC 1
Z9 1
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 15
PY 2015
VL 112
IS 37
BP E5115
EP E5115
DI 10.1073/pnas.1513441112
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5OW
UT WOS:000361393700003
PM 26318165
ER

PT J
AU Kang, ZG
   Goldstein, SD
   Yu, YK
   Meltzer, PS
   Loeb, DM
   Cao, L
AF Kang, Zhigang
   Goldstein, Seth D.
   Yu, Yunkai
   Meltzer, Paul S.
   Loeb, David M.
   Cao, Liang
TI Caspase-8 expression is predictive of tumour response to death receptor
   5 agonist antibody in Ewing's sarcoma
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Ewing's sarcoma; predictive biomarker; death receptor 5; conatumumab;
   caspase-8
ID APOPTOSIS-INDUCING LIGAND; CANCER-CELLS; 1ST-LINE TREATMENT;
   CONATUMUMAB; TRAIL; COMBINATION; SURVIVAL; GROWTH; RESPONSIVENESS;
   APO2L/TRAIL
AB Background: Despite good initial response to chemotherapy, 30% of Ewing's sarcoma (EWS) patients with localised tumours develop recurrent disease, associated with poor prognosis. The aim of this study was to address this challenge by conducting preclinical evaluation of a death receptor targeted agent in vitro and in vivo, and by identifying predictive biomarkers.
   Methods: Cell viability assays, drug dose responses, immunoblots, rescue with gene transfer, mice tumour models, and statistical comparisons of tumour growth and Kaplan-Meier survival curves.
   Results: This study shows that many EWS cell lines are selectively sensitive to a death receptor DR5 antibody and are more resistant to a DR4 antibody. Preclinical evaluation of these cell lines indicates their sensitivity to human DR5 agonist antibody conatumumab in vitro, which induces rapid activation of caspase-8 and apoptosis. We also found that sensitivity to conatumumab correlates with expression of caspase-8. Furthermore, the catalytic activity of caspase-8 is both necessary and sufficient to confer this sensitivity. In vivo, conatumumab is active against an EWS cell line and a patient-derived xenograft with higher caspase-8 expression, but is not effective against another with lower caspase-8 expression.
   Conclusions: These studies suggest the potential of conatumumab as a therapeutic agent against EWS and caspase-8 as a predictive biomarker for sensitivity.
C1 [Kang, Zhigang; Yu, Yunkai; Meltzer, Paul S.; Cao, Liang] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Kang, Zhigang] Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA.
   [Goldstein, Seth D.; Loeb, David M.] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
RP Cao, L (reprint author), NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM caoli@mail.nih.gov
FU US National Cancer Institute (NCI); NCI, NIH [HHSN261200800001E]
FX We are very grateful to Dr Jeff Wiezorek of Amgen for providing
   conatumumab, Drs Michael Lenardo and Lixin Zheng for CASP8 and
   CASP8<SUP>mt</SUP> (C360S) expression plasmids, Lee Helman for EWS cell
   lines, Chand Khanna for EWS PDX tumours, and Arnulfo Mendoza for
   excellent technical assistance. This research was supported by the
   Intramural Research Program of the US National Cancer Institute (NCI).
   This project was also funded in part with federal funds from the NCI,
   NIH, under contract HHSN261200800001E. The Giant Food Children's Cancer
   Research Fund also helped support this work in part. 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 organisations imply endorsement by the US
   Government. No potential financial or personal conflict of interest.
NR 34
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD SEP 15
PY 2015
VL 113
IS 6
BP 894
EP 901
DI 10.1038/bjc.2015.298
PG 8
WC Oncology
SC Oncology
GA CR7AI
UT WOS:000361499300006
PM 26291055
ER

PT J
AU Siberry, GK
   Patel, K
   Bellini, WJ
   Karalius, B
   Purswani, MU
   Burchett, SK
   Meyer, WA
   Sowers, SB
   Ellis, A
   Van Dyke, RB
AF Siberry, George K.
   Patel, Kunjal
   Bellini, William J.
   Karalius, Brad
   Purswani, Murli U.
   Burchett, Sandra K.
   Meyer, William A., III
   Sowers, Sun Bae
   Ellis, Angela
   Van Dyke, Russell B.
CA Pediat HIV AIDS Cohort Study PHACS
TI Immunity to Measles, Mumps, and Rubella in US Children With Perinatal
   HIV Infection or Perinatal HIV Exposure Without Infection
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE perinatal HIV; measles; mumps; rubella; immunity
ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNIZATION STATUS; UNINFECTED INFANTS;
   CONJUGATE VACCINE; ZAMBIAN CHILDREN; IMMUNOGENICITY; RESPONSES;
   ANTIBODY; POPULATION; REVACCINATION
AB Background. Children with perinatal human immunodeficiency virus (HIV) infection (PHIV) may not be protected against measles, mumps, and rubella (MMR) because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV-infected and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort.
   Methods. PHIV and HEU children were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007 to 2009. At annual visits, demographic, laboratory, immunization, and clinical data were abstracted and serologic specimens collected. Most recent serologic specimen was used to determine measles seroprotection by plaque reduction neutralization assay and rubella seroprotection and mumps seropositivity by enzyme immunoassay. Sustained combination antiretroviral therapy (cART) was defined as taking cART for at least 3 months.
   Results. Among 428 PHIV and 221 HEU PHACS participants, the prevalence was significantly lower in PHIV children for measles seroprotection (57% [95% confidence interval {CI}, 52%-62%] vs 99% [95% CI, 96%-100%]), rubella seroprotection (65% [95% CI, 60%-70%] vs 98% [95% CI, 95%-100%]), and mumps seropositivity (59% [95% CI, 55%-64%] vs 97% [95% CI, 94%-99%]). On multivariable analysis, greater number of vaccine doses while receiving sustained cART and higher nadir CD4 percentage between last vaccine dose and serologic testing independently improved the cumulative prediction of measles seroprotection in PHIV. Predictors of rubella seroprotection and mumps seropositivity were similar.
   Conclusions. High proportions of PHIV-infected children, but not HEU children, lack serologic evidence of immunity to MMR, despite documented immunization and current cART. Effective cART before immunization is a strong predictor of current seroimmunity.
C1 [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Patel, Kunjal; Karalius, Brad] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Ctr Biostat AIDS Res, Boston, MA USA.
   [Bellini, William J.; Sowers, Sun Bae] Ctr Dis Control & Prevent, Measles Mumps Rubella & Herpesviruses Lab Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
   [Purswani, Murli U.] Bronx Lebanon Hosp Ctr, Albert Einstein Coll Med, New York, NY USA.
   [Burchett, Sandra K.] Boston Childrens Hosp, Boston, MA USA.
   [Burchett, Sandra K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
   [Bellini, William J.] Quest Diagnost, Baltimore, MD USA.
   [Ellis, Angela] Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA.
   [Van Dyke, Russell B.] Tulane Univ, Sch Med, New Orleans, LA 70118 USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, 6100 Executive Blvd,Rm 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; National Institute on Drug Abuse; National Institute of
   Allergy and Infectious Diseases; Office of AIDS Research; National
   Institute of Mental Health; National Institute of Neurological Disorders
   and Stroke; National Institute on Deafness and Other Communication
   Disorders; National Heart, Lung, and Blood Institute; National Institute
   of Dental and Craniofacial Research; National Institute on Alcohol Abuse
   and Alcoholism; Harvard University School of Public Health [U01
   HD052102]; Tulane University School of Medicine [U01 HD052104]
FX The PHACS was supported by the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development with co-funding from the National
   Institute on Drug Abuse, the National Institute of Allergy and
   Infectious Diseases, the Office of AIDS Research, the National Institute
   of Mental Health, the National Institute of Neurological Disorders and
   Stroke, the National Institute on Deafness and Other Communication
   Disorders, the National Heart, Lung, and Blood Institute, the National
   Institute of Dental and Craniofacial Research, and the National
   Institute on Alcohol Abuse and Alcoholism, through cooperative
   agreements with the Harvard University School of Public Health (U01
   HD052102; PI: George Seage; Project Director: Julie Alperen) and the
   Tulane University School of Medicine (U01 HD052104; PI: Russell Van
   Dyke; Co-PI: Kenneth Rich; Project Director: Patrick Davis). Serologic
   assays were performed in a US federal government (CDC) laboratory.
NR 37
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U1 0
U2 12
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 SEP 15
PY 2015
VL 61
IS 6
BP 988
EP 995
DI 10.1093/cid/civ440
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CR6OY
UT WOS:000361468200024
PM 26060291
ER

PT J
AU Siberry, GK
   Jacobson, DL
   Kalkwarf, HJ
   Wu, JW
   DiMeglio, LA
   Yogev, R
   Knapp, KM
   Wheeler, JJ
   Butler, L
   Hazra, R
   Miller, TL
   Seage, GR
   Van Dyke, RB
   Barr, E
   Davtyan, M
   Mofenson, LM
   Rich, KC
AF Siberry, George K.
   Jacobson, Denise L.
   Kalkwarf, Heidi J.
   Wu, Julia W.
   DiMeglio, Linda A.
   Yogev, Ram
   Knapp, Katherine M.
   Wheeler, Justin J.
   Butler, Laurie
   Hazra, Rohan
   Miller, Tracie L.
   Seage, George R., III
   Van Dyke, Russell B.
   Barr, Emily
   Davtyan, Mariam
   Mofenson, Lynne M.
   Rich, Kenneth C.
CA Pediat HIV AIDS Cohort Study
TI Lower Newborn Bone Mineral Content Associated With Maternal Use of
   Tenofovir Disoproxil Fumarate During Pregnancy
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE HIV; infant bone mineral content; tenofovir; intrauterine exposure
ID HUMAN-IMMUNODEFICIENCY-VIRUS; VITAMIN-D SUPPLEMENTATION; ANTIRETROVIRAL
   THERAPY; UNINFECTED CHILDREN; ABACAVIR-LAMIVUDINE; RANDOMIZED-TRIAL;
   GROWTH OUTCOMES; RHESUS MACAQUES; PRETERM INFANTS; IN-UTERO
AB Background. Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero.
   Methods. We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates.
   Results. Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2;P = .013) in the tenofovir-exposed infants.
   Conclusions. Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies.
C1 [Siberry, George K.; Hazra, Rohan; Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Jacobson, Denise L.] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA.
   [Kalkwarf, Heidi J.] Cincinnati Childrens Hosp Med Ctr, Div Gen & Community Pediat, Cincinnati, OH 45229 USA.
   [Wu, Julia W.; Seage, George R., III] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
   [DiMeglio, Linda A.] Indiana Univ Sch Med, Sect Pediat Endocrinol Diabetol, Dept Pediat, Riley Hosp Children,Indiana Univ Hlth, Indianapolis, IN 46202 USA.
   [Yogev, Ram] Northwestern Univ, Lurie Childrens Hosp, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Knapp, Katherine M.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
   [Wheeler, Justin J.] Tufts Univ, Body Composit Anal Ctr, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA USA.
   [Butler, Laurie] Frontier Sci Technol & Res Fdn, Amherst, NY USA.
   [Miller, Tracie L.] Univ Miami, Dept Pediat, Miller Sch Med, Coral Gables, FL 33124 USA.
   [Van Dyke, Russell B.] Tulane Univ, Dept Pediat, Sch Med, New Orleans, LA 70118 USA.
   [Barr, Emily] Univ Colorado, Childrens Hosp Colorado, Dept Infect Dis, Denver, CO 80202 USA.
   [Davtyan, Mariam] Child & Adolescent Ctr Infect Dis & Virol, LAC USC Maternal, Los Angeles, CA USA.
   [Rich, Kenneth C.] Univ Illinois, Dept Pediat, Chicago, IL USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis MPID Branch, NIH, 6100 Executive Blvd,Rm 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; National Institute on Drug Abuse; National Institute of
   Allergy and Infectious Diseases; Office of AIDS Research; National
   Institute of Mental Health; National Institute of Neurological Disorders
   and Stroke; National Institute on Deafness and Other Communication
   Disorders; National Heart Lung and Blood Institute; National Institute
   of Dental and Craniofacial Research; National Institute on Alcohol Abuse
   and Alcoholism; Harvard University School of Public Health [U01
   HD052102]; Tulane University School of Medicine [U01 HD052104]
FX The study was supported by the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development with cofunding from the National
   Institute on Drug Abuse, the National Institute of Allergy and
   Infectious Diseases, the Office of AIDS Research, the National Institute
   of Mental Health, the National Institute of Neurological Disorders and
   Stroke, the National Institute on Deafness and Other Communication
   Disorders, the National Heart Lung and Blood Institute, the National
   Institute of Dental and Craniofacial Research, and the National
   Institute on Alcohol Abuse and Alcoholism, through cooperative
   agreements with the Harvard University School of Public Health (U01
   HD052102; principal investigator: G. R. S.; project director: Julie
   Alperen) and the Tulane University School of Medicine (U01 HD052104;
   principal investigator: R. B. V-D.; co-principal investigator: K. C. R.;
   project director: Patrick Davis). Data management services were provided
   by Frontier Science and Technology Research Foundation (principal
   investigator: Suzanne Siminski), and regulatory services and logistical
   support were provided by Westat, Inc (principal investigator: Julie
   Davidson). Centralized DXA management and reading services were provided
   by Tufts DXA Center (principal investigator: Roger A. Fielding, PhD,
   Senior Scientist and Director, Nutrition, Exercise Physiology, and
   Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center
   on Aging Tufts University, Professor of Nutrition and Medicine, Friedman
   School of Nutrition Science and Policy Tufts University School of
   Medicine; Associate Director, Boston Claude D. Pepper Older Americans
   Independence Center).
NR 42
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U1 0
U2 2
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 SEP 15
PY 2015
VL 61
IS 6
BP 996
EP 1003
DI 10.1093/cid/civ437
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CR6OY
UT WOS:000361468200025
PM 26060285
ER

PT J
AU Machiela, MJ
   Ho, BM
   Fisher, VA
   Hua, X
   Chanock, SJ
AF Machiela, Mitchell J.
   Ho, Brian M.
   Fisher, Victoria A.
   Hua, Xing
   Chanock, Stephen J.
TI Limited evidence that cancer susceptibility regions are preferential
   targets for somatic mutation
SO GENOME BIOLOGY
LA English
DT Article
ID COMPREHENSIVE MOLECULAR CHARACTERIZATION; INTEGRATED GENOMIC
   CHARACTERIZATION; COMMON GENETIC-VARIANTS; CYCLIN D1 EXPRESSION; CELL
   LUNG-CANCER; BREAST-CANCER; PROSTATE-CANCER; BLADDER-CANCER; DRIVER
   MUTATIONS; OVARIAN-CANCER
AB Background: Genome wide-association studies have successfully identified several hundred independent loci harboring common cancer susceptibility alleles that are distinct from the more than 110 cancer predisposition genes. The latter are generally characterized by disruptive mutations in coding genes that have been established as 'drivers' of cancer in large somatic sequencing studies. We set out to determine whether, similarly, common cancer susceptibility loci map to genes that have altered frequencies of mutation.
   Results: In our analysis of the intervals defined by the cancer susceptibility markers, we observed that cancer susceptibility regions have gene mutation frequencies comparable to background mutation frequencies. Restricting analyses to genes that have been determined to be pleiotropic across cancer types, genes affected by expression quantitative trait loci, or functional genes indicates that most cancer susceptibility genes classified into these subgroups do not display mutation frequencies that deviate from those expected. We observed limited evidence that cancer susceptibility regions that harbor common alleles with small estimated effect sizes are preferential targets for altered somatic mutation frequencies.
   Conclusions: Our findings suggest a complex interplay between germline susceptibility and somatic mutation, underscoring the cumulative effect of common variants on redundant pathways as opposed to driver genes. Complex biological pathways and networks likely link these genetic features of carcinogenesis, particularly as they relate to distinct polygenic models for each cancer type.
C1 [Machiela, Mitchell J.; Ho, Brian M.; Fisher, Victoria A.; Hua, Xing; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Machiela, MJ (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM mitchell.machiela@nih.gov
OI Machiela, Mitchell/0000-0001-6538-9705
NR 72
TC 3
Z9 3
U1 2
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-6906
EI 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD SEP 15
PY 2015
VL 16
AR 193
DI 10.1186/s13059-015-0755-5
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CR6JC
UT WOS:000361451400004
PM 26374197
ER

PT J
AU Kim, GY
   Lee, YM
   Cho, JH
   Pan, CJ
   Jun, HS
   Springer, DA
   Mansfield, BC
   Chou, JY
AF Kim, Goo-Young
   Lee, Young Mok
   Cho, Jun-Ho
   Pan, Chi-Jiunn
   Jun, Hyun Sik
   Springer, Danielle A.
   Mansfield, Brian C.
   Chou, Janice Y.
TI Mice expressing reduced levels of hepatic glucose-6-phosphatase-alpha
   activity do not develop age-related insulin resistance or obesity
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GLYCOGEN-STORAGE-DISEASE; CALORIE RESTRICTION; GLUCOSE-PRODUCTION;
   ENERGY-METABOLISM; LIPID-METABOLISM; GENE-THERAPY; IA; PGC-1-ALPHA;
   SENSITIVITY; DEFICIENCY
AB Glycogen storage disease type-Ia (GSD-Ia) is caused by a lack of glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC) activity. We have shown that gene therapy mediated by a recombinant adeno-associated virus (rAAV) vector expressing human G6Pase-alpha normalizes blood glucose homeostasis in the global G6pc knockout (G6pc(-/-)) mice for 70-90 weeks. The treated G6pc(-/-) mice expressing 3-63% of normal hepatic G6Pase-alpha activity (AAV mice) produce endogenous hepatic glucose levels 61-68% of wildtype littermates, have a leaner phenotype and exhibit fasting blood insulin levels more typical of young adult mice. We now show that unlike wild-type mice, the lean AAV mice have increased caloric intake and do not develop age-related obesity or insulin resistance. Pathway analysis shows that signaling by hepatic carbohydrate response element binding protein that improves glucose tolerance and insulin signaling is activated in AAV mice. In addition, several longevity factors in the calorie restriction pathway, including the NADH shuttle systems, NAD(+) concentrations and the AMP-activated protein kinase/sirtuin 1/peroxisome proliferator-activated receptor-gamma coactivator 1 alpha pathway are upregulated in the livers of AAV mice. The finding that partial restoration of hepatic G6Pase-alpha activity in GSD-Ia mice not only attenuates the phenotype of hepatic G6Pase-alpha deficiency but also prevents the development of age-related obesity and insulin resistance seen in wild-type mice may suggest relevance of the G6Pase-alpha enzyme to obesity and diabetes.
C1 [Kim, Goo-Young; Lee, Young Mok; Cho, Jun-Ho; Pan, Chi-Jiunn; Jun, Hyun Sik; Mansfield, Brian C.; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA.
   [Springer, Danielle A.] NHLBI, Mouse Phenotyping Core Facil, NIH, Bethesda, MD 20892 USA.
   [Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD 21046 USA.
RP Chou, JY (reprint author), NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chouja@mail.nih.gov
FU Intramural Research Program of the 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 of the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health.
NR 36
TC 1
Z9 1
U1 2
U2 4
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 SEP 15
PY 2015
VL 24
IS 18
BP 5115
EP 5125
DI 10.1093/hmg/ddv230
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CR4PE
UT WOS:000361317200005
PM 26089201
ER

PT J
AU Young, MJ
   Humble, MM
   DeBalsi, KL
   Sun, KY
   Copeland, WC
AF Young, Matthew J.
   Humble, Margaret M.
   DeBalsi, Karen L.
   Sun, Kathie Y.
   Copeland, William C.
TI POLG2 disease variants: analyses reveal a dominant negative heterodimer,
   altered mitochondrial localization and impaired respiratory capacity
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DNA-POLYMERASE-GAMMA; MULTIPLE MTDNA DELETIONS; ACCESSORY SUBUNIT;
   MAMMALIAN EMBRYOGENESIS; NUCLEOIDS; CELLS; BIOENERGETICS; MAINTENANCE;
   HOLOENZYME; MUTATIONS
AB Human mitochondrial DNA (mtDNA) is replicated and repaired by the mtDNA polymerase gamma, pol gamma. Pol gamma is composed of three subunits encoded by two nuclear genes: (1) POLG codes for the 140-kilodalton (kDa) catalytic subunit, p140 and (2) POLG2 encodes the similar to 110-kDa homodimeric accessory subunit, p55. Specific mutations are associated with POLG-or POLG2-related disorders. During DNA replication the p55 accessory subunit binds to p140 and increases processivity by preventing pol gamma's dissociation from the template. To date, studies have demonstrated that homodimeric p55 disease variants are deficient in the ability to stimulate p140; however, all patients currently identified with POLG2-related disorders are heterozygotes. In these patients, we expect p55 to occur as 25% wild-type (WT) homodimers, 25% variant homodimers and 50% heterodimers. We report the development of a tandem affinity strategy to isolate p55 heterodimers. The WT/G451E p55 heterodimer impairs pol gamma. function in vitro, demonstrating that the POLG2 c.1352G> A/p.G451E mutation encodes a dominant negative protein. To analyze the subcellular consequence of disease mutations in HEK293 cells, we designed plasmids encoding p55 disease variants tagged with green fluorescent protein (GFP). P205R and L475DfsX2 p55 variants exhibit irregular diffuse mitochondrial fluorescence and unlike WT p55, they fail to form distinct puncta associated with mtDNA nucleoids. Furthermore, homogenous preparations of P205R and L475DfsX2 p55 form aberrant reducible multimers. We predict that abnormal protein folding or aggregation or both contribute to the pathophysiology of these disorders. Examination of mitochondrial bioenergetics in stable cell lines overexpressing GFP-tagged p55 variants revealed impaired mitochondrial reserve capacity.
C1 [Young, Matthew J.; Humble, Margaret M.; DeBalsi, Karen L.; Sun, Kathie Y.; Copeland, William C.] NIEHS, Genome Integr & Struct Biol Lab, DHHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Copeland, WC (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, 111 TW Alexander Dr,Bldg 101,Rm E316, Res Triangle Pk, NC 27709 USA.
EM copelan1@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
   Environmental Health Sciences [ES 065078]; NIH Pathway [1K99ES022638-01]
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute of Environmental Health Sciences (ES 065078 to
   WCC) and by a NIH Pathway to Independence Award to M.J.Y.
   (1K99ES022638-01).
NR 42
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Z9 6
U1 0
U2 3
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 SEP 15
PY 2015
VL 24
IS 18
BP 5184
EP 5197
DI 10.1093/hmg/ddv240
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CR4PE
UT WOS:000361317200010
PM 26123486
ER

PT J
AU Liu, GX
   Sgobio, C
   Gu, XL
   Sun, LX
   Lin, X
   Yu, J
   Parisiadou, L
   Xie, CS
   Sastry, N
   Ding, JH
   Lohr, KM
   Miller, GW
   Mateo, Y
   Lovinger, DM
   Cai, HB
AF Liu, Guoxiang
   Sgobio, Carmelo
   Gu, Xinglong
   Sun, Lixin
   Lin, Xian
   Yu, Jia
   Parisiadou, Loukia
   Xie, Chengsong
   Sastry, Namratha
   Ding, Jinhui
   Lohr, Kelly M.
   Miller, Gary W.
   Mateo, Yolanda
   Lovinger, David M.
   Cai, Huaibin
TI Selective expression of Parkinson's disease-related Leucine-rich repeat
   kinase 2 G2019S missense mutation in midbrain dopaminergic neurons
   impairs dopamine release and dopaminergic gene expression
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MUTANT ALPHA-SYNUCLEIN; LRRK2 EXPRESSION; MICE; BRAIN;
   NEURODEGENERATION; PHOSPHORYLATION; PITX3; NURR1; LOCALIZATION;
   DEGRADATION
AB Preferential dysfunction/degeneration of midbrain substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons contributes to the main movement symptoms manifested in Parkinson's disease (PD). Although the Leucine-rich repeat kinase 2 (LRRK2) G2019S missense mutation (LRRK2 G2019S) is the most common causative genetic factor linked to PD, the effects of LRRK2 G2019S on the function and survival of SNpc DA neurons are poorly understood. Using a binary gene expression system, we generated transgenic mice expressing either wild-type human LRRK2 (WT mice) or the LRRK2 G2019S mutation (G2019S mice) selectively in the midbrain DA neurons. Here we show that overexpression of LRRK2 G2019S did not induce overt motor abnormalities or substantial SNpc DA neuron loss. However, the LRRK2 G2019S mutation impaired dopamine homeostasis and release in aged mice. This reduction in dopamine content/ release coincided with the degeneration of DA axon terminals and decreased expression of DA neuron-enriched genes tyrosine hydroxylase (TH), vesicular monoamine transporter 2, dopamine transporter and aldehyde dehydrogenase 1. These factors are responsible for dopamine synthesis, transport and degradation, and their expression is regulated by transcription factor paired-like homeodomain 3 (PITX3). Levels of Pitx3 mRNA and protein were similarly decreased in the SNpc DA neurons of aged G2019S mice. Together, these findings suggest that PITX3-dependenttranscription regulation could be one of the many potential mechanisms by which LRRK2 G2019S acts in SNpc DA neurons, resulting in downregulation of its downstream target genes critical for dopamine homeostasis and release.
C1 [Liu, Guoxiang; Sgobio, Carmelo; Gu, Xinglong; Sun, Lixin; Lin, Xian; Yu, Jia; Parisiadou, Loukia; Xie, Chengsong; Sastry, Namratha; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Ding, Jinhui] NIA, Bioinformat Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Liu, Guoxiang; Parisiadou, Loukia; Sastry, Namratha] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Lohr, Kelly M.; Miller, Gary W.] Emory Univ, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA.
   [Mateo, Yolanda; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A112,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA.
EM caih@mail.nih.gov
RI gu, xinglong/A-3054-2011; 
OI gu, xinglong/0000-0002-0437-5606; Sastry, Namratha/0000-0003-4056-6044
FU intramural research programs of the National Institutes of Health
   (NIH)-National Institute on Aging [AG000928, AG000944]; NIH-National
   Institute on Alcohol Abuse and Alcoholism
FX This work was supported in part by the intramural research programs of
   the National Institutes of Health (NIH)-National Institute on Aging
   (grants AG000928 and AG000944 to H.C.) and NIH National Institute on
   Alcohol Abuse and Alcoholism (D.M.L.).
NR 59
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U1 0
U2 4
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 SEP 15
PY 2015
VL 24
IS 18
BP 5299
EP 5312
DI 10.1093/hmg/ddv249
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CR4PE
UT WOS:000361317200019
PM 26123485
ER

PT J
AU Zhang, CA
   Doherty, JA
   Burgess, S
   Hung, RJ
   Lindstrom, S
   Kraft, P
   Gong, J
   Amos, CI
   Sellers, TA
   Monteiro, ANA
   Chenevix-Trench, G
   Bickeboller, H
   Risch, A
   Brennan, P
   Mckay, JD
   Houlston, RS
   Landi, MT
   Timofeeva, MN
   Wang, YF
   Heinrich, J
   Kote-Jarai, Z
   Eeles, RA
   Muir, K
   Wiklund, F
   Gronberg, H
   Berndt, SI
   Chanock, SJ
   Schumacher, F
   Haiman, CA
   Henderson, BE
   Al Olama, AA
   Andrulis, IL
   Hopper, JL
   Chang-Claude, J
   John, EM
   Malone, KE
   Gammon, MD
   Ursin, G
   Whittemore, AS
   Hunter, DJ
   Gruber, SB
   Knight, JA
   Hou, LF
   Le Marchand, L
   Newcomb, PA
   Hudson, TJ
   Chan, AT
   Li, L
   Woods, MO
   Ahsan, H
   Pierce, BL
AF Zhang, Chenan
   Doherty, Jennifer A.
   Burgess, Stephen
   Hung, Rayjean J.
   Lindstroem, Sara
   Kraft, Peter
   Gong, Jian
   Amos, Christopher I.
   Sellers, Thomas A.
   Monteiro, Alvaro N. A.
   Chenevix-Trench, Georgia
   Bickeboeller, Heike
   Risch, Angela
   Brennan, Paul
   Mckay, James D.
   Houlston, Richard S.
   Landi, Maria Teresa
   Timofeeva, Maria N.
   Wang, Yufei
   Heinrich, Joachim
   Kote-Jarai, Zsofia
   Eeles, Rosalind A.
   Muir, Ken
   Wiklund, Fredrik
   Gronberg, Henrik
   Berndt, Sonja I.
   Chanock, Stephen J.
   Schumacher, Fredrick
   Haiman, Christopher A.
   Henderson, Brian E.
   Al Olama, Ali Amin
   Andrulis, Irene L.
   Hopper, John L.
   Chang-Claude, Jenny
   John, Esther M.
   Malone, Kathleen E.
   Gammon, Marilie D.
   Ursin, Giske
   Whittemore, Alice S.
   Hunter, David J.
   Gruber, Stephen B.
   Knight, Julia A.
   Hou, Lifang
   Le Marchand, Loic
   Newcomb, Polly A.
   Hudson, Thomas J.
   Chan, Andrew T.
   Li, Li
   Woods, Michael O.
   Ahsan, Habibul
   Pierce, Brandon L.
CA GECCO
   GAME-ON Network
   CORECT
   DRIVE
   ELLIPSE
   FOCI
   TRICL
TI Genetic determinants of telomere length and risk of common cancers: a
   Mendelian randomization study
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE METAANALYSIS; SHANGHAI WOMENS HEALTH; LUNG-CANCER;
   PROSTATE-CANCER; OVARIAN-CANCER; SUSCEPTIBILITY LOCI; COLORECTAL-CANCER;
   CIGARETTE-SMOKING; DNA-DAMAGE; ASSOCIATION
AB Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 x 10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 x 10(-6)). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk.
C1 [Zhang, Chenan; Ahsan, Habibul; Pierce, Brandon L.] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA.
   [Ahsan, Habibul; Pierce, Brandon L.] Univ Chicago, Ctr Canc Epidemiol & Prevent, Chicago, IL 60637 USA.
   [Ahsan, Habibul] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Ahsan, Habibul; Pierce, Brandon L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Doherty, Jennifer A.] Dartmouth Coll, Epidemiol & Biostat Sect, Geisel Sch Med, Lebanon, NH 03756 USA.
   [Amos, Christopher I.] Dartmouth Coll, Dept Community & Family Med, Ctr Genom Med, Geisel Sch Med, Lebanon, NH 03756 USA.
   [Burgess, Stephen] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Al Olama, Ali Amin] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
   [Hung, Rayjean J.] Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp, Toronto, ON, Canada.
   [Lindstroem, Sara; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Gong, Jian; Malone, Kathleen E.; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
   [Sellers, Thomas A.; Monteiro, Alvaro N. A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA.
   [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
   [Bickeboeller, Heike] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, D-37073 Gottingen, Germany.
   [Risch, Angela] DKFZ, German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany.
   [Risch, Angela] TLRC H, Heidelberg, Germany.
   [Brennan, Paul; Mckay, James D.; Timofeeva, Maria N.] Int Agcy Res Canc, F-69372 Lyon, France.
   [Houlston, Richard S.; Wang, Yufei; Kote-Jarai, Zsofia; Eeles, Rosalind A.] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
   [Landi, Maria Teresa; Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US Publ Hlth Serv, NIH, Bethesda, MD 20892 USA.
   [Heinrich, Joachim] Helmholtz Zentrum Munchen, Inst Epidemiol 1, German Res Ctr Environm Hlth, Neuherberg, Germany.
   [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, London, England.
   [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, Sutton, Surrey, England.
   [Muir, Ken] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
   [Muir, Ken] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
   [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
   [Schumacher, Fredrick; Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
   [Andrulis, Irene L.] Univ Toronto, Mt Sinai Hosp, Mol Genet Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada.
   [Hopper, John L.] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne Sch Populat & Global Hlth, Parkville, Vic 3052, Australia.
   [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
   [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
   [Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
   [Ursin, Giske] Kreftregisteret, Canc Registry Norway, Oslo, Norway.
   [John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [Gruber, Stephen B.] Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
   [Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ontario Canc Genet Network, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
   [Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
   [Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Hou, Lifang] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
   [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI USA.
   [Newcomb, Polly A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
   [Zhang, Chenan; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada.
   [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
   [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
   [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
   [Li, Li] Case Western Reserve Univ, Dept Family Med & Community Hlth, Cleveland, OH 44106 USA.
   [Woods, Michael O.] Mem Univ St Johns, Fac Med, Discipline Genet, St Johns, NF, Canada.
RP Pierce, BL (reprint author), Univ Chicago, Dept Publ Hlth Sci, 5841 S Maryland Ave MC2000, Chicago, IL 60637 USA.
EM brandonpierce@uchicago.edu
RI Knight, Julia/A-6843-2012; Hung, Rayjean/A-7439-2013; Andrulis,
   Irene/E-7267-2013; Risch, Angela/H-2669-2013; 
OI Eeles, Rosalind/0000-0002-3698-6241; Risch, Angela/0000-0002-8026-5505;
   Pierce, Brandon/0000-0002-7829-952X; Burgess,
   Stephen/0000-0001-5365-8760; Houlston, Richard/0000-0002-5268-0242
FU Genetic Associations and Mechanisms in Oncology Network, GAME-ON:
   Discovery, Biology, and Risk of Inherited Variants in Breast Cancer,
   DRIVE [U19 CA148065]; Colorectal Transdisciplinary Study, CORECT [U19
   CA148107]; Transdisciplinary Research in Cancer of the Lung, TRICL [U19
   CA148127]; Follow-up of ovarian cancer genetic association and
   interaction studies, FOCI [U19 CA148112]; Elucidating Loci Involved in
   Prostate Cancer Susceptibility, ELLIPSE [U19 CA148537]; Genetics and
   Epidemiology of Colorectal Cancer Consortium, GECCO: National Cancer
   Institute, National Institutes of Health, US Department of Health and
   Human Services [U01 CA137088, R01 CA059045]; National Institute of
   Health, National Institute on Aging [T32AG000243, P30AG012857]; Cancer
   Research Foundation Young Investigator Award [R01 ES020506, U01
   HG007601]; Wellcome Trust [100114]; NHMRC; University of Cambridge (COAF
   Open Access block grant)
FX This work was supported by the Genetic Associations and Mechanisms in
   Oncology Network, GAME-ON: Discovery, Biology, and Risk of Inherited
   Variants in Breast Cancer, DRIVE, PI: D.J.H. (U19 CA148065); Colorectal
   Transdisciplinary Study, CORECT, PI: S.B.G. (U19 CA148107);
   Transdisciplinary Research in Cancer of the Lung, TRICL, PI: C.A. (U19
   CA148127); Follow-up of ovarian cancer genetic association and
   interaction studies, FOCI, PI: T.A. S. (U19 CA148112); Elucidating Loci
   Involved in Prostate Cancer Susceptibility, ELLIPSE, PI: B.E.H. (U19
   CA148537); Genetics and Epidemiology of Colorectal Cancer Consortium,
   GECCO: National Cancer Institute, National Institutes of Health, US
   Department of Health and Human Services (U01 CA137088, R01 CA059045);
   National Institute of Health, National Institute on Aging (T32AG000243;
   P30AG012857) to C.Z.; Cancer Research Foundation Young Investigator
   Award, R01 ES020506, and U01 HG007601 to BLP; The Wellcome Trust
   (100114) to S.B.; The NHMRC Senior Principal Research Fellow to G.C.T.
   Funding to pay the Open Access publication charges for this article was
   provided by the University of Cambridge (COAF Open Access block grant).
NR 69
TC 20
Z9 20
U1 2
U2 16
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 SEP 15
PY 2015
VL 24
IS 18
BP 5356
EP 5366
DI 10.1093/hmg/ddv252
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CR4PE
UT WOS:000361317200024
PM 26138067
ER

PT J
AU Gianella, S
   Redd, AD
   Grabowski, MK
   Tobian, AAR
   Serwadda, D
   Newell, K
   Patel, EU
   Kalibbala, S
   Ssebbowa, P
   Gray, RH
   Quinn, TC
   Reynolds, SJ
AF Gianella, Sara
   Redd, Andrew D.
   Grabowski, Mary K.
   Tobian, Aaron A. R.
   Serwadda, David
   Newell, Kevin
   Patel, Eshan U.
   Kalibbala, Sarah
   Ssebbowa, Paschal
   Gray, Ronald H.
   Quinn, Thomas C.
   Reynolds, Steven J.
TI Vaginal Cytomegalovirus Shedding Before and After Initiation of
   Antiretroviral Therapy in Rakai, Uganda
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE acyclovir; antiretroviral therapy (ART); cytomegalovirus (CMV); human
   immunodeficiency virus (HIV); immune reconstitution inflammatory
   syndrome (IRIS); reactivation; Uganda
ID RECONSTITUTION INFLAMMATORY SYNDROME; SIMPLEX-VIRUS TYPE-2;
   GENITAL-TRACT; HIV TYPE-1; WOMEN; TRANSMISSION; ACYCLOVIR
AB Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.
C1 [Gianella, Sara] Univ Calif San Diego, Dept Infect Dis, La Jolla, CA 92093 USA.
   [Redd, Andrew D.; Patel, Eshan U.; Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [Redd, Andrew D.; Quinn, Thomas C.; Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
   [Grabowski, Mary K.; Tobian, Aaron A. R.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
   [Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Serwadda, David; Kalibbala, Sarah; Ssebbowa, Paschal; Gray, Ronald H.; Reynolds, Steven J.] Rakai Hlth Sci Program, Entebbe, Uganda.
   [Serwadda, David] Makerere Univ, Inst Publ Hlth, Kampala, Uganda.
   [Newell, Kevin] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA.
RP Gianella, S (reprint author), Univ Calif San Diego, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM gianella@ucsd.edu
OI Patel, Eshan/0000-0003-2174-5004
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health; National Institutes
   of Health (NIH) [1K23AI093152-01A1]; Doris Duke Charitable Foundation
   Clinician Scientist Development Award [22006.02]; National Cancer
   Institute, NIH [HHSN261200800001E]; NIH [T32AI102623]; Doris Duke
   Charitable Foundation;  [PO1 AI-30731-19];  [P30-AI027763];  [P30
   AI036214];  [AI100665];  [7-UM1 AI068636-07];  [R24AI106039]; 
   [UL1TR000100]
FX This work was supported by the Division of Intramural Research, National
   Institute of Allergy and Infectious Diseases, National Institutes of
   Health, and in part through program project grant PO1 AI-30731-19,
   P30-AI027763, P30 AI036214, AI100665, 7-UM1 AI068636-07, R24AI106039,
   UL1TR000100. A. A. R. T. was supported by the National Institutes of
   Health (NIH) 1K23AI093152-01A1 and the Doris Duke Charitable Foundation
   Clinician Scientist Development Award (#22006.02). This project has been
   funded in part with federal funds from the National Cancer Institute,
   NIH, under Contract No. HHSN261200800001E. M. K. G. was supported by NIH
   T32AI102623 and the Doris Duke Charitable Foundation.
NR 15
TC 6
Z9 6
U1 0
U2 2
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 SEP 15
PY 2015
VL 212
IS 6
BP 899
EP 903
DI 10.1093/infdis/jiv135
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CR4EW
UT WOS:000361285600008
PM 25743428
ER

PT J
AU Bailey, JR
   Dowd, KA
   Snider, AE
   Osburn, WO
   Mehta, SH
   Kirk, GD
   Thomas, DL
   Ray, SC
AF Bailey, Justin R.
   Dowd, Kimberly A.
   Snider, Anna E.
   Osburn, William O.
   Mehta, Shruti H.
   Kirk, Gregory D.
   Thomas, David L.
   Ray, Stuart C.
TI CD4(+) T-Cell-Dependent Reduction in Hepatitis C Virus-Specific
   Neutralizing Antibody Responses After Coinfection With Human
   Immunodeficiency Virus
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HCV; HIV; coinfection; neutralizing antibody
ID LIVER-DISEASE; NATURAL-HISTORY; PD-1 EXPRESSION; SOURCE OUTBREAK; HCV
   INFECTION; CLEARANCE; APPEARANCE; EXHAUSTION; EVOLUTION; RITUXIMAB
AB Background. Human immunodeficiency virus (HIV) infection leads to lower rates of hepatitis C virus (HCV) clearance after acute infection, higher HCV viremia, and accelerated progression of HCV-related fibrosis. The mechanisms underlying this acceleration of HCV progression by HIV are poorly understood, but HIV-induced dysfunction in the anti-HCV humoral immune response may play a role.
   Methods.aEuro integral To define the effect of HIV coinfection on the anti-HCV antibody response, we measured anti-HCV envelope binding antibody titers, neutralizing antibody (nAb) titers, and nAb breadth of serum from HCV-infected subjects isolated longitudinally before and after incident HIV infection.
   Results.aEuro integral A significant reduction in HCV envelope-specific binding antibody and nAb titers was detected in subjects with CD4(+) T-cell counts < 350/mm(3) after HIV infection, and subjects with CD4(+) T-cell counts < 200/mm(3) also showed a reduction in nAb breadth. Subjects who maintained CD4(+) T-cell counts a parts per thousand yen350/mm(3) displayed little to no decline in antibody levels.
   Conclusions.aEuro integral Depletion of CD4(+) T cells by HIV infection results in a global decline in the anti-HCV envelope antibody response, including binding antibody titers, nAb titers, and nAb breadth.
C1 [Bailey, Justin R.; Snider, Anna E.; Osburn, William O.; Kirk, Gregory D.; Thomas, David L.; Ray, Stuart C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
   [Ray, Stuart C.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
   [Mehta, Shruti H.; Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Dowd, Kimberly A.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Ray, SC (reprint author), Johns Hopkins Univ, Sch Med, 855 N Wolfe St,Ste 530, Baltimore, MD 21205 USA.
EM sray@jhmi.edu
RI Ray, Stuart/B-7527-2008
OI Ray, Stuart/0000-0002-1051-7260
FU National Institutes of Health [K08 AI102761, U19 AI088791, R37 DA013806,
   R01 DA012568, R56 DA004334]; Johns Hopkins University Center for AIDS
   Research [P30 AI094189]
FX This work was supported by the National Institutes of Health (grants K08
   AI102761, U19 AI088791, R37 DA013806, R01 DA012568, and R56 DA004334)
   and the Johns Hopkins University Center for AIDS Research (grant P30
   AI094189).
NR 42
TC 8
Z9 8
U1 0
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 SEP 15
PY 2015
VL 212
IS 6
BP 914
EP 923
DI 10.1093/infdis/jiv139
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CR4EW
UT WOS:000361285600011
PM 25754978
ER

PT J
AU Reiner, RC
   Geary, M
   Atkinson, PM
   Smith, DL
   Gething, PW
AF Reiner, Robert C., Jr.
   Geary, Matthew
   Atkinson, Peter M.
   Smith, David L.
   Gething, Peter W.
TI Seasonality of Plasmodium falciparum transmission: a systematic review
SO MALARIA JOURNAL
LA English
DT Review
DE Plasmodium falciparum; Seasonality; Climatic drivers
ID SUB-SAHARAN AFRICA; MALARIA TRANSMISSION; CLIMATE-CHANGE; HEALTH IMPACT;
   AGE-PATTERNS; MODEL; TEMPERATURE; SETTINGS; DYNAMICS; WEATHER
AB Background: Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has "strongly seasonal" transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized.
   Methods: The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts.
   Results and discussion: 152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both).
   Discussion: Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location.
   Conclusions: The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales.
C1 [Reiner, Robert C., Jr.; Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Reiner, Robert C., Jr.] Indiana Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Bloomington, IN USA.
   [Reiner, Robert C., Jr.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
   [Geary, Matthew] Univ Chester, Dept Biol Sci, Chester, Cheshire, England.
   [Atkinson, Peter M.] Univ Lancaster, Fac Sci & Technol, Lancaster LA1 4YR, England.
   [Atkinson, Peter M.] Univ Utrecht, Fac Geosci, NL-3584 CS Utrecht, Netherlands.
   [Atkinson, Peter M.] Queens Univ Belfast, Sch Geog Archaeol & Palaeoecol, Belfast BT7 1NN, Antrim, North Ireland.
   [Atkinson, Peter M.] Univ Southampton, Geog & Environm, Southampton SO17 1BJ, Hants, England.
   [Smith, David L.] Ctr Dis Dynam Econ & Policy, Washington, DC USA.
   [Smith, David L.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
RP Reiner, RC (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM rcreiner@indiana.edu
OI Gething, Peter/0000-0001-6759-5449
FU Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
   the Science and Technology Directory, Department of Homeland Security,
   and Fogarty International Center, National Institutes of Health; Bill &
   Melinda Gates Foundation [OPP1110495]; University of Utrecht; UK Medical
   Research Council (MRC) [K00669X]; UK Department for International
   Development (DFID) under the MRC/DFID Concordat agreement [K00669X];
   Bill and Melinda Gates Foundation [OPP1068048, OPP1106023]
FX This work was supported by the Research and Policy for Infectious
   Disease Dynamics (RAPIDD) program of the Science and Technology
   Directory, Department of Homeland Security, and Fogarty International
   Center, National Institutes of Health. DLS is funded by a grant from the
   Bill & Melinda Gates Foundation (OPP1110495), which also supports RCR.
   PMA is grateful to the University of Utrecht for supporting him with The
   Belle van Zuylen Chair. PWG is a Career Development Fellow (K00669X)
   jointly funded by the UK Medical Research Council (MRC) and the UK
   Department for International Development (DFID) under the MRC/DFID
   Concordat agreement and receives support from the Bill and Melinda Gates
   Foundation (OPP1068048, OPP1106023).
NR 48
TC 5
Z9 5
U1 1
U2 22
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD SEP 15
PY 2015
VL 14
AR 343
DI 10.1186/s12936-015-0849-2
PG 14
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CR5CW
UT WOS:000361358200001
PM 26370142
ER

PT J
AU Chopra, V
   Flanders, SA
   Saint, S
   Woller, SC
   O'Grady, NP
   Safdar, N
   Trerotola, SO
   Saran, R
   Moureau, N
   Wiseman, S
   Pittiruti, M
   Akl, EA
   Lee, AY
   Courey, A
   Swaminathan, L
   LeDonne, J
   Becker, C
   Krein, SL
   Bernstein, SJ
AF Chopra, Vineet
   Flanders, Scott A.
   Saint, Sanjay
   Woller, Scott C.
   O'Grady, Naomi P.
   Safdar, Nasia
   Trerotola, Scott O.
   Saran, Rajiv
   Moureau, Nancy
   Wiseman, Stephen
   Pittiruti, Mauro
   Akl, Elie A.
   Lee, Agnes Y.
   Courey, Anthony
   Swaminathan, Lakshmi
   LeDonne, Jack
   Becker, Carol
   Krein, Sarah L.
   Bernstein, Steven J.
TI The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC):
   Results From a Multispecialty Panel Using the RAND/UCLA Appropriateness
   Method
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
AB Use of peripherally inserted central catheters (PICCs) has grown substantially in recent years. Increasing use has led to the realization that PICCs are associated with important complications, including thrombosis and infection. Moreover, some PICCs may not be placed for clinically valid reasons. Defining appropriate indications for insertion, maintenance, and care of PICCs is thus important for patient safety.
   An international panel was convened that applied the RAND/UCLA Appropriateness Method to develop criteria for use of PICCs. After systematic reviews of the literature, scenarios related to PICC use, care, and maintenance were developed according to patient population (for example, general hospitalized, critically ill, cancer, kidney disease), indication for insertion (infusion of peripherally compatible infusates vs. vesicants), and duration of use (<= 5 days, 6 to 14 days, 15 to 30 days, or >= 31 days). Within each scenario, appropriateness of PICC use was compared with that of other venous access devices.
   After review of 665 scenarios, 253 (38%) were rated as appropriate, 124 (19%) as neutral/uncertain, and 288 (43%) as inappropriate. For peripherally compatible infusions, PICC use was rated as inappropriate when the proposed duration of use was 5 or fewer days. Midline catheters and ultrasonography-guided peripheral intravenous catheters were preferred to PICCs for use between 6 and 14 days. In critically ill patients, nontunneled central venous catheters were preferred over PICCs when 14 or fewer days of use were likely. In patients with cancer, PICCs were rated as appropriate for irritant or vesicant infusion, regardless of duration.
   The panel of experts used a validated method to develop appropriate indications for PICC use across patient populations. These criteria can be used to improve care, inform quality improvement efforts, and advance the safety of medical patients.
C1 Univ Michigan, Sch Med, Patient Safety Enhancement Program, Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI 48109 USA.
   [Chopra, Vineet] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA.
   Oakwood Hosp, Dearborn, MI USA.
   Intermt Med Ctr, Murray, KY USA.
   Univ Utah, Sch Med, Salt Lake City, UT USA.
   NIH, Ctr Clin, Bethesda, MD 20892 USA.
   Greater Baltimore Med Ctr, Baltimore, MD USA.
   William S Middleton Mem Vet Affairs Hosp, Madison, WI USA.
   Univ Wisconsin, Sch Med, Div Infect Dis, Madison, WI USA.
   Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
   PICC Excellence, Hartwell, GA USA.
   Univ Cattolica Sacro Cuore, Rome, Italy.
   Amer Univ Beirut, Beirut, Lebanon.
   Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
RP Chopra, V (reprint author), Univ Michigan, Inst Healthcare Policy & Innovat, North Campus Res Complex,2800 Plymouth Rd,Bldg 16, Ann Arbor, MI 48109 USA.
EM vineetc@umich.edu
OI Moureau, Nancy/0000-0002-6338-0990
FU AHRQ HHS [1-K08-HS022835-01, K08 HS022835]
NR 0
TC 25
Z9 26
U1 2
U2 8
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 SEP 15
PY 2015
VL 163
IS 6
SU S
BP S1
EP +
DI 10.7326/M15-0744
PG 48
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR5FV
UT WOS:000361367000001
PM 26369828
ER

PT J
AU Lheureux, S
   Karakasis, K
   Kohn, EC
   Oza, AM
AF Lheureux, Stephanie
   Karakasis, Katherine
   Kohn, Elise C.
   Oza, Amit M.
TI Ovarian cancer treatment: The end of empiricism?
SO CANCER
LA English
DT Review
DE ovarian cancer; treatment; strategy; biology; biomarkers
ID PHASE-III TRIAL; RECURRENT EPITHELIAL OVARIAN; PEGYLATED LIPOSOMAL
   DOXORUBICIN; PLATINUM-BASED CHEMOTHERAPY; GYNECOLOGIC-ONCOLOGY-GROUP;
   GRADE SEROUS CARCINOMA; CIRCULATING TUMOR DNA; MAINTENANCE THERAPY;
   INTERGROUP TRIAL; PRIMARY PERITONEAL
AB The diagnosis, investigation, and management of ovarian cancer are in a state of fluxbalancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence-informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer. Cancer 2015;121:3203-3211. (c) 2015 American Cancer Society.
   The authors discuss the current understanding of the biology of ovarian cancer, diagnostic and treatment strategies, and high-priority directions for investigation.
C1 [Lheureux, Stephanie; Karakasis, Katherine; Oza, Amit M.] Princess Margaret Canc Ctr, Div Med Oncol & Hematol, Bras Family Drug Dev Program, Toronto, ON, Canada.
   [Kohn, Elise C.] NIH, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Oza, AM (reprint author), Univ Toronto, Princess Margaret Canc Ctr, 610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM amit.oza@uhn.ca
NR 87
TC 9
Z9 10
U1 0
U2 22
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 SEP 15
PY 2015
VL 121
IS 18
BP 3203
EP 3211
DI 10.1002/cncr.29481
PG 9
WC Oncology
SC Oncology
GA CQ7DN
UT WOS:000360763200008
PM 26096019
ER

PT J
AU Nilubol, N
   Kebebew, E
AF Nilubol, Naris
   Kebebew, Electron
TI Reply to most patients with a small papillary thyroid carcinoma enjoy an
   excellent prognosis and may be managed with minimally invasive therapy
   or active surveillance
SO CANCER
LA English
DT Letter
ID CANCER; SURVIVAL; SURGERY; EXTENT
C1 [Nilubol, Naris; Kebebew, Electron] NCI, Ctr Canc Res, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
RP Nilubol, N (reprint author), NCI, Ctr Canc Res, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
FU Intramural NIH HHS
NR 7
TC 1
Z9 1
U1 1
U2 1
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 SEP 15
PY 2015
VL 121
IS 18
BP 3365
EP 3366
DI 10.1002/cncr.29467
PG 2
WC Oncology
SC Oncology
GA CQ7DN
UT WOS:000360763200030
PM 26079720
ER

PT J
AU Andrade, BB
   Kumar, NP
   Amaral, EP
   Riteau, N
   Mayer-Barber, KD
   Tosh, KW
   Maier, N
   Conceicao, EL
   Kubler, A
   Sridhar, R
   Banurekha, VV
   Jawahar, MS
   Barbosa, T
   Manganiello, VC
   Moss, J
   Fontana, JR
   Marciano, BE
   Sampaio, EP
   Olivier, KN
   Holland, SM
   Jackson, SH
   Moayeri, M
   Leppla, S
   Sereti, I
   Barber, DL
   Nutman, TB
   Babu, S
   Sher, A
AF Andrade, Bruno B.
   Kumar, Nathella Pavan
   Amaral, Eduardo P.
   Riteau, Nicolas
   Mayer-Barber, Katrin D.
   Tosh, Kevin W.
   Maier, Nolan
   Conceicao, Elisabete L.
   Kubler, Andre
   Sridhar, Rathinam
   Banurekha, Vaithilingam V.
   Jawahar, Mohideen S.
   Barbosa, Theolis
   Manganiello, Vincent C.
   Moss, Joel
   Fontana, Joseph R.
   Marciano, Beatriz E.
   Sampaio, Elizabeth P.
   Olivier, Kenneth N.
   Holland, Steven M.
   Jackson, Sharon H.
   Moayeri, Mahtab
   Leppla, Stephen
   Sereti, Irini
   Barber, Daniel L.
   Nutman, Thomas B.
   Babu, Subash
   Sher, Alan
TI Heme Oxygenase-1 Regulation of Matrix Metalloproteinase-1 Expression
   Underlies Distinct Disease Profiles in Tuberculosis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MYCOBACTERIUM-TUBERCULOSIS; CARBON-MONOXIDE; ANTHRAX TOXIN; PULMONARY;
   MMP-1; INFECTION; POLYMORPHISMS; CYTOTOXICITY; SARCOIDOSIS; ACTIVATION
AB Pulmonary tuberculosis (TB) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (MMPs). The interplay between these distinct pathological processes and the implications for TB diagnosis and disease staging are poorly understood. Heme oxygenase-1 (HO-1) levels were previously shown to distinguish active from latent TB, as well as successfully treated Mycobacterium tuberculosis infection. MMP-1 expression is also associated with active TB. In this study, we measured plasma levels of these two important biomarkers in distinct TB cohorts from India and Brazil. Patients with active TB expressed either very high levels of HO-1 and low levels of MMP-1 or the converse. Moreover, TB patients with either high HO-1 or MMP-1 levels displayed distinct clinical presentations, as well as plasma inflammatory marker profiles. In contrast, in an exploratory North American study, inversely correlated expression of HO-1 and MMP-1 was not observed in patients with other nontuberculous lung diseases. To assess possible regulatory interactions in the biosynthesis of these two enzymes at the cellular level, we studied the expression of HO-1 and MMP-1 in M. tuberculosis-infected human and murine macrophages. We found that infection of macrophages with live virulent M. tuberculosis is required for robust induction of high levels of HO-1 but not MMP-1. In addition, we observed that CO, a product of M. tuberculosis-induced HO-1 activity, inhibits MMP-1 expression by suppressing c-Jun/AP-1 activation. These findings reveal a mechanistic link between oxidative stress and tissue remodeling that may find applicability in the clinical staging of TB patients.
C1 [Andrade, Bruno B.; Amaral, Eduardo P.; Riteau, Nicolas; Mayer-Barber, Katrin D.; Tosh, Kevin W.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Andrade, Bruno B.; Conceicao, Elisabete L.; Barbosa, Theolis] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Lab Integrado Microbiol & Imunorregulacao, Unidade Med Invest, BR-40296710 Salvador, BA, Brazil.
   [Kumar, Nathella Pavan; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras 600031, Tamil Nadu, India.
   [Kumar, Nathella Pavan; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.] Natl Inst Res TB, Madras 600031, Tamil Nadu, India.
   [Maier, Nolan; Moayeri, Mahtab; Leppla, Stephen] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Kubler, Andre] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England.
   [Sridhar, Rathinam] Govt Stanley Med Hosp, Madras 600001, Tamil Nadu, India.
   [Manganiello, Vincent C.; Moss, Joel; Fontana, Joseph R.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
   [Marciano, Beatriz E.; Sampaio, Elizabeth P.; Olivier, Kenneth N.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Jackson, Sharon H.] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [Sereti, Irini] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Barber, Daniel L.] NIAID, T Lymphocyte Biol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Nutman, Thomas B.; Babu, Subash] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Andrade, BB (reprint author), Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Lab Integrado Microbiol & Imunorregulacao, Rua Waldemar Falcao 121, BR-40296710 Salvador, BA, Brazil.
EM bruno.andrade@bahia.fiocruz.br
RI Amaral, Eduardo/M-2456-2014; 
OI Amaral, Eduardo/0000-0001-5465-8113; Barbosa,
   Theolis/0000-0003-1928-0404
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health; National Heart,
   Lung, and Blood Institute Intramural Research Program; Fundacao de
   Amparo a Pesquisa do Estado da Bahia; Conselho Nacional de
   Desenvolvimento Cientifico e Tecnologico, Brazil [028/2010]; Coordenacao
   de Aperfeicoamento de Pessoal de Nivel Superior, Brazil
FX This work was supported by the Division of Intramural Research, National
   Institute of Allergy and Infectious Diseases, National Institutes of
   Health. J.M., V.C.M., and J.R.F. were supported by the National Heart,
   Lung, and Blood Institute Intramural Research Program. The Brazilian
   study was funded by Fundacao de Amparo a Pesquisa do Estado da Bahia and
   Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil
   (Grant 028/2010). E.L.C. received a research fellowship and B.B.A.
   received a research award from the Coordenacao de Aperfeicoamento de
   Pessoal de Nivel Superior, Brazil.
NR 45
TC 10
Z9 11
U1 1
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD SEP 15
PY 2015
VL 195
IS 6
BP 2763
EP 2773
DI 10.4049/jimmunol.1500942
PG 11
WC Immunology
SC Immunology
GA CR0GP
UT WOS:000360996800027
PM 26268658
ER

PT J
AU Akintunde, ME
   Rose, M
   Krakowiak, P
   Heuer, L
   Ashwood, P
   Hansen, R
   Hertz-Picciotto, I
   de Water, JV
AF Akintunde, Marjannie Eloi
   Rose, Melissa
   Krakowiak, Paula
   Heuer, Luke
   Ashwood, Paul
   Hansen, Robin
   Hertz-Picciotto, Irva
   de Water, Judy Van
TI Increased production of IL-17 in children with autism spectrum disorders
   and co-morbid asthma
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Article
DE Autism; IL-17; Asthma; Food allergies
ID BRAIN-BARRIER DISRUPTION; T-CELLS; CHILDHOOD AUTISM; TH17 CELLS;
   INFLAMMATION; DISEASES; INTERLEUKIN-17; AUTOIMMUNITY; LYMPHOCYTES;
   ENVIRONMENT
AB Inflammation and asthma have both been reported in some children with autism spectrum disorder (ASD). To further assess this connection, peripheral immune cells isolated from young children with ASD and typically developing (TD) controls and the production of cytokines IL-17, -13, and -4 assessed following ex vivo mitogen stimulation. Notably, IL-17 production was significantly higher following stimulation in ASD children compared to controls. Moreover, IL-17 was increased in ASD children with co-morbid asthma compared to controls with the same condition. In conclusion, children with ASD exhibited a differential response to T cell stimulation with elevated IL-17 production compared to controls. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Akintunde, Marjannie Eloi; Heuer, Luke; de Water, Judy Van] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Sch Med, Davis, CA 95616 USA.
   [Akintunde, Marjannie Eloi; Rose, Melissa; Ashwood, Paul; Hansen, Robin; Hertz-Picciotto, Irva; de Water, Judy Van] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA.
   [Rose, Melissa; Krakowiak, Paula; Heuer, Luke; Ashwood, Paul; Hansen, Robin; Hertz-Picciotto, Irva; de Water, Judy Van] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA.
   [Rose, Melissa; Krakowiak, Paula; Hertz-Picciotto, Irva] Univ Calif Davis, Sch Publ Hlth Sci, Davis, CA 95616 USA.
   [Ashwood, Paul] Sch Med, Dept Microbiol & Immunol, Washington, DC USA.
   [Hansen, Robin] Univ Calif Davis, Sch Med, Dept Pediat, Davis, CA 95616 USA.
RP Akintunde, ME (reprint author), UC Davis MIND Inst, UC Davis Sch Med, Div Rheumatol Allergy & Clin Immunol, 6512 Genome & Biomed Sci Facil 451 Hlth Sci Dr, Davis, CA 95616 USA.
EM mdeloi@ucdavis.edu
OI Akintunde, Marjannie/0000-0002-6673-9452
FU National Institute of Environmental Health Sciences (NIEHS) pre-doctoral
   training program in Environmental Health Sciences [T32-ES007058-33];
   NIEHS Center for Children's Environmental Health [2P01ES011269-11];
   Environmental Protection Agency (EPA) [83543201]; NIEHS [R01ES015359];
   NICHD [IDDRC 054, U54HD079125]
FX The National Institute of Environmental Health Sciences (NIEHS)
   pre-doctoral training program in Environmental Health Sciences
   (T32-ES007058-33) funded M.E.A. This study was funded by the NIEHS
   Center for Children's Environmental Health and Environmental Protection
   Agency (EPA) grants (2P01ES011269-11, 83543201 respectively), the
   NIEHS-funded CHARGE study (R01ES015359), and the NICHD funded IDDRC 054
   (U54HD079125). We also thank the staff of the CHARGE study, and families
   involved in this research.
NR 63
TC 6
Z9 6
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD SEP 15
PY 2015
VL 286
BP 33
EP 41
DI 10.1016/j.jneuroim.2015.07.003
PG 9
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA CQ9RG
UT WOS:000360952100006
PM 26298322
ER

PT J
AU Conti, MA
   Saleh, AD
   Brinster, LR
   Cheng, H
   Chen, Z
   Cornelius, S
   Liu, CY
   Ma, XF
   Van Waes, C
   Adelstein, RS
AF Conti, Mary Anne
   Saleh, Anthony D.
   Brinster, Lauren R.
   Cheng, Hui
   Chen, Zhong
   Cornelius, Shaleeka
   Liu, Chengyu
   Ma, Xuefei
   Van Waes, Carter
   Adelstein, Robert S.
TI Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium
   results in squamous cell carcinoma
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MYH9-RELATED DISEASE; CANCER GENOMICS; ABLATION; ISOFORM; MODELS;
   DOMAIN; HEAD
AB To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (A(Nkx)/A(Nkx)) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 A(Nkx)/A(Nkx)) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from a different embryonic stem cell clone was tested. This second line also develops SCC indistinguishable from the first (15/15). In A(Nkx)/A(Nkx) mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis.
C1 [Conti, Mary Anne; Ma, Xuefei; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, Bethesda, MD 20814 USA.
   [Saleh, Anthony D.; Cheng, Hui; Chen, Zhong; Cornelius, Shaleeka; Van Waes, Carter] NIDCD, Head & Neck Surg Branch, Bethesda, MD 20892 USA.
   [Brinster, Lauren R.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
   [Liu, Chengyu] NHLBI, Transgen Core Facil, NIH, Bethesda, MD 20892 USA.
RP Conti, MA (reprint author), NHLBI, Mol Cardiol Lab, Bethesda, MD 20814 USA.
EM Contim@mail.nih.gov
OI Adelstein, Robert/0000-0002-8683-2144
FU Division of Intramural Research, NHLBI [HL-004218]; NIDCD, NIH
   [ZIA-DC-000074]
FX We thank members of the Laboratory of Molecular Cardiology for helpful
   comments and discussion during the course of this work and Dr. Sachiyo
   Kawamoto for critical reading of the manuscript. We are grateful for the
   excellent technical assistance provided by Dalton Saunders and for the
   advice and assistance of Drs. Daniela Malide and Christian A. Combs of
   the NHLBI Light Microscopy Core Facility. We thank Dr. Richard Harvey
   for kindly supplying the Nkx2.5Cre recombinase mice. This work was
   supported by the Division of Intramural Research, NHLBI (HL-004218) and
   intramural project ZIA-DC-000074, NIDCD, NIH. Ethics Statement: All
   methods were carried out in accordance with the approved guidelines of
   the ACUC, NHLBI, NIH. All experimental protocols were approved by the
   ACUC, NHLBI, NIH.
NR 21
TC 0
Z9 0
U1 0
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 SEP 15
PY 2015
VL 5
AR 14068
DI 10.1038/srep14068
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR2RG
UT WOS:000361177400006
PM 26369831
ER

PT J
AU Pommier, Y
   Kiselev, E
   Marchand, C
AF Pommier, Yves
   Kiselev, Evgeny
   Marchand, Christophe
TI Interfacial inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Topoisomerase; Integrase; Chemotherapy; Natural products; Pharmacology
ID MAMMALIAN TOPOISOMERASE-II; STRUCTURAL BASIS; ALPHA-AMANITIN; DNA
   CLEAVAGE; ANTIBACTERIAL AGENTS; INTEGRASE INHIBITORS; ANTICANCER DRUGS;
   CAMPTOTHECIN; MECHANISM; COMPLEX
AB Targeting macromolecular interface is a general mechanism by which natural products inactivate macromolecular complexes by stabilizing normally transient intermediates. Demonstrating interfacial inhibition mechanism ultimately relies on the resolution of drug-macromolecule structures. This review focuses on medicinal drugs that trap protein-DNA complexes by binding at protein-DNA interfaces. It provides proof-of-concept and detailed structural and mechanistic examples for topoisomerase inhibitors and HIV integrase inhibitors. Additional examples of recent interfacial inhibitors for protein-DNA interfaces are provided, as well as prospects for targeting previously 'undruggable' targets including transcription, replication and chromatin remodeling complexes. References and discussion are included for interfacial inhibitors of protein-protein interfaces. Published by Elsevier Ltd.
C1 [Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
   NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RI Marchand, Christophe/D-8559-2016
FU Center for Cancer Research; Intramural Program of the National Cancer
   Institute [Z01 BC 006161, Z01 BC 007333]; National Institute of General
   Medical Sciences Postdoctoral Research Associate (PRAT) Program, US
   National Institutes of Health
FX We acknowledge support from the Center for Cancer Research, the
   Intramural Program of the National Cancer Institute (Z01 BC 006161 and
   Z01 BC 007333) and the National Institute of General Medical Sciences
   Postdoctoral Research Associate (PRAT) Program, US National Institutes
   of Health.
NR 50
TC 3
Z9 3
U1 1
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD SEP 15
PY 2015
VL 25
IS 18
BP 3961
EP 3965
DI 10.1016/j.bmcl.2015.07.032
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA CP2ZX
UT WOS:000359747700040
PM 26235949
ER

PT J
AU Rubicz, R
   Zhao, SS
   April, C
   Wright, JL
   Kolb, S
   Coleman, I
   Lin, DW
   Nelson, PS
   Ostrander, EA
   Feng, ZD
   Fan, JB
   Stanford, JL
AF Rubicz, Rohina
   Zhao, Shanshan
   April, Craig
   Wright, Jonathan L.
   Kolb, Suzanne
   Coleman, Ilsa
   Lin, Daniel W.
   Nelson, Peter S.
   Ostrander, Elaine A.
   Feng, Ziding
   Fan, Jian-Bing
   Stanford, Janet L.
TI Expression of Cell Cycle-Regulated Genes and Prostate Cancer Prognosis
   in a Population-Based Cohort
SO PROSTATE
LA English
DT Article
DE cell cycle-regulated genes; gene expression; patient outcomes;
   population-based cohort; prostate cancer
ID BREAST-CANCER; CLINICAL IMPLICATIONS; THYMIDINE KINASE; PROGRESSION;
   SIGNATURE; SURVIVAL; RISK; PROLIFERATION; LYMPHOMA; MARKER
AB BACKGROUND. Prostate cancer (PCa) is clinically and biologically heterogeneous, making it difficult to predict at detection whether it will take an indolent or aggressive disease course. Cell cycle-regulated genes may be more highly expressed in actively dividing cells, with transcript levels reflecting tumor growth rate. Here, we evaluated expression of cell cycle genes in relation to PCa outcomes in a population-based cohort.
   METHODS. Gene expression data were generated from tumor tissues obtained at radical prostatectomy for 383 population-based patients (12.3-years average follow-up). The overall mean and individual transcript levels of 30 selected cell cycle genes was compared between patients with no evidence of recurrence (73%) and those who recurred (27%) or died (7%) from PCa.
   RESULTS. The multivariate adjusted hazard ratio (HR) for a change from the 25th to 75th percentile of mean gene expression level (range 8.02-10.05) was 1.25 (95%CI 0.96-1.63; P=0.10) for PCa recurrence risk, and did not vary substantially by Gleason score, TMPRSS2-ERG fusion status, or family history of PCa. For lethal PCa, the HR for a change (25th to 75th percentile) in mean gene expression level was 2.04 (95%CI 1.26-3.31; P=0.004), adjusted for clinicopathological variables. The ROC curve for mean gene expression level alone (AUC=0.740) did not perform as well as clinicopathological variables alone (AUC=0.803) for predicting lethal PCa, and the addition of mean gene expression to clinicopathological variables did not substantially improve prediction (AUC=0.827; P=0.18). Higher TK1 expression was strongly associated with both recurrent (P=6.7x10(-5)) and lethal (P=6.4x10(-6)) PCa.
   CONCLUSIONS. Mean expression level for 30 selected cell cycle-regulated genes was unrelated to recurrence risk, but was associated with a twofold increase in risk of lethal PCa. However, gene expression had less discriminatory accuracy than clinical variables alone for predicting lethal events. Transcript levels for several genes in the panel were significantly overexpressed in lethal versus non-recurrent PCa. (c) 2015 Wiley Periodicals, Inc.
C1 [Rubicz, Rohina; Zhao, Shanshan; Wright, Jonathan L.; Kolb, Suzanne; Lin, Daniel W.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [April, Craig; Fan, Jian-Bing] Illumina Inc, San Diego, CA USA.
   [Wright, Jonathan L.; Lin, Daniel W.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA.
   [Coleman, Ilsa; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
   [Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
   [Nelson, Peter S.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
   [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Feng, Ziding] Univ Texas Hlth Sci Ctr Houston, Dept Biostat, Houston, TX 77030 USA.
   [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Rubicz, R (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,M4-A402, Seattle, WA 98109 USA.
EM rrubicz@fredhutch.org
OI Ostrander, Elaine/0000-0001-6075-9738
FU NCI, NIH [R01 CA056678, R01 CA092579, P50 CA097186]; Fred Hutchinson
   Cancer Research Center; Prostate Cancer Foundation
FX Grant sponsor: NCI, NIH; Grant numbers: R01 CA056678; R01 CA092579; P50
   CA097186; Grant sponsor: Fred Hutchinson Cancer Research Center; Grant
   sponsor: Prostate Cancer Foundation.
NR 33
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD SEP 15
PY 2015
VL 75
IS 13
BP 1354
EP 1362
DI 10.1002/pros.23016
PG 9
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA CP2MN
UT WOS:000359711300002
PM 25990700
ER

PT J
AU Winchester, DA
   Till, C
   Goodman, PJ
   Tangen, CM
   Santella, RM
   Johnson-Pais, TL
   Leach, RJ
   Xu, JF
   Zheng, SL
   Thompson, IM
   Lucia, MS
   Lippmann, SM
   Parnes, HL
   Dluzniewski, PJ
   Isaacs, WB
   De Marzo, AM
   Drake, CG
   Platz, EA
AF Winchester, Danyelle A.
   Till, Cathee
   Goodman, Phyllis J.
   Tangen, Catherine M.
   Santella, Regina M.
   Johnson-Pais, Teresa L.
   Leach, Robin J.
   Xu, Jianfeng
   Zheng, S. Lilly
   Thompson, Ian M.
   Lucia, M. Scott
   Lippmann, Scott M.
   Parnes, Howard L.
   Dluzniewski, Paul J.
   Isaacs, William B.
   De Marzo, Angelo M.
   Drake, Charles G.
   Platz, Elizabeth A.
TI Variation in Genes Involved in the Immune Response and Prostate Cancer
   Risk in the Placebo Arm of the Prostate Cancer Prevention Trial
SO PROSTATE
LA English
DT Article
DE genes; prostate cancer; inflammation risk
ID GENOME-WIDE ASSOCIATION; IL-10 POLYMORPHISMS; VARIANTS; METAANALYSIS;
   INFLAMMATION; ANTIGEN; MEN; RNASEL; REPLICATION; POPULATION
AB BACKGROUND. We previously found that inflammation in benign prostate tissue is associated with an increased odds of prostate cancer, especially higher-grade disease. Since part of this link may be due to genetics, we evaluated the association between single nucleotide polymorphisms (SNPs) in immune response genes and prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial.
   METHODS. We genotyped 16 candidate SNPs in IL1, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and seven tagSNPs in IL10 in 881 prostate cancer cases and 848 controls negative for cancer on an end-of-study biopsy. Cases and controls were non-Hispanic white and frequency matched on age and family history. We classified cases as lower (Gleason sum <7; N=674) and higher (7-10; N=172) grade, and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history.
   RESULTS. The minor allele (C) of rs3212227 in IL12(p40) was associated with an increased risk of total (log additive: OR=1.30, 95%CI 1.10-1.53; P-trend=0.0017) and lower-grade (OR=1.36, 95%CI 1.15-1.62; P-trend=0.0004) prostate cancer. The minor allele (A) of rs4073 in IL8 was possibly associated with a decreased risk of higher-grade (OR=0.81, 95%CI 0.64-1.02; P-trend=0.07), but not total disease. None of the other candidates was associated with risk. The minor alleles of IL10 tagSNPs rs1800890 (A; OR=0.87, 95%CI: 0.75-0.99; P-trend=0.04) and rs3021094 (C; OR=1.31, 95%CI 1.03-1.66, P-trend=0.03) were associated with risk; the latter also with lower- (P-trend=0.04) and possibly higher- (P-trend=0.06) grade disease. These patterns were similar among men with PSA <2ng/ml at biopsy.
   CONCLUSION. Variation in some immune response genes may be associated with prostate cancer risk. These associations were not fully explained by PSA-associated detection bias. Our findings generally support the role of inflammation in the etiology of prostate cancer. (c) 2015 Wiley Periodicals, Inc.
C1 [Winchester, Danyelle A.; Dluzniewski, Paul J.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
   [Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98104 USA.
   [Santella, Regina M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
   [Johnson-Pais, Teresa L.; Leach, Robin J.; Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
   [Xu, Jianfeng; Zheng, S. Lilly] NorthShore Univ Hlth Syst, Program Personalized Canc Care, Evanston, IL USA.
   [Xu, Jianfeng; Zheng, S. Lilly] NorthShore Univ Hlth Syst, Dept Surg, Evanston, IL USA.
   [Zheng, S. Lilly] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
   [Lucia, M. Scott] Univ Colorado, Denver Sch Med, Dept Pathol, Aurora, CO USA.
   [Lippmann, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
   [Parnes, Howard L.] NCI, Prostate & Urol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Isaacs, William B.; De Marzo, Angelo M.; Drake, Charles G.; Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA.
   [Isaacs, William B.; De Marzo, Angelo M.; Drake, Charles G.; Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA.
   [Isaacs, William B.; De Marzo, Angelo M.; Drake, Charles G.; Platz, Elizabeth A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
   [De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Drake, Charles G.] Johns Hopkins Univ, Sch Med, Dept Immunol, Baltimore, MD USA.
RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM eplatz1@jhu.edu
FU Public Health Service [P01 CA108964, U10 CA37429, UM1 CA182883, P30
   CA054174, P30 CA006973]; National Cancer Institute [T32 CA009314]
FX Grant sponsor: Public Health Service; Grant numbers: P01 CA108964; U10
   CA37429; UM1 CA182883; P30 CA054174; P30 CA006973; Grant sponsor:
   National Cancer Institute; Grant number: T32 CA009314.
NR 41
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD SEP 15
PY 2015
VL 75
IS 13
BP 1403
EP 1418
DI 10.1002/pros.23021
PG 16
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA CP2MN
UT WOS:000359711300007
PM 26047319
ER

PT J
AU Antwi, SO
   Steck, SE
   Su, LJ
   Hebert, JR
   Zhang, HM
   Fontham, ETH
   Smith, GJ
   Bensen, JT
   Mohler, JL
   Arab, L
AF Antwi, Samuel O.
   Steck, Susan E.
   Su, L. Joseph
   Hebert, James R.
   Zhang, Hongmei
   Fontham, Elizabeth T. H.
   Smith, Gary J.
   Bensen, Jeannette T.
   Mohler, James L.
   Arab, Lenore
TI Dietary, Supplement, and Adipose Tissue Tocopherol Levels in Relation to
   Prostate Cancer Aggressiveness Among African and European Americans: The
   North Carolina-Louisiana Prostate Cancer Project (PCaP)
SO PROSTATE
LA English
DT Article
DE prostate cancer; vitamin E; tocopherols; diet; supplement; adipose
   tissue; nutritional biomarkers
ID RANDOMIZED CONTROLLED-TRIAL; VITAMIN-E; RACIAL-DIFFERENCES; PREVENTION
   TRIAL; ALPHA-TOCOPHEROL; BETA-CAROTENE; UNITED-STATES; ANTIGEN ERA;
   SELF-REPORT; RISK
AB BACKGROUND. Controversies remain over the safety and efficacy of vitamin E (i.e., -tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined.
   METHODS. This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n=1,023) and European-American (EA, n=1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates.
   RESULTS. Dietary intakes of -and -tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: -tocopherol, 0.34 (0.17-0.69), P-trend=0.006; -tocopherol, 0.45 (0.21-0.95) P-trend=0.007]. Inverse associations between dietary and supplemental -tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary -tocopherol, 0.58 (0.28-1.19), P-trend=0.20; supplemental -tocopherol, 0.64 (0.31-1.21) P-trend=0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of -tocopherol for EAs 1.43 (0.66-3.11) and AAs 0.66 (0.27-1.62)].
   CONCLUSIONS. The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. (c) 2015 Wiley Periodicals, Inc.
C1 [Antwi, Samuel O.] Mayo Clin, Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
   [Steck, Susan E.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
   [Steck, Susan E.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Canc Prevent & Control Program, Columbia, SC 29208 USA.
   [Su, L. Joseph] NCI, NIH, Rockville, MD USA.
   [Zhang, Hongmei] Univ Memphis, Dept Epidemiol Biostat & Environm Hlth, Memphis, TN 38152 USA.
   [Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA USA.
   [Smith, Gary J.; Mohler, James L.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA.
   [Bensen, Jeannette T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
   [Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Steck, SE (reprint author), Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, 915 Greene St,Room 236, Columbia, SC 29208 USA.
EM ssteck@sc.edu
FU North Carolina-Louisiana Prostate Cancer Project [17-03-2-0052]; SPARC
   from Office of the Vice President for Research at the University of
   South Carolina; graduate scholar fellowship from Center for Colon Cancer
   Research; University of South Carolina
FX Grant sponsor: The North Carolina-Louisiana Prostate Cancer Project;
   Grant number: 17-03-2-0052; Grant sponsor: This study was conducted
   while Dr. Samuel Antwi was a graduate student at the University of South
   Carolina. He was supported partially by SPARC (Support to Promote
   Advancement of Research and Creativity) grant from the Office of the
   Vice President for Research at the University of South Carolina, and a
   graduate scholar fellowship grant from the Center for Colon Cancer
   Research, University of South Carolina.
NR 62
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD SEP 15
PY 2015
VL 75
IS 13
BP 1419
EP 1435
DI 10.1002/pros.23025
PG 17
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA CP2MN
UT WOS:000359711300008
PM 26053590
ER

PT J
AU Qin, M
   Zeidler, Z
   Moulton, K
   Krych, L
   Xia, ZY
   Smith, CB
AF Qin, Mei
   Zeidler, Zachary
   Moulton, Kristen
   Krych, Leland
   Xia, Zengyan
   Smith, Carolyn B.
TI Endocannabinoid-mediated improvement on a test of aversive memory in a
   mouse model of fragile X syndrome
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Fragile X syndrome; FAAH; Passive avoidance; Propofol; Fmr1 KO mice;
   Memory
ID CEREBRAL PROTEIN-SYNTHESIS; ACID AMIDE HYDROLASE; FMR1 KNOCKOUT MICE;
   PROPOFOL; ANXIETY; ACTIVATION; SYSTEM; AUTISM; RATES
AB Silencing the gene FMR1 in fragile X syndrome (FXS) with consequent loss of its protein product, FMRP, results in intellectual disability, hyperactivity, anxiety, seizure disorders, and autism-like behavior. In a mouse model (Fmr1 knockout (KO)) of FXS, a deficit in performance on the passive avoidance test of learning and memory is a robust phenotype. We report that drugs acting on the endocannabinoid (eCB) system can improve performance on this test. We present three lines of evidence: (1) Propofol (reported to inhibit fatty acid amide hydrolase (FAAH) activity) administered 30 min after training on the passive avoidance test improved performance in Frm1 KO mice but had no effect on wild type (WT). FAAH catalyzes the metabolism of the eCB, anandamide, so its inhibition should result in increased anandamide levels. (2) The effect of propofol was blocked by prior administration of the cannabinoid receptor 1 antagonist AM-251. (3) Treatment with the FAAH inhibitor, URB-597, administered 30 min after training on the passive avoidance test also improved performance in Fmrl KO mice but had no effect on WT. Our results indicate that the eCB system is involved in FXS and suggest that the eCB system is a promising target for treatment of FXS. Published by Elsevier B.V.
C1 [Qin, Mei; Zeidler, Zachary; Moulton, Kristen; Krych, Leland; Xia, Zengyan; Smith, Carolyn B.] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Bethesda, MD 20892 USA.
RP Smith, CB (reprint author), NIMH, Sect Neuroadaptat & Prot Metab, NIH, 10 Ctr Dr,Bldg 10,Rm 2D54, Bethesda, MD 20892 USA.
EM beebe@mail.nih.gov
OI Zeidler, Zachary/0000-0001-6539-4360
FU Intramural Research Program of the National Institute of Mental Health,
   National Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Mental Health, National Institutes of Health.
NR 26
TC 6
Z9 6
U1 2
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD SEP 15
PY 2015
VL 291
BP 164
EP 171
DI 10.1016/j.bbr.2015.05.003
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CN5FI
UT WOS:000358454800020
PM 25979787
ER

PT J
AU Tugarinov, V
   Libich, DS
   Meyer, V
   Roche, J
   Clore, GM
AF Tugarinov, Vitali
   Libich, David S.
   Meyer, Virginia
   Roche, Julien
   Clore, G. Marius
TI The Energetics of a Three-State Protein Folding System Probed by
   High-Pressure Relaxation Dispersion NMR Spectroscopy
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE high-pressure NMR spectroscopy; kinetics; protein folding; proteins;
   relaxation dispersion
ID DEPENDENT NMR; COMPRESSIBILITY; PERTURBATION; INTERMEDIATE;
   DENATURATION; STABILITY; EXCHANGE; CAVITIES; DYNAMICS; PATHWAY
AB The energetic and volumetric properties of a three-state protein folding system, comprising a metastable triple mutant of the Fyn SH3 domain, have been investigated using pressure-dependent N-15-relaxation dispersion NMR from 1 to 2500 bar. Changes in partial molar volumes (Delta V) and isothermal compressibilities (Delta K-T) between all the states along the folding pathway have been determined to reasonable accuracy. The partial volume and isothermal compressibility of the folded state are 100 mLmol(-1) and 40 mu Lmol(-1) bar(-1), respectively, higher than those of the unfolded ensemble. Of particular interest are the findings related to the energetic and volumetric properties of the on-pathway folding intermediate. While the latter is energetically close to the unfolded state, its volumetric properties are similar to those of the folded protein. The compressibility of the intermediate is larger than that of the folded state reflecting the less rigid nature of the former relative to the latter.
C1 [Tugarinov, Vitali; Libich, David S.; Meyer, Virginia; Roche, Julien; Clore, G. Marius] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tugarinov, V (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
EM vitali.tugarinov@nih.gov; mariusc@mail.nih.gov
FU Intramural Program of NIDDK, NIH; AIDS Targeted Antiviral Program of
   Office of Director of NIH
FX This work was supported by the Intramural Program of NIDDK, NIH and by
   the AIDS Targeted Antiviral Program of the Office of the Director of the
   NIH (to G.M.C.).
NR 26
TC 2
Z9 2
U1 6
U2 15
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD SEP 14
PY 2015
VL 54
IS 38
BP 11157
EP 11161
DI 10.1002/anie.201505416
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA CU2YJ
UT WOS:000363389400029
PM 26352026
ER

PT J
AU Cunningham, TJ
   Brade, T
   Sandell, LL
   Lewandoski, M
   Trainor, PA
   Colas, A
   Mercola, M
   Duester, G
AF Cunningham, Thomas J.
   Brade, Thomas
   Sandell, Lisa L.
   Lewandoski, Mark
   Trainor, Paul A.
   Colas, Alexandre
   Mercola, Mark
   Duester, Gregg
TI Retinoic Acid Activity in Undifferentiated Neural Progenitors Is
   Sufficient to Fulfill Its Role in Restricting Fgf8 Expression for
   Somitogenesis
SO PLOS ONE
LA English
DT Article
ID STEM-CELL DIFFERENTIATION; BODY AXIS EXTENSION; MOUSE EMBRYO; FATE
   SPECIFICATION; SIGNALING PATHWAYS; MESODERM FORMATION; PRIMITIVE STREAK;
   LIMB DEVELOPMENT; SEGMENTATION; RECEPTOR
AB Bipotent axial stem cells residing in the caudal epiblast during late gastrulation generate neuroectodermal and presomitic mesodermal progeny that coordinate somitogenesis with neural tube formation, but the mechanism that controls these two fates is not fully understood. Retinoic acid (RA) restricts the anterior extent of caudal fibroblast growth factor 8 (Fgf8) expression in both mesoderm and neural plate to control somitogenesis and neurogenesis, however it remains unclear where RA acts to control the spatial expression of caudal Fgf8. Here, we found that mouse Raldh2-/- embryos, lacking RA synthesis and displaying a consistent small somite defect, exhibited abnormal expression of key markers of axial stem cell progeny, with decreased Sox2+ and Sox1+ neuroectodermal progeny and increased Tbx6+ presomitic mesodermal progeny. The Raldh2-/- small somite defect was rescued by treatment with an FGF receptor antagonist. Rdh10 mutants, with a less severe RA synthesis defect, were found to exhibit a small somite defect and anterior expansion of caudal Fgf8 expression only for somites 1-6, with normal somite size and Fgf8 expression thereafter. Rdh10 mutants were found to lack RA activity during the early phase when somites are small, but at the 6-somite stage RA activity was detected in neural plate although not in presomitic mesoderm. Expression of a dominant-negative RA receptor in mesoderm eliminated RA activity in presomitic mesoderm but did not affect somitogenesis. Thus, RA activity in the neural plate is sufficient to prevent anterior expansion of caudal Fgf8 expression associated with a small somite defect. Our studies provide evidence that RA restriction of Fgf8 expression in undifferentiated neural progenitors stimulates neurogenesis while also restricting the anterior extent of the mesodermal Fgf8 mRNA gradient that controls somite size, providing new insight into the mechanism that coordinates somitogenesis with neurogenesis.
C1 [Cunningham, Thomas J.; Brade, Thomas; Colas, Alexandre; Mercola, Mark; Duester, Gregg] Sanford Burnham Prebys Med Discovery Inst, Dev Aging & Regenerat Program, La Jolla, CA 92037 USA.
   [Trainor, Paul A.] Stowers Inst Med Res, Kansas City, MO USA.
   [Trainor, Paul A.] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA.
   [Sandell, Lisa L.] Univ Louisville, Dept Mol Cellular & Craniofacial Biol, Louisville, KY 40292 USA.
   [Lewandoski, Mark] NCI, Lab Canc & Dev Biol, NIH, Frederick, MD 21701 USA.
   [Colas, Alexandre; Mercola, Mark] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
RP Duester, G (reprint author), Sanford Burnham Prebys Med Discovery Inst, Dev Aging & Regenerat Program, La Jolla, CA 92037 USA.
EM duester@SBPdiscovery.org
OI Cunningham, Thomas/0000-0002-4751-3140; Trainor,
   Paul/0000-0003-2774-3624; Sandell, Lisa/0000-0002-1735-8223
FU National Institutes of Health [GM062848, DE016082]; Stowers Institute
   for Medical Research
FX This work was supported by National Institutes of Health grants GM062848
   (GD) and DE016082 (PT) (www.nih.gov), and the Stowers Institute for
   Medical Research (PT) (www.stowers.org). The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 56
TC 5
Z9 5
U1 1
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 SEP 14
PY 2015
VL 10
IS 9
AR e0137894
DI 10.1371/journal.pone.0137894
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8KS
UT WOS:000361601100172
PM 26368825
ER

PT J
AU Hartley, SW
   Coon, SL
   Savastano, LE
   Mullikin, JC
   Fu, C
   Klein, DC
AF Hartley, Stephen W.
   Coon, Steven L.
   Savastano, Luis E.
   Mullikin, James C.
   Fu, Cong
   Klein, David C.
CA NISC Comparative Sequencing
TI Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on
   the Rat Pineal Transcriptome
SO PLOS ONE
LA English
DT Article
ID SEROTONIN N-ACETYLTRANSFERASE; PARAVENTRICULAR NUCLEUS AREA; CYCLIC-AMP
   MECHANISM; RNA-SEQ; MELATONIN SYNTHESIS; GENE-EXPRESSION;
   SUPRACHIASMATIC NUCLEUS; CIRCADIAN EXPRESSION; NEUROPEPTIDE-Y; GLAND
AB The term neurotranscriptomics is used here to describe genome-wide analysis of neural control of transcriptomes. In this report, next-generation RNA sequencing was using to analyze the effects of neonatal (5-days-of-age) surgical stimulus deprivation on the adult rat pineal transcriptome. In intact animals, more than 3000 coding genes were found to exhibit differential expression (adjusted-p < 0.001) on a night/day basis in the pineal gland (70% of these increased at night, 376 genes changed more than 4-fold in either direction). Of these, more than two thousand genes were not previously known to be differentially expressed on a night/day basis. The night/day changes in expression were almost completely eliminated by neonatal removal (SCGX) or decentralization (DCN) of the superior cervical ganglia (SCG), which innervate the pineal gland. Other than the loss of rhythmic variation, surgical stimulus deprivation had little impact on the abundance of most genes; of particular interest, expression levels of the melatonin-synthesis-related genes Tph1, Gch1, and Asmt displayed little change (less than 35%) following DCN or SCGX. However, strong and consistent changes were observed in the expression of a small number of genes including the gene encoding Serpina1, a secreted protease inhibitor that might influence extracellular architecture. Many of the genes that exhibited night/day differential expression in intact animals also exhibited similar changes following in vitro treatment with norepinephrine, a superior cervical ganglia transmitter, or with an analog of cyclic AMP, a norepinephrine second messenger in this tissue. These findings are of significance in that they establish that the pineal-defining transcriptome is established prior to the neonatal period. Further, this work expands our knowledge of the biological process under neural control in this tissue and underlines the value of RNA sequencing in revealing how neurotransmission influences cell biology.
C1 [Hartley, Stephen W.; Mullikin, James C.] NHGRI, Comparat Genom Anal Unit, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
   [Coon, Steven L.; Fu, Cong; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
   [Savastano, Luis E.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
   [NISC Comparative Sequencing] NHGRI, NIH, Intramural Sequencing Ctr, Rockville, MD 20852 USA.
RP Klein, DC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Sci Director, NIH, Bethesda, MD 20892 USA.
EM kleind@mail.nih.gov
FU Intramural Research Program, National Human Genome Research Institute,
   National Institutes of Health, Bethesda, MD; Intramural Research Program
   of the Eunice Kennedy Shriver National Institute of Child Health and
   Human Development, National Institutes of Health, Bethesda, MD
FX This work was supported by the Intramural Research Program, National
   Human Genome Research Institute, National Institutes of Health,
   Bethesda, MD 20892; and, the Intramural Research Program of the Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health, Bethesda, MD 20892.
NR 56
TC 6
Z9 6
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 14
PY 2015
VL 10
IS 9
AR e0137548
DI 10.1371/journal.pone.0137548
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8KS
UT WOS:000361601100082
PM 26367423
ER

PT J
AU Meier, ER
   Byrnes, C
   Weissman, M
   Lee, YT
   Miller, JL
AF Meier, Emily Riehm
   Byrnes, Colleen
   Weissman, Maxine
   Lee, Y. Terry
   Miller, Jeffery L.
TI Absolute Reticulocyte Count Acts as a Surrogate for Fetal Hemoglobin in
   Infants and Children with Sickle Cell Anemia
SO PLOS ONE
LA English
DT Article
ID RED-BLOOD-CELLS; DISEASE; ERYTHROPOIESIS; ERYTHROCYTES; HYDROXYUREA;
   EXPRESSION; SURVIVAL; DEATH; RISK
AB Hemoglobin switching is largely complete in humans by six months of age. Among infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). The objective of this study was to determine if absolute reticulocyte count (ARC) is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study. Hematologic data, including ARC and HbF levels, were measured at steady state. F-cells were enumerated by flow cytometry. Initial studies compared infants with ARC greater than or equal to 200 K/mu L (ARC >= 200) based upon the previously reported utility of this threshold as a predictive marker for SCA severity. Mean HbF and F-cell levels were significantly lower in the ARC >= 200 group when compared to the ARC < 200 group. Both HbF and F-cell percentages were negatively correlated to ARC in infants and in children between the ages of 1 and 9 years. However, the inverse relationship was lost after the age of 10 years. Overall, decreased expression and distribution of HbF during childhood SCA is well-correlated with increased reticulocyte production and release into the peripheral blood. As such, these data further support the clinical use of reticulocyte enumeration as a disease severity biomarker for childhood sickle cell anemia.
C1 [Meier, Emily Riehm; Byrnes, Colleen; Lee, Y. Terry; Miller, Jeffery L.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
   [Meier, Emily Riehm] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
   [Weissman, Maxine] NIH, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA.
   [Meier, Emily Riehm] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA.
RP Miller, JL (reprint author), NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
EM jm7f@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases; NIH National Center for Advancing
   Translational Sciences [UL1TR000075, KL2TR000076]
FX The Intramural Research Program of the National Institute of Diabetes
   and Digestive and Kidney Diseases supported this work. Dr. Meier is
   supported by Award Numbers UL1TR000075 and KL2TR000076 from the NIH
   National Center for Advancing Translational Sciences. The contents are
   solely the responsibility of the authors and do not necessarily
   represent the official views of the National Center for Advancing
   Translational Sciences or the National Institutes of Health. The authors
   have no conflicts of interest to disclose.
NR 21
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 14
PY 2015
VL 10
IS 9
AR e0136672
DI 10.1371/journal.pone.0136672
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8KS
UT WOS:000361601100020
PM 26366562
ER

PT J
AU Moodie, Z
   Metch, B
   Bekker, LG
   Churchyard, G
   Nchabeleng, M
   Mlisana, K
   Laher, F
   Roux, S
   Mngadi, K
   Innes, C
   Mathebula, M
   Allen, M
   Bentley, C
   Gilbert, PB
   Robertson, M
   Kublin, J
   Corey, L
   Gray, GE
AF Moodie, Zoe
   Metch, Barbara
   Bekker, Linda-Gail
   Churchyard, Gavin
   Nchabeleng, Maphoshane
   Mlisana, Koleka
   Laher, Fatima
   Roux, Surita
   Mngadi, Kathryn
   Innes, Craig
   Mathebula, Matsontso
   Allen, Mary
   Bentley, Carter
   Gilbert, Peter B.
   Robertson, Michael
   Kublin, James
   Corey, Lawrence
   Gray, Glenda E.
TI Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial
   Participants Supports Increased HIV-1 Acquisition among Vaccinated Men
SO PLOS ONE
LA English
DT Article
ID DOUBLE-BLIND; T-CELLS; HVTN 503/PHAMBILI; IMMUNE ACTIVATION;
   HEALTHY-ADULTS; EFFICACY TRIAL; SOUTH-AFRICA; ADENOVIRUS; SAFETY;
   IMMUNOGENICITY
AB Background
   The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study.
   Methods
   HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models.
   Results
   Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08-2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62).
   Conclusion
   The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women.
C1 [Moodie, Zoe; Metch, Barbara; Bentley, Carter; Gilbert, Peter B.; Kublin, James; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
   [Bekker, Linda-Gail; Roux, Surita] Univ Cape Town, Desmond Tutu HIV Fdn, ZA-7925 Cape Town, South Africa.
   [Churchyard, Gavin] Aurum Inst Hlth Res, Johannesburg, South Africa.
   [Churchyard, Gavin] Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa.
   [Churchyard, Gavin] London Sch Hyg & Trop Med, London WC1, England.
   [Nchabeleng, Maphoshane; Mathebula, Matsontso] Sefako Makgatho Hlth Sci Univ, Mecru Clin Res Unit, Pretoria, South Africa.
   [Mngadi, Kathryn] CAPRISA, Durban, South Africa.
   [Mlisana, Koleka; Mngadi, Kathryn] Univ KwaZulu Natal, Sch Lab Med & Med Sci, Durban, South Africa.
   [Mlisana, Koleka; Mngadi, Kathryn] Natl Hlth Lab Serv, Durban, South Africa.
   [Laher, Fatima; Gray, Glenda E.] Univ Witwatersrand, Fac Hlth Sci, Perinatal HIV Res Unit, Johannesburg, South Africa.
   [Innes, Craig] Aurum Inst Clin Res Site, Klerksdorp, South Africa.
   [Allen, Mary] NIAID, Vaccine Res Program, Div Aids, NIH, Rockville, MD USA.
   [Robertson, Michael] Merck Res Labs, West Point, PA USA.
   [Gray, Glenda E.] South African Med Res Council, Cape Town, South Africa.
RP Moodie, Z (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
EM zoe@fredhutch.org
FU National Institute of Allergy and Infectious Diseases [UM1 AI068614, UM1
   AI068618, UM1 AI068635, UM1 AI069453, UM1 AI069519, UM1 AI069469]; Merck
   and Co Inc.; Division of Acquired Immunodeficiency Syndrome of the US
   National Institute of Allergy and Infectious Diseases (NIAID); Merck
   Research Laboratories
FX This work was supported by grants from the National Institute of Allergy
   and Infectious Diseases to the HIV Vaccine Trials Network (UM1 AI068614,
   UM1 AI068618, UM1 AI068635, UM1 AI069453, UM1 AI069519, UM1 AI069469) as
   well as Merck and Co Inc. Role of the funding source: The study and
   report were reviewed by the Division of Acquired Immunodeficiency
   Syndrome of the US National Institute of Allergy and Infectious Diseases
   (NIAID) and Merck Research Laboratories. The corresponding author had
   full access to all the data in the study and had final responsibility
   for the decision to submit for publication. Merck Research Laboratories
   provided support in the form of salary for author Robertson [MR] and
   provision of study products. NIAID and MR contributed to the study
   design, review of data analysis, the decision to publish, and review of
   the manuscript. The specific roles of the NIAID and MR authors are
   articulated in the 'author contributions' section.
NR 23
TC 4
Z9 4
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 14
PY 2015
VL 10
IS 9
AR e0137666
DI 10.1371/journal.pone.0137666
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8KS
UT WOS:000361601100102
PM 26368824
ER

PT J
AU Kortum, RL
   Morrison, DK
AF Kortum, Robert L.
   Morrison, Deborah K.
TI Path Forward for RAF Therapies: Inhibition of Monomers and Dimers
SO CANCER CELL
LA English
DT Editorial Material
ID MUTANT MELANOMA; DIMERIZATION; RESISTANCE
AB Current BRAF inhibitors block signaling from monomeric BRAF(V600E), but not from oncogenic RAS, which requires RAF dimerization. In this issue of Cancer Cell, Yao and colleagues investigate why current drugs are ineffective against RAF dimers, while Peng and colleagues describe a pan-RAF inhibitor targeting both monomeric and dimeric RAF.
C1 [Kortum, Robert L.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol & Mol Therapeut, Bethesda, MD 20814 USA.
   [Kortum, Robert L.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM morrisod@mail.nih.gov
NR 10
TC 4
Z9 4
U1 1
U2 8
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 SEP 14
PY 2015
VL 28
IS 3
BP 279
EP 281
DI 10.1016/j.ccell.2015.08.006
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CR5YS
UT WOS:000361420900005
PM 26373275
ER

PT J
AU Fulgenzi, G
   Tomassoni-Ardori, F
   Babini, L
   Becker, J
   Barrick, C
   Puverel, S
   Tessarollo, L
AF Fulgenzi, Gianluca
   Tomassoni-Ardori, Francesco
   Babini, Lucia
   Becker, Jodi
   Barrick, Colleen
   Puverel, Sandrine
   Tessarollo, Lino
TI BDNF modulates heart contraction force and long-term homeostasis through
   truncated TrkB.T1 receptor activation
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID NEUROTROPHIC FACTOR; IN-VIVO; CARDIAC MYOCYTES; CYTOSOLIC CA2+; CELLS;
   EXPRESSION; SURVIVAL; RELEASE; MOUSE; MECHANISM
AB Brain-derived neurotrophic factor (BDNF) is critical for mammalian development and plasticity of neuronal circuitries affecting memory, mood, anxiety, pain sensitivity, and energy homeostasis. Here we report a novel unexpected role of BDNF in regulating the cardiac contraction force independent of the nervous system innervation. This function is mediated by the truncated TrkB.T1 receptor expressed in cardiomyocytes. Loss of TrkB.T1 in these cells impairs calcium signaling and causes cardiomyopathy. TrkB.T1 is activated by BDNF produced by cardiomyocytes, suggesting an autocrine/paracrine loop. These findings unveil a novel signaling mechanism in the heart that is activated by BDNF and provide evidence for a global role of this neurotrophin in the homeostasis of the organism by signaling through different TrkB receptor isoforms.
C1 [Fulgenzi, Gianluca; Tomassoni-Ardori, Francesco; Babini, Lucia; Becker, Jodi; Barrick, Colleen; Puverel, Sandrine; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
   [Fulgenzi, Gianluca] Marche Polytech Univ, Dept Mol & Clin Sci, I-60020 Ancona, Italy.
RP Tessarollo, L (reprint author), NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM tessarol@mail.nih.gov
FU National Institutes of Health Intramural Research Program, Center for
   Cancer Research, and National Cancer Institute
FX This work was supported by the National Institutes of Health Intramural
   Research Program, Center for Cancer Research, and National Cancer
   Institute.
NR 40
TC 3
Z9 3
U1 0
U2 12
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 SEP 14
PY 2015
VL 210
IS 6
BP 1003
EP 1012
DI 10.1083/jcb.201502100
PG 10
WC Cell Biology
SC Cell Biology
GA CR5XL
UT WOS:000361417600014
PM 26347138
ER

PT J
AU Teos, LY
   Zhang, Y
   Cotrim, AP
   Swaim, W
   Won, JH
   Ambrus, J
   Shen, L
   Bebris, L
   Grisius, M
   Jang, SI
   Yule, DI
   Ambudkar, IS
   Alevizos, I
AF Teos, Leyla Y.
   Zhang, Yu
   Cotrim, Ana P.
   Swaim, William
   Won, Jon H.
   Ambrus, Julian
   Shen, Long
   Bebris, Lolita
   Grisius, Margaret
   Jang, Shyh-Ing
   Yule, David I.
   Ambudkar, Indu S.
   Alevizos, Ilias
TI IP3R deficit underlies loss of salivary fluid secretion in Sjogren's
   Syndrome
SO SCIENTIFIC REPORTS
LA English
DT Article
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; GLAND ACINAR-CELLS; EXOCRINE
   SECRETION; FLUORESCENT DYE; CA2+ RELEASE; MOUSE MODELS; LOCALIZATION;
   LYMPHOTOXIN; INVOLVEMENT; ACTIVATION
AB The autoimmune exocrinopathy, Sjogren's syndrome (SS), is associated with secretory defects in patients, including individuals with mild lymphocytic infiltration and minimal glandular damage. The mechanism(s) underlying the secretory dysfunction is not known. We have used minor salivary gland biopsies from SS patients and healthy individuals to assess acinar cell function in morphologically intact glandular areas. We report that agonist-regulated intracellular Ca2+ release, critically required for Ca2+ entry and fluid secretion, is defective in acini from SS patients. Importantly, these acini displayed reduction in IP3R2 and IP3R3, but not AQP5 or STIM1. Similar decreases in IP3R and carbachol (CCh)-stimulated [Ca2+](i) elevation were detected in acinar cells from lymphotoxin-alpha (LT alpha) transgenic (TG) mice, a model for (SS). Treatment of salivary glands from healthy individuals with LT alpha, a cytokine linked to disease progression in SS and IL14 alpha mice, reduced Ca2+ signaling. Together, our findings reveal novel IP3R deficits in acinar cells that underlie secretory dysfunction in SS patients.
C1 [Teos, Leyla Y.; Cotrim, Ana P.; Bebris, Lolita; Grisius, Margaret; Jang, Shyh-Ing; Alevizos, Ilias] NIDCR, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, MPTB, NIH, Bethesda, MD 20892 USA.
   [Teos, Leyla Y.; Swaim, William; Ambudkar, Indu S.] NIDCR, Secretory & Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA.
   [Zhang, Yu; Won, Jon H.; Yule, David I.] Univ Rochester, Dept Pharmacol & Physiol, Rochester, NY 14642 USA.
   [Ambrus, Julian; Shen, Long] SUNY Buffalo, Sch Med & Biomed Sci, Dept Med, Div Allergy Immunol & Rheumatol, Buffalo, NY 14203 USA.
RP Ambudkar, IS (reprint author), NIDCR, Secretory & Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA.
EM alevizosi@nidcr.nih.gov; indu.ambudkar@nih.gov; alevizosi@nidcr.nih.gov
FU NIDCR-IRP;  [DE014756]
FX We would like to thank Gabor Illei, D.M.D., Ph.D., for his invaluable
   advice in planning and discussing the human SS experiments as well as
   interpreting the data. Funding for this study was provided by NIDCR-IRP
   to Indu Ambudkar and Ilias Alevizos and by DE014756 awarded to David
   Yule.
NR 51
TC 7
Z9 7
U1 1
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 SEP 14
PY 2015
VL 5
AR 13953
DI 10.1038/srep13953
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR1RE
UT WOS:000361101700001
PM 26365984
ER

PT J
AU Sudmant, PH
   Mallick, S
   Nelson, BJ
   Hormozdiari, F
   Krumm, N
   Huddleston, J
   Coe, BP
   Baker, C
   Nordenfelt, S
   Bamshad, M
   Jorde, LB
   Posukh, OL
   Sahakyan, H
   Watkins, WS
   Yepiskoposyan, L
   Abdullah, MS
   Bravi, CM
   Capelli, C
   Hervig, T
   Wee, JTS
   Tyler-Smith, C
   van Driem, G
   Romero, IG
   Jha, AR
   Karachanak-Yankova, S
   Toncheva, D
   Comas, D
   Henn, B
   Kivisild, T
   Ruiz-Linares, A
   Sajantila, A
   Metspalu, E
   Parik, J
   Villems, R
   Starikovskaya, EB
   Ayodo, G
   Beall, CM
   Di Rienzo, A
   Hammer, MF
   Khusainova, R
   Khusnutdinova, E
   Klitz, W
   Winkler, C
   Labuda, D
   Metspalu, M
   Tishkoff, SA
   Dryomov, S
   Sukernik, R
   Patterson, N
   Reich, D
   Eichler, EE
AF Sudmant, Peter H.
   Mallick, Swapan
   Nelson, Bradley J.
   Hormozdiari, Fereydoun
   Krumm, Niklas
   Huddleston, John
   Coe, Bradley P.
   Baker, Carl
   Nordenfelt, Susanne
   Bamshad, Michael
   Jorde, Lynn B.
   Posukh, Olga L.
   Sahakyan, Hovhannes
   Watkins, W. Scott
   Yepiskoposyan, Levon
   Abdullah, M. Syafiq
   Bravi, Claudio M.
   Capelli, Cristian
   Hervig, Tor
   Wee, Joseph T. S.
   Tyler-Smith, Chris
   van Driem, George
   Romero, Irene Gallego
   Jha, Aashish R.
   Karachanak-Yankova, Sena
   Toncheva, Draga
   Comas, David
   Henn, Brenna
   Kivisild, Toomas
   Ruiz-Linares, Andres
   Sajantila, Antti
   Metspalu, Ene
   Parik, Jueri
   Villems, Richard
   Starikovskaya, Elena B.
   Ayodo, George
   Beall, Cynthia M.
   Di Rienzo, Anna
   Hammer, Michael F.
   Khusainova, Rita
   Khusnutdinova, Elza
   Klitz, William
   Winkler, Cheryl
   Labuda, Damian
   Metspalu, Mait
   Tishkoff, Sarah A.
   Dryomov, Stanislav
   Sukernik, Rem
   Patterson, Nick
   Reich, David
   Eichler, Evan E.
TI Global diversity, population stratification, and selection of human
   copy-number variation
SO SCIENCE
LA English
DT Article
ID HUMAN GENOME SEQUENCE; SEGMENTAL DUPLICATIONS; CODING VARIATION;
   POLYMORPHISMS; ASSOCIATION; DELETION; HISTORY; REGIONS; AUTISM;
   MICRODELETION
AB In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.
C1 [Sudmant, Peter H.; Nelson, Bradley J.; Hormozdiari, Fereydoun; Krumm, Niklas; Huddleston, John; Coe, Bradley P.; Baker, Carl; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Mallick, Swapan; Nordenfelt, Susanne; Patterson, Nick; Reich, David] Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA USA.
   [Mallick, Swapan; Nordenfelt, Susanne; Patterson, Nick; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Bamshad, Michael] Univ Washington, Dept Pediat, Seattle, WA 98119 USA.
   [Jorde, Lynn B.] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84112 USA.
   [Posukh, Olga L.] Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Novosibirsk 630090, Russia.
   [Posukh, Olga L.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
   [Sahakyan, Hovhannes; Metspalu, Ene; Parik, Jueri; Villems, Richard; Metspalu, Mait] Estonian Bioctr, Evolutionary Biol Grp, EE-51010 Tartu, Estonia.
   [Sahakyan, Hovhannes; Yepiskoposyan, Levon] Natl Acad Sci Armenia, Inst Mol Biol, Lab Ethnogen, Yerevan 0014, Armenia.
   [Watkins, W. Scott] Univ Utah, Eccles Inst Human Genet, Dept Human Genet, Salt Lake City, UT 84112 USA.
   [Abdullah, M. Syafiq] Raja Isteri Pengiran Anak Saleha RIPAS Hosp, Bandar Seri Begawan, Brunei Darussal, Brunei.
   [Bravi, Claudio M.] CCT CONICET, Inst Multidisciplinario Biol Celular IMBICE, Lab Genet Mol Poblac, Rio Cuarto, Argentina.
   [Bravi, Claudio M.] CICPBA, Rio Cuarto, Argentina.
   [Capelli, Cristian] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Hervig, Tor] Univ Bergen, Dept Clin Sci, N-5021 Bergen, Norway.
   [Wee, Joseph T. S.] Natl Canc Ctr Singapore, Singapore, Singapore.
   [Tyler-Smith, Chris] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
   [van Driem, George] Univ Bern, Inst Linguist, CH-3012 Bern, Switzerland.
   [Romero, Irene Gallego; Jha, Aashish R.; Di Rienzo, Anna] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Karachanak-Yankova, Sena; Toncheva, Draga] Med Univ Sofia, Natl Human Genome Ctr, Dept Med Genet, Sofia 1431, Bulgaria.
   [Comas, David] CSIC UPF, Dept Ciencies Expt, Inst Biol Evolut, Barcelona 08003, Spain.
   [Henn, Brenna] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA.
   [Kivisild, Toomas] Univ Cambridge, Div Biol Anthropol, Cambridge CB2 1QH, England.
   [Ruiz-Linares, Andres] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Sajantila, Antti] Univ Helsinki, Dept Forens Med, Helsinki 00014, Finland.
   [Metspalu, Ene] Univ Tartu, Dept Evolutionary Biol, EE-5101 Tartu, Estonia.
   [Starikovskaya, Elena B.; Dryomov, Stanislav; Sukernik, Rem] Russian Acad Sci, Siberian Branch, Inst Mol & Cellular Biol, Lab Human Mol Genet, Novosibirsk 630090, Russia.
   [Ayodo, George] Ctr Global Hlth & Child Dev, Kisumu 40100, Kenya.
   [Beall, Cynthia M.] Case Western Reserve Univ, Dept Anthropol, Cleveland, OH 44106 USA.
   [Hammer, Michael F.] Univ Arizona, Div Biotechnol, Arizona Res Labs, Tucson, AZ 85721 USA.
   [Khusainova, Rita; Khusnutdinova, Elza] Russian Acad Sci, Ufa Res Ctr, Inst Biochem & Genet, Ufa 450054, Russia.
   [Khusainova, Rita; Khusnutdinova, Elza] Bashkir State Univ, Dept Genet & Fundamental Med, Ufa 450074, Russia.
   [Klitz, William] Univ Calif Berkeley, Integrat Biol, Berkeley, CA 94720 USA.
   [Winkler, Cheryl] NCI, Bas Res Lab, Ctr Canc Res, Leidos Biomed Res Inc,Frederick Natl Lab, Ft Detrick, MD 21702 USA.
   [Labuda, Damian] Univ Montreal, Ctr Hosp Univ CHU St Justine, Dept Pediat, Montreal, PQ H3T 1C5, Canada.
   [Tishkoff, Sarah A.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Tishkoff, Sarah A.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   [Dryomov, Stanislav] Russian Acad Sci, Inst Archaeol & Ethnog, Siberian Branch, Dept Paleolith Archaeol, Novosibirsk 630090, Russia.
   [Sukernik, Rem] Altai State Univ, Barnaul 656000, Russia.
   [Reich, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Huddleston, John; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
RP Eichler, EE (reprint author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM eee@gs.washington.edu
RI Starikovskaya, Elena/N-5636-2015; Metspalu, Mait/G-8671-2015; Dryomov,
   Stanislav/N-5476-2015; Sukernik, Rem/N-6990-2015; Coe,
   Bradley/A-2878-2009; Khusnutdinova, Elza/A-4810-2013; Posukh,
   Olga/Q-6065-2016; 
OI Metspalu, Mait/0000-0003-3099-9161; Posukh, Olga/0000-0003-1352-3591;
   Gallego Romero, Irene/0000-0003-1613-8998; Sudmant,
   Peter/0000-0002-9573-8248
FU National Cancer Institute, NIH [HHSN26120080001E]; NIH, National Cancer
   Institute, Center for Cancer Research; NIH [2R01HG002385, 5DP1ES022577
   05, 1R01DK104339-01, 1R01GM113657-01]; Paul G. Allen Family Foundation
   [11631]; Simons Foundation [SFARI 280376]; HOMINID grant from the NSF
   [BCS-1032255]; European Research Council [FP7 - 26213]; Ministry of
   Education and Science, Russian Federation [14.Z50.31.0010]; Estonian
   Research Council [IUT24-1]; European Regional Development Fund (European
   Union) through the Centre of Excellence in Genomics; University of
   Tartu; Wellcome Trust [098051]; NSF [0924726, 1153911]
FX We are grateful to the volunteers who donated the DNA samples used in
   this study. This project has been funded in part with federal funds from
   the National Cancer Institute, NIH, 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 the
   mention of trade names, commercial products, or organizations imply
   endorsement by the U.S. government. This research was supported in part
   by the Intramural Research Program of the NIH, National Cancer
   Institute, Center for Cancer Research. This work was also partly
   supported by NIH grant 2R01HG002385 and a grant (11631) from the Paul G.
   Allen Family Foundation to E.E.E. The sequencing for this study was
   supported by a grant from the Simons Foundation to D.R. (SFARI 280376)
   and by a HOMINID grant from the NSF to D.R. (BCS-1032255). T.K. is
   supported by a European Research Council Starting Investigator grant
   (FP7 - 26213). R.S. and S.D. received support from the Ministry of
   Education and Science, Russian Federation (14.Z50.31.0010). H.S., E.M.,
   R.V., and M.M. are supported by Institutional Research Funding from the
   Estonian Research Council IUT24-1 and by the European Regional
   Development Fund (European Union) through the Centre of Excellence in
   Genomics to Estonian Biocentre and University of Tartu. S.A.T. is
   supported by NIH grants 5DP1ES022577 05, 1R01DK104339-01, and
   1R01GM113657-01. C.T.-S. is supported by Wellcome Trust grant 098051.
   C.M.B. is supported by the NSF (award numbers 0924726 and 1153911).
   E.E.E. and D.R. are investigators of the Howard Hughes Medical
   Institute. Data are deposited into ENA (PRJEB9586 or ERP010710), and
   variant calls are deposited in dbVar (PRJNA285786). E.E.E. is on the
   scientific advisory board of DNAnexus, Incorporated, and is a consultant
   for Kunming University of Science and Technology (KUST) as part of the
   1000 China Talent Program.
NR 50
TC 38
Z9 40
U1 5
U2 30
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 SEP 11
PY 2015
VL 349
IS 6253
AR aab3761
DI 10.1126/science.aab3761
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ9XH
UT WOS:000360968400033
PM 26249230
ER

PT J
AU Pushko, P
   Pujanauski, LM
   Sun, XJ
   Pearce, M
   Hidajat, R
   Kort, T
   Schwartzman, LM
   Tretyakova, I
   Liu, CQ
   Taubenberger, JK
   Tumpey, TM
AF Pushko, Peter
   Pujanauski, Lindsey M.
   Sun, Xiangjie
   Pearce, Melissa
   Hidajat, Rachmat
   Kort, Thomas
   Schwartzman, Louis M.
   Tretyakova, Irina
   Liu Chunqing
   Taubenberger, Jeffery K.
   Tumpey, Terrence M.
TI Recombinant H7 hemagglutinin forms subviral particles that protect mice
   and ferrets from challenge with H7N9 influenza virus
SO VACCINE
LA English
DT Article
DE Influenza; H7N9; Influenza vaccine; Virus-like particles; VLP
ID AVIAN INFLUENZA; IMMUNE-RESPONSES; H5N1 VIRUSES; INTRANASAL VACCINATION;
   CONFERS PROTECTION; CANDIDATE VACCINE; CONTROLLED-TRIAL; HEALTHY-ADULTS;
   A(H7N9) VIRUS; INFECTION
AB A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant approaches including hemagglutinin (HA) and virus-like particles (VLPs) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. While high immunogenicity of VLP vaccines has been attributed to the native conformation of HA arranged in the regular repeated patterns within virus-like structures, there is limited data regarding molecular organization of HA within recombinant HA vaccine preparations. In this study, the full-length recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9 cells. We showed that purified full-length rH7 retained functional ability to agglutinate red blood cells and formed oligomeric pleomorphic subviral particles (SVPs) of similar to 20 nm in diameter composed of approximately 10 HAO molecules. No significant quantities of free monomeric HAO were observed in rH7 preparation by size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs was confirmed in the mouse and ferret challenge models suggesting that SVPs can be used for vaccination against H7N9 virus. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Pushko, Peter; Hidajat, Rachmat; Kort, Thomas; Tretyakova, Irina] Medigen Inc, Frederick, MD 21701 USA.
   [Liu Chunqing] Wuhan Siqiyuan Ltd, Wuhan, Peoples R China.
   [Pujanauski, Lindsey M.; Schwartzman, Louis M.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, NIH, Bethesda, MD 20892 USA.
   [Sun, Xiangjie; Pearce, Melissa; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA.
RP Pushko, P (reprint author), Medigen Inc, 8420 Gas House Pike,Suite S, Frederick, MD 21701 USA.
EM ppushko@medigen-usa.com
OI Pujanandez, Lindsey/0000-0002-2982-3700
FU NIH NIAID [1R01AI111532]; USDA NIFA [2013-33610-21041]; Intramural
   Research Program of the National Institute of Allergy and Infectious
   Diseases, National Institutes of Health
FX We thank Darrell Kapczynski (SEPRL, USDA) for H7-specific antiserum. We
   also thank Noah Horn, Raphael Prather, Brian Nickols, Xia Lei, and
   Xiaohui Li for valuable contributions and discussions. LMP current
   address is The American Association of Immunologists, 9650 Rockville
   Pike, Bethesda, MD, USA. This research was supported in part by grants
   1R01AI111532 (NIH NIAID) and 2013-33610-21041 (USDA NIFA) to P.P., and
   in part by the Intramural Research Program of the National Institute of
   Allergy and Infectious Diseases, National Institutes of Health. We thank
   the Comparative Medicine Branch (NIAID, NIH) for assistance with the
   mouse studies. The findings and conclusions in this report are those of
   the authors and do not necessarily reflect the views of the funding
   agencies.
NR 52
TC 8
Z9 8
U1 0
U2 3
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 SEP 11
PY 2015
VL 33
IS 38
BP 4975
EP 4982
DI 10.1016/j.vaccine.2015.07.026
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CR8EE
UT WOS:000361583100035
PM 26207590
ER

PT J
AU Fufa, TD
   Byun, JS
   Wakano, C
   Fernandez, AG
   Pise-Masison, CA
   Gardner, K
AF Fufa, Temesgen D.
   Byun, Jung S.
   Wakano, Clay
   Fernandez, Alfonso G.
   Pise-Masison, Cynthia A.
   Gardner, Kevin
TI The Tax oncogene enhances ELL incorporation into p300 and P-TEFb
   containing protein complexes to activate transcription
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE ELL; p300; P-TEFb; HTLV-1; Tax; Transcription
ID RNA-POLYMERASE-II; MAMMALIAN MEDIATOR COMPLEX; ELONGATION COMPLEX; HIV-1
   TAT; LEUKEMIA; DSIF; MLL; PROMOTER; RELEASE; GENE
AB The eleven-nineteen lysine-rich leukemia protein (ELL) is a key regulator of RNA polymerase II mediated transcription. ELL facilitates RNA polymerase II transcription pause site entry and release by dynamically interacting with p300 and the positive transcription elongation factor b (P-TEFb). In this study, we investigated the role of ELL during the HTLV-1 Tax oncogene induced transactivation. We show that ectopic expression of Tax enhances ELL incorporation into p300 and P-TEFb containing transcriptional complexes and the subsequent recruitment of these complexes to target genes in vivo. Depletion of ELL abrogates Tax induced transactivation of the immediate early genes Fos, Egr2 and NF-kappa B, suggesting that ELL is an essential cellular cofactor of the Tax oncogene. Thus, our study identifies a novel mechanism of ELL-dependent transactivation of immediate early genes by Tax and provides the rational for further defining the genome-wide targets of Tax and ELL. Published by Elsevier Inc.
C1 [Fufa, Temesgen D.; Byun, Jung S.; Wakano, Clay; Fernandez, Alfonso G.; Pise-Masison, Cynthia A.; Gardner, Kevin] NCI, Bethesda, MD 20892 USA.
RP Gardner, K (reprint author), NCI, 37 Convent Dr,Rm 1042, Bethesda, MD 20892 USA.
EM gardnerk@mail.nih.gov
FU Intramural Research Program of NCI; National Institutes of Health
FX Part of this work was submitted to Howard University (Washington, DC) to
   fulfill, in part, Ph.D. dissertation research requirements for T.D.F. We
   would like to thank Ms. Cynthia M. Haggerty and Mr. Jesse Quintero
   (National Cancer Institute, Bethesda, MD) for assistance with cell
   culture. Funding for the study was provided through the Intramural
   Research Program of NCI, the National Institutes of Health.
NR 34
TC 2
Z9 2
U1 0
U2 0
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 SEP 11
PY 2015
VL 465
IS 1
BP 5
EP 11
DI 10.1016/j.bbrc.2015.07.072
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CR5XI
UT WOS:000361417300003
PM 26188510
ER

PT J
AU Nata, T
   Basheer, A
   Cocchi, F
   van Besien, R
   Massoud, R
   Jacobson, S
   Azimi, N
   Tagaya, Y
AF Nata, Toshie
   Basheer, Asjad
   Cocchi, Fiorenza
   van Besien, Richard
   Massoud, Raya
   Jacobson, Steven
   Azimi, Nazli
   Tagaya, Yutaka
TI Targeting the Binding Interface on a Shared Receptor Subunit of a
   Cytokine Family Enables the Inhibition of Multiple Member Cytokines with
   Selectable Target Spectrum
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACTIVATED KILLER-CELLS; CELIAC-DISEASE; T-CELLS; RHEUMATOID-ARTHRITIS;
   NATURAL-KILLER; INTRAEPITHELIAL LYMPHOCYTES; LYMPHOID DEVELOPMENT;
   ULCERATIVE-COLITIS; TRANSGENIC MICE; BETA-CHAIN
AB The common gamma molecule (gamma c) is a shared signaling receptor subunit used by six gamma c-cytokines. These cytokines play crucial roles in the differentiation of the mature immune system and are involved in many human diseases. Moreover, recent studies suggest that multiple gamma c-cytokines are pathogenically involved in a single disease, thus making the shared gamma c-molecule a logical target for therapeutic intervention. However, the current therapeutic strategies seem to lack options to treat such cases, partly because of the lack of appropriate neutralizing antibodies recognizing the gamma c and, more importantly, because of the inherent and practical limitations in the use of monoclonal antibodies. By targeting the binding interface of the gamma c and cytokines, we successfully designed peptides that not only inhibit multiple gamma c-cytokines but with a selectable target spectrum. Notably, the lead peptide inhibited three gamma c-cytokines without affecting the other three or non-gamma c-cytokines. Biological and mutational analyses of our peptide provide new insights to our current understanding on the structural aspect of the binding of gamma c-cytokines the gamma c-molecule. Furthermore, we provide evidence that our peptide, when conjugated to polyethylene glycol to gain stability in vivo, efficiently blocks the action of one of the target cytokines in animal models. Collectively, our technology can be expanded to target various combinations of gamma c-cytokines and thereby will provide a novel strategy to the current anti-cytokine therapies against immune, inflammatory, and malignant diseases.
C1 [Nata, Toshie; Cocchi, Fiorenza; van Besien, Richard; Tagaya, Yutaka] Univ Maryland, Sch Med, Inst Human Virol, Cell Biol Lab,Div Basic Sci, Baltimore, MD 21201 USA.
   [Basheer, Asjad; Azimi, Nazli] BIONIZ Inc, Irvine, CA 92618 USA.
   [Massoud, Raya; Jacobson, Steven] NINDS, Sect Neuroimmunol, NIH, Bethesda, MD 20890 USA.
RP Tagaya, Y (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Cell Biol Lab,Div Basic Sci, Baltimore, MD 21201 USA.
EM ytagaya@ihv.umaryland.edu
FU BIONIZ; Institute of Human Virology, University of Maryland School of
   Medicine
FX This work was supported in part by research funding from BIONIZ (to
   T.N., F.C., and Y.T.) and in part by internal research funding from the
   Institute of Human Virology, University of Maryland School of Medicine.
   This work was authored, in whole or in part, by National Institutes of
   Health staff. A. B. is an employee of BIONIZ, Inc. N. A. is the founder
   of BIONIZ. BIONIZ holds the United States patent for the technology
   behind this work and the concept and peptides used in this paper. We
   also declare that these financial involvements of BIONIZ did not
   undermine the scientific objectivity and integrity of the presented
   work.
NR 68
TC 4
Z9 4
U1 3
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 SEP 11
PY 2015
VL 290
IS 37
BP 22338
EP 22351
DI 10.1074/jbc.M115.661074
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CR2PB
UT WOS:000361171500003
PM 26183780
ER

PT J
AU Smarr, MM
   Grantz, KL
   Sundaram, R
   Maisog, JM
   Kannan, K
   Louis, GMB
AF Smarr, Melissa M.
   Grantz, Katherine L.
   Sundaram, Rajeshwari
   Maisog, Jose M.
   Kannan, Kurunthachalam
   Louis, Germaine M. Buck
TI Parental urinary biomarkers of preconception exposure to bisphenol A and
   phthalates in relation to birth outcomes
SO ENVIRONMENTAL HEALTH
LA English
DT Article
DE Bisphenol A; Phthalates; Preconception exposure; Birth weight; Head
   circumference; Ponderal index; Endocrine disruptors
ID DI(2-ETHYLHEXYL)PHTHALATE DEHP; TEMPORAL VARIABILITY; PROSPECTIVE
   COHORT; CIGARETTE-SMOKING; MATERNAL EXPOSURE; OXIDATIVE STRESS;
   ENVIRONMENT LIFE; COUPLE FECUNDITY; DETECTION LIMITS; US POPULATION
AB Background: Bisphenol A (BPA) and phthalates are ubiquitous non-persistent endocrine disrupting chemicals whose relation with infant birth size is not clearly understood.
   Methods: We examined associations between maternal and paternal preconception urinary concentrations of total BPA and 14 phthalate metabolites and birth size for 233 infants. Multiple linear regression models were used to estimate parental quartiles of BPA and phthalates in relation to birth weight, length, head circumference, and ponderal index with separate models run for each parent adjusting for age, smoking, body mass index, education, alcohol, parity, and creatinine. Models also included an interaction term for each chemical and infant sex and were further adjusted to include the other partner's chemical concentrations.
   Results: In maternal models adjusted for partner's exposure and covariates, reductions in birth weight (range: 178-215 g; p < 0.05) were observed for the 2nd quartile of maternal monomethyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate and mono-n-octyl phthalate when compared with the 1st quartiles. The 3rd quartile of monoethylhexyl phthalate (mEHP) was also associated with a 200.16 g (95 % CI: -386.90, -13.42) reduction. Similar reductions in birth weight were observed for the 2nd quartile of paternal mEHP (beta = -191.93 g; 95 % CI: -381.61, -2.25). Additionally, select maternal urinary metabolites were associated with decreased head circumference, birth length and gestational age. However, paternal concentrations were generally associated with increased birth length and gestational age.
   Conclusions: We observed some suggestion that preconception maternal and paternal urinary concentration of BPA and specific phthalate metabolites may be associated with smaller birth size and increased gestational age, though the findings appeared to be parent and chemical specific.
C1 [Smarr, Melissa M.; Grantz, Katherine L.; Sundaram, Rajeshwari; Maisog, Jose M.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
   [Kannan, Kurunthachalam] New York State Dept Hlth, Div Environm Hlth Sci, Wadsworth Ctr, Albany, NY USA.
   [Kannan, Kurunthachalam] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA.
RP Smarr, MM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM melissa.smarr@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490; Sundaram,
   Rajeshwari/0000-0002-6918-5002; Grantz, Katherine/0000-0003-0276-8534
FU National Institutes of Health, Intramural Research Program, Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358, HHSN27500001]
FX Funded by the National Institutes of Health, Intramural Research
   Program, Eunice Kennedy Shriver National Institute of Child Health and
   Human Development (contracts N01-HD-3-3355; N01-HD-3-3356;
   NOH-HD-3-3358; HHSN27500001).
NR 59
TC 4
Z9 4
U1 3
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD SEP 11
PY 2015
VL 14
AR 73
DI 10.1186/s12940-015-0060-5
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA CR0RE
UT WOS:000361030100001
PM 26362861
ER

PT J
AU Li, JC
   Yang, DZ
   Wang, W
   Piao, SL
   Zhou, JY
   Saiyin, WJ
   Zheng, CY
   Sun, HC
   Li, Y
AF Li, Jichen
   Yang, Dezhao
   Wang, Wei
   Piao, Songlin
   Zhou, Jianyu
   Saiyin, Wuliji
   Zheng, Changyu
   Sun, Hongchen
   Li, Yu
TI Inhibition of autophagy by 3-MA enhances IL-24-induced apoptosis in
   human oral squamous cell carcinoma cells
SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
LA English
DT Article
DE OSCC; Interleukin-24; Autophagy inhibition; Apoptosis; Gene therapy
ID GENE-TRANSFER; CANCER-CELLS; IN-VITRO; MDA-7/IL-24; ADENOVIRUS; VECTORS;
   PACLITAXEL; ANTITUMOR; CYTOKINE; PROTEIN
AB Background: Interleukin-24(IL-24), also referred to as melanoma differentiation-associated gene-7(mda-7), is a unique member of the IL-10 gene family, which displays nearly ubiquitous cancer-specific toxicity. The most notable feature of IL-24 is selectively induced growth suppression and apoptosis in various cancer cells, with no harmful effects toward normal cells. Autophagy is a self-protective mechanism in many kinds of tumor cells that respond to anticancer treatment. It is reported that autophagy inhibition could enhance the effects of many kinds of anticancer treatments, including gene therapy. However, whether IL-24 is effective to treat oral squamous cell carcinomas (OSCC) and if autophagy inhibition could improve the anticancer effect of IL-24 towards OSCC is has not been detected.
   Methods: MTT assays were carried out to determine the cell proliferation; Transfection was used to gene transfer; Western Blot was performed to detect the protein level of LC3II, P62, Beclin 1, Cleaved caspase-3, beta-Tubulin and beta-actin; Apoptosis rates and cell cycle alteration were analyzed using flow cytometry; Autophagy induction was confirmed by MDC staining, GFP-LC3 staining and transmission electron microscopy. Amount of IL-24 in the culture medium was quantified by ELISA. Apoptosis in vivo was analyzed by TUNEL assay. HE staining was used to observe the morphology of the samples.
   Results: In the present study, we proved that IL-24 have a novel anticancer effect towards KB cells and that autophagy inhibition could improve the anticancer effect of IL-24. IL-24 treated cells showed autophagy characteristics and autophagy inhibition by 3-methyladenine (3-MA) significantly enhanced IL-24-induced apoptosis. Similar results were obtained in the KB cells xenograft tumor model.
   Conclusions: These results suggest that the combination of autophagy inhibitors and IL- 24 based on the AdLTR(2)EF1 alpha-mediated gene transfer could be a promising way to cure OSCC.
C1 [Li, Jichen; Li, Yu] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150001, Peoples R China.
   [Yang, Dezhao; Wang, Wei; Piao, Songlin; Zhou, Jianyu; Saiyin, Wuliji] Harbin Med Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Harbin 150001, Peoples R China.
   [Zheng, Changyu] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
   [Sun, Hongchen] Jilin Univ, Sch Stomatol, Dept Oral Pathol, Changchun 130021, Peoples R China.
RP Sun, HC (reprint author), Jilin Univ, Sch Stomatol, Dept Oral Pathol, 1500 Qinghua Rd, Changchun 130021, Peoples R China.
EM hcsun@mail.jlu.edu.cn; liyugene@hit.edu.cn
FU Returned Student Science Fund of Heilongjiang province [LC2009C04];
   National Natural Science Foundation Committee of International
   Cooperation Bureau, People's Republic of China [30672338]
FX We thank Ronald C. Inglehart for helpful discussions and assistance with
   writing. This work was supported by the Returned Student Science Fund
   (LC2009C04) of Heilongjiang province and National Natural Science
   Foundation Committee of International Cooperation Bureau (30672338),
   People's Republic of China.
NR 26
TC 7
Z9 7
U1 2
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-9966
J9 J EXP CLIN CANC RES
JI J. Exp. Clin. Cancer Res.
PD SEP 11
PY 2015
VL 34
AR 97
DI 10.1186/s13046-015-0211-0
PG 13
WC Oncology
SC Oncology
GA CR2SM
UT WOS:000361180700001
PM 26361755
ER

PT J
AU Scott, DW
   Mottok, A
   Ennishi, D
   Wright, GW
   Farinha, P
   Ben-Neriah, S
   Kridel, R
   Barry, GS
   Hother, C
   Abrisqueta, P
   Boyle, M
   Meissner, B
   Telenius, A
   Savage, KJ
   Sehn, LH
   Slack, GW
   Steidl, C
   Staudt, LM
   Connors, JM
   Rimsza, LM
   Gascoyne, RD
AF Scott, David W.
   Mottok, Anja
   Ennishi, Daisuke
   Wright, George W.
   Farinha, Pedro
   Ben-Neriah, Susana
   Kridel, Robert
   Barry, Garrett S.
   Hother, Christoffer
   Abrisqueta, Pau
   Boyle, Merrill
   Meissner, Barbara
   Telenius, Adele
   Savage, Kerry J.
   Sehn, Laurie H.
   Slack, Graham W.
   Steidl, Christian
   Staudt, Louis M.
   Connors, Joseph M.
   Rimsza, Lisa M.
   Gascoyne, Randy D.
TI Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin
   Determined by Digital Gene Expression in Formalin-Fixed
   Paraffin-Embedded Tissue Biopsies
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RITUXIMAB PLUS CYCLOPHOSPHAMIDE; MOLECULAR SUBTYPES; SURVIVAL;
   CHEMOTHERAPY; BCL2; MYC; VINCRISTINE; DOXORUBICIN; PREDNISONE;
   ALGORITHMS
AB Purpose
   To evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression-based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers).
   Patients and Methods
   Reproducibility of COO assignment using the Lymph2Cx assay was tested employing repeated sampling within tumor biopsies and changes in reagent lots. The assay was then applied to pretreatment formalin-fixed paraffin-embedded tissue (FFPET) biopsies from 344 patients with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays.
   Results
   The Lymph2Cx assay provided concordant COO calls in 96% of 49 repeatedly sampled tumor biopsies and in 100% of 83 FFPET biopsies tested across reagent lots. Critically, no frank misclassification (activated B-cell-like DLBCL to germinal center B-cell-like DLBCL or vice versa) was observed. Patients with activated B-cell-like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell-like DLBCL (log-rank P < .001 for time to progression, progression-free survival, disease-specific survival, and overall survival). In pairwise multivariable analyses, COO was associated with outcomes independent of IPI score and MYC/BCL2 immunohistochemistry. The prognostic significance of COO was particularly evident in patients with intermediate IPI scores and the non-MYC-positive/BCL2-positive subgroup (log-rank P < .001 for time to progression).
   Conclusion
   Assignment of DLBCL COO by the Lymph2Cx assay using FFPET biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression. (C) 2015 by American Society of Clinical Oncology
C1 [Scott, David W.; Mottok, Anja; Ennishi, Daisuke; Farinha, Pedro; Ben-Neriah, Susana; Kridel, Robert; Barry, Garrett S.; Hother, Christoffer; Abrisqueta, Pau; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Savage, Kerry J.; Sehn, Laurie H.; Slack, Graham W.; Steidl, Christian; Connors, Joseph M.; Gascoyne, Randy D.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Wright, George W.; Staudt, Louis M.] NCI, Bethesda, MD 20892 USA.
   [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA.
RP Scott, DW (reprint author), British Columbia Canc Res Ctr, 675 West 10th Ave,Room 11-114, Vancouver, BC V5Z 1L3, Canada.
EM dscott8@bccancer.bcca
OI Farinha, Pedro/0000-0001-9364-9391
FU Terry Fox Foundation; British Columbia Cancer Foundation; Mildred Scheel
   Cancer Foundation
FX Supported by the Terry Fox Foundation and by the British Columbia Cancer
   Foundation (D.W.S.); A.M. holds fellowship awarded by the Mildred Scheel
   Cancer Foundation.
NR 24
TC 33
Z9 34
U1 3
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 10
PY 2015
VL 33
IS 26
BP 2848
EP +
DI 10.1200/JCO.2014.60.2383
PG 10
WC Oncology
SC Oncology
GA CX9ID
UT WOS:000366017800006
PM 26240231
ER

PT J
AU Park, JH
   Anderson, WF
   Gail, MH
AF Park, Ju-Hyun
   Anderson, William F.
   Gail, Mitchell H.
TI Improvements in US Breast Cancer Survival and Proportion Explained by
   Tumor Size and Estrogen-Receptor Status
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID UNITED-STATES; RANDOMIZED-TRIALS; EUROPEAN COUNTRIES; ADJUVANT THERAPY;
   MORTALITY; TRENDS; PATTERNS; DENMARK; DEATHS; IMPACT
AB Purpose
   Breast cancer mortality began declining in many Western countries during the late 1980s. We estimated the proportion of improvements in stage-and age-specific breast cancer survival in the United States explained by tumor size or estrogen receptor (ER) status.
   Methods
   We estimated hazard ratios for breast cancer-specific death from time of invasive breast cancer diagnosis in the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 Registries Database from 1973 to 2010, with and without stratification by tumor size and ER status.
   Results
   Hazards from breast cancer-specific death declined from 1973 to 2010, not only in the first 5 years after diagnosis, but also thereafter. Stratification by tumor size explained less than 17% of the improvements comparing 2005 to 2010 versus 1973 to 1979, except for women age >= 70 years with local (49%) or regional (38%) disease. Tumor size usually accounted for more of the improvement in the first 5 years after diagnosis than later. Additional adjustment for ER status (positive, negative, or unknown) from 1990 to 2010 did not explain much more of the improvement, except for women age >= 70 years within 5 years after diagnosis.
   Conclusion
   Most stage-specific survival improvement in women younger than age 70 years old is unexplained by tumor size and ER status, suggesting a key role for treatment. In the first 5 years after diagnosis, tumor size contributed importantly for women >= 70 years old with local and regional stage, and stratification by tumor size and ER status explained even more of the survival improvement among women age >= 70 years. (C) 2015 by American Society of Clinical Oncology
C1 [Park, Ju-Hyun] Dongguk Univ, Seoul, South Korea.
   [Anderson, William F.; Gail, Mitchell H.] NCI, Bethesda, MD 20892 USA.
RP Gail, MH (reprint author), NCI, 9609 Med Ctr Dr,7E138, Rockville, MD 20850 USA.
EM gailm@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health;
   National Cancer Institute, Division of Cancer Epidemiology and Genetics;
   Basic Science Research Program through the National Research Foundation
   of Korea - Ministry of Science, ICT & Future Planning
   [NRF-2013R1A1A1009737]
FX Supported by the Intramural Research Program of the National Institutes
   of Health, National Cancer Institute, Division of Cancer Epidemiology
   and Genetics (J-H.P., W.F.A., and M.H.G.) and by the Basic Science
   Research Program through the National Research Foundation of Korea
   funded by the Ministry of Science, ICT & Future Planning (Grant No.
   NRF-2013R1A1A1009737) (J.-H.P).
NR 37
TC 17
Z9 17
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 10
PY 2015
VL 33
IS 26
BP 2870
EP +
DI 10.1200/JCO.2014.59.9191
PG 8
WC Oncology
SC Oncology
GA CX9ID
UT WOS:000366017800009
PM 26195709
ER

PT J
AU Huffman, JE
   de Vries, PS
   Morrison, AC
   Sabater-Lleal, M
   Kacprowski, T
   Auer, PL
   Brody, JA
   Chasman, DI
   Chen, MH
   Guo, XQ
   Lin, LA
   Marioni, RE
   Muller-Nurasyid, M
   Yanek, LR
   Pankratz, N
   Grove, ML
   de Maat, MPM
   Cushman, M
   Wiggins, KL
   Qi, LH
   Sennblad, B
   Harris, SE
   Polasek, O
   Riess, H
   Rivadeneira, F
   Rose, LM
   Goel, A
   Taylor, KD
   Teumer, A
   Uitterlinden, AG
   Vaidya, D
   Yao, J
   Tang, WH
   Levy, D
   Waldenberger, M
   Becker, DM
   Folsom, AR
   Giulianini, F
   Greinacher, A
   Hofman, A
   Huang, CC
   Kooperberg, C
   Silveira, A
   Starr, JM
   Strauch, K
   Strawbridge, RJ
   Wright, AF
   McKnight, B
   Franco, OH
   Zakai, N
   Mathias, RA
   Psaty, BM
   Ridker, PM
   Tofler, GH
   Volker, U
   Watkins, H
   Fornage, M
   Hamsten, A
   Deary, IJ
   Boerwinkle, E
   Koenig, W
   Rotter, JI
   Hayward, C
   Dehghan, A
   Reiner, AP
   O'Donnell, CJ
   Smith, NL
AF Huffman, Jennifer E.
   de Vries, Paul S.
   Morrison, Alanna C.
   Sabater-Lleal, Maria
   Kacprowski, Tim
   Auer, Paul L.
   Brody, Jennifer A.
   Chasman, Daniel I.
   Chen, Ming-Huei
   Guo, Xiuqing
   Lin, Li-An
   Marioni, Riccardo E.
   Mueller-Nurasyid, Martina
   Yanek, Lisa R.
   Pankratz, Nathan
   Grove, Megan L.
   de Maat, Moniek P. M.
   Cushman, Mary
   Wiggins, Kerri L.
   Qi, Lihong
   Sennblad, Bengt
   Harris, Sarah E.
   Polasek, Ozren
   Riess, Helene
   Rivadeneira, Fernando
   Rose, Lynda M.
   Goel, Anuj
   Taylor, Kent D.
   Teumer, Alexander
   Uitterlinden, Andre G.
   Vaidya, Dhananjay
   Yao, Jie
   Tang, Weihong
   Levy, Daniel
   Waldenberger, Melanie
   Becker, Diane M.
   Folsom, Aaron R.
   Giulianini, Franco
   Greinacher, Andreas
   Hofman, Albert
   Huang, Chiang-Ching
   Kooperberg, Charles
   Silveira, Angela
   Starr, John M.
   Strauch, Konstantin
   Strawbridge, Rona J.
   Wright, Alan F.
   McKnight, Barbara
   Franco, Oscar H.
   Zakai, Neil
   Mathias, Rasika A.
   Psaty, Bruce M.
   Ridker, Paul M.
   Tofler, Geoffrey H.
   Voelker, Uwe
   Watkins, Hugh
   Fornage, Myriam
   Hamsten, Anders
   Deary, Ian J.
   Boerwinkle, Eric
   Koenig, Wolfgang
   Rotter, Jerome I.
   Hayward, Caroline
   Dehghan, Abbas
   Reiner, Alex P.
   O'Donnell, Christopher J.
   Smith, Nicholas L.
TI Rare and low-frequency variants and their association with plasma levels
   of fibrinogen, FVII, FVIII, and vWF
SO BLOOD
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; VON-WILLEBRAND-FACTOR; CORONARY-HEART-DISEASE;
   FACTOR-VIII; VONWILLEBRAND DISEASE; AFRICAN-AMERICANS; SEQUENCE
   VARIANTS; COMPOUND HETEROZYGOSITY; CIRCULATING FIBRINOGEN;
   CARDIOVASCULAR-DISEASE
AB Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] >= 0.01 and < 0.05) and rare (MAF < 0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n=2) andrare (n=10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways.
C1 [Huffman, Jennifer E.; Wright, Alan F.; Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
   [Huffman, Jennifer E.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Cardiovasc Epidemiol & Human Genom Branch, Framingham, MA USA.
   [Huffman, Jennifer E.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
   [Huffman, Jennifer E.; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [de Vries, Paul S.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
   [Morrison, Alanna C.; Lin, Li-An; Grove, Megan L.; Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
   [Sabater-Lleal, Maria; Sennblad, Bengt; Silveira, Angela; Strawbridge, Rona J.; Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden.
   Univ Med & Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany.
   Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
   [Brody, Jennifer A.; Wiggins, Kerri L.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
   [Chasman, Daniel I.; Rose, Lynda M.; Giulianini, Franco; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
   [Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA.
   [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [Guo, Xiuqing; Taylor, Kent D.; Yao, Jie; Rotter, Jerome I.] Harbor Univ Los Calif Angeles UCLA, Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA USA.
   [Guo, Xiuqing; Taylor, Kent D.; Rotter, Jerome I.] Harbor Univ Los Calif Angeles UCLA, Med Ctr, Dept Pediat, Torrance, CA USA.
   [Lin, Li-An; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
   [Marioni, Riccardo E.; Harris, Sarah E.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
   [Marioni, Riccardo E.; Harris, Sarah E.] Univ Edinburgh, MRC Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.
   [Marioni, Riccardo E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
   [Mueller-Nurasyid, Martina; Strauch, Konstantin] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Genet Epidemiol, Neuherberg, Germany.
   [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Munich, Germany.
   [Mueller-Nurasyid, Martina; Waldenberger, Melanie] German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
   [Yanek, Lisa R.; Vaidya, Dhananjay; Becker, Diane M.; Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Program,Div Gen Internal Med, Baltimore, MD 21205 USA.
   [Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [de Maat, Moniek P. M.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands.
   [Cushman, Mary; Zakai, Neil] Univ Vermont, Dept Med, Colchester, VT USA.
   [Cushman, Mary; Zakai, Neil] Univ Vermont, Dept Pathol, Colchester, VT USA.
   [Qi, Lihong] Univ Calif Davis, Davis, CA 95616 USA.
   [Sennblad, Bengt] Karolinska Inst, Sci Life Lab, Stockholm, Sweden.
   [Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia.
   German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol 2, Neuherberg, Germany.
   Univ Ulm, Sch Med, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
   [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
   [Goel, Anuj; Watkins, Hugh] Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Div Cardiovasc Med, Oxford OX3 9DU, England.
   [Teumer, Alexander] Univ Med Greifswald, Inst Community Med, Clin & Epidemiol Res Dept, Study Hlth Pomerania, Greifswald, Germany.
   [Vaidya, Dhananjay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
   [Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Res Unit Mol Epidemiol, Neuherberg, Germany.
   [Becker, Diane M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
   [Greinacher, Andreas] Univ Med Greifswald, Dept Transfus Med, Inst Immunol & Transfus Med, Greifswald, Germany.
   [Kooperberg, Charles; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Starr, John M.] Univ Edinburgh, Dept Psychol, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
   [Strauch, Konstantin] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
   [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA.
   [Psaty, Bruce M.; Reiner, Alex P.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
   [Psaty, Bruce M.; Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
   Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia.
   [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
   [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Koenig, Wolfgang] Tech Univ Munich, German Heart Ctr Munich, D-80290 Munich, Germany.
   [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Vet Affairs Off Res & Dev, Seattle, WA USA.
RP Smith, NL (reprint author), 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA.
EM nlsmith@u.washington.edu
RI Polasek, Ozren/B-6002-2011; Waldenberger, Melanie/B-5355-2014;
   Kacprowski, Tim/K-8650-2013; Lin, LiAn/C-5819-2017; 
OI Polasek, Ozren/0000-0002-5765-1862; Rivadeneira,
   Fernando/0000-0001-9435-9441; Watkins, Hugh/0000-0002-5287-9016;
   Strawbridge, Rona/0000-0001-8506-3585; Vaidya,
   Dhananjay/0000-0002-7164-1601; Waldenberger,
   Melanie/0000-0003-0583-5093; Kacprowski, Tim/0000-0002-5393-2413; Lin,
   LiAn/0000-0003-2731-1346; Dehghan, Abbas/0000-0001-6403-016X; Sabater
   Lleal, Maria/0000-0002-0128-379X
FU Amgen; ZOLL Lifecor; Johnson Johnson; Nestle Nutrition (Nestec Ltd.);
   Metagenics Inc.; AXA
FX D.V. is a consultant for MBC, Inc. D.I.C. and P.M.R. have received
   funding for exome chip genotyping in the Women's Genome Health Study and
   collaborative scientific support from Amgen. B.M.P. serves on the data
   and safety management board for a clinical trial of a device funded by
   the manufacturer (ZOLL Lifecor) and on the Steering Committee of the
   Yale Open Data Access Project funded by Johnson & Johnson. O.H.F. is
   employed by ErasmusAGE, a center for aging research across the life
   course funded by Nestle Nutrition (Nestec Ltd.), Metagenics Inc., and
   AXA. Nestle Nutrition, Metagenics Inc., and AXA had no role in the
   design and conduct of the study, the collection, management, analysis,
   and interpretation of the data, or in the preparation, review, or
   approval of the manuscript. The remaining authors declare no competing
   financial interests
NR 71
TC 5
Z9 5
U1 0
U2 4
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 SEP 10
PY 2015
VL 126
IS 11
BP E19
EP E29
DI 10.1182/blood-2015-02-624551
PG 11
WC Hematology
SC Hematology
GA CU4EK
UT WOS:000363479500001
PM 26105150
ER

PT J
AU Sukumar, M
   Roychoudhuri, R
   Restifo, NP
AF Sukumar, Madhusudhanan
   Roychoudhuri, Rahul
   Restifo, Nicholas P.
TI Nutrient Competition: A New Axis of Tumor Immunosuppression
SO CELL
LA English
DT Editorial Material
ID CANCER
AB It is thought that cancer cells engage in Warburg metabolism to meet intrinsic biosynthetic requirements of cell growth and proliferation. Papers by Chang et al. and Ho et al. show that Warburg metabolism enables tumor cells to restrict glucose availability to T cells, suppressing anti-tumor immunity.
C1 [Sukumar, Madhusudhanan; Roychoudhuri, Rahul; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Restifo, NP (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM restifo@nih.gov
RI Roychoudhuri, Rahul/A-7442-2010; 
OI Roychoudhuri, Rahul/0000-0002-5392-1853; Restifo, Nicholas
   P./0000-0003-4229-4580
FU Wellcome Trust [105663]
NR 10
TC 3
Z9 3
U1 5
U2 15
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 SEP 10
PY 2015
VL 162
IS 6
BP 1206
EP 1208
DI 10.1016/j.cell.2015.08.064
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CR3QL
UT WOS:000361247900008
PM 26359979
ER

PT J
AU Eickhoff, S
   Brewitz, A
   Gerner, MY
   Klauschen, F
   Komander, K
   Hemmi, H
   Garbi, N
   Kaisho, T
   Germain, RN
   Kastenmuller, W
AF Eickhoff, Sarah
   Brewitz, Anna
   Gerner, Michael Y.
   Klauschen, Frederick
   Komander, Karl
   Hemmi, Hiroaki
   Garbi, Natalio
   Kaisho, Tsuneyasu
   Germain, Ronald Nathan
   Kastenmueller, Wolfgang
TI Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic
   Cell Interactions
SO CELL
LA English
DT Article
ID ANTIGEN-PRESENTING CELLS; LYMPH-NODE; IN-VIVO; CROSS-PRESENTATION;
   CD8-T-CELL MEMORY; CD4-T-CELL HELP; CD8(+); RESPONSES; CD4(+); SUBSET
AB Host defense against viruses and intracellular parasites depends on effector CD8(+) T cells, whose optimal clonal expansion, differentiation, and memory properties require signals from CD4(+) T cells. Here, we addressed the role of dendritic cell (DC) subsets in initial activation of the two T cell types and their co-operation. Surprisingly, initial priming of CD4(+) and CD8(+) T cells was spatially segregated within the lymph node and occurred on different DCs with temporally distinct patterns of antigen presentation via MHCI versus MHCII molecules. DCs that co-present antigen via both MHC molecules were detected at a later stage; these XCR1(+) DCs are the critical platform involved in CD4(+) T cell augmentation of CD8(+) T cell responses. These findings delineate the complex choreography of cellular interactions underlying effective cell-mediated antiviral responses, with implications for basic DC subset biology, as well as for translational application to the development of vaccines that evoke optimal T cell immunity.
C1 [Eickhoff, Sarah; Brewitz, Anna; Komander, Karl; Garbi, Natalio; Kastenmueller, Wolfgang] Univ Bonn, Inst Expt Immunol, D-53105 Bonn, Germany.
   [Gerner, Michael Y.; Germain, Ronald Nathan] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
   [Klauschen, Frederick] Charite, Inst Pathol, D-10117 Berlin, Germany.
   [Hemmi, Hiroaki; Kaisho, Tsuneyasu] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Lab Immune Regulat, Suita, Osaka 5650871, Japan.
   [Hemmi, Hiroaki; Kaisho, Tsuneyasu] RIKEN Ctr Integrat Med Sci IMS RCAI, Lab Inflammatory Regulat, Yokohama, Kanagawa 2300045, Japan.
RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rgermain@nih.gov; wkastenm@uni-bonn.de
FU NIAID; NIH; DFG Excellence Cluster ImmunoSensation in Bonn, Germany
   [SFB670/SFB704]; NRW-Ruckkehrerprogramm of the German state of
   Northrhine-Westfalia; Kishimoto Foundation; Ministry of Education,
   Culture, Sports, Science and Technology of Japan (MEXT); Japan Society
   for the Promotion of Science; Human Frontier Science Program (HFSP)
   [RGY007/2011]; Einstein Foundation Berlin; Intramural Research Program
FX We would like to thank S. Ebbinghaus and S. Rathmann for technical
   assistance; C. Kurts for scientific discussions and critically reading
   the manuscript; G. Sutter for help with generation of recombinant (rec.)
   MVA's; J. Bennink, R.M. Kedl, P. Knolle, and D.H. Busch for kindly
   providing VV-OVA, LM-B8R, AdOVA, and MHCI multimers, respectively. This
   research was supported by the Intramural Research Program, NIAID, and
   NIH. W.K. and N.G. are members of the DFG Excellence Cluster
   ImmunoSensation in Bonn, Germany and are supported by grant
   SFB670/SFB704. W.K. is supported by NRW-Ruckkehrerprogramm of the German
   state of Northrhine-Westfalia. T.K. was supported by the Kishimoto
   Foundation, grants from The Ministry of Education, Culture, Sports,
   Science and Technology of Japan (MEXT), and Japan Society for the
   Promotion of Science. F.K. was supported by the Human Frontier Science
   Program (HFSP RGY007/2011) and the Einstein Foundation Berlin.
NR 46
TC 30
Z9 31
U1 3
U2 21
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 SEP 10
PY 2015
VL 162
IS 6
BP 1322
EP 1337
DI 10.1016/j.cell.2015.08.004
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CR3QL
UT WOS:000361247900021
PM 26296422
ER

PT J
AU Mistry, SN
   Shonberg, J
   Draper-Joyce, CJ
   Herenbrink, CK
   Michino, M
   Shi, L
   Christopoulos, A
   Capuano, B
   Scammells, PJ
   Lane, JR
AF Mistry, Shailesh N.
   Shonberg, Jeremy
   Draper-Joyce, Christopher J.
   Herenbrink, Carmen Klein
   Michino, Mayako
   Shi, Lei
   Christopoulos, Arthur
   Capuano, Ben
   Scammells, Peter J.
   Lane, J. Robert
TI Discovery of a Novel Class of Negative Allosteric Modulator of the
   Dopamine D-2 Receptor Through Fragmentation of a Bitopic Ligand
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; PROTEIN-COUPLED RECEPTORS;
   BIASED-AGONISM; D3 RECEPTOR; SELECTIVITY; ANTAGONIST; PHARMACOLOGY;
   MECHANISM; D-3; DERIVATIVES
AB Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)-ethyl)cyclohexyl)-1H-indole-2-carboxamide (0269652) (1) adopts a bitopic pose at one protomer of a dopamine D-2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2-carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an "allosteric lead", we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology.
C1 [Mistry, Shailesh N.; Shonberg, Jeremy; Capuano, Ben; Scammells, Peter J.] Monash Univ, Monash Inst Pharmaceut Sci, Med Chem, Parkville, Vic 3052, Australia.
   [Draper-Joyce, Christopher J.; Herenbrink, Carmen Klein; Christopoulos, Arthur; Lane, J. Robert] Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia.
   [Michino, Mayako; Shi, Lei] NIDA, Computat Chem & Mol Biophys Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Shi, Lei] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA.
   [Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA.
RP Scammells, PJ (reprint author), Monash Univ, Monash Inst Pharmaceut Sci, Med Chem, 381 Royal Parade, Parkville, Vic 3052, Australia.
EM Peter.Scammells@monash.edu; Rob.Lane@monash.edu
RI Mistry, Shailesh/O-2697-2014; 
OI Mistry, Shailesh/0000-0002-2252-1689; Lane, J.
   Robert/0000-0002-7361-7875
FU National Health and Medical Research Council (NHMRC) [APP1049654,
   APP1011920, 519461]; Australian Research Council (ARC) [DP110100687];
   Australian Postgraduate Awards
FX This research was supported by project grants APP1049654 and APP1011920
   of the National Health and Medical Research Council (NHMRC), Discovery
   grant DP110100687 of the Australian Research Council (ARC), and program
   grant 519461 (NHMRC). J.R.L. is a R. D. Wright Biomedical Career
   Development Fellow (1052304, NHMRC) and a Larkin's Fellow (Monash
   University, Australia). J.S. and CJD-J acknowledge Australian
   Postgraduate Awards.
NR 51
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Z9 5
U1 1
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD SEP 10
PY 2015
VL 58
IS 17
BP 6819
EP 6843
DI 10.1021/acs.medchem.5b00585
PG 25
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CR3SY
UT WOS:000361254600008
PM 26258690
ER

PT J
AU Curreli, F
   Do Kwon, Y
   Zhang, HT
   Scacalossi, D
   Belov, DS
   Tikhonov, AA
   Andreev, IA
   Altieri, A
   Kurkin, AV
   Kwong, PD
   Debnath, AK
AF Curreli, Francesca
   Do Kwon, Young
   Zhang, Hongtao
   Scacalossi, Daniel
   Belov, Dmitry S.
   Tikhonov, Artur A.
   Andreev, Ivan A.
   Altieri, Andrea
   Kurkin, Alexander V.
   Kwong, Peter D.
   Debnath, Asim K.
TI Structure-Based Design of a Small Molecule CD4-Antagonist with Broad
   Spectrum Anti-HIV-1 Activity
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 ENTRY INHIBITORS; GP120 ENVELOPE
   GLYCOPROTEIN; MURINE LEUKEMIA-VIRUS; CD4 MIMICS; ENV CLONES; X-RAY;
   CONFORMATIONAL-CHANGES; CHEMOKINE RECEPTORS; ANTIVIRAL ACTIVITY
AB Earlier we reported the discovery and design of NBD-556 and their analogs which demonstrated their potential as HIV-1 entry inhibitors. However, progress in developing these inhibitors has been stymied by their CD4-agonist properties, an unfavorable trait for use as drug. Here, we demonstrate the successful conversion of a full CD4-agonist (NBD-556) through a partial CD4-agonist (NBD-09027), to a full CD4-antagonist (NBD-11021) by structure-based modification of the critical oxalamide midregion, previously thought to be intolerant of modification. NBD-11021 showed unprecedented neutralization breath for this class of inhibitors, with pan-neutralization against a panel of 56 Env-pseudotyped HIV-1 representing diverse subtypes of clinical isolates (IC50 as low as 270 nM). The cocrystal structure of NED-11021 complexed to a monomeric HIV-1 gp120 core revealed its detail binding characteristics. The study is expected to provide a framework for further development of NBD series as HIV-1 entry inhibitors for clinical application against AIDS.
C1 [Curreli, Francesca; Zhang, Hongtao; Scacalossi, Daniel; Debnath, Asim K.] New York Blood Ctr, Lindsey F Kimball Res Inst, Lab Mol Modeling & Drug Design, New York, NY 10065 USA.
   [Do Kwon, Young; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Belov, Dmitry S.; Tikhonov, Artur A.; Andreev, Ivan A.; Altieri, Andrea; Kurkin, Alexander V.] Moscow MV Lomonosov State Univ, EDASA Sci, Moscow 119992, Russia.
RP Debnath, AK (reprint author), New York Blood Ctr, Lindsey F Kimball Res Inst, Lab Mol Modeling & Drug Design, New York, NY 10065 USA.
EM adebnath@nybloodcenter.org
RI Kwon, Young Do/A-6957-2010
FU NIH [RO1 AI104416]; New York Blood Center; U.S. Department of Energy,
   Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; Intramural
   AIDS Targeted Antiretroviral Program (IATAP) of the NIH; Vaccine
   Research Center
FX This study was supported by funds from NIH Grant RO1 AI104416 (A.K.D.)
   and the New York Blood Center (A.K.D.), by Intramural funding to the
   Vaccine Research Center, and by the Intramural AIDS Targeted
   Antiretroviral Program (IATAP) of the NIH. Use of sector 22 (Southeast
   Region Collaborative Access Team) at the Advanced Photon Source was
   supported by the U.S. Department of Energy, Basic Energy Sciences,
   Office of Science Contract W-31-109-Eng-38. We thank Nicole Doria-Rose
   and John Mascola of Vaccine Research Center, NIH, for guidance and
   consultation. We thank Vijay Nandi of the New York Blood Center for her
   assistance in statistical analyses. We thank Carol Lackman-Smith,
   Junzhong Peng, and Jiayi Wei of Southern Research Institute (SR) for
   performing the HIV RT and integrase assays.
NR 85
TC 6
Z9 6
U1 3
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD SEP 10
PY 2015
VL 58
IS 17
BP 6909
EP 6927
DI 10.1021/acs.jmedchem.5b00709
PG 19
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CR3SY
UT WOS:000361254600013
PM 26301736
ER

PT J
AU Ghosh, AK
   Martyr, CD
   Osswald, HL
   Sheri, VR
   Kassekert, LA
   Chen, SJ
   Agniswamy, J
   Wang, YF
   Hayashi, H
   Aoki, M
   Weber, IT
   Mitsuya, H
AF Ghosh, Arun K.
   Martyr, Cuthbert D.
   Osswald, Heather L.
   Sheri, Venkat Reddy
   Kassekert, Luke A.
   Chen, Shujing
   Agniswamy, Johnson
   Wang, Yuan-Fang
   Hayashi, Hironori
   Aoki, Manabu
   Weber, Irene T.
   Mitsuya, Hiroaki
TI Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran
   Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions:
   Synthesis, Biological Evaluation, and Protein Ligand X-ray Studies
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID RESOLUTION CRYSTAL-STRUCTURES; 2,3 WITTIG REARRANGEMENT; COMBAT
   DRUG-RESISTANCE; IN-VITRO; ANTIRETROVIRAL THERAPY; ASYMMETRIC INDUCTION;
   DARUNAVIR; COMPLEXES; REPLICATION; PENETRATION
AB Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligand binding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolution X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of G1y48 as well as with the backbone NH of G1y48 in the flap region of the enzyme active site. These ligand binding site interactions are possibly responsible for their potent activity.
C1 [Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.; Sheri, Venkat Reddy; Kassekert, Luke A.; Chen, Shujing] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
   [Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.; Sheri, Venkat Reddy; Kassekert, Luke A.; Chen, Shujing] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
   [Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis, Atlanta, GA 30303 USA.
   [Hayashi, Hironori; Aoki, Manabu; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Biomed Sci, Dept Infect Dis, Kumamoto 8608556, Japan.
   [Hayashi, Hironori; Aoki, Manabu; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Biomed Sci, Dept Hematol, Kumamoto 8608556, Japan.
   [Aoki, Manabu] Kumamoto Hlth Sci Univ, Dept Med Technol, Kumamoto 8615598, Japan.
   [Hayashi, Hironori; Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Ctr Clin Sci, Tokyo 1628655, Japan.
   [Aoki, Manabu; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
FU National Institutes of Health [GM53386, GM62920]; Intramural Research
   Program of Center for Cancer Research, National Cancer Institute,
   National Institutes of Health; Ministry of Education, Culture, Sports,
   Science, and Technology of Japan (Monbu Kagakusho); Ministry of Health,
   Welfare, and Labor of Japan; Clinical and Epidemiological Studies of
   Emerging and Reemerging Infectious Diseases (Renkei Jigyo) of
   Monbu-Kagakusho
FX This research was supported by the National Institutes of Health (Grant
   GM53386, to A.K.G.; and Grant GM62920,to I.T.W.). X-ray data were
   collected at the southeast Regional collabrative access team (SER-CAT)
   beamline 22BM at the Advanced Photon Source, Argonne National
   Laboratory. Use of the Advanced Photon Source was supported by the US
   Department of Energy, Basic Energy Sciences, Office of Science, under
   Contract No. W-31-109-Eng-38. This work was also supported by the
   Intramural Research Program of the Center for Cancer Research, National
   Cancer Institute, National Institutes of Health, and in part by a
   Grant-in-Aid for Scientific Research (Priority Areas) from the Ministry
   of Education, Culture, Sports, Science, and Technology of Japan (Monbu
   Kagakusho), a Grant for Promotion of AIDS Research from the Ministry of
   Health, Welfare, and Labor of Japan, and the Grant to the Cooperative
   Research Project on Clinical and Epidemiological Studies of Emerging and
   Reemerging Infectious Diseases (Renkei Jigyo) of Monbu-Kagakusho. The
   authors would like to thank the Purdue University Center for Cancer
   Research, which supports the shared NMR and mass spectrometry
   facilities.
NR 46
TC 2
Z9 2
U1 1
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD SEP 10
PY 2015
VL 58
IS 17
BP 6994
EP 7006
DI 10.1021/acs.jmedchem.5b00900
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CR3SY
UT WOS:000361254600019
PM 26306007
ER

PT J
AU Zhu, JJ
   Sammons, MA
   Donahue, G
   Dou, ZX
   Vedadi, M
   Getlik, M
   Barsyte-Lovejoy, D
   Al-Awar, R
   Katona, BW
   Shilatifard, A
   Huang, J
   Hua, XX
   Arrowsmith, CH
   Berger, SL
AF Zhu, Jiajun
   Sammons, Morgan A.
   Donahue, Greg
   Dou, Zhixun
   Vedadi, Masoud
   Getlik, Matthaus
   Barsyte-Lovejoy, Dalia
   Al-Awar, Rima
   Katona, Bryson W.
   Shilatifard, Ali
   Huang, Jing
   Hua, Xianxin
   Arrowsmith, Cheryl H.
   Berger, Shelley L.
TI Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer
   growth
SO NATURE
LA English
DT Article
ID MIXED-LINEAGE LEUKEMIA; LI-FRAUMENI-SYNDROME; HOX GENE-EXPRESSION;
   METHYLTRANSFERASE ACTIVITY; HISTONE METHYLTRANSFERASE; MLL; MENIN;
   TRANSCRIPTION; INHIBITORS; BINDING
AB TP53 (which encodes p53 protein) is the most frequently mutated gene among all human cancers. Prevalent p53 missense mutations abrogate its tumour suppressive function and lead to a 'gain-of-function' (GOF) that promotes cancer. Here we show that p53 GOF mutants bind to and upregulate chromatin regulatory genes, including the methyltransferases MLL1 (also known as KMT2A), MLL2 (also known as KMT2D), and acetyltransferase MOZ (also known as KAT6A or MYST3), resulting in genome-wide increases of histone methylation and acetylation. Analysis of The Cancer Genome Atlas shows specific upregulation of MLL1, MLL2, and MOZ in p53 GOF patient-derived tumours, but not in wild-type p53 or p53 null tumours. Cancer cell proliferation is markedly lowered by genetic knockdown of MLL1 or by pharmacological inhibition of the MLL1 methyltransferase complex. Our study reveals a novel chromatin mechanism underlying the progression of tumours with GOF p53, and suggests new possibilities for designing combinatorial chromatin-based therapies for treating individual cancers driven by prevalent GOF p53 mutations.
C1 [Zhu, Jiajun; Sammons, Morgan A.; Donahue, Greg; Dou, Zhixun; Berger, Shelley L.] Univ Penn, Cell & Dev Biol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Zhu, Jiajun; Sammons, Morgan A.; Donahue, Greg; Dou, Zhixun; Berger, Shelley L.] Univ Penn, Epigenet Program, Philadelphia, PA 19104 USA.
   [Zhu, Jiajun] Univ Penn, Perelman Sch Med, Biomed Grad Studies, Philadelphia, PA 19104 USA.
   [Vedadi, Masoud; Barsyte-Lovejoy, Dalia; Arrowsmith, Cheryl H.] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
   [Vedadi, Masoud; Al-Awar, Rima] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada.
   [Getlik, Matthaus; Al-Awar, Rima] Ontario Inst Canc Res, Drug Discovery Program, Toronto, ON M5G 0A3, Canada.
   [Katona, Bryson W.; Hua, Xianxin] Univ Penn, Perelman Sch Med, Dept Canc Biol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   [Shilatifard, Ali] Northwestern Univ, Dept Biochem & Mol Genet, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Huang, Jing] NCI, Canc & Stem Cell Epigenet, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Arrowsmith, Cheryl H.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON M5G 2C4, Canada.
   [Arrowsmith, Cheryl H.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C4, Canada.
RP Berger, SL (reprint author), Univ Penn, Cell & Dev Biol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM bergers@upenn.edu
RI Huang, Jing/A-2566-2009; Zhu, Jiajun/R-6196-2016
OI Huang, Jing/0000-0002-7163-5156; Zhu, Jiajun/0000-0002-1760-3081
FU NIH [R01 CA078831, R01 GM069905]; American Cancer Society; ITMAT of the
   University of Pennsylvania; AbbVie; Bayer; Boehringer Ingelheim; Genome
   Canada through the Ontario Genomics Institute [OGI-055];
   GlaxoSmithKline; Janssen; Lilly Canada; Merck; Novartis Research
   Foundation; Ontario Ministry of Economic Development and Innovation;
   Pfizer; Takeda; Wellcome Trust [092809/Z/10/Z]; Canadian Cancer Society
   Research Institute
FX We thank M. Tainsky for the LFS cell lines; A. Weller, J. Glover and the
   Stem Cell and Xenograft Core at the University of Pennsylvania for help
   with the tumour xenograft experiments. S.L.B. is supported by NIH grant
   R01 CA078831. M.A.S. is supported by a Postdoctoral Fellowship from the
   American Cancer Society. X.H. is supported in part by a pilot grant from
   ITMAT of the University of Pennsylvania. A.S. is supported by NIH grant
   R01 GM069905. The Structural Genomics Consortium is a registered charity
   (number 1097737) that receives funds from AbbVie, Bayer, Boehringer
   Ingelheim, Genome Canada through the Ontario Genomics Institute
   (OGI-055), GlaxoSmithKline, Janssen, Lilly Canada, Merck, the Novartis
   Research Foundation, the Ontario Ministry of Economic Development and
   Innovation, Pfizer, Takeda, and the Wellcome Trust (092809/Z/10/Z).
   Funding was also provided to C.H.A. from the Canadian Cancer Society
   Research Institute.
NR 42
TC 58
Z9 61
U1 11
U2 47
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 SEP 10
PY 2015
VL 525
IS 7568
BP 206
EP +
DI 10.1038/nature15251
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ9IM
UT WOS:000360927400029
PM 26331536
ER

PT J
AU Dosemeci, A
   Toy, D
   Reese, TS
   Tao-Cheng, JH
AF Dosemeci, Ayse
   Toy, Dana
   Reese, Thomas S.
   Tao-Cheng, Jung-Hwa
TI AIDA-1 Moves out of the Postsynaptic Density Core under Excitatory
   Conditions
SO PLOS ONE
LA English
DT Article
ID DOMAIN-ASSOCIATED PROTEIN-1; NEURONS; SYNGAP; MANNER
AB AIDA-1 is highly enriched in postsynaptic density (PSD) fractions and is considered a major component of the PSD complex. In the present study, immunogold electron microscopy was applied to determine localization as well as the activity-induced redistribution of AIDA-1 at the PSD using two antibodies that recognize two different epitopes. In cultured rat hippocampal neurons under basal conditions, immunogold label for AIDA-1 is mostly located within the dense core of the PSD, with a median distance of similar to 30 nm from the postsynaptic membrane. Under excitatory conditions, such as depolarization with high K+ (90 mM, 2 min) or application of NMDA (50 mu M, 2 min), AIDA-1 label density at the PSD core is reduced to 40% of controls and the median distance of label from the postsynaptic membrane increases to similar to 55 nm. The effect of excitatory conditions on the postsynaptic distribution of AIDA-1 is reversed within 30 minutes after returning to control conditions. The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95. Activity-induced transient translocation of these abundant proteins from the PSD core could promote structural flexibility, vacate sites on PSD-95 for the insertion of other components and thus may create a window for synaptic modification.
C1 [Dosemeci, Ayse; Toy, Dana; Reese, Thomas S.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
   [Tao-Cheng, Jung-Hwa] NINDS, EM Facil, NIH, Bethesda, MD 20892 USA.
RP Dosemeci, A (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM dosemeca@mail.nih.gov
FU Intramural Research Program of the National Institute of Neurological
   Disorders and Stroke, National Institutes of Health, USA
FX The work was supported by the Intramural Research Program of the
   National Institute of Neurological Disorders and Stroke, National
   Institutes of Health, USA.
NR 19
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 10
PY 2015
VL 10
IS 9
AR e0137216
DI 10.1371/journal.pone.0137216
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ9WL
UT WOS:000360965800034
PM 26356309
ER

PT J
AU Gupta, K
   Afonin, KA
   Viard, M
   Herrero, V
   Kasprzak, W
   Kagiampakis, I
   Kim, T
   Koyfman, AY
   Puri, A
   Stepler, M
   Sappe, A
   KewalRamani, VN
   Grinberg, S
   Linder, C
   Heldman, E
   Blumenthal, R
   Shapiro, BA
AF Gupta, Kshitij
   Afonin, Kirill A.
   Viard, Mathias
   Herrero, Virginia
   Kasprzak, Wojciech
   Kagiampakis, Ioannis
   Kim, Taejin
   Koyfman, Alexey Y.
   Puri, Anu
   Stepler, Marissa
   Sappe, Alison
   KewalRamani, Vineet N.
   Grinberg, Sarina
   Linder, Charles
   Heldman, Eliahu
   Blumenthal, Robert
   Shapiro, Bruce A.
TI Bolaamphiphiles as carriers for siRNA delivery: From chemical syntheses
   to practical applications
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Bolaamphiphiles; Molecular dynamics simulations; Cryo-EM; FRET; siRNA
   drug delivery; RNAi induced gene silencing
ID LIPID-BASED NANOPARTICLES; ATOMIC-FORCE MICROSCOPY; RNA NANOPARTICLES;
   EMERGING FIELD; CANCER-THERAPY; IN-SILICO; VESICLES; NANOTECHNOLOGY;
   THERAPEUTICS; DESIGN
AB In this study we have investigated a new class of cationic lipids - "bolaamphiphiles" or "bolas" - for their ability to efficiently deliver small interfering RNAs (siRNAs) to cancer cells. The bolas of this study consist of a hydrophobic chain with one or more positively charged head groups at each end. Recently, we reported that micelles of the bolas GLH-19 and GLH-20 (derived from vernonia oil) efficiently deliver siRNAs, while having relatively low toxicities in vitro and in vivo. Our previous studies validated that; bolaamphiphiles can be designed to vary the magnitude of siRNA shielding, its delivery, and its subsequent release. To further understand the structural features of bolas critical for siRNAs delivery, new structurally related bolas (GLH-58 and GLH-60) were designed and synthesized from jojoba oil. Both bolas have similar hydrophobic domains and contain either one, in GLH-58, or two, in GLH-60 positively charged head groups at each end of the hydrophobic core. We have computationally predicted and experimentally validated that GLH-58 formed more stable nano sized micelles than GLH-60 and performed significantly better in comparison to GLH-60 for siRNA delivery. GLH-58/siRNA complexes demonstrated better efficiency in silencing the expression of the GFP gene in human breast cancer cells at concentrations of 5 mu g/mL, well below the toxic dose. Moreover, delivery of multiple different siRNAs targeting the HIV genome demonstrated further inhibition of virus production. Published by Elsevier B.V.
C1 [Gupta, Kshitij; Afonin, Kirill A.; Viard, Mathias; Kim, Taejin; Puri, Anu; Stepler, Marissa; Sappe, Alison; KewalRamani, Vineet N.; Blumenthal, Robert; Shapiro, Bruce A.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
   [Herrero, Virginia; Grinberg, Sarina] Ben Gurion Univ Negev, Dept Chem, Beer Sheva, Israel.
   [Viard, Mathias; Kasprzak, Wojciech] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab, Frederick, MD 21702 USA.
   [Koyfman, Alexey Y.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Natl Ctr Macromol Imaging, Houston, TX 77030 USA.
   [Linder, Charles] Ben Gurion Univ Negev, Dept Biotechnol, IL-84105 Beer Sheva, Israel.
   [Heldman, Eliahu] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem & Pharmacol, Beer Sheva, Israel.
   [Afonin, Kirill A.] Univ N Carolina, Dept Chem, Charlotte, NC 28223 USA.
   [Gupta, Kshitij] NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA.
   [Kagiampakis, Ioannis] Indian Inst Sci, Dept Inorgan & Phys Chem, Bangalore 560012, Karnataka, India.
RP Shapiro, BA (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM shapirbr@mail.nih.gov
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [ZIA BC011061-08];
   NCI NIH HHS [HHSN261200800001E]; NIGMS NIH HHS [P41 GM103832,
   P41GM103832]; PHS HHS [HHSN 261200800001E]
NR 43
TC 5
Z9 5
U1 3
U2 47
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD SEP 10
PY 2015
VL 213
BP 142
EP 151
DI 10.1016/j.jconrel.2015.06.041
PG 10
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA CP6KQ
UT WOS:000359996500266
PM 26151705
ER

PT J
AU Pomann, GM
   Sweeney, EM
   Reich, DS
   Staicu, AM
   Shinohara, RT
AF Pomann, Gina-Maria
   Sweeney, Elizabeth M.
   Reich, Daniel S.
   Staicu, Ana-Maria
   Shinohara, Russell T.
TI Scan-stratified case-control sampling for modeling blood-brain barrier
   integrity in multiple sclerosis
SO STATISTICS IN MEDICINE
LA English
DT Article
DE case-control sampling; logistic regression; magnetic resonance imaging;
   multiple sclerosis
ID NEPHROGENIC SYSTEMIC FIBROSIS; DIAGNOSTIC-CRITERIA; LESIONS; MRI;
   GADOLINIUM; SEGMENTATION; GUIDELINES; ESTIMATOR; DISEASE
AB Multiple sclerosis (MS) is an immune-mediated neurological disease that causes morbidity and disability. In patients with MS, the accumulation of lesions in the white matter of the brain is associated with disease progression and worse clinical outcomes. Breakdown of the blood-brain barrier in newer lesions is indicative of more active disease-related processes and is a primary outcome considered in clinical trials of treatments for MS. Such abnormalities in active MS lesions are evaluated in vivo using contrast-enhanced structural MRI, during which patients receive an intravenous infusion of a costly magnetic contrast agent. In some instances, the contrast agents can have toxic effects. Recently, local image regression techniques have been shown to have modest performance for assessing the integrity of the blood-brain barrier based on imaging without contrast agents. These models have centered on the problem of cross-sectional classification in which patients are imaged at a single study visit and pre-contrast images are used to predict post-contrast imaging. In this paper, we extend these methods to incorporate historical imaging information, and we find the proposed model to exhibit improved performance. We further develop scan-stratified case-control sampling techniques that reduce the computational burden of local image regression models, while respecting the low proportion of the brain that exhibits abnormal vascular permeability. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Pomann, Gina-Maria] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
   [Sweeney, Elizabeth M.; Reich, Daniel S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
   [Sweeney, Elizabeth M.; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA.
   [Staicu, Ana-Maria] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA.
   [Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Shinohara, RT (reprint author), Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM rshi@upenn.edu
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU National Science Foundation [DGE-0946818]; NIH from the National
   Institute of Neurological Disorders and Stroke [RO1 NS085211]; NINDS
FX Pomann's research is supported by the National Science Foundation under
   grant no. DGE-0946818. Pomann, Shinohara, Staicu, and Sweeney are
   partially funded by the NIH grant RO1 NS085211 from the National
   Institute of Neurological Disorders and Stroke. The study was supported
   in part by the Intramural Research Program of NINDS. This work
   represents the opinions of the researchers and not necessarily that of
   the granting organizations.
NR 25
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD SEP 10
PY 2015
VL 34
IS 20
BP 2872
EP 2880
DI 10.1002/sim.6520
PG 9
WC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Medicine, Research &
   Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Research & Experimental
   Medicine; Mathematics
GA CN4SW
UT WOS:000358421500006
PM 25939401
ER

PT J
AU Wu, JJ
   Li, WW
   Shao, YM
   Avey, D
   Fu, BS
   Gillen, J
   Hand, T
   Ma, SM
   Liu, X
   Miley, W
   Konrad, A
   Neipel, F
   Stuerzl, M
   Whitby, D
   Li, H
   Zhu, FX
AF Wu, Jian-jun
   Li, Wenwei
   Shao, Yaming
   Avey, Denis
   Fu, Bishi
   Gillen, Joseph
   Hand, Travis
   Ma, Siming
   Liu, Xia
   Miley, Wendell
   Konrad, Andreas
   Neipel, Frank
   Stuerzl, Michael
   Whitby, Denise
   Li, Hong
   Zhu, Fanxiu
TI Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein
SO CELL HOST & MICROBE
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; CYCLIC GMP-AMP; INTERFERON ANTIVIRAL
   RESPONSE; I-LIKE RECEPTORS; CYTOSOLIC DNA; SIMPLEX-VIRUS;
   MYCOBACTERIUM-TUBERCULOSIS; SIGNALING PATHWAY; IMMUNE-RESPONSES; STING
   PATHWAY
AB Invading viral DNA can be recognized by the host cytosolic DNA sensor, cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in production of the second messenger cGAMP, which directs the adaptor protein STING to stimulate production of type I interferons (IFNs). Although several DNA viruses are sensed by cGAS, viral strategies targeting cGAS are virtually unknown. We report here that Kaposi's sarcoma-associated herpesvirus (KSHV) ORF52, an abundant gammaherpesvirus-specific tegument protein, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity through a mechanism involving both cGAS binding and DNA binding. Moreover, ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA, suggesting conserved inhibitory mechanisms. Furthermore, KSHV infection evokes cGAS-dependent responses that can limit the infection, and an ORF52 null mutant exhibits increased cGAS signaling. Our findings reveal a mechanism through which gammaherpesviruses antagonize host cGAS DNA sensing.
C1 [Wu, Jian-jun; Li, Wenwei; Avey, Denis; Fu, Bishi; Gillen, Joseph; Ma, Siming; Liu, Xia; Zhu, Fanxiu] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
   [Shao, Yaming; Hand, Travis; Li, Hong] Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA.
   [Li, Hong] Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA.
   [Miley, Wendell; Whitby, Denise] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Viral Oncol Sect, Frederick, MD 21702 USA.
   [Konrad, Andreas; Stuerzl, Michael] Univ Erlangen Nurnberg, Univ Med Ctr Erlangen, Dept Surg, Div Mol & Expt Surg, D-91054 Erlangen, Germany.
   [Neipel, Frank] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany.
RP Zhu, FX (reprint author), Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA.
EM fzhu@bio.fsu.edu
RI Shao, Yaming/J-6555-2013; Sturzl, Michael/B-3019-2015; 
OI Sturzl, Michael/0000-0002-9276-2824; Wu, Jianjun/0000-0003-4518-8361
FU NIH [R01 DE016680, F31 CA183250, R01 GM099604, R01 GM66958]; National
   Cancer Institute, NIH [HHSN261200800001E]
FX We thank Drs. Kevin Brulois, Katherine Fitzgerald, Adolfo Garcia-Sastre,
   David Gilbert, Young-Kwon Hong, Pingwei Li, Michael Malim, Jinjong
   Myoung, Charles Rice, Ren Sun, Hengli Tang, Scott Wong, and Feng Zhang
   for reagents. We thank the Florida State University hybridoma facility
   for generating anti-ORF52 antibodies. We thank Dr. Lijun Sun for his
   helpful advice regarding the IRF3 dimerization assay. We also thank Ms.
   Jen Kennedy at the Florida State University for editorial assistance. We
   thank Drs. Betty Gaffney, Kenneth Roux, Beth Stroupe, and Hengli Tang
   and allmembers of the Zhu lab for helpful comments and discussion. This
   work was supported by NIH grants R01 DE016680 (to F.Z.), F31 CA183250
   (to D.A.), and R01 GM099604 and R01 GM66958 (to H.L.) and in part by the
   National Cancer Institute, NIH (contract number HHSN261200800001E).
NR 67
TC 29
Z9 29
U1 2
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD SEP 9
PY 2015
VL 18
IS 3
BP 333
EP 344
DI 10.1016/j.chom.2015.07.015
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CR3RA
UT WOS:000361249400011
PM 26320998
ER

PT J
AU Moody, MA
   Gao, F
   Gurley, TC
   Amos, JD
   Kumar, A
   Hora, B
   Marshall, DJ
   Whitesides, JF
   Xia, SM
   Parks, R
   Lloyd, KE
   Hwang, KK
   Lu, XZ
   Bonsignori, M
   Finzi, A
   Vandergrift, NA
   Alam, SM
   Ferrari, G
   Shen, XY
   Tomaras, GD
   Kamanga, G
   Cohen, MS
   Sam, NE
   Kapiga, S
   Gray, ES
   Tumba, NL
   Morris, L
   Zolla-Pazner, S
   Gorny, MK
   Mascola, JR
   Hahn, BH
   Shaw, GM
   Sodroski, JG
   Liao, HX
   Montefiori, DC
   Hraber, PT
   Korber, BT
   Haynes, BF
AF Moody, M. Anthony
   Gao, Feng
   Gurley, Thaddeus C.
   Amos, Joshua D.
   Kumar, Amit
   Hora, Bhavna
   Marshall, Dawn J.
   Whitesides, John F.
   Xia, Shi-Mao
   Parks, Robert
   Lloyd, Krissey E.
   Hwang, Kwan-Ki
   Lu, Xiaozhi
   Bonsignori, Mattia
   Finzi, Andres
   Vandergrift, Nathan A.
   Alam, S. Munir
   Ferrari, Guido
   Shen, Xiaoying
   Tomaras, Georgia D.
   Kamanga, Gift
   Cohen, Myron S.
   Sam, Noel E.
   Kapiga, Saidi
   Gray, Elin S.
   Tumba, Nancy L.
   Morris, Lynn
   Zolla-Pazner, Susan
   Gorny, Miroslaw K.
   Mascola, John R.
   Hahn, Beatrice H.
   Shaw, George M.
   Sodroski, Joseph G.
   Liao, Hua-Xin
   Montefiori, David C.
   Hraber, Peter T.
   Korber, Bette T.
   Haynes, Barton F.
TI Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing
   Antibodies Select Neutralization-Resistant Viruses
SO CELL HOST & MICROBE
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; GLYCOPROTEIN GP120; NAIVE INDIVIDUALS; INFECTION;
   RESPONSES; ENVELOPE; EVOLUTION; VACCINE; ESCAPE; PATHWAYS
AB The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs anti-bodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.
C1 [Moody, M. Anthony; Gao, Feng; Gurley, Thaddeus C.; Amos, Joshua D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn J.; Whitesides, John F.; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey E.; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Vandergrift, Nathan A.; Alam, S. Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia D.; Morris, Lynn; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA.
   [Moody, M. Anthony] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
   [Moody, M. Anthony; Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
   [Gao, Feng; Vandergrift, Nathan A.; Alam, S. Munir; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Alam, S. Munir; Montefiori, David C.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
   [Ferrari, Guido; Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
   [Finzi, Andres] Univ Montreal, CHUM, Ctr Rech, Montreal, PQ H2X 0A9, Canada.
   [Finzi, Andres] Univ Montreal, Dept Microbiol Infectol & Immunol, Montreal, PQ H2X 0A9, Canada.
   [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H2X 1P1, Canada.
   [Kamanga, Gift] Univ North Carolina Project, Kamuzu Cent Hosp, Lilongwe, Malawi.
   [Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
   [Cohen, Myron S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
   [Cohen, Myron S.] Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA.
   [Cohen, Myron S.] Univ N Carolina, Dept Immunol, Chapel Hill, NC 27599 USA.
   [Sam, Noel E.] Kilimanjaro Christian Med Ctr, Moshi 25102, Tanzania.
   [Kapiga, Saidi] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.
   [Gray, Elin S.; Tumba, Nancy L.; Morris, Lynn] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa.
   [Zolla-Pazner, Susan; Gorny, Miroslaw K.] NYU, Sch Med, Dept Pathol, New York, NY 10010 USA.
   [Zolla-Pazner, Susan] Vet Affairs New York Harbor Healthcare Syst, New York, NY 10010 USA.
   [Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Sodroski, Joseph G.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
   [Hraber, Peter T.; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
RP Moody, MA (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA.
EM moody007@mc.duke.edu; feng.gao@dm.duke.edu; hayne002@mc.duke.edu
RI Tomaras, Georgia/J-5041-2016; 
OI Korber, Bette/0000-0002-2026-5757; , Lynn/0000-0003-3961-7828; Gorny,
   Miroslaw/0000-0002-2714-8780; Hraber, Peter/0000-0002-2920-4897; Gray,
   Elin/0000-0002-8613-3570
FU Bill and Melinda Gates Foundation; Center for HIV/AIDS Vaccine
   Immunology (CHAVI) [U19 AI067854]; Center for HIV/AIDS Vaccine
   Immunology-Immunogen Discovery grant (CHAVI-ID) [UM1 AI100645]; CAVD
   [OPP1032325]; Duke Center for AIDS Research Flow Cytometry and Virology
   cores (CFAR) [P30-AI-64518]; NIH [P01 AI 100151]; Department of Veterans
   Affairs
FX We regret that due to space limitations we were unable to cite many
   excellent papers of our colleagues. HJ16 was generously donated by
   Davide Corti (Institute for Research in Biomedicine, Bellinzona,
   Switzerland). Support was provided by a Collaboration for AIDS Vaccine
   Discovery grant to B.F.H. from the Bill and Melinda Gates Foundation,
   the Center for HIV/AIDS Vaccine Immunology (CHAVI; grant U19 AI067854),
   and the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery grant
   (CHAVI-ID; grant UM1 AI100645). Further support was provided by CAVD
   funding for the CTVIMC, grant number OPP1032325; the Duke Center for
   AIDS Research Flow Cytometry and Virology cores (CFAR; P30-AI-64518);
   NIH grant P01 AI 100151 (S.Z.-P.); and funds from the Department of
   Veterans Affairs. We thank Daniel M. Kozink, Florence Perrin, and Abby
   J. Cooper for expert technical support.
NR 33
TC 15
Z9 15
U1 2
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD SEP 9
PY 2015
VL 18
IS 3
BP 354
EP 362
DI 10.1016/j.chom.2015.08.006
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CR3RA
UT WOS:000361249400013
PM 26355218
ER

PT J
AU Dhawan, D
   Paoloni, M
   Shukradas, S
   Choudhury, DR
   Craig, BA
   Ramos-Vara, JA
   Hahn, N
   Bonney, PL
   Khanna, C
   Knapp, DW
AF Dhawan, Deepika
   Paoloni, Melissa
   Shukradas, Shweta
   Choudhury, Dipanwita Roy
   Craig, Bruce A.
   Ramos-Vara, Jose A.
   Hahn, Noah
   Bonney, Patty L.
   Khanna, Chand
   Knapp, Deborah W.
TI Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes
   of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human
   Invasive Bladder Cancer
SO PLOS ONE
LA English
DT Article
ID TRANSITIONAL-CELL CARCINOMA; HUMAN BREAST-TUMORS; URINARY-BLADDER;
   MOLECULAR PORTRAITS; TARGETED THERAPY; LUNG-CANCER; PHASE-III;
   LAPATINIB; ERLOTINIB; PATHWAYS
AB More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC) this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.
C1 [Dhawan, Deepika; Bonney, Patty L.; Knapp, Deborah W.] Purdue Univ, Dept Vet Clin Sci, Coll Vet Med, W Lafayette, IN 47907 USA.
   [Dhawan, Deepika; Ramos-Vara, Jose A.; Knapp, Deborah W.] Purdue Univ, Purdue Oncol Sci Ctr, W Lafayette, IN 47907 USA.
   [Paoloni, Melissa; Khanna, Chand] NCI, CCR Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Shukradas, Shweta; Choudhury, Dipanwita Roy] Strand Genom Inc, Dept Bioinformat, San Francisco, CA USA.
   [Craig, Bruce A.] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA.
   [Ramos-Vara, Jose A.] Purdue Univ, Dept Comparat Pathobiol, Coll Vet Med, W Lafayette, IN 47907 USA.
   [Hahn, Noah] Johns Hopkins Univ, Sch Med, Dept Oncol & Urol, Baltimore, MD USA.
   [Knapp, Deborah W.] Purdue Univ, Ctr Canc Res, W Lafayette, IN 47907 USA.
RP Knapp, DW (reprint author), Purdue Univ, Dept Vet Clin Sci, Coll Vet Med, W Lafayette, IN 47907 USA.
EM knappd@purdue.edu
RI Craig, Bruce/D-5797-2017
OI Craig, Bruce/0000-0001-9346-467X
FU Comparative Oncology Program within the Intramural NCI; Strand Genomics
   Inc.
FX This study was supported by private donations for bladder cancer
   research made to the Purdue Comparative Oncology Program. At the time
   the work was done, MP and CK worked in the National Cancer Institute's
   Comparative Oncology Program. Additional funding for a portion of this
   work was provided by the Comparative Oncology Program within the
   Intramural NCI. Strand Genomics Inc. provided support in the form of
   salaries for authors SS and DRC, but did not have any additional role in
   the study design, data collection and analysis, decision to publish, or
   preparation of the manuscript. The specific roles of these authors are
   articulated in the 'author contributions' section.
NR 49
TC 2
Z9 2
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 9
PY 2015
VL 10
IS 9
AR e0136688
DI 10.1371/journal.pone.0136688
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ9KG
UT WOS:000360932800045
PM 26352142
ER

PT J
AU Maranhao, B
   Biswas, P
   Gottsch, ADH
   Navani, M
   Naeem, MA
   Suk, J
   Chu, J
   Khan, SN
   Poleman, R
   Akram, J
   Riazuddin, S
   Lee, P
   Riazuddin, SA
   Hejtmancik, JF
   Ayyagari, R
AF Maranhao, Bruno
   Biswas, Pooja
   Gottsch, Alexander D. H.
   Navani, Mili
   Naeem, Muhammad Asif
   Suk, John
   Chu, Justin
   Khan, Sheen N.
   Poleman, Rachel
   Akram, Javed
   Riazuddin, Sheikh
   Lee, Pauline
   Riazuddin, S. Amer
   Hejtmancik, J. Fielding
   Ayyagari, Radha
TI Investigating the Molecular Basis of Retinal Degeneration in a Familial
   Cohort of Pakistani Decent by Exome Sequencing
SO PLOS ONE
LA English
DT Article
ID LEBER CONGENITAL AMAUROSIS; RECESSIVE RETINITIS-PIGMENTOSA;
   GENOTYPE-PHENOTYPE CORRELATION; STATIONARY NIGHT BLINDNESS; MUTATIONS;
   DYSTROPHY; DISEASE; GENES; IDENTIFICATION; REVEALS
AB Purpose
   To define the molecular basis of retinal degeneration in consanguineous Pakistani pedigrees with early onset retinal degeneration.
   Methods
   A cohort of 277 individuals representing 26 pedigrees from the Punjab province of Pakistan was analyzed. Exomes were captured with commercial kits and sequenced on an Illumina HiSeq 2500. Candidate variants were identified using standard tools and analyzed using exomeSuite to detect all potentially pathogenic changes in genes implicated in retinal degeneration. Segregation analysis was performed by dideoxy sequencing and novel variants were additionally investigated for their presence in ethnicity-matched controls.
   Results
   We identified a total of nine causal mutations, including six novel variants in RPE65, LCA5, USH2A, CNGB1, FAM161A, CERKL and GUCY2D as the underlying cause of inherited retinal degenerations in 13 of 26 pedigrees. In addition to the causal variants, a total of 200 variants each observed in five or more unrelated pedigrees investigated in this study that were absent from the dbSNP, HapMap, 1000 Genomes, NHLBI ESP6500, and ExAC databases were identified, suggesting that they are common in, and unique to the Pakistani population.
   Conclusions
   We identified causal mutations associated with retinal degeneration in nearly half of the pedigrees investigated in this study through next generation whole exome sequencing. All novel variants detected in this study through exome sequencing have been cataloged providing a reference database of variants common in, and unique to the Pakistani population.
C1 [Maranhao, Bruno; Biswas, Pooja; Navani, Mili; Suk, John; Chu, Justin; Poleman, Rachel; Lee, Pauline; Ayyagari, Radha] Univ Calif La Jolla, Dept Ophthalmol, La Jolla, CA USA.
   [Gottsch, Alexander D. H.; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Naeem, Muhammad Asif; Khan, Sheen N.; Riazuddin, Sheikh; Riazuddin, S. Amer] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
   [Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
   [Akram, Javed; Riazuddin, Sheikh] Shaheed Zulfiqar Ali Bhutto Med Univ, Natl Ctr Genet Dis, Islamabad, Pakistan.
   [Hejtmancik, J. Fielding] NEI, OGVF Branch, NIH, Bethesda, MD 20892 USA.
RP Hejtmancik, JF (reprint author), NEI, OGVF Branch, NIH, Bethesda, MD 20892 USA.
EM f3h@helix.nih.gov; rayyagari@ucsd.edu
FU Foundation Fighting Blindness, Research to Prevent Blindness
   [NIH-EY21237, P30-EY22589]
FX The Foundation Fighting Blindness, Research to Prevent Blindness (to
   Department of Ophthalmology at UCSD, La Jolla, and Wilmer Eye Institute,
   Johns Hopkins University, Baltimore, MD), NIH-EY21237, P30-EY22589.
NR 42
TC 6
Z9 6
U1 1
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 SEP 9
PY 2015
VL 10
IS 9
AR e0136561
DI 10.1371/journal.pone.0136561
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ9KG
UT WOS:000360932800040
PM 26352687
ER

PT J
AU Louis, JM
   Deshmukh, L
   Sayer, JM
   Aniana, A
   Clore, GM
AF Louis, John M.
   Deshmukh, Lalit
   Sayer, Jane M.
   Aniana, Annie
   Clore, G. Marius
TI Mutations Proximal to Sites of Autoproteolysis and the alpha-Helix That
   Co-evolve under Drug Pressure Modulate the Autoprocessing and Vitality
   of HIV-1 Protease
SO BIOCHEMISTRY
LA English
DT Article
ID ACTIVE-SITE; RESISTANCE MUTATIONS; RETROVIRAL PROTEASES; CLINICAL
   INHIBITORS; FITNESS MUTATIONS; GAG POLYPROTEIN; STABILITY; DYNAMICS;
   BINDING; GENERATION
AB N-Terminal self-cleavage (autoprocessing) of the HIV-1 protease precursor is crucial for liberating the active dimer. Under drug pressure, evolving mutations are predicted to modulate autoprocessing, and the reduced catalytic activity of the mature protease (PR) is likely compensated by enhanced conformational/dimer stability and reduced susceptibility to self-degradation (autoproteolysis). One such highly evolved, multidrug resistant protease, PR20, bears 19 mutations contiguous to sites of autoproteolysis in retroviral proteases, namely clusters 1-3 comprising residues 30-37, 60-67, and 88-95, respectively, accounting for 11 of the 19 mutations. By systematically replacing corresponding clusters in PR with those of PR20, and vice versa, we assess their influence on the properties mentioned above and observe no strict correlation. A 10-35-fold decrease in the cleavage efficiency of peptide substrates by PR20, relative to PR, is reflected by an only similar to 4-fold decrease in the rate of Gag processing with no change in cleavage order. Importantly, optimal N-terminal autoprocessing requires all 19 PR20 mutations as evaluated in vitro using the model precursor TFR-PR20 in which PR is flanked by the transframe region. Substituting PR20 cluster 3 into TFR-PR (TFR-PRPR20-3) requires the presence of PR20 cluster 1 and/or 2 for autoprocessing. In accordance, substituting PR clusters 1 and 2 into TFR-PR20 affects the rate of autoprocessing more drastically (>300-fold) compared to that of TFR-PRPR20-3 because of the cumulative effect of eight noncluster mutations present in TFR-PR20PR-12. Overall, these studies imply that drug resistance involves a complex synchronized selection of mutations modulating all of the properties mentioned above governing PR regulation and function.
C1 [Louis, John M.; Deshmukh, Lalit; Sayer, Jane M.; Aniana, Annie; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, US Dept HHS, Bethesda, MD USA.
RP Louis, JM (reprint author), NIDDK, LCP, NIH, Bldg 5,Room B2-29, Bethesda, MD 20892 USA.
EM johnl@niddk.nih.gov
RI Deshmukh, Lalit/C-5073-2015
FU National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health (NIH); Office of the Director, NIH
FX This research was supported by the Intramural Research Program of the
   National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health (NIH), and the Intramural AIDS-Targeted
   Program of the Office of the Director, NIH (to G.M.C.).
NR 52
TC 5
Z9 5
U1 3
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD SEP 8
PY 2015
VL 54
IS 35
BP 5414
EP 5424
DI 10.1021/acs.biochem.5b00759
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CR1LO
UT WOS:000361086500004
PM 26266692
ER

PT J
AU Kurima, K
   Ebrahim, S
   Pan, BF
   Sedlacek, M
   Sengupta, P
   Millis, BA
   Cui, RJ
   Nakanishi, H
   Fujikawa, T
   Kawashima, Y
   Choi, BY
   Monahan, K
   Holt, JR
   Griffith, AJ
   Kachar, B
AF Kurima, Kiyoto
   Ebrahim, Seham
   Pan, Bifeng
   Sedlacek, Miloslav
   Sengupta, Prabuddha
   Millis, Bryan A.
   Cui, Runjia
   Nakanishi, Hiroshi
   Fujikawa, Taro
   Kawashima, Yoshiyuki
   Choi, Byung Yoon
   Monahan, Kelly
   Holt, Jeffrey R.
   Griffith, Andrew J.
   Kachar, Bechara
TI TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian
   Inner Ear Hair Cell Stereocilia
SO CELL REPORTS
LA English
DT Article
ID CHANNEL-LIKE PROTEINS; TIP-LINK; MOUSE COCHLEA; FUNCTIONAL MATURATION;
   TRANSDUCTION CHANNEL; PROTOCADHERIN 15; HEARING-LOSS; MYOSIN VIIA;
   CONDUCTANCE; DOMINANT
AB Mechanosensitive ion channels at stereocilia tips mediate mechanoelectrical transduction (MET) in inner ear sensory hair cells. Transmembrane channel-like 1 and 2 (TMC1 and TMC2) are essential for MET and are hypothesized to be components of the MET complex, but evidence for their predicted spatiotemporal localization in stereocilia is lacking. Here, we determine the stereocilia localization of the TMC proteins in mice expressing TMC1-mCherry and TMC2-AcGFP. Functionality of the tagged proteins was verified by transgenic rescue of MET currents and hearing in Tmc1(Delta/Delta); Tmc2(Delta/Delta) mice. TMC1-mCherry and TMC2-AcGFP localize along the length of immature stereocilia. However, as hair cells develop, the two proteins localize predominantly to stereocilia tips. Both TMCs are absent from the tips of the tallest stereocilia, where MET activity is not detectable. This distribution was confirmed for the endogenous proteins by immunofluorescence. These data are consistent with TMC1 and TMC2 being components of the stereocilia MET channel complex.
C1 [Kurima, Kiyoto; Nakanishi, Hiroshi; Kawashima, Yoshiyuki; Choi, Byung Yoon; Monahan, Kelly; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Mol Biol & Genet Sect, NIH, Bethesda, MD 20892 USA.
   [Ebrahim, Seham; Sedlacek, Miloslav; Millis, Bryan A.; Cui, Runjia; Fujikawa, Taro; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
   [Pan, Bifeng; Holt, Jeffrey R.] Harvard Univ, Sch Med, Dept Otolaryngol, FM Kirby Neurobiol Ctr,Boston Childrens Hosp, Boston, MA 02115 USA.
   [Sengupta, Prabuddha] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Biol & Genet Sect, NIH, Bethesda, MD 20892 USA.
EM griffita@nidcd.nih.gov; kacharb@nidcd.nih.gov
FU NIH [Z01-DC000002, Z01-DC000060]; NIH/NIDCD [RO1-DC013521]
FX We thank Elizabeth Wilson, James McGehee, and Patrick Diers for mouse
   management. Work was supported by NIH intramural research funds
   Z01-DC000002 (to B.K.) and Z01-DC000060 (to A.J.G.). B.P. and J.R.H.
   were supported by NIH/NIDCD RO1-DC013521.
NR 33
TC 11
Z9 12
U1 4
U2 14
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 SEP 8
PY 2015
VL 12
IS 10
BP 1606
EP 1617
DI 10.1016/j.celrep.2015.07.058
PG 12
WC Cell Biology
SC Cell Biology
GA CQ9WI
UT WOS:000360965500010
PM 26321635
ER

PT J
AU Xiao, TJ
   Wongtrakoongate, P
   Trainor, C
   Felsenfeld, G
AF Xiao, Tiaojiang
   Wongtrakoongate, Patompon
   Trainor, Cecelia
   Felsenfeld, Gary
TI CTCF Recruits Centromeric Protein CENP-E to the
   Pericentromeric/Centromeric Regions of Chromosomes through Unusual
   CTCF-Binding Sites
SO CELL REPORTS
LA English
DT Article
ID GENOME ORGANIZATION; KINETOCHORE; MITOSIS; DNA; METHYLATION; INSULATOR;
   COHESIN; HETEROCHROMATIN; PROGRESSION; SEGREGATION
AB The role of CTCF in stabilizing long-range interactions between chromatin sites essential for maintaining nuclear architecture is well established. Most of these interactions involve recruitment of the cohesin complex to chromatin via CTCF. We find that CTCF also interacts with the centromeric protein CENP-E both in vitro and in vivo. We identified CTCF sites in pericentric/centromeric DNA and found that, early in mitosis, CTCF binds and recruits CENP-E to these sites. Unlike most known CTCF genomic sites, the CTCF-binding sites in the pericentric/centromeric regions interact strongly with the C-terminal fingers of CTCF. Overexpression of a small CENP-E fragment, targeted to these CTCF sites, results in a delay in alignment of some chromosomes during mitosis, suggesting that the recruitment of CENP-E by CTCF is physiologically important. We conclude that CTCF helps recruit CENP-E to the centromere during mitosis and that it may do so through a structure stabilized by the CTCF/CENP-E complex.
C1 [Xiao, Tiaojiang; Wongtrakoongate, Patompon; Trainor, Cecelia; Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Wongtrakoongate, Patompon] Mahidol Univ, Dept Biochem, Fac Sci, Bangkok 10400, Thailand.
RP Felsenfeld, G (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gary.felsenfeld@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases, NIH
FX We thank Dr. Gaelle Lefevre and Dr. Gregory Riddick as well as other
   members of our laboratory for their help. We also thank Dr. Don W.
   Cleveland for the CENP-E plasmid. This work was supported by the
   Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases, NIH.
NR 39
TC 3
Z9 3
U1 2
U2 9
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 SEP 8
PY 2015
VL 12
IS 10
BP 1704
EP 1714
DI 10.1016/j.celrep.2015.08.005
PG 11
WC Cell Biology
SC Cell Biology
GA CQ9WI
UT WOS:000360965500018
PM 26321640
ER

PT J
AU Menke, A
   Casagrande, S
   Geiss, L
   Cowie, CC
AF Menke, Andy
   Casagrande, Sarah
   Geiss, Linda
   Cowie, Catherine C.
TI Prevalence of and Trends in Diabetes Among Adults in the United States,
   1988-2012
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID BODY-MASS INDEX; HEALTH-INSURANCE COVERAGE; FASTING PLASMA-GLUCOSE;
   NATIONAL-HEALTH; US ADULTS; OBESITY; POPULATION; PARTICIPANTS; CUTOFFS
AB IMPORTANCE Previous studies have shown increasing prevalence of diabetes in the United States. New US data are available to estimate prevalence of and trends in diabetes.
   OBJECTIVE To estimate the recent prevalence and update US trends in total diabetes, diagnosed diabetes, and undiagnosed diabetes using National Health and Nutrition Examination Survey (NHANES) data.
   DESIGN, SETTING, AND PARTICIPANTS Cross-sectional surveys conducted between 1988-1994 and 1999-2012 of nationally representative samples of the civilian, noninstitutionalized US population; 2781 adults from 2011-2012 were used to estimate recent prevalence and an additional 23 634 adults from 1988-2010 were used to estimate trends.
   MAIN OUTCOMES AND MEASURES The prevalence of diabetes was defined using a previous diagnosis of diabetes or, if diabetes was not previously diagnosed, by (1) a hemoglobin A(1c) level of 6.5% or greater or a fasting plasma glucose (FPG) level of 126 mg/dL or greater (hemoglobin A1c or FPG definition) or (2) additionally including 2-hour plasma glucose (2-hour PG) level of 200mg/dL or greater (hemoglobin A1c, FPG, or 2-hour PG definition). Prediabetes was defined as a hemoglobin A1c level of 5.7% to 6.4%, an FPG level of 100 mg/dL to 125 mg/dL, or a 2-hour PG level of 140 mg/dL to 199 mg/dL.
   RESULTS In the overall 2011-2012 population, the unadjusted prevalence (using the hemoglobin A1c, FPG, or 2-hour PG definitions for diabetes and prediabetes) was 14.3%(95% CI, 12.2%-16.8%) for total diabetes, 9.1% (95% CI, 7.8%-10.6%) for diagnosed diabetes, 5.2% (95% CI, 4.0%-6.9%) for undiagnosed diabetes, and 38.0%(95% CI, 34.7%-41.3%) for prediabetes; among those with diabetes, 36.4%(95% CI, 30.5%-42.7%) were undiagnosed. The unadjusted prevalence of total diabetes (using the hemoglobin A1c or FPG definition) was 12.3%(95% CI, 10.8%-14.1%); among those with diabetes, 25.2%(95% CI, 21.1%-29.8%) were undiagnosed. Compared with non-Hispanic white participants (11.3%[95% CI, 9.0%-14.1%]), the age-standardized prevalence of total diabetes (using the hemoglobin A1c, FPG, or 2-hour PG definition) was higher among non-Hispanic black participants (21.8%[95% CI, 17.7%-26.7%]; P < .001), non-Hispanic Asian participants (20.6%[95% CI, 15.0%-27.6%]; P = .007), and Hispanic participants (22.6%[95% CI, 18.4%-27.5%]; P < .001). The age-standardized percentage of cases that were undiagnosed was higher among non-Hispanic Asian participants (50.9%[95% CI, 38.3%-63.4%]; P = .004) and Hispanic participants (49.0% [95% CI, 40.8%-57.2%]; P = .02) than all other racial/ethnic groups. The age-standardized prevalence of total diabetes (using the hemoglobin A1c or FPG definition) increased from 9.8%(95% CI, 8.9%-10.6%) in 1988-1994 to 10.8%(95% CI, 9.5%-12.0%) in 2001-2002 to 12.4%(95% CI, 10.8%-14.2%) in 2011-2012 (P < .001 for trend) and increased significantly in every age group, in both sexes, in every racial/ethnic group, by all education levels, and in all poverty income ratio tertiles.
   CONCLUSIONS AND RELEVANCE In 2011-2012, the estimated prevalence of diabetes was 12% to 14% among US adults, depending on the criteria used, with a higher prevalence among participants who were non-Hispanic black, non-Hispanic Asian, and Hispanic. Between 1988-1994 and 2011-2012, the prevalence of diabetes increased in the overall population and in all subgroups evaluated.
C1 [Menke, Andy; Casagrande, Sarah] Social & Sci Syst Inc, Silver Spring, MD 20910 USA.
   [Geiss, Linda] US Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
   [Cowie, Catherine C.] NIDDK, NIH, Bethesda, MD USA.
RP Menke, A (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave, Silver Spring, MD 20910 USA.
EM amenke@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
   [GS10F0381L]
FX This work was supported by contract GS10F0381L from the National
   Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
NR 23
TC 138
Z9 139
U1 4
U2 24
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 SEP 8
PY 2015
VL 314
IS 10
BP 1021
EP 1029
DI 10.1001/jama.2015.10029
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CQ8FA
UT WOS:000360840700014
PM 26348752
ER

PT J
AU Stoll, BJ
   Hansen, NI
   Bell, EF
   Walsh, MC
   Carlo, WA
   Shankaran, S
   Laptook, AR
   Sanchez, PJ
   Van Meurs, KP
   Wyckoff, M
   Das, A
   Hale, EC
   Ball, MB
   Newman, NS
   Schibler, K
   Poindexter, BB
   Kennedy, KA
   Cotten, CM
   Watterberg, KL
   D'Angio, CT
   DeMauro, SB
   Truog, WE
   Devaskar, U
   Higgins, RD
AF Stoll, Barbara J.
   Hansen, Nellie I.
   Bell, Edward F.
   Walsh, Michele C.
   Carlo, Waldemar A.
   Shankaran, Seetha
   Laptook, Abbot R.
   Sanchez, Pablo J.
   Van Meurs, Krisa P.
   Wyckoff, Myra
   Das, Abhik
   Hale, Ellen C.
   Ball, M. Bethany
   Newman, Nancy S.
   Schibler, Kurt
   Poindexter, Brenda B.
   Kennedy, Kathleen A.
   Cotten, C. Michael
   Watterberg, Kristi L.
   D'Angio, Carl T.
   DeMauro, Sara B.
   Truog, William E.
   Devaskar, Uday
   Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst
TI Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm
   Neonates, 1993-2012
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID BIRTH-WEIGHT OUTCOMES; EXTREMELY PREMATURE-INFANTS; LATE-ONSET SEPSIS;
   NATIONAL-INSTITUTE; CHILD-HEALTH; RESEARCH NETWORK; WEEKS GESTATION;
   UNITED-STATES; NECROTIZING ENTEROCOLITIS; ANTENATAL CORTICOSTEROIDS
AB IMPORTANCE Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality.
   OBJECTIVE To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers.
   DESIGN, SETTING, PARTICIPANTS Prospective registry of 34 636 infants, 22 to 28 weeks' gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012.
   EXPOSURES Extremely preterm birth.
   MAIN OUTCOMES AND MEASURES Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex.
   RESULTS Use of antenatal corticosteroids increased from 1993 to 2012 (24%[348 of 1431 infants]) to 87%(1674 of 1919 infants]; P < .001), as did cesarean delivery (44%[625 of 1431 births] to 64%[1227 of 1921]; P < .001). Delivery room intubation decreased from 80%(1144 of 1433 infants) in 1993 to 65%(1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8%(141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7%(120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks [37% {109 of 296} to 27%{85 of 320}]; adjusted relative risk [RR], 0.93 [95% CI, 0.92-0.94]). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks' gestation (26 weeks, 50%[130 of 258] to 55%[164 of 297]; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks' gestation (27%[41 of 152] to 33%[50 of 150]; adjusted RR, 1.09 [95% CI, 1.05-1.14]) and 24 weeks (63%[156 of 248] to 65%[174 of 269]; adjusted RR, 1.05 [95% CI, 1.03-1.07]), with smaller relative increases for infants at 25 and 27 weeks' gestation, and no change for infants at 22, 26, and 28 weeks' gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks' gestation, with no change for infants at 22 to 24 weeks' gestation.
   CONCLUSIONS AND RELEVANCE Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks' gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions.
C1 [Stoll, Barbara J.; Hale, Ellen C.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
   [Hansen, Nellie I.] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA.
   [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
   [Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
   [Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
   [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
   [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
   [Sanchez, Pablo J.] Ohio State Univ, Nationwide Childrens Hosp, Dept Pediat, Ctr Perinatal Res, Columbus, OH 43210 USA.
   [Van Meurs, Krisa P.; Ball, M. Bethany] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA.
   [Van Meurs, Krisa P.; Ball, M. Bethany] Lucile Packard Childrens Hosp, Palo Alto, CA USA.
   [Wyckoff, Myra] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [Das, Abhik] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA.
   [Schibler, Kurt] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH 45229 USA.
   [Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
   [Kennedy, Kathleen A.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
   [Cotten, C. Michael] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
   [Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
   [D'Angio, Carl T.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
   [DeMauro, Sara B.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
   [Truog, William E.] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA.
   [Devaskar, Uday] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Stoll, BJ (reprint author), Emory Univ, Sch Med, Dept Pediat, 1760 Haygood Dr,Ste W400, Atlanta, GA 30322 USA.
EM bstoll@emory.edu
RI Patel, Ravi/B-7218-2011
OI Patel, Ravi/0000-0002-7444-5550
FU National Institutes of Health (NIH); Eunice Kennedy Shriver NICHD;
   National Center for Research Resources; National Center for Advancing
   Translational Sciences
FX The National Institutes of Health (NIH), the Eunice Kennedy Shriver
   NICHD, the National Center for Research Resources, and the National
   Center for Advancing Translational Sciences provided grant support for
   the NRN Generic Database Study to maintain a high-risk preterm infant
   registry through cooperative agreements.
NR 44
TC 94
Z9 97
U1 3
U2 13
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 SEP 8
PY 2015
VL 314
IS 10
BP 1039
EP 1051
DI 10.1001/jama.2015.10244
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA CQ8FA
UT WOS:000360840700016
PM 26348753
ER

PT J
AU Harhay, MO
   Kizer, JR
   Criqui, MH
   Lima, JAC
   Tracy, R
   Bluemke, DA
   Kawut, SM
AF Harhay, Michael O.
   Kizer, Jorge R.
   Criqui, Michael H.
   Lima, Joao A. C.
   Tracy, Russell
   Bluemke, David A.
   Kawut, Steven M.
TI Adipokines and the Right Ventricle: The MESA-RV Study
SO PLOS ONE
LA English
DT Article
ID HEART-FAILURE; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS MESA;
   WEIGHT-LOSS; OBESITY; LEPTIN; HYPERTROPHY; ADIPONECTIN; MASS;
   INFLAMMATION
AB Objective
   Obesity is associated with changes in both right (RV) and left (LV) ventricular morphology, but the biological basis of this finding is not well established. We examined whether adipokine levels were associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.
   Methods
   We examined relationships of leptin, resistin, TNF-alpha, and adiponectin with RV morphology and function (from cardiac MRI) in participants (n = 1,267) free of clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of each adipokine with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF).
   Results
   Higher leptin levels were associated with significantly lower levels of RV mass, RVEDV, RVESV and stroke volume, but not RVEF, after adjustment for age, gender, race, height and weight. These associations were somewhat attenuated but still significant after adjustment for traditional risk factors and covariates, and were completely attenuated when correcting for the respective LV measures. There were no significant interactions of age, gender, or race/ethnicity on the relationship between the four adipokines and RV structure or function.
   Conclusions
   Leptin levels are associated with favorable RV morphology in a multi-ethnic population free of cardiovascular disease, however these associations may be explained by a yet to be understood bi-ventricular process as this association was no longer present after adjustment for LV values. These findings complement the associations previously shown between adipokines and LV structure and function in both healthy and diseased patients. The mechanisms linking adipokines to healthy cardiovascular function require further investigation.
C1 [Harhay, Michael O.; Kawut, Steven M.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
   [Harhay, Michael O.; Kawut, Steven M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
   [Harhay, Michael O.; Kawut, Steven M.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Kizer, Jorge R.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
   [Criqui, Michael H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA.
   [Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
   [Tracy, Russell] Univ Vermont, Sch Med, Dept Lab Med, Burlington, VT 05405 USA.
   [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD USA.
RP Kawut, SM (reprint author), Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
EM kawut@upenn.edu
OI Bluemke, David/0000-0002-8323-8086; Harhay, Michael/0000-0002-0553-674X
FU National Institutes of Health [F31-HL127947, R01-HL086719, R01-HL077612,
   RO1-HL088451, N01-HC95159 - HC95165, N01-HC95169]
FX The following National Institutes of Health grants and contracts
   provided funding for this study: F31-HL127947 (to MOH), R01-HL086719,
   R01-HL077612, RO1-HL088451, N01-HC95159 - HC95165, N01-HC95169. The
   authors thank the MESA investigators, staff, and participants for their
   valuable contributions. A full list of participating MESA Investigators
   and institutions can be found at http://www.mesa-nhlbi.org. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 36
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 8
PY 2015
VL 10
IS 9
AR e0136818
DI 10.1371/journal.pone.0136818
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ8YQ
UT WOS:000360897600013
PM 26348768
ER

PT J
AU Khiati, S
   Baechler, SA
   Factor, VM
   Zhang, HL
   Huang, SYN
   Rosa, ID
   Sourbier, C
   Neckers, L
   Thorgeirsson, SS
   Pommier, Y
AF Khiati, Salim
   Baechler, Simone A.
   Factor, Valentina M.
   Zhang, Hongliang
   Huang, Shar-yin N.
   Rosa, Ilaria Dalla
   Sourbier, Carole
   Neckers, Leonard
   Thorgeirsson, Snorri S.
   Pommier, Yves
TI Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver
   regeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE liver regeneration; mitochondrial topoisomerase I; cell proliferation;
   mitochondrial DNA replication; mitochondrial homeostasis
ID CARBON-TETRACHLORIDE; DNA TOPOISOMERASES; ETHIDIUM BROMIDE; III-ALPHA;
   CELLS; TRANSCRIPTION; GROWTH; HEPATOCYTES; MAINTENANCE; INHIBITION
AB The liver has an exceptional replicative capacity following partial hepatectomy or chemical injuries. Cellular proliferation requires increased production of energy and essential metabolites, which critically depend on the mitochondria. To determine whether Top1mt, the vertebrate mitochondrial topoisomerase, is involved in this process, we studied liver regeneration after carbon tetrachloride (CCl4) administration. TOP1mt knockout (KO) mice showed a marked reduction in regeneration and hepatocyte proliferation. The hepatic mitochondrial DNA (mtDNA) failed to increase during recovery from CC(l)4 exposure. Reduced glutathione was also depleted, indicating increased reactive oxygen species (ROS). Steady-state levels of ATP, O-2 consumption, mtDNA, and mitochondrial mass were also reduced in primary hepatocytes from CCl4-treated KO mice. To further test whether Top1mt acted by enabling mtDNA regeneration, we tested TOP1mt KO fibroblasts and human colon carcinoma HCT116 cells and measured mtDNA after 3-d treatment with ethidium bromide. Both types of TOP1mt knockout cells showed defective mtDNA regeneration following mtDNA depletion. Our study demonstrates that Top1mt is required for normal mtDNA homeostasis and for linking mtDNA expansion with hepatocyte proliferation.
C1 [Khiati, Salim; Baechler, Simone A.; Zhang, Hongliang; Huang, Shar-yin N.; Rosa, Ilaria Dalla; Pommier, Yves] NCI, Dev Therapeut Branch, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
   [Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Lab Expt Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Sourbier, Carole; Neckers, Leonard] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Intramural Programs of the National Cancer Institute, Center of Cancer
   Research Grant [Z01 BC006161]
FX We thank K. Nagashima and U. Baxa for EM support and the
   Pathology/Histology Laboratory, Frederick National Laboratory for Cancer
   Research (S. Florea, L. Dutko, J. Krolus, G. V. Rivera, B. Gouker, and
   D. Butcher for liver tissue staining and R. Smith for blood analysis).
   Our studies are supported by the Intramural Programs of the National
   Cancer Institute, Center of Cancer Research Grant Z01 BC006161.
NR 39
TC 3
Z9 3
U1 1
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 8
PY 2015
VL 112
IS 36
BP 11282
EP 11287
DI 10.1073/pnas.1511016112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR0FW
UT WOS:000360994900048
PM 26305952
ER

PT J
AU Tanigawa, S
   Sharma, N
   Hall, MD
   Nishinakamura, R
   Perantoni, AO
AF Tanigawa, Shunsuke
   Sharma, Nirmala
   Hall, Michael D.
   Nishinakamura, Ryuichi
   Perantoni, Alan O.
TI Preferential Propagation of Competent SIX2+Nephronic Progenitors by
   LIF/ROCKi Treatment of the Metanephric Mesenchyme
SO STEM CELL REPORTS
LA English
DT Article
ID EMBRYONIC STEM-CELLS; KIDNEY DEVELOPMENT; NEPHRON PROGENITORS; RENAL
   DEVELOPMENT; GROWTH-FACTOR; MOUSE KIDNEY; DIFFERENTIATION; ACTIVATION;
   INDUCTION; LIF
AB Understanding the mechanisms responsible for nephrogenic stem cell preservation and commitment is fundamental to harnessing the potential of the metanephric mesenchyme (MM) for nephron regeneration. Accordingly, we established a culture model that preferentially expands the MM SIX2+ progenitor pool using leukemia inhibitory factor (LIF), a Rho kinase inhibitor (ROCKi), and extracellular matrix. Passaged MM cells express the key stem cell regulators Six2 and Pax2 and remain competent to respond to WNT4 induction and form mature tubular epithelia and glomeruli. Mechanistically, LIF activates STAT, which binds to a Stat consensus sequence in the Six2 proximal promoter and sustains SIX2 levels. ROCKi, on the other hand, attenuates the LIF-induced differentiation activity of JNK. Concomitantly, the combination of LIF/ROCKi upregulates Slug expression and activates YAP, which maintains SIX2, PAX2, and SALL1. Using this novel model, our study underscores the pivotal roles of SIX2 and YAP in MM stem cell stability.
C1 [Tanigawa, Shunsuke; Sharma, Nirmala; Hall, Michael D.; Perantoni, Alan O.] NCI, Frederick, MD 21702 USA.
   [Tanigawa, Shunsuke; Nishinakamura, Ryuichi] Kumamoto Univ, Dept Kidney Dev, Inst Mol Embryol & Genet, Kumamoto 8600811, Japan.
   [Tanigawa, Shunsuke; Nishinakamura, Ryuichi] Kumamoto Univ, Program Leading Grad Sch, Hlth Life Sci Interdisciplinary & Glocal Global &, Kumamoto 8600811, Japan.
RP Perantoni, AO (reprint author), NCI, Frederick, MD 21702 USA.
EM perantoa@mail.nih.gov
FU Japanese Society for the Promotion of Science; KAKENHI from the Ministry
   of Education, Culture, Sports, Science and Technology (MEXT) of Japan
   [26860640]; Intramural Research Program of the NIH, NCI, CCR
FX This work was supported by a fellowship from the Japanese Society for
   the Promotion of Science (to S.T.), grant KAKENHI 26860640 from the
   Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
   Japan (to S.T.), and the Intramural Research Program of the NIH, NCI,
   CCR. We thank Drs. Taguchi, Kaku, Ohmori, and Fujimura for technical
   guidance. We thank Drs. Lewandoski and Mackem for a critical review of
   the manuscript.
NR 37
TC 7
Z9 7
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2213-6711
J9 STEM CELL REP
JI Stem Cell Rep.
PD SEP 8
PY 2015
VL 5
IS 3
BP 435
EP 447
DI 10.1016/j.stemcr.2015.07.015
PG 13
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA CR0LD
UT WOS:000361009200011
PM 26321142
ER

PT J
AU Abdulla, S
   Adam, I
   Adjei, GO
   Adjuik, MA
   Alemayehu, B
   Allan, R
   Arinaitwe, E
   Ashley, EA
   Ba, MS
   Barennes, H
   Barnes, KI
   Bassat, Q
   Baudin, E
   Berens-Riha, N
   Bjorkman, A
   Bompart, F
   Bonnet, M
   Borrmann, S
   Bousema, T
   Brasseur, P
   Bukirwa, H
   Checchi, F
   Dahal, P
   D'Alessandro, U
   Desai, M
   Dicko, A
   Djimde, AA
   Dorsey, G
   Doumbo, OK
   Drakeley, CJ
   Duparc, S
   Eshetu, T
   Espie, E
   Etard, JF
   Faiz, AM
   Falade, CO
   Fanello, CI
   Faucher, JF
   Faye, B
   Faye, O
   Filler, S
   Flegg, JA
   Fofana, B
   Fogg, C
   Gadalla, NB
   Gaye, O
   Genton, B
   Gething, PW
   Gil, JP
   Gonzalez, R
   Grandesso, F
   Greenhouse, B
   Greenwood, B
   Grivoyannis, A
   Guerin, PJ
   Guthmann, JP
   Hamed, K
   Hamour, S
   Hay, SI
   Hodel, EM
   Humphreys, GS
   Hwang, J
   Ibrahim, ML
   Jima, D
   Jones, JJ
   Jullien, V
   Juma, E
   Kachur, PS
   Kager, PA
   Kamugisha, E
   Kamya, MR
   Karema, C
   Kayentao, K
   Kiechel, JR
   Kironde, F
   Kofoed, PE
   Kremsner, PG
   Krishna, S
   Lameyre, V
   Lell, B
   Lima, A
   Makanga, M
   Malik, EM
   Marsh, K
   Martensson, A
   Massougbodji, A
   Menan, H
   Menard, D
   Menendez, C
   Mens, PF
   Meremikwu, M
   Moreira, C
   Nabasumba, C
   Nambozi, M
   Ndiaye, JL
   Ngasala, BE
   Nikiema, F
   Nsanzabana, C
   Ntoumi, F
   Oguike, M
   Ogutu, BR
   Olliaro, P
   Omar, SA
   Ouedraogo, JB
   Owusu-Agyei, S
   Penali, LK
   Pene, M
   Peshu, J
   Piola, P
   Plowe, CV
   Premji, Z
   Price, RN
   Randrianarivelojosia, M
   Rombo, L
   Roper, C
   Rosenthal, PJ
   Sagara, I
   Same-Ekobo, A
   Sawa, P
   Schallig, HDFH
   Schramm, B
   Seck, A
   Shekalaghe, SA
   Sibley, CH
   Sinou, V
   Sirima, SB
   Som, FA
   Sow, D
   Staedke, SG
   Stepniewska, K
   Sutherland, CJ
   Swarthout, TD
   Sylla, K
   Talisuna, AO
   Taylor, WRJ
   Temu, EA
   Thwing, JI
   Tine, RCK
   Tinto, H
   Tommasini, S
   Toure, OA
   Ursing, J
   Vaillant, MT
   Valentini, G
   Van den Broek, I
   Van Vugt, M
   Ward, SA
   Winstanley, PA
   Yavo, W
   Yeka, A
   Zolia, YM
   Zongo, I
AF Abdulla, Salim
   Adam, Ishag
   Adjei, George O.
   Adjuik, Martin A.
   Alemayehu, Bereket
   Allan, Richard
   Arinaitwe, Emmanuel
   Ashley, Elizabeth A.
   Ba, Mamadou S.
   Barennes, Hubert
   Barnes, Karen I.
   Bassat, Quique
   Baudin, Elisabeth
   Berens-Riha, Nicole
   Bjoerkman, Anders
   Bompart, Francois
   Bonnet, Maryline
   Borrmann, Steffen
   Bousema, Teun
   Brasseur, Philippe
   Bukirwa, Hasifa
   Checchi, Francesco
   Dahal, Prabin
   D'Alessandro, Umberto
   Desai, Meghna
   Dicko, Alassane
   Djimde, Abdoulaye A.
   Dorsey, Grant
   Doumbo, Ogobara K.
   Drakeley, Chris J.
   Duparc, Stephan
   Eshetu, Teferi
   Espie, Emmanuelle
   Etard, Jean-Francois
   Faiz, Abul M.
   Falade, Catherine O.
   Fanello, Caterina I.
   Faucher, Jean-Francois
   Faye, Babacar
   Faye, Oumar
   Filler, Scott
   Flegg, Jennifer A.
   Fofana, Bakary
   Fogg, Carole
   Gadalla, Nahla B.
   Gaye, Oumar
   Genton, Blaise
   Gething, Peter W.
   Gil, Jose P.
   Gonzalez, Raquel
   Grandesso, Francesco
   Greenhouse, Bryan
   Greenwood, Brian
   Grivoyannis, Anastasia
   Guerin, Philippe J.
   Guthmann, Jean-Paul
   Hamed, Kamal
   Hamour, Sally
   Hay, Simon I.
   Hodel, Eva Maria
   Humphreys, Georgina S.
   Hwang, Jimee
   Ibrahim, Maman L.
   Jima, Daddi
   Jones, Joel J.
   Jullien, Vincent
   Juma, Elizabeth
   Kachur, Patrick S.
   Kager, Piet A.
   Kamugisha, Erasmus
   Kamya, Moses R.
   Karema, Corine
   Kayentao, Kassoum
   Kiechel, Jean-Rene
   Kironde, Fred
   Kofoed, Poul-Erik
   Kremsner, Peter G.
   Krishna, Sanjeev
   Lameyre, Valerie
   Lell, Bertrand
   Lima, Angeles
   Makanga, Michael
   Malik, ElFatih M.
   Marsh, Kevin
   Martensson, Andreas
   Massougbodji, Achille
   Menan, Herve
   Menard, Didier
   Menendez, Clara
   Mens, Petra F.
   Meremikwu, Martin
   Moreira, Clarissa
   Nabasumba, Carolyn
   Nambozi, Michael
   Ndiaye, Jean-Louis
   Ngasala, Billy E.
   Nikiema, Frederic
   Nsanzabana, Christian
   Ntoumi, Francine
   Oguike, Mary
   Ogutu, Bernhards R.
   Olliaro, Piero
   Omar, Sabah A.
   Ouedraogo, Jean-Bosco
   Owusu-Agyei, Seth
   Penali, Louis K.
   Pene, Mbaye
   Peshu, Judy
   Piola, Patrice
   Plowe, Christopher V.
   Premji, Zul
   Price, Ric N.
   Randrianarivelojosia, Milijaona
   Rombo, Lars
   Roper, Cally
   Rosenthal, Philip J.
   Sagara, Issaka
   Same-Ekobo, Albert
   Sawa, Patrick
   Schallig, Henk D. F. H.
   Schramm, Birgit
   Seck, Amadou
   Shekalaghe, Seif A.
   Sibley, Carol H.
   Sinou, Vronique
   Sirima, Sodiomon B.
   Som, Fabrice A.
   Sow, Doudou
   Staedke, Sarah G.
   Stepniewska, Kasia
   Sutherland, Colin J.
   Swarthout, Todd D.
   Sylla, Khadime
   Talisuna, Ambrose O.
   Taylor, Walter R. J.
   Temu, Emmanuel A.
   Thwing, Julie I.
   Tine, Roger C. K.
   Tinto, Halidou
   Tommasini, Silva
   Toure, Offianan A.
   Ursing, Johan
   Vaillant, Michel T.
   Valentini, Giovanni
   Van den Broek, Ingrid
   Van Vugt, Michele
   Ward, Stephen A.
   Winstanley, Peter A.
   Yavo, William
   Yeka, Adoke
   Zolia, Yah M.
   Zongo, Issaka
CA WWARN Artemisinin Based
TI Clinical determinants of early parasitological response to ACTs in
   African patients with uncomplicated falciparum malaria: a literature
   review and meta-analysis of individual patient data
SO BMC MEDICINE
LA English
DT Review
ID RESISTANT PLASMODIUM-FALCIPARUM; PARASITE CLEARANCE;
   ARTEMETHER-LUMEFANTRINE; ARTEMISININ RESISTANCE; COMBINATION THERAPY;
   IN-VIVO; EFFICACY; ARTESUNATE; CHILDREN; CAMBODIA
AB Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs).
   Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data.
   Results: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degrees C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine).
   Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.
C1 [Abdulla, Salim; Shekalaghe, Seif A.] Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
   [Adam, Ishag] Univ Khartoum, Fac Med, Khartoum, Sudan.
   [Adjei, George O.] Univ Ghana, Sch Med, Ctr Trop Clin Pharmacol & Therapeut, Accra, Ghana.
   [Adjuik, Martin A.] INDEPTH Network Secretariat, Accra, Ghana.
   [Alemayehu, Bereket] Int Ctr AIDS Care & Treatment Programs, Addis Ababa, Ethiopia.
   [Allan, Richard; Baudin, Elisabeth; Temu, Emmanuel A.] MENTOR Initiat, Crawley, England.
   [Arinaitwe, Emmanuel; Staedke, Sarah G.] Infect Dis Res Collaborat, Kampala, Uganda.
   [Ashley, Elizabeth A.; Checchi, Francesco; Espie, Emmanuelle; Etard, Jean-Francois; Grandesso, Francesco; Nabasumba, Carolyn; Schramm, Birgit] Epictr, Paris, France.
   [Ba, Mamadou S.; Faye, Babacar; Faye, Oumar; Gaye, Oumar; Ndiaye, Jean-Louis; Pene, Mbaye; Sow, Doudou; Sylla, Khadime; Tine, Roger C. K.] Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal.
   [Barennes, Hubert; Ouedraogo, Jean-Bosco; Tinto, Halidou] Ctr Muraz, Bobo Dioulasso, Burkina Faso.
   [Barennes, Hubert] French Foreign Affairs, Biarritz, France.
   [Barnes, Karen I.] WorldWide Antimalarial Resistance Network WWARN, Cape Town, South Africa.
   [Barnes, Karen I.] Univ Cape Town, Dept Med, Div Clin Pharmacol, ZA-7925 Cape Town, South Africa.
   [Bassat, Quique; Gonzalez, Raquel; Menendez, Clara] Ctr Invest Saude Manhica, Manhica, Mozambique.
   [Bassat, Quique; Eshetu, Teferi; Gonzalez, Raquel; Menendez, Clara] Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Hosp Clin, Barcelona, Spain.
   [Berens-Riha, Nicole] Univ Munich LMU, Med Ctr, Div Infect Dis & Trop Med, Munich, Germany.
   [Berens-Riha, Nicole] LMU, German Ctr Infect Res DZIF, Munich, Germany.
   [Bjoerkman, Anders; Martensson, Andreas] Karolinska Inst, Dept Microbiol Tumour & Cell Biol, Stockholm, Sweden.
   [Bompart, Francois; Lameyre, Valerie] Sanofi Aventis, Direct Acces Med Access Med, Gentilly, France.
   [Bonnet, Maryline] Epictr, Geneva, Switzerland.
   [Borrmann, Steffen; Marsh, Kevin; Peshu, Judy] Wellcome Trust Res Programme, Kenya Med Res Inst, Kilifi, Kenya.
   [Borrmann, Steffen; Kremsner, Peter G.; Lell, Bertrand; Ntoumi, Francine] Univ Tubingen, Inst Trop Med, Tubingen, Germany.
   [Borrmann, Steffen; Drakeley, Chris J.] German Ctr Infect Res, Tubingen, Germany.
   [Bousema, Teun; Gadalla, Nahla B.; Oguike, Mary; Sutherland, Colin J.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Infect & Immun, London WC1, England.
   [Bousema, Teun] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Njimegen, Netherlands.
   [Brasseur, Philippe] IRD, Dakar, Senegal.
   [Bukirwa, Hasifa; Yeka, Adoke] Uganda Malaria Surveillance Project, Kampala, Uganda.
   [Dahal, Prabin; Flegg, Jennifer A.; Guerin, Philippe J.; Humphreys, Georgina S.; Moreira, Clarissa; Nsanzabana, Christian; Price, Ric N.; Sibley, Carol H.; Stepniewska, Kasia] WorldWide Antimalarial Resistance Network WWARN, Oxford, England.
   [Dahal, Prabin; Guerin, Philippe J.; Humphreys, Georgina S.; Marsh, Kevin; Moreira, Clarissa; Nsanzabana, Christian; Olliaro, Piero; Price, Ric N.; Stepniewska, Kasia] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.
   [D'Alessandro, Umberto] Inst Trop Med, Unit Malariol, B-2000 Antwerp, Belgium.
   [D'Alessandro, Umberto] MRC Unit, Fajara, Gambia.
   [D'Alessandro, Umberto; Greenwood, Brian] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Dis Control, London WC1, England.
   [Desai, Meghna; Hwang, Jimee; Kachur, Patrick S.; Thwing, Julie I.] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA.
   [Dicko, Alassane; Djimde, Abdoulaye A.; Doumbo, Ogobara K.; Fofana, Bakary; Kayentao, Kassoum; Sagara, Issaka] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali.
   [Dicko, Alassane] Univ Bamako, Fac Med Pharm & Dent, Dept Publ Hlth, Bamako, Mali.
   [Dorsey, Grant; Greenhouse, Bryan; Rosenthal, Philip J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   [Duparc, Stephan] Med Malaria Venture, Geneva, Switzerland.
   [Eshetu, Teferi] Jimma Univ, Dept Med Lab Sci & Pathol, Jimma, Ethiopia.
   [Etard, Jean-Francois] IRD, Montpellier, France.
   [Faiz, Abul M.] Mahidol Univ, Fac Trop Med, Bangkok, Thailand.
   [Falade, Catherine O.] Univ Ibadan, Coll Med, Dept Pharmacol & Therapeut, Ibadan, Nigeria.
   [Fanello, Caterina I.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand.
   [Faucher, Jean-Francois] IRD, Mother & Child Hlth Trop Res Unit, Paris, France.
   [Faucher, Jean-Francois] Univ Paris 05, PRES Sorbonne Paris Cite, Paris, France.
   [Faucher, Jean-Francois] Univ Besancon, Med Ctr, Dept Infect Dis, F-25030 Besancon, France.
   [Filler, Scott] Global Fund Fight AIDS TB & Malaria, Geneva, Switzerland.
   [Flegg, Jennifer A.] Monash Univ, Sch Math Sci, Melbourne, Vic 3004, Australia.
   [Flegg, Jennifer A.] Monash Univ, Monash Acad Cross & Interdisciplinary Math Applic, Melbourne, Vic 3004, Australia.
   [Fogg, Carole] Univ Portsmouth, Portsmouth Hosp NHS Trust, Portsmouth, Hants, England.
   [Gadalla, Nahla B.] Natl Res Ctr, Res Inst Trop Med, Dept Epidemiol, Khartoum, Sudan.
   [Gadalla, Nahla B.] NIAID, Rockville, MD USA.
   [Genton, Blaise; Hodel, Eva Maria; Temu, Emmanuel A.] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.
   [Genton, Blaise] Univ Lausanne Hosp, Div Infect Dis, Lausanne, Switzerland.
   [Genton, Blaise] Univ Lausanne Hosp, Dept Ambulatory Care & Community Med, Lausanne, Switzerland.
   [Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
   [Gil, Jose P.] Karolinska Inst, Pharmacogenet Sect, Drug Resistance Unit, Dept Physiol & Pharmacol, Stockholm, Sweden.
   [Gil, Jose P.] Univ Lisbon, Fac Sci, Biosyst & Integrat Sci Inst BioISI, P-1699 Lisbon, Portugal.
   [Gil, Jose P.] SUNY Binghamton, Harpur Coll Arts & Sci, Binghamton, NY USA.
   [Grivoyannis, Anastasia] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA.
   [Guthmann, Jean-Paul] Inst Veille Sanit, Dept Malad Infect, St Maurice, France.
   [Hamed, Kamal] Novartis Pharmaceut, E Hanover, NJ USA.
   [Hamour, Sally] Royal Free Hosp, UCL Ctr Nephrol, London NW3 2QG, England.
   [Hay, Simon I.; Lima, Angeles] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
   [Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
   [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Hodel, Eva Maria] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England.
   [Hwang, Jimee] Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA.
   [Ibrahim, Maman L.] Ctr Rech Med & Sanit, Niamey, Niger.
   [Jima, Daddi] Fed Minist Hlth, Addis Ababa, Ethiopia.
   [Jones, Joel J.; Zolia, Yah M.] Minist Hlth & Social Welf, Natl Malaria Control Programme, Monrovia, Liberia.
   [Jullien, Vincent] Univ Paris 05, AP HP, Paris, France.
   [Juma, Elizabeth] Kenya Govt Med Res Ctr, Nairobi, Kenya.
   [Kager, Piet A.; Mens, Petra F.] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands.
   [Kamugisha, Erasmus] Catholic Univ Hlth & Allied Sci, Mwanza, Tanzania.
   [Kamya, Moses R.] Makerere Univ, Coll Hlth Sci, Kampala, Uganda.
   [Karema, Corine] Minist Hlth, Malaria & Other Parasit Dis Div RBC, Kigali, Rwanda.
   [Kiechel, Jean-Rene] Drugs Neglected Dis initiat, Geneva, Switzerland.
   [Kironde, Fred] Makerere Univ, Dept Biochem, Kampala, Uganda.
   [Kofoed, Poul-Erik; Ursing, Johan] Projecto Saude Bandim, Bissau, Guinea Bissau.
   [Kofoed, Poul-Erik] Kolding Cty Hosp, Dept Paediat, Kolding, Denmark.
   [Kremsner, Peter G.; Lell, Bertrand] Ctr Rech Med Lambarene, Lambarene, Gabon.
   [Krishna, Sanjeev] Univ London, Inst Infect & Immun, London, England.
   Operat Ctr Barcelona Athens, Med Sans Frontieres, Barcelona, Spain.
   [Makanga, Michael] European & Dev Countries Clin Trials Partnership, Cape Town, South Africa.
   [Malik, ElFatih M.] Fed Minist Hlth, Khartoum, Sudan.
   [Martensson, Andreas] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
   [Martensson, Andreas] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden.
   [Massougbodji, Achille] Univ Abomey Calavi, FSS, CERPAGE, Cotonou, Benin.
   [Menan, Herve] Univ Cocody, Fac Pharm, Dept Parasitol, Abidjan, Cote Ivoire.
   [Menard, Didier] Inst Pasteur Cambodia, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia.
   [Mens, Petra F.; Schallig, Henk D. F. H.] KIT Biomed Res, Royal Trop Inst, Amsterdam, Netherlands.
   [Meremikwu, Martin] Univ Calabar, Dept Paediat, Calabar, Nigeria.
   [Meremikwu, Martin] Inst Trop Dis Res & Prevent, Calabar, Nigeria.
   [Nabasumba, Carolyn] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda.
   [Nambozi, Michael] Trop Dis Res Ctr, Ndola, Zambia.
   [Ngasala, Billy E.; Premji, Zul] Muhimbili Univ Hlth & Allied Sci, Dept Parasitol, Dar Es Salaam, Tanzania.
   [Ngasala, Billy E.; Ursing, Johan] Karolinska Inst, Dept Med Solna, Infect Dis Unit, Malaria Res, Stockholm, Sweden.
   [Nikiema, Frederic; Ouedraogo, Jean-Bosco; Som, Fabrice A.; Tinto, Halidou; Zongo, Issaka] Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso.
   [Ntoumi, Francine] Univ Marien Ngouabi, FCRM, Fac Sci Sante, Brazzaville, Congo.
   [Ogutu, Bernhards R.] United States Army Med Res Unit, Kenya Med Res Inst, Kisumu, Kenya.
   [Olliaro, Piero; Taylor, Walter R. J.] UNICEF UNDP World Bank WHO Special Programme Res, Geneva, Switzerland.
   [Omar, Sabah A.] Kenya Govt Med Res Ctr, Ctr Biotechnol Res & Dev, Nairobi, Kenya.
   [Owusu-Agyei, Seth] Kintampo Hlth Res Ctr, Kintampo, Ghana.
   [Penali, Louis K.; Seck, Amadou] WorldWide Antimalarial Resistance Network WWARN W, Dakar, Senegal.
   [Piola, Patrice] Inst Pasteur Madagascar, Epidemiol Unit, Antananarivo, Madagascar.
   [Plowe, Christopher V.] Univ Maryland, Sch Med, Howard Hughes Med Inst, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
   [Price, Ric N.] Menzies Sch Hlth Res, Darwin, NT, Australia.
   [Price, Ric N.] Charles Darwin Univ, Darwin, NT 0909, Australia.
   [Randrianarivelojosia, Milijaona] Inst Pasteur Madagascar, Malaria Res Unit, Antananarivo, Madagascar.
   [Rombo, Lars] Karolinska Inst, Karolinska Univ Hosp, Infect Dis Unit, Malaria Res Lab,Dept Med, Stockholm, Sweden.
   [Rombo, Lars] Malarsjukhuset, Dept Infect Dis, S-63188 Eskilstuna, Sweden.
   [Rombo, Lars] Clin Res Ctr, Uppsala, Sweden.
   [Roper, Cally] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Pathogen Mol Biol, London WC1, England.
   [Same-Ekobo, Albert] Ctr Hosp Univ Yaounde, Fac Med & Sci Biomed, Yaounde, Cameroon.
   [Sawa, Patrick] Int Ctr Insect Physiol & Ecol, Human Hlth Div, Mbita, Kenya.
   [Shekalaghe, Seif A.] Kilimanjaro Christian Med Ctr, Kilimanjaro Clin Med Res Inst, Moshi, Tanzania.
   [Sibley, Carol H.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Sinou, Vronique] Aix Marseille Univ, Fac Pharm, UMR MD3, Marseille, France.
   [Sirima, Sodiomon B.] CNRFP, Ouagadougou, Burkina Faso.
   [Staedke, Sarah G.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Clin Res, London WC1, England.
   [Swarthout, Todd D.; Van den Broek, Ingrid] Med Sans Frontieres, London, England.
   [Talisuna, Ambrose O.] East Africa Reg Ctr, WorldWide Antimalarial Resistance Network WWARN, Nairobi, Kenya.
   [Talisuna, Ambrose O.] Univ Oxford, KEMRI, Wellcome Trust Res Programme, Nairobi, Kenya.
   [Taylor, Walter R. J.] Hop Cantonal Univ Geneva, Serv Med Int & Humanitaire, Geneva, Switzerland.
   [Temu, Emmanuel A.] Univ Basel, Basel, Switzerland.
   [Tommasini, Silva; Valentini, Giovanni] Sigma Tau Ind Farmaceut Riunite SpA, Rome, Italy.
   [Toure, Offianan A.] Inst Pasteur Cote Ivoire, Malariol Dept, Abidjan, Cote Ivoire.
   [Vaillant, Michel T.] CRP Sante, Ctr Hlth Studies, Methodol & Stat Unit, Luxembourg, Luxembourg.
   [Vaillant, Michel T.] Univ Bordeaux 2, Unite Bases Therapeut Inflammat & Infect 3677, F-33076 Bordeaux, France.
   [Van den Broek, Ingrid] Natl Inst Publ Hlth & Environm, Ctr Infect Dis Control, NL-3720 BA Bilthoven, Netherlands.
   [Van Vugt, Michele] Univ Amsterdam, Acad Med Ctr, Ctr Trop Med & Travel Med, Div Infect Dis, NL-1012 WX Amsterdam, Netherlands.
   [Ward, Stephen A.] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England.
   [Winstanley, Peter A.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
   [Yavo, William] Univ Cocody, Fac Pharmaceut & Biol Sci, Dept Parasitol & Mycol, Abidjan, Cote Ivoire.
   [Yavo, William] Natl Inst Publ Hlth, Malaria Res & Control Ctr, Abidjan, Cote Ivoire.
RP Abdulla, S (reprint author), Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med WorldWide Antimalarial Res, Oxford, England.
RI Roper, Cally/K-2989-2013; Bousema, Teun/N-3574-2014; Ward,
   Steve/G-6003-2015; Hay, Simon/F-8967-2015; 
OI Guerin, Philippe/0000-0002-6008-2963; Hamed, Kamal/0000-0003-1896-9736;
   Humphreys, Georgina/0000-0001-9947-0034; Price,
   Richard/0000-0003-2000-2874; Gething, Peter/0000-0001-6759-5449; Roper,
   Cally/0000-0002-6545-309X; Ward, Steve/0000-0003-2331-3192; Hay,
   Simon/0000-0002-0611-7272; GADALLA, NAHLA/0000-0002-6177-6705; Flegg,
   Jennifer/0000-0002-8809-726X; Dahal, Prabin/0000-0002-2158-846X;
   Sutherland, Colin/0000-0003-1592-6407
FU Bill & Melinda Gates Foundation
FX WWARN is funded by a Bill & Melinda Gates Foundation grant. The funder
   did not participate in the study protocol development or the writing of
   the paper.
NR 59
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U1 2
U2 23
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD SEP 7
PY 2015
VL 13
AR 212
DI 10.1186/s12916-015-0445-x
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA CQ7SO
UT WOS:000360804700001
ER

PT J
AU Panagiotou, OA
   Befano, BL
   Gonzalez, P
   Rodriguez, AC
   Herrero, R
   Schiller, JT
   Kreimer, AR
   Schiffman, M
   Hildesheim, A
   Wilcox, AJ
   Wacholder, S
AF Panagiotou, Orestis A.
   Befano, Brian L.
   Gonzalez, Paula
   Cecilia Rodriguez, Ana
   Herrero, Rolando
   Schiller, John T.
   Kreimer, Aimee R.
   Schiffman, Mark
   Hildesheim, Allan
   Wilcox, Allen J.
   Wacholder, Sholom
CA Costa Rica HPV Vaccine Trial Cvt
TI Effect of bivalent human papillomavirus vaccination on pregnancy
   outcomes: long term observational follow-up in the Costa Rica HPV
   Vaccine Trial
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Article
ID AS04-ADJUVANTED VACCINE; CLINICAL-TRIALS; POOLED ANALYSIS; POSITIVE
   REPORT; DOUBLE-BLIND; SAFETY; EFFICACY; WOMEN; IMMUNIZATION; MISCARRIAGE
AB OBJECTIVE
   To examine the effect of the bivalent human papillomavirus (HPV) vaccine on miscarriage.
   DESIGN
   Observational long term follow-up of a randomized, double blinded trial combined with an independent unvaccinated population based cohort.
   SETTING
   Single center study in Costa Rica.
   PARTICIPANTS
   7466 women in the trial and 2836 women in the unvaccinated cohort enrolled at the end of the randomized trial and in parallel with the observational trial component.
   INTERVENTION
   Women in the trial were assigned to receive three doses of bivalent HPV vaccine (n=3727) or the control hepatitis A vaccine (n=3739). Crossover bivalent HPV vaccination occurred in the hepatitis A vaccine arm at the end of the trial. Women in the unvaccinated cohort received (n=2836) no vaccination.
   MAIN OUTCOME MEASURE
   Risk of miscarriage, defined by the US Centers for Disease Control and Prevention as fetal loss within 20 weeks of gestation, in pregnancies exposed to bivalent HPV vaccination in less than 90 days and any time from vaccination compared with pregnancies exposed to hepatitis A vaccine and pregnancies in the unvaccinated cohort.
   RESULTS
   Of 3394 pregnancies conceived at any time since bivalent HPV vaccination, 381 pregnancies were conceived less than 90 days from vaccination. Unexposed pregnancies comprised 2507 pregnancies conceived after hepatitis A vaccination and 720 conceived in the unvaccinated cohort. Miscarriages occurred in 451 (13.3%) of all exposed pregnancies, in 50 (13.1%) of the pregnancies conceived less than 90 days from bivalent HPV vaccination, and in 414 (12.8%) of the unexposed pregnancies, of which 316 (12.6%) were in the hepatitis A vaccine group and 98 (13.6%) in the unvaccinated cohort. The relative risk of miscarriage for pregnancies conceived less than 90 days from vaccination compared with all unexposed pregnancies was 1.02 (95% confidence interval 0.78 to 1.34, one sided P=0.436) in unadjusted analyses. Results were similar after adjusting for age at vaccination (relative risk 1.15, one sided P=0.17), age at conception (1.03, P=0.422), and calendar year (1.06, P=0.358), and in stratified analyses. Among pregnancies conceived at any time from bivalent HPV vaccination, exposure was not associated with an increased risk of miscarriage overall or in subgroups, except for miscarriages at weeks 13-20 of gestation (relative risk 1.35, 95% confidence interval 1.02 to 1.77, one sided P=0.017).
   CONCLUSIONS
   There is no evidence that bivalent HPV vaccination affects the risk of miscarriage for pregnancies conceived less than 90 days from vaccination. The increased risk estimate for miscarriages in a subgroup of pregnancies conceived any time after vaccination may be an artifact of a thorough set of sensitivity analyses, but since a genuine association cannot totally be ruled out, this signal should nevertheless be explored further in existing and future studies.
C1 [Panagiotou, Orestis A.; Kreimer, Aimee R.; Schiffman, Mark; Hildesheim, Allan; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Befano, Brian L.] Informat Management Serv Inc, Calverton, MD USA.
   [Gonzalez, Paula; Cecilia Rodriguez, Ana] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
   [Gonzalez, Paula; Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France.
   [Schiller, John T.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Bethesda, MD USA.
RP Panagiotou, OA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM orestis.panagiotou@nih.gov; wacholds@mail.nih.gov
OI Wilcox, Allen/0000-0002-3376-1311
FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on
   Women's Health; National Institute of Environmental Health Sciences,
   National Institutes of Health
FX The Costa Rica HPV Vaccine Trial is a longstanding collaboration between
   investigators in Costa Rica and the US National Cancer Institute (NCI).
   The trial is sponsored and funded by the NCI (contract N01-CP-11005),
   with funding support from the National Institutes of Health Office of
   Research on Women's Health. GlaxoSmithKline (GSK) Biologicals provided
   vaccine and support for aspects of the trial associated with regulatory
   submission needs of the company under a clinical trials agreement (FDA
   BB-IND 7920) during the four year, randomized blinded phase of our
   study. This manuscript was not prepared in collaboration with GSK
   Biologicals investigators, and GSK Biologicals had no role in the study
   design and the collection, analysis, and interpretation of data from CVT
   in this paper, or in the writing of the article. GSK Biologicals took no
   part in the decision to submit an article for publication. The analysis
   reported here was supported by the intramural research programs of the
   NCI and the National Institute of Environmental Health Sciences, both
   parts of the National Institutes of Health.
NR 45
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U2 14
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD SEP 7
PY 2015
VL 351
AR h4358
DI 10.1136/bmj.h4358
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR4CL
UT WOS:000361279300001
PM 26346155
ER

PT J
AU Captur, G
   Karperien, AL
   Li, CM
   Zemrak, F
   Tobon-Gomez, C
   Gao, XX
   Bluemke, DA
   Elliott, PM
   Petersen, SE
   Moon, JC
AF Captur, Gabriella
   Karperien, Audrey L.
   Li, Chunming
   Zemrak, Filip
   Tobon-Gomez, Catalina
   Gao, Xuexin
   Bluemke, David A.
   Elliott, Perry M.
   Petersen, Steffen E.
   Moon, James C.
TI Fractal frontiers in cardiovascular magnetic resonance: towards clinical
   implementation
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Review
DE Cardiovascular magnetic resonance; Segmentation; Image processing
ID HYPERTROPHIC CARDIOMYOPATHY; DIMENSION ANALYSIS; IMAGE; MRI; LACUNARITY;
   SCHIZOPHRENIA; ORGANIZATION; TRABECULAE
AB Many of the structures and parameters that are detected, measured and reported in cardiovascular magnetic resonance (CMR) have at least some properties that are fractal, meaning complex and self-similar at different scales. To date however, there has been little use of fractal geometry in CMR; by comparison, many more applications of fractal analysis have been published in MR imaging of the brain.
   This review explains the fundamental principles of fractal geometry, places the fractal dimension into a meaningful context within the realms of Euclidean and topological space, and defines its role in digital image processing. It summarises the basic mathematics, highlights strengths and potential limitations of its application to biomedical imaging, shows key current examples and suggests a simple route for its successful clinical implementation by the CMR community.
   By simplifying some of the more abstract concepts of deterministic fractals, this review invites CMR scientists (clinicians, technologists, physicists) to experiment with fractal analysis as a means of developing the next generation of intelligent quantitative cardiac imaging tools.
C1 [Captur, Gabriella; Elliott, Perry M.; Moon, James C.] UCL, UCL Inst Cardiovasc Sci, London WC1E 6BT, England.
   [Captur, Gabriella; Zemrak, Filip; Elliott, Perry M.; Petersen, Steffen E.; Moon, James C.] Heart Hosp, Div Cardiovasc Imaging, London W1G 8PH, England.
   [Karperien, Audrey L.] Charles Sturt Univ, Sch Community Hlth, Ctr Res Complex Syst, Albury, NSW 2640, Australia.
   [Li, Chunming] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
   [Zemrak, Filip; Petersen, Steffen E.] Queen Mary Univ London, Barts & London Sch Med & Dent, Cardiovasc Biomed Res Unit, London, England.
   [Tobon-Gomez, Catalina] Kings Coll London, Div Imaging Sci & Biomed Engn, London WC2R 2LS, England.
   [Gao, Xuexin] Circle Cardiovasc Imaging Inc, Calgary, AB T2P 3P2, Canada.
   [Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MA USA.
   Barts Heart Ctr, London, England.
RP Moon, JC (reprint author), UCL, UCL Inst Cardiovasc Sci, Gower St, London WC1E 6BT, England.
EM j.moon@ucl.ac.uk
RI Petersen, Steffen/A-8389-2011; 
OI Petersen, Steffen/0000-0003-4622-5160; Bluemke,
   David/0000-0002-8323-8086; moon, james/0000-0001-8071-1491
FU Higher Education Funding Council for England; UK National Institute for
   Health Research, University College London, Biomedical Research Centre;
   NIHR BRC University College London; Intramural research program,
   National Institutes of Health
FX JCM: Higher Education Funding Council for England and the UK National
   Institute for Health Research, University College London, Biomedical
   Research Centre; GC: NIHR BRC University College London. DAB: Intramural
   research program, National Institutes of Health.
NR 42
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U2 9
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 SEP 7
PY 2015
VL 17
AR 80
DI 10.1186/s12968-015-0179-0
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
   Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
   Medical Imaging
GA CQ5VP
UT WOS:000360674100001
PM 26346700
ER

PT J
AU Shreif, Z
   Striegel, DA
   Periwal, V
AF Shreif, Zeina
   Striegel, Deborah A.
   Periwal, Vipul
TI The jigsaw puzzle of sequence phenotype inference: Piecing together
   Shannon entropy, importance sampling, and Empirical Bayes
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Systems biology; Quantitative sequence activity models; Protein binding
   microarrays; Transcription factor binding activity; Binding motifs;
   Model induction
ID FACTOR-BINDING SITES; UNIVERSAL DNA MICROARRAYS; TRANSCRIPTION FACTORS;
   MODELS; PROTEIN; SPECIFICITIES; DISCOVERY; DESIGN; GENERATION; COMPACT
AB A nucleotide sequence 35 base pairs long can take 1,180,591,620,717,411,303,424 possible values. An example of systems biology datasets, protein binding microarrays, contain activity data from about 40,000 such sequences. The discrepancy between the number of possible configurations and the available activities is enormous. Thus, albeit that systems biology datasets are large in absolute terms, they oftentimes require methods developed for rare events due to the combinatorial increase in the number of possible configurations of biological systems. A plethora of techniques for handling large datasets, such as Empirical Bayes, or rare events, such as importance sampling, have been developed in the literature, but these cannot always be simultaneously utilized. Here we introduce a principled approach to Empirical Bayes based on importance sampling, information theory, and theoretical physics in the general context of sequence phenotype model induction. We present the analytical calculations that underlie our approach. We demonstrate the computational efficiency of the approach on concrete examples, and demonstrate its efficacy by applying the theory to publicly available protein binding microarray transcription factor datasets and to data on synthetic cAMP-regulated enhancer sequences. As further demonstrations, we find transcription factor binding motifs, predict the activity of new sequences and extract the locations of transcription factor binding sites. In summary, we present a novel method that is efficient (requiring minimal computational time and reasonable amounts of memory), has high predictive power that is comparable with that of models with hundreds of parameters, and has a limited number of optimized parameters, proportional to the sequence length. Published by Elsevier Ltd.
C1 [Shreif, Zeina; Striegel, Deborah A.; Periwal, Vipul] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Periwal, V (reprint author), NIDDKD, Lab Biol Modeling, NIH, Bldg 12A,12 South Dr, Bethesda, MD 20892 USA.
EM shreifzz@mail.nih.gov; Deborah.striegel@nih.gov; vipulp@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health, NIDDK
FX This work was supported by Intramural Research Program of the National
   Institutes of Health, NIDDK. We thank Arthur Sherman, Carson Chow and
   Terry Hwa for helpful conversations.
NR 39
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U1 1
U2 3
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 SEP 7
PY 2015
VL 380
BP 399
EP 413
DI 10.1016/j.jtbi.2015.06.010
PG 15
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology
GA CO9ON
UT WOS:000359505200039
PM 26092377
ER

PT J
AU Abbasi, A
   Khalaj, M
   Akiyama, K
   Mukai, Y
   Matsumoto, H
   Acosta, TJ
   Said, N
   Yoshida, M
   Kunieda, T
AF Abbasi, Abdolrahim
   Khalaj, Maryam
   Akiyama, Kouyou
   Mukai, Yoshiyuki
   Matsumoto, Hirokazu
   Acosta, Tomas J.
   Said, Neveen
   Yoshida, Midori
   Kunieda, Tetsuo
TI Lack of Rev7 function results in development of tubulostromal adenomas
   in mouse ovary
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article
DE Gonadotropin; Ovarian tumors; Rev7; Translesion DNA polymerase
ID DNA-POLYMERASE-ZETA; CANCER; MUTATION; MICE; TUMORIGENESIS; EXPRESSION;
   GROWTH; CELLS; GENE; RESPONSES
AB Rev7 is a subunit of Pol zeta one of the translesion DNA synthesis (as) polymerases involved in DNA damage repair. We recently found that Rev7 is also essential for germ cell development in mouse. In the present study, we found the development of ovarian tumors in Rev7 mutant mouse, suggesting the involvement of TB deficiency in the etiology of ovarian tumor. The Rev7 mutant mice showed complete lack of oocytes and follicles in the ovary. The lack of follicles causes a significant increase of gonadotropin level and an increase in the proliferation of ovarian cells. As a result, the weight of the ovaries of Rev7 mutant mice increased with age and they developed tubulostromal adenomas. However, the remarkable overgrowth of ovaries occurred after gonadotropin level decreases at older ages, suggesting gonadotropin-independent progression of the ovarian tumors. In addition, the Rev7 mutant fibroblasts and ovarian cells showed significant accumulation of DNA damage. These findings suggest that not only increased gonadotropin levels but also lack of DNA damage repair function could be responsible for the development of ovarian tumors in the Rev7 mutant mouse. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Abbasi, Abdolrahim; Khalaj, Maryam; Kunieda, Tetsuo] Okayama Univ, Grad Sch Environm & Life Sci, Okayama 7008530, Japan.
   [Abbasi, Abdolrahim; Khalaj, Maryam] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
   [Akiyama, Kouyou] Okayama Univ, Adv Sci Res Ctr, Okayama 7008530, Japan.
   [Mukai, Yoshiyuki] Okayama Univ, Fac Agr, Okayama 7008530, Japan.
   [Matsumoto, Hirokazu; Acosta, Tomas J.; Kunieda, Tetsuo] Okayama Univ, Grad Sch Environm & Life Sci, Okayama 7008530, Japan.
   [Said, Neveen] Univ Virginia, Sch Med, Dept Radiat Oncol, Charlottesville, VA 22908 USA.
   [Yoshida, Midori] Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan.
RP Kunieda, T (reprint author), Okayama Univ, Grad Sch Environm & Life Sci, Okayama 7008530, Japan.
EM tkunieda@okayama-u.ac.jp
FU Japan Society for the Promotion of Science
FX This work was partially supported by a grant from the Japan Society for
   the Promotion of Science. We thank Drs. J. J. Eppig, M. A. Handel, and
   J. C. Schimenti for providing the repro22 mutant mice produced by the
   ReproGenomics Program at The Jackson Laboratory.
NR 30
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U1 0
U2 3
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 SEP 5
PY 2015
VL 412
IS C
BP 19
EP 25
DI 10.1016/j.mce.2015.05.022
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA CP5XO
UT WOS:000359958900003
PM 26004212
ER

PT J
AU Vergara-Jaque, A
   Fenollar-Ferrer, C
   Kaufmann, D
   Forrest, LR
AF Vergara-Jaque, Ariela
   Fenollar-Ferrer, Cristina
   Kaufmann, Desiree
   Forrest, Lucy R.
TI Repeat-swap homology modeling of secondary active transporters: updated
   protocol and prediction of elevator-type mechanisms
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE neurotransmitter; membrane protein; secondary transport; alternating
   access; asymmetry exchange; glutamate; concentrative nucleoside
   transporter
ID MEMBRANE-PROTEINS; ALTERNATING ACCESS; NEUROTRANSMITTER TRANSPORTERS;
   CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; TOPOLOGY; SYMMETRY; SEQUENCE;
   DATABASE; BINDING
AB Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, Glt(Ph), in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called "repeat-swap modeling" to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeatswap homology modeling protocol, and calibrate the accuracy of the method using Glt(Ph), for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of Glt(Ph). The repeat-swapped model of VcCNT predicts that nucleoside transport also occurs via an elevator-like mechanism.
C1 [Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desiree; Forrest, Lucy R.] NINDS, Computat Struct Biol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Forrest, LR (reprint author), NINDS, Computat Struct Biol Sect, Porter Neurosci Res Ctr, NIH, 35 Convent Dr MSC 3761, Bethesda, MD 20892 USA.
EM lucy.forrest@nih.gov
FU Division of Intramural Research of the NIH, National Institute of
   Neurological Disorders and Stroke; L'Oreal Chile-UNESCO Women in Science
   fellowship; L'Oreal-UNESCO Rising Talent Award
FX This research was supported in part by the Division of Intramural
   Research of the NIH, National Institute of Neurological Disorders and
   Stroke. AV-J is recipient of the L'Oreal Chile-UNESCO Women in Science
   fellowship and the L'Oreal-UNESCO Rising Talent Award. We thank Ahmad
   Reza Mehdipour for his contribution to developing the repeat-swap
   protocol, Jose Faraldo-Gomez for useful discussions, and Gary Rudnick
   for suggesting the definition of elevator mechanisms.
NR 47
TC 6
Z9 6
U1 0
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
   SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD SEP 4
PY 2015
VL 6
AR 183
DI 10.3389/fphar.2015.00183
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CX3RQ
UT WOS:000365617300001
PM 26388773
ER

PT J
AU Liao, XH
   Yuan, L
   Zhao, TD
   Dai, ZJ
   Shu, N
   Xia, MR
   Yang, YH
   Evans, A
   He, Y
AF Liao, Xuhong
   Yuan, Lin
   Zhao, Tengda
   Dai, Zhengjia
   Shu, Ni
   Xia, Mingrui
   Yang, Yihong
   Evans, Alan
   He, Yong
TI Spontaneous functional network dynamics and associated structural
   substrates in the human brain
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE connectomics; functional dynamics; graph theory; hub; small-world;
   sliding window
ID TEST-RETEST RELIABILITY; RESTING-STATE NETWORKS; CONNECTIVITY DYNAMICS;
   CORTICAL HUBS; GLOBAL SIGNAL; MRI; CORTEX; FMRI; ORGANIZATION;
   REGRESSION
AB Recent imaging connectomics studies have demonstrated that the spontaneous human brain functional networks derived from resting-state functional MRI (R-fMRI) include many non-trivial topological properties, such as highly efficient small-world architecture and densely connected hub regions. However, very little is known about dynamic functional connectivity (D-FC) patterns of spontaneous human brain networks during rest and about how these spontaneous brain dynamics are constrained by the underlying structural connectivity. Here, we combined sub-second multiband R-fMRI data with graph theoretical approaches to comprehensively investigate the dynamic characteristics of the topological organization of human whole-brain functional networks, and then employed diffusion imaging data in the same participants to further explore the associated structural substrates. At the connection level, we found that human whole-brain D-FC patterns spontaneously fluctuated over time, while homotopic D-FC exhibited high connectivity strength and low temporal variability. At the network level, dynamic functional networks exhibited time-varying but evident small-world and assortativity architecture, with several regions (e.g., insula, sensorimotor cortex and medial prefrontal cortex) emerging as functionally persistent hubs (i.e., highly connected regions) while possessing large temporal variability in their degree centrality. Finally, the temporal characteristics (i.e., strength and variability) of the connectional and nodal properties of the dynamic brain networks were significantly associated with their structural counterparts. Collectively, we demonstrate the economical, efficient, and flexible characteristics of dynamic functional coordination in large-scale human brain networks during rest, and highlight their relationship with underlying structural connectivity, which deepens our understandings of spontaneous brain network dynamics in humans.
C1 [Liao, Xuhong; Yuan, Lin; Zhao, Tengda; Dai, Zhengjia; Shu, Ni; Xia, Mingrui; He, Yong] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
   [Liao, Xuhong; Yuan, Lin; Zhao, Tengda; Dai, Zhengjia; Shu, Ni; Xia, Mingrui; He, Yong] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China.
   [Liao, Xuhong] Hangzhou Normal Univ, Ctr Cognit & Brain Disorders, Hangzhou, Zhejiang, Peoples R China.
   [Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA.
   [Evans, Alan] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada.
RP He, Y (reprint author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
EM yong.he@bnu.edu.cn
FU National Key Basic Research Program of China [2014CB846102,
   2013CB837300]; Natural Science Foundation of China [11205041, 81401479,
   91432115, 31221003]; National Science Fund for Distinguished Young
   Scholars [81225012]; Beijing Natural Science Foundation
   [Z151100003915082]; Open Research Fund of the State Key Laboratory of
   Cognitive Neuroscience and Learning [CNIXB1307]
FX This work was supported by the National Key Basic Research Program of
   China (Grant Nos. 2014CB846102 and 2013CB837300), the Natural Science
   Foundation of China (Grant Nos. 11205041, 81401479, 91432115, and
   31221003), the National Science Fund for Distinguished Young Scholars
   (Grant No. 81225012), Beijing Natural Science Foundation (Grant No.
   Z151100003915082) and the Open Research Fund of the State Key Laboratory
   of Cognitive Neuroscience and Learning (CNIXB1307).
NR 87
TC 3
Z9 4
U1 2
U2 17
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
   SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD SEP 4
PY 2015
VL 9
AR 478
DI 10.3389/fnhum.7015.00478
PG 17
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA CR4PW
UT WOS:000361319700001
PM 26388757
ER

PT J
AU Sathe, L
   Bolinger, C
   Amin-ul Mannan, M
   Dever, TE
   Dey, M
AF Sathe, Leena
   Bolinger, Cheryl
   Amin-ul Mannan, M.
   Dever, Thomas E.
   Dey, Madhusudan
TI Evidence That Base-pairing Interaction between Intron and mRNA Leader
   Sequences Inhibits Initiation of HAC1 mRNA Translation in Yeast
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID UNFOLDED PROTEIN-RESPONSE; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR;
   SACCHAROMYCES-CEREVISIAE; EUKARYOTIC RIBOSOMES; SECONDARY STRUCTURE;
   CODON SELECTION; MECHANISM; HELICASE; PATHWAY
AB The Hac1 transcription factor in yeast up-regulates a collection of genes that control protein homeostasis. Base-pairing interactions between sequences in the intron and the 5'-untranslated region (5' UTR) of the HAC1 mRNA represses Hac1 protein production under basal conditions, whereas cytoplasmic splicing of the intron by the Ire1 kinase-endonuclease, activated under endoplasmic reticulum stress conditions, relieves the inhibition and enables Hac1 synthesis. Using a random mutational screen as well as site-directed mutagenesis, we identify point mutations within the 5' UTR-intron interaction site that derepress translation of the unspliced HAC1 mRNA. We also show that insertion of an in-frame AUG start codon upstream of the interaction site releases the translational block, demonstrating that an elongating ribosome can disrupt the interaction. Moreover, overexpression of translation initiation factor eIF4A, a helicase, enhances production of Hac1 from an mRNA containing an upstream AUG start codon at the beginning of the base-paired region. These results suggest that the major block of translation occurs at the initiation stage. Supporting this interpretation, the point mutations that enhanced Hac1 production resulted in an increased percentage of the HAC1 mRNA associating with polysomes versus free ribosomal subunits. Thus, our results provide evidence that the 5' UTR-intron interaction represses translation initiation on the unspliced HAC1 mRNA.
C1 [Sathe, Leena; Amin-ul Mannan, M.; Dey, Madhusudan] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA.
   [Bolinger, Cheryl; Dever, Thomas E.] Eunice Kennedy Shriver NICHD, NIH, Bethesda, MD 20892 USA.
RP Dever, TE (reprint author), NIH, Bldg 6,Rm 228,6 Ctr Dr, Bethesda, MD 20892 USA.
EM tdever@nih.gov; deym@uwm.edu
RI Regan, Clinton/E-6250-2012; 
OI Dever, Thomas/0000-0001-7120-9678
FU National Institutes of Health (NIH) [1R15GM101575-01]; Intramural
   Research Program of the NIH (NICHD); Research Growth Initiative
   (UW-Milwaukee Graduate School)
FX This work was supported, in whole or in part, by National Institutes of
   Health (NIH) Grants 1R15GM101575-01 (to M. D.) and by the Intramural
   Research Program of the N<INF>I</INF>H (NICHD; to T. E. D.). This work
   was also supported by Research Growth Initiative (UW-Milwaukee Graduate
   School; to M. D.). The authors declare that they have no conflicts of
   interest with the contents of this article.
NR 47
TC 3
Z9 3
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 4
PY 2015
VL 290
IS 36
BP 21821
EP 21832
DI 10.1074/jbc.M115.649335
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CQ9XI
UT WOS:000360968500005
PM 26175153
ER

PT J
AU Tsai, LCL
   Xie, L
   Dore, K
   Xie, L
   Del Rio, JC
   King, CC
   Martinez-Ariza, G
   Hulme, C
   Malinow, R
   Bourne, PE
   Newton, AC
AF Tsai, Li-Chun Lisa
   Xie, Lei
   Dore, Kim
   Xie, Li
   Del Rio, Jason C.
   King, Charles C.
   Martinez-Ariza, Guillermo
   Hulme, Christopher
   Malinow, Roberto
   Bourne, Philip E.
   Newton, Alexandra C.
TI Zeta Inhibitory Peptide Disrupts Electrostatic Interactions That
   Maintain Atypical Protein Kinase C in Its Active Conformation on the
   Scaffold p62
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMPA RECEPTOR TRAFFICKING; ENCODED FLUORESCENT REPORTER; PKC-ZETA;
   SYNAPTIC PLASTICITY; SPATIOTEMPORAL DYNAMICS; DOMAIN; MEMORY;
   TRANSLOCATION; DOCKING; BINDING
AB Atypical protein kinase C (aPKC) enzymes signal on protein scaffolds, yet how they are maintained in an active conformation on scaffolds is unclear. A myristoylated peptide based on the autoinhibitory pseudosubstrate fragment of the atypical PKC zeta, zeta inhibitory peptide (ZIP), has been extensively used to inhibit aPKC activity; however, we have previously shown that ZIP does not inhibit the catalytic activity of aPKC isozymes in cells (Wu-Zhang, A. X., Schramm, C. L., Nabavi, S., Malinow, R., and Newton, A. C. (2012) J. Biol. Chem. 287, 12879-12885). Here we sought to identify a bona fide target of ZIP and, in so doing, unveiled a novel mechanism by which aPKCs are maintained in an active conformation on a protein scaffold. Specifically, we used protein-protein interaction network analysis, structural modeling, and protein-protein docking to predict that ZIP binds an acidic surface on the Phox and Bem1 (PB1) domain of p62, an interaction validated by peptide array analysis. Using a genetically encoded reporter for PKC activity fused to the p62 scaffold, we show that ZIP inhibits the activity of wild-type aPKC, but not a construct lacking the pseudosubstrate. These data support a model in which the pseudosubstrate of aPKCs is tethered to the acidic surface on p62, locking aPKC in an open, signaling-competent conformation. ZIP competes for binding to the acidic surface, resulting in displacement of the pseudosubstrate of aPKC and re-engagement in the substrate-binding cavity. This study not only identifies a cellular target for ZIP, but also unveils a novel mechanism by which scaffolded aPKC is maintained in an active conformation.
C1 [Tsai, Li-Chun Lisa; Del Rio, Jason C.; Newton, Alexandra C.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Dore, Kim; Malinow, Roberto] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Xie, Li] Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA.
   [King, Charles C.] Univ Calif San Diego, Pediat Diabet Res Ctr, La Jolla, CA 92093 USA.
   [Xie, Lei] CUNY, Hunter Coll, Dept Comp Sci, New York, NY 10065 USA.
   [Martinez-Ariza, Guillermo; Hulme, Christopher] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.
   [Bourne, Philip E.] NIH, Off Director, Bethesda, MD 20892 USA.
RP Newton, AC (reprint author), Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
EM anewton@ucsd.edu
RI Regan, Clinton/E-6250-2012; 
OI Martinez-Ariza, Guillermo/0000-0003-2002-3958
FU National Institutes of Health [P01 DK54441]; University of California
   San Diego through Training Program in Diabetes Research from the
   National Institute of Diabetes and Digestive and kidney Diseases
   [5T32DK007494]; University of California San Diego Graduate Training
   Program in Cellular and Molecular Pharmacology from the National
   Institute of General Medical Sciences [T32GM007752]
FX This work was supported by National Institutes of Health Grant P01
   DK54441 (to A. C. N.). The authors declare that they have no conflicts
   of interest with the contents of this article.; Supported in part by the
   University of California San Diego through Training Program in Diabetes
   Research 5T32DK007494 from the National Institute of Diabetes and
   Digestive and kidney Diseases.; Supported in part by the University of
   California San Diego Graduate Training Program in Cellular and Molecular
   Pharmacology through Training Grant T32GM007752 from the National
   Institute of General Medical Sciences.
NR 56
TC 7
Z9 7
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 4
PY 2015
VL 290
IS 36
BP 21845
EP 21856
DI 10.1074/jbc.M115.676221
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CQ9XI
UT WOS:000360968500007
PM 26187466
ER

PT J
AU Wang, CD
   Kam, RKT
   Shi, WL
   Xia, Y
   Chen, XF
   Cao, Y
   Sun, JM
   Du, YZ
   Lu, G
   Chen, ZJ
   Chan, WY
   Chan, SO
   Deng, Y
   Zhao, H
AF Wang, Chengdong
   Kam, Richard Kin Ting
   Shi, Weili
   Xia, Yin
   Chen, Xiongfong
   Cao, Ying
   Sun, Jianmin
   Du, Yanzhi
   Lu, Gang
   Chen, Zijiang
   Chan, Wood Yee
   Chan, Sun On
   Deng, Yi
   Zhao, Hui
TI The Proto-oncogene Transcription Factor Ets1 Regulates Neural Crest
   Development through Histone Deacetylase 1 to Mediate Output of Bone
   Morphogenetic Protein Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CELL-CYCLE PROGRESSION; XENOPUS-EMBRYOS; PARAXIAL MESODERM;
   BINDING-PROTEIN; INDUCTION; EXPRESSION; SPECIFICATION; WNT; ACTIVATION;
   MIGRATION
AB The neural crest (NC) is a transient, migratory cell population that differentiates into a large variety of tissues including craniofacial cartilage, melanocytes, and peripheral nervous system. NC is initially induced at the border of neural plate and non-neural ectoderm by balanced regulation of multiple signaling pathways among which an intermediate bone morphogenetic protein (BMP) signaling is essential for NC formation. ets1, a proto-oncogene playing important roles in tumor invasion, has also been implicated in delamination of NC cells. In this study, we investigated Ets1 function in NC formation using Xenopus. Overexpression of ets1 repressed NC formation through down-regulation of BMP signaling. Moreover, ets1 repressed the BMP-responsive gene id3 that is essential for NC formation. Conversely, overexpression of id3 can partially rescue the phenotype of NC inhibition induced by ectopic ets1. Mechanistically, we found that Ets1 binds to id3 promoter as well as histone deacetylase 1, suggesting that Ets1 recruits histone deacetylase 1 to the promoter of id3, thereby inducing histone deacetylation of the id3 promoter. Thus, our studies indicate that Ets1 regulates NC formation through attenuating BMP signaling epigenetically.
C1 [Wang, Chengdong; Kam, Richard Kin Ting; Xia, Yin; Lu, Gang; Chan, Wood Yee; Chan, Sun On; Zhao, Hui] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
   [Shi, Weili] Chinese Univ Hong Kong, Fac Med, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.
   [Deng, Yi] South Univ Sci & Technol China, Dept Biol, Shenzhen Key Lab Cell Microenvironm, Shenzhen 518055, Peoples R China.
   [Xia, Yin; Lu, Gang; Chan, Wood Yee; Chan, Sun On; Zhao, Hui] Chinese Univ Hong Kong, Shenzhen Res Inst, Shenzhen 518057, Peoples R China.
   [Chen, Xiongfong] NCI, Adv Biomed Comp Ctr, NIH, Frederick, MD 21702 USA.
   [Cao, Ying] Nanjing Univ, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China.
   [Cao, Ying] Minist Educ, Key Lab Model Anim Dis Study, Nanjing 210061, Jiangsu, Peoples R China.
   [Sun, Jianmin] Lund Univ, Dept Lab Med, Translat Canc Res & Stem Cell Ctr, S-22381 Lund, Sweden.
   [Du, Yanzhi; Chen, Zijiang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Key Lab Assisted Reprod & Reprod Genet, Shanghai 200135, Peoples R China.
RP Zhao, H (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
EM zhaohui@cuhk.edu.hk
RI Zhao, Hui/B-8429-2016
FU Research Grants Council of Hong Kong [CUHK413/12, CUHK480709,
   CUHK432/12]; Lo Kwee-Seong Biomedical Research Fund; National Basic
   Research Program of China [81200566]
FX This work is supported by Research Grants Council of Hong Kong Grants
   N_CUHK413/12 and CUHK480709 (to H. Z.) and N_CUHK432/12 (to Y. X.), the
   Lo Kwee-Seong Biomedical Research Fund (to H. Z.), and National Basic
   Research Program of China Grant 81200566 (to Y. D.). The authors declare
   that they have no conflicts of interest with the contents of this
   article.
NR 62
TC 3
Z9 4
U1 1
U2 9
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 SEP 4
PY 2015
VL 290
IS 36
BP 21925
EP 21938
DI 10.1074/jbc.M115.644864
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CQ9XI
UT WOS:000360968500014
PM 26198637
ER

PT J
AU Zhao, YG
   Ma, CA
   Wu, LM
   Iwai, K
   Ashwell, JD
   Oltz, EM
   Ballard, DW
   Jain, A
AF Zhao, Yongge
   Ma, Chi A.
   Wu, Liming
   Iwai, Kazuhiro
   Ashwell, Jonathan D.
   Oltz, Eugene M.
   Ballard, Dean W.
   Jain, Ashish
TI CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling
   and Early Embryogenesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NF-KAPPA-B; ECTODERMAL DYSPLASIA; IMMUNE-DEFICIENCY; ACTIVATION; MICE;
   POLYUBIQUITINATION; INFLAMMATION; APOPTOSIS; DOMAIN; GENE
AB NF-kappa B essential modulator (NEMO) and cylindromatosis protein (CYLD) are intracellular proteins that regulate the NF-kappa B signaling pathway. Although mice with either CYLD deficiency or an alteration in the zinc finger domain of NEMO (K392R) are born healthy, we found that the combination of these two gene defects in double mutant (DM) mice is early embryonic lethal but can be rescued by the absence of TNF receptor 1 (TNFR1). Notably, NEMO was not recruited into the TNFR1 complex of DM cells, and consequently NF-kappa B induction by TNF was severely impaired and DM cells were sensitized to TNF-induced cell death. Interestingly, the TNF signaling defects can be fully rescued by reconstitution of DM cells with CYLD lacking ubiquitin hydrolase activity but not with CYLD mutated in TNF receptor-associated factor 2 (TRAF2) or NEMO binding sites. Therefore, our data demonstrate an unexpected non-catalytic function for CYLD as an adapter protein between TRAF2 and the NEMO zinc finger that is important for TNF-induced NF-kappa B signaling during embryogenesis.
C1 [Zhao, Yongge; Ma, Chi A.; Wu, Liming; Jain, Ashish] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
   [Iwai, Kazuhiro] Kyoto Univ, Grad Sch Med, Dept Mol & Cellular Physiol, Kyoto 6068501, Japan.
   [Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
   [Oltz, Eugene M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Ballard, Dean W.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
RP Zhao, YG (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Clin Res Ctr, Rm 5-W-5832,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM yongge.zhao@nih.gov; ashish.jain1@merck.com
RI Regan, Clinton/E-6250-2012
FU Intramural Research Program of the National Institutes of Health, NIAID;
   National Institutes of Health [CA082556, AI052379]
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health, NIAID, and National Institutes of Health
   Grants CA082556 and AI052379 (to D. W. B). The authors declare that they
   have no conflicts of interest with the contents of this article.
NR 25
TC 0
Z9 1
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 4
PY 2015
VL 290
IS 36
BP 22076
EP 22084
DI 10.1074/jbc.M115.658096
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CQ9XI
UT WOS:000360968500026
PM 26224629
ER

PT J
AU Artlett, CM
   Sassi-Gaha, S
   Ramos, RC
   Miller, FW
   Rider, LG
AF Artlett, Carol M.
   Sassi-Gaha, Sihem
   Ramos, Ronald C.
   Miller, Frederick W.
   Rider, Lisa G.
TI Chimeric cells of maternal origin do not appear to be pathogenic in the
   juvenile idiopathic inflammatory myopathies or muscular dystrophy
SO ARTHRITIS RESEARCH & THERAPY
LA English
DT Article
ID LUPUS-ERYTHEMATOSUS; MICROCHIMERISM; DERMATOMYOSITIS; CHILDREN;
   DISEASES; CANCER; WOMEN; LESIONS
AB Introduction: Microchimeric cells have been studied for over a decade, with conflicting reports on their presence and role in autoimmune and other inflammatory diseases. To determine whether microchimeric cells were pathogenic or mediating tissue repair in inflammatory myopathies, we phenotyped and quantified microchimeric cells in juvenile idiopathic inflammatory myopathies (JIIM), muscular dystrophy (MD), and noninflammatory control muscle tissues.
   Method: Fluorescence immunophenotyping for infiltrating cells with sequential fluorescence in situ hybridization was performed on muscle biopsies from ten patients with JIIM, nine with MD and ten controls.
   Results: Microchimeric cells were significantly increased in MD muscle (0.079 +/- 0.024 microchimeric cells/mm(2) tissue) compared to controls (0.019 +/- 0.007 cells/mm(2) tissue, p = 0.01), but not elevated in JIIM muscle (0.043 +/- 0.015 cells/mm(2)). Significantly more CD4+ and CD8+ microchimeric cells were in the muscle of patients with MD compared with controls (mean 0.053 +/- 0.020/mm(2) versus 0 +/- 0/mm(2) p = 0.003 and 0.043 +/- 0.023/mm(2) versus 0 +/- 0/mm(2) p = 0.025, respectively). No differences in microchimeric cells between JIIM, MD, and noninflammatory controls were found for CD3+, Class II+, CD25+, CD45RA+, and CD123+ phenotypes, and no microchimeric cells were detected in CD20, CD83, or CD45RO populations. The locations of microchimeric cells were similar in all three conditions, with MD muscle having more microchimeric cells in perimysial regions than controls, and JIIM having fewer microchimeric muscle nuclei than MD. Microchimeric inflammatory cells were found, in most cases, at significantly lower proportions than autologous cells of the same phenotype.
   Conclusions: Microchimeric cells are not specific to autoimmune disease, and may not be important in muscle inflammation or tissue repair in JIIM.
C1 [Artlett, Carol M.; Sassi-Gaha, Sihem] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19129 USA.
   [Ramos, Ronald C.] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA.
   [Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Dept Hlth & Human Serv, Environm Autoimmun Grp,Program Clin Res, Bethesda, MD 20892 USA.
RP Rider, LG (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, Environm Autoimmun Grp,Program Clin Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM riderl@mail.nih.gov
OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU Intramural Research Program of the NIH; National Institute of
   Environmental Health Sciences; Myositis Association
FX We thank Dr. Kathleen Patterson of Children's Hospital Medical Center,
   Seattle, WA, USA for the muscular dystrophy and control muscle biopsies
   and Dr. Ann Reed for JIIM biopsies and for staining for CD123. We also
   thank Drs. Christine Castro and Ira Berkower for their critical
   evaluation and assessment of the manuscript. This research was supported
   in part by the Intramural Research Program of the NIH, National
   Institute of Environmental Health Sciences and by a grant from The
   Myositis Association.
NR 37
TC 0
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U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1478-6354
EI 1478-6362
J9 ARTHRITIS RES THER
JI Arthritis Res. Ther.
PD SEP 4
PY 2015
VL 17
AR 238
DI 10.1186/s13075-015-0732-0
PG 9
WC Rheumatology
SC Rheumatology
GA CQ4WO
UT WOS:000360605500001
PM 26338728
ER

PT J
AU Powers, CM
   Mills, KA
   Morris, SA
   Klaessig, F
   Gaheen, S
   Lewinski, N
   Hendren, CO
AF Powers, Christina M.
   Mills, Karmann A.
   Morris, Stephanie A.
   Klaessig, Fred
   Gaheen, Sharon
   Lewinski, Nastassja
   Hendren, Christine Ogilvie
TI Nanocuration workflows: Establishing best practices for identifying,
   inputting, and sharing data to inform decisions on nanomaterials
SO BEILSTEIN JOURNAL OF NANOTECHNOLOGY
LA English
DT Article
DE curation; informatics; nanoinformatics; nanomaterials; workflows
AB There is a critical opportunity in the field of nanoscience to compare and integrate information across diverse fields of study through informatics (i.e., nanoinformatics). This paper is one in a series of articles on the data curation process in nanoinformatics (nanocuration). Other articles in this series discuss key aspects of nanocuration (temporal metadata, data completeness, database integration), while the focus of this article is on the nanocuration workflow, or the process of identifying, inputting, and reviewing nanomaterial data in a data repository. In particular, the article discusses: 1) the rationale and importance of a defined workflow in nanocuration, 2) the influence of organizational goals or purpose on the workflow, 3) established workflow practices in other fields, 4) current workflow practices in nanocuration, 5) key challenges for workflows in emerging fields like nanomaterials, 6) examples to make these challenges more tangible, and 7) recommendations to address the identified challenges. Throughout the article, there is an emphasis on illustrating key concepts and current practices in the field. Data on current practices in the field are from a group of stakeholders active in nanocuration. In general, the development of workflows for nanocuration is nascent, with few individuals formally trained in data curation or utilizing available nanocuration resources (e.g., ISA-TAB-Nano). Additional emphasis on the potential benefits of cultivating nanomaterial data via nanocuration processes (e.g., capability to analyze data from across research groups) and providing nanocuration resources (e.g., training) will likely prove crucial for the wider application of nanocuration workflows in the scientific community.
C1 [Powers, Christina M.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
   [Mills, Karmann A.] RTI Int, Res Triangle Pk, NC 27709 USA.
   [Morris, Stephanie A.] NCI, Off Canc Nanotechnol Res, NIH, Bethesda, MD 20892 USA.
   [Klaessig, Fred] Penn Bio Nano Syst LLC, Doylestown, PA 18901 USA.
   [Gaheen, Sharon] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
   [Lewinski, Nastassja] Virginia Commonwealth Univ, Dept Chem & Life Sci Engn, Richmond, VA 23284 USA.
   [Hendren, Christine Ogilvie] Duke Univ, Ctr Environm Implicat NanoTechnol CEINT, Durham, NC 27708 USA.
RP Hendren, CO (reprint author), Duke Univ, Ctr Environm Implicat NanoTechnol CEINT, POB 90287,121 Hudson Hall, Durham, NC 27708 USA.
EM christine.hendren@duke.edu
RI Lewinski, Nastassja/E-2993-2012
OI Lewinski, Nastassja/0000-0002-9335-9949
FU National Science Foundation (NSF); Environmental Protection Agency (EPA)
   under NSF Cooperative Agreement [DBI-1266252, EF-0830093]; National
   Institutes of Health (NIH) [HHSN268201000022C]
FX Authors are grateful to Mervi Heiskanen (NIH/NCI) for her time and
   technical expertise to provide tools that supported collaboration on
   this article. C.O.H. would like to gratefully acknowledge the Center for
   the Environmental Implications of NanoTechnology (CEINT) funding from
   National Science Foundation (NSF) and the Environmental Protection
   Agency (EPA) under NSF Cooperative Agreement DBI-1266252 and EF-0830093.
   RTI International, developers of the Nanomaterial Registry, would like
   to thank the National Institutes of Health (NIH) for funding their work,
   under contract HHSN268201000022C. The views, opinions, and content in
   this article are those of the authors and do not necessarily represent
   the views, opinions, or policies of their respective employers or
   organizations Mention of trade names, commercial products, or
   organizations does not imply endorsement by the U.S. government.
NR 10
TC 2
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U1 4
U2 11
PU BEILSTEIN-INSTITUT
PI FRANKFURT AM MAIN
PA TRAKEHNER STRASSE 7-9, FRANKFURT AM MAIN, 60487, GERMANY
SN 2190-4286
J9 BEILSTEIN J NANOTECH
JI Beilstein J. Nanotechnol.
PD SEP 4
PY 2015
VL 6
BP 1860
EP 1871
DI 10.3762/bjnano.6.189
PG 12
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
   Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA CQ4VF
UT WOS:000360602000001
PM 26425437
ER

PT J
AU Segre, JA
AF Segre, Julia A.
TI Microbial growth dynamics and human disease
SO SCIENCE
LA English
DT Editorial Material
ID METAGENOMIC SAMPLES; IDENTIFICATION; GENOME
C1 NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Segre, JA (reprint author), NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
EM jsegre@nhgri.nih.gov
NR 13
TC 0
Z9 0
U1 5
U2 21
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 SEP 4
PY 2015
VL 349
IS 6252
BP 1058
EP 1059
DI 10.1126/science.aad0781
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ5FO
UT WOS:000360628900022
PM 26339017
ER

PT J
AU Fisher, DE
   Shrager, S
   Shea, SJ
   Burke, GL
   Klein, R
   Wong, TY
   Klein, BE
   Cotch, MF
AF Fisher, Diana E.
   Shrager, Sandi
   Shea, Steven J.
   Burke, Gregory L.
   Klein, Ronald
   Wong, Tien Y.
   Klein, Barbara E.
   Cotch, Mary Frances
TI Visual Impairment in White, Chinese, Black, and Hispanic Participants
   from the Multi-Ethnic Study of Atherosclerosis Cohort
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Multi-ethnic; prevalence; risk factors; uncorrected refractive error;
   visual impairment
ID BLUE MOUNTAINS EYE; UNDERCORRECTED REFRACTIVE ERRORS; ANGELES LATINO
   EYE; UNITED-STATES; VISION LOSS; OLDER POPULATION; US ADULTS; RISK
   INDICATORS; HEALTH BURDEN; PREVALENCE
AB Purpose: To describe the prevalence of visual impairment and examine its association with demographic, socioeconomic, and health characteristics in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.Methods: Visual acuity data were obtained from 6134 participants, aged 46-87 years at time of examination between 2002 and 2004 (mean age 64 years, 47.6% male), from six communities in the United States. Visual impairment was defined as presenting visual acuity 20/50 or worse in the better-seeing eye. Risk factors were included in multivariable logistic regression models to determine their impact on visual impairment for men and women in each racial/ethnic group.Results: Among all participants, 6.6% (n=421) had visual impairment, including 5.6% of men (n = 178) and 7.5% of women (n=243). Prevalence of impairment ranged from 4.2% (n=52) and 6.0% (n=77) in white men and women, respectively, to 7.6% (n=37) and 11.6% (n=44) in Chinese men and women, respectively. Older age was significantly associated with visual impairment in both men and women, particularly in those with lower socioeconomic status, but the effects of increasing age were more pronounced in men. Two-thirds of participants already wore distance correction, and not unexpectedly, a lower prevalence of visual impairment was seen in this group; however, 2.4% of men and 3.5% of women with current distance correction had correctable visual impairment, most notably among seniors.Conclusion: Even in the U.S. where prevalence of refractive correction is high, both visual impairment and uncorrected refractive error represent current public health challenges.
C1 [Fisher, Diana E.; Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
   [Shrager, Sandi] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Shea, Steven J.] Columbia Univ, Dept Med, New York, NY USA.
   [Shea, Steven J.] Columbia Univ, Dept Epidemiol, New York, NY USA.
   [Burke, Gregory L.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
   [Klein, Ronald; Klein, Barbara E.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
   [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
   [Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
RP Fisher, DE (reprint author), NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM diana.fisher@nih.gov
OI Cotch, Mary Frances/0000-0002-2046-4350
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
   N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
   N01-HC-95167, N01-HC-95168, N01-HC-95169]; NCRR [UL1-RR-024156,
   UL1-RR-025005]; National Institute of Health (NIH) [HL69979-03];
   Intramural Research Program at the National Eye Institute [ZIAEY000403]
FX This research was supported by contracts N01-HC-95159, N01-HC-95160,
   N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
   N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart,
   Lung, and Blood Institute and by grants UL1-RR-024156 and UL1-RR-025005
   from NCRR. Additional support was provided by National Institute of
   Health (NIH) grant HL69979-03 (Klein R, Wong TY) and the Intramural
   Research Program at the National Eye Institute (ZIAEY000403).
NR 33
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U1 1
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0928-6586
EI 1744-5086
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD SEP 3
PY 2015
VL 22
IS 5
BP 321
EP 332
DI 10.3109/09286586.2015.1066395
PG 12
WC Ophthalmology
SC Ophthalmology
GA DD2MD
UT WOS:000369755700005
PM 26395659
ER

PT J
AU Rajput, B
   Murphy, TD
   Pruitt, KD
AF Rajput, Bhanu
   Murphy, Terence D.
   Pruitt, Kim D.
TI RefSeq curation and annotation of antizyme and antizyme inhibitor genes
   in vertebrates
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ORNITHINE-DECARBOXYLASE ANTIZYME; NONREDUNDANT SEQUENCE DATABASE;
   ZEBRAFISH DANIO-RERIO; MESSENGER-RNA; ARGININE DECARBOXYLASE;
   EXPRESSION; MOUSE; SPERMATOGENESIS; CONSERVATION; TRANSCRIPTS
AB Polyamines are ubiquitous cations that are involved in regulating fundamental cellular processes such as cell growth and proliferation; hence, their intracellular concentration is tightly regulated. Antizyme and antizyme inhibitor have a central role in maintaining cellular polyamine levels. Antizyme is unique in that it is expressed via a novel programmed ribosomal frameshifting mechanism. Conventional computational tools are unable to predict a programmed frameshift, resulting in misannotation of antizyme transcripts and proteins on transcript and genomic sequences. Correct annotation of a programmed frameshifting event requires manual evaluation. Our goal was to provide an accurately curated and annotated Reference Sequence (RefSeq) data set of antizyme transcript and protein records across a broad taxonomic scope that would serve as standards for accurate representation of these gene products. As antizyme and antizyme inhibitor proteins are functionally connected, we also curated antizyme inhibitor genes to more fully represent the elegant biology of polyamine regulation. Manual review of genes for three members of the antizyme family and two members of the antizyme inhibitor family in 91 vertebrate organisms resulted in a total of 461 curated RefSeq records.
C1 [Rajput, Bhanu; Murphy, Terence D.; Pruitt, Kim D.] Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20894 USA.
RP Pruitt, KD (reprint author), Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM pruitt@ncbi.nlm.nih.gov
FU Intramural Research Program of the NIH, National Library of Medicine
FX Funding for this work and the open access charge: Intramural Research
   Program of the NIH, National Library of Medicine.
NR 43
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U1 0
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 SEP 3
PY 2015
VL 43
IS 15
BP 7270
EP 7279
DI 10.1093/nar/gkv713
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CR4LJ
UT WOS:000361303300016
PM 26170238
ER

PT J
AU Fliegauf, M
   Bryant, VL
   Frede, N
   Slade, C
   Woon, ST
   Lehnert, K
   Winzer, S
   Bulashevska, A
   Scerri, T
   Leung, E
   Jordan, A
   Keller, B
   de Vries, E
   Cao, HZ
   Yang, F
   Schaffer, AA
   Warnatz, K
   Browett, P
   Douglass, J
   Ameratunga, RV
   van der Meer, JWM
   Grimbacher, B
AF Fliegauf, Manfred
   Bryant, Vanessa L.
   Frede, Natalie
   Slade, Charlotte
   Woon, See-Tarn
   Lehnert, Klaus
   Winzer, Sandra
   Bulashevska, Alla
   Scerri, Thomas
   Leung, Euphemia
   Jordan, Anthony
   Keller, Baerbel
   de Vries, Esther
   Cao, Hongzhi
   Yang, Fang
   Schaeffer, Alejandro A.
   Warnatz, Klaus
   Browett, Peter
   Douglass, Jo
   Ameratunga, Rohan V.
   van der Meer, Jos W. M.
   Grimbacher, Bodo
TI Haploinsufficiency of the NF-kappa B1 Subunit p50 in Common Variable
   Immunodeficiency
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID NF-KAPPA-B; ANHIDROTIC ECTODERMAL DYSPLASIA; SELECTIVE IGA DEFICIENCY;
   NFKB1 PROMOTER POLYMORPHISM; DNA-SEQUENCING DATA; REGULATORY T-CELLS;
   AUTOSOMAL-DOMINANT; IMMUNE-DEFICIENCY; SIGNALING PATHWAY;
   ULCERATIVE-COLITIS
AB Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In -90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor-site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF-kappa B pathway). The altered protein bearing an internal deletion (p.Asp191_Lys244delinsGlu; p105 Delta Ex8) is degraded, but is not processed to p50AEx8. Altered NF-kappa B1 proteins were also undetectable in a German CVID-affected family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50-translated from the non-mutated alleles-were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-kappa B1 p50 haploinsufficiency.
C1 [Fliegauf, Manfred; Frede, Natalie; Winzer, Sandra; Bulashevska, Alla; Keller, Baerbel; Warnatz, Klaus; Grimbacher, Bodo] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Germany.
   [Fliegauf, Manfred; Frede, Natalie; Winzer, Sandra; Bulashevska, Alla; Keller, Baerbel; Warnatz, Klaus; Grimbacher, Bodo] Univ Freiburg, D-79108 Freiburg, Germany.
   [Bryant, Vanessa L.; Slade, Charlotte; Scerri, Thomas; Douglass, Jo] Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic 3052, Australia.
   [Bryant, Vanessa L.; Slade, Charlotte; Scerri, Thomas] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
   [Slade, Charlotte; Douglass, Jo] Royal Melbourne Hosp, Dept Allergy & Clin Immunol, Parkville, Vic 3050, Australia.
   [Woon, See-Tarn; Ameratunga, Rohan V.] Auckland City Hosp, Dept Virol & Immunol, Auckland 1023, New Zealand.
   [Lehnert, Klaus] Univ Auckland, Sch Biol Sci, Auckland 1142, New Zealand.
   [Leung, Euphemia; Browett, Peter] Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1142, New Zealand.
   [Leung, Euphemia; Browett, Peter] Univ Auckland, Mol Med & Pathol Dept, Auckland 1142, New Zealand.
   [Jordan, Anthony] Auckland City Hosp, Dept Clin Immunol, Auckland 1023, New Zealand.
   [de Vries, Esther] Jeroen Bosch Hosp, Dept Pediat, NL-5200 ME Shertogenbosch, Netherlands.
   [Cao, Hongzhi; Yang, Fang] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Schaeffer, Alejandro A.] NIH, NCBI, US Dept HHS, Bethesda, MD 20892 USA.
   [Douglass, Jo] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia.
   [van der Meer, Jos W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 HP Nijmegen, Netherlands.
   [Grimbacher, Bodo] UCL, Inst Immun & Transplantat, London WC1E 6BT, England.
RP Grimbacher, B (reprint author), Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Germany.
EM bodo.grimbacher@uniklinik-freiburg.de
RI van der Meer, Jos/C-8521-2013
OI van der Meer, Jos/0000-0001-5120-3690
FU German Federal Ministry of Education and Research [01EO1303]; E:med
   SysINFLAME Collaborative Project 1 [01ZX1306]; Australian National
   Health and Medical Research Council [1054925]; Auckland Medical Research
   Foundation; Auckland District Health Board Charitable Trust; New Zealand
   eScience Infrastructure; Intramural Research Program of the NIH,
   National Library of Medicine; National Health and Medical Research
   Council [1075666]
FX We are deeply grateful to all the affected individuals and their
   families who participated in this study. We thank Mary Buchta, Franziska
   Nussbaumer, Pay la Mrovecova, Katrin Hubscher, Tobias Kratina, and
   Isabella Kong for their excellent technical assistance. We thank Marcel
   van Deuren for sharing clinical data on the Dutch family. This study was
   supported by the German Federal Ministry of Education and Research
   (01EO1303), E:med SysINFLAME Collaborative Project 1 (01ZX1306), the
   Australian National Health and Medical Research Council (1054925) and
   the Auckland Medical Research Foundation, the Auckland District Health
   Board Charitable Trust, and the New Zealand eScience Infrastructure.
   This work was supported in part by the Intramural Research Program of
   the NIH, National Library of Medicine. C.S. was supported by National
   Health and Medical Research Council postgraduate scholarship 1075666.
NR 68
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U1 2
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 SEP 3
PY 2015
VL 97
IS 3
BP 389
EP 403
DI 10.1016/j.ajhg.2015.07.008
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA CR1KW
UT WOS:000361084700003
PM 26279205
ER

PT J
AU Johnston, JJ
   Sanchez-Contreras, MY
   Keppler-Noreuil, KM
   Sapp, J
   Crenshaw, M
   Finch, NA
   Cormier-Daire, V
   Rademakers, R
   Sybert, VP
   Biesecker, LG
AF Johnston, Jennifer J.
   Sanchez-Contreras, Monica Y.
   Keppler-Noreuil, Kim M.
   Sapp, Julie
   Crenshaw, Molly
   Finch, NiCole A.
   Cormier-Daire, Valerie
   Rademakers, Rosa
   Sybert, Virginia P.
   Biesecker, Leslie G.
TI A Point Mutation in PDGFRB Causes Autosomal-Dominant Penttinen Syndrome
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID BASAL GANGLIA CALCIFICATION; INFANTILE MYOFIBROMATOSIS; RECEPTOR
AB Penttinen syndrome is a distinctive disorder characterized by a prematurely aged appearance with lipoatrophy, epidermal and dermal atrophy along with hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acro-osteolysis. All individuals have been simplex cases. Exome sequencing of an affected individual identified a de novo c.1994T>C p.Va1665Ala variant in PDGFRB, which encodes the platelet-derived growth factor receptor P. Three additional unrelated individuals with this condition were shown to have the identical variant in PDGFRB. Distinct mutations in PDGFRB have been shown to cause infantile myofibromatosis, idiopathic basal ganglia calcification, and an overgrowth disorder with dysmorphic facies and psychosis, none of which overlaps with the clinical findings in Penttinen syndrome. We evaluated the functional consequence of this causative variant on the PDGFRB signaling pathway by transfecting mutant and wild-type cDNA into HeLa cells, and transfection showed ligand-independent constitutive signaling through STAT3 and PLCy. Penttinen syndrome is a clinically distinct genetic condition caused by a PDGFRB gain-of-function mutation that is associated with a specific and unusual perturbation of receptor function.
C1 [Johnston, Jennifer J.; Keppler-Noreuil, Kim M.; Sapp, Julie; Crenshaw, Molly; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Sanchez-Contreras, Monica Y.; Finch, NiCole A.; Rademakers, Rosa] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
   [Cormier-Daire, Valerie] Univ Paris 05, Sorbonne Paris Cite, INSERM, Dept Genet,UMR1163, F-75006 Paris, France.
   [Cormier-Daire, Valerie] Hop Necker Enfants Malad, AP HP, Inst Imagine, F-75006 Paris, France.
   [Sybert, Virginia P.] Univ Washington, Sch Med, Div Med Genet, Seattle, WA 98195 USA.
   [Sybert, Virginia P.] Grp Hlth Cooperat Puget Sound, Dermatol, Seattle, WA 98112 USA.
RP Biesecker, LG (reprint author), NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
EM lesb@mail.nih.gov
OI Sanchez-Contreras, Monica/0000-0002-3092-2781
FU Intramural Research Program of the National Human Genome Research
   Institute of the NIH; National Institute of Neurological Disorders and
   Stroke [P50 NS072187]
FX This work was supported by the Intramural Research Program of the
   National Human Genome Research Institute of the NIH and by the National
   Institute of Neurological Disorders and Stroke grant P50 NS072187. The
   authors are grateful to the individuals and their families for their
   support and cooperation in this work. We thank Dr. Brian Brooks and Dr.
   Thomas Darling for their involvement and help with individual 1, Dr.
   Judith Martin for her involvement and help with individual 4, Dr.
   Heather Brandling-Bennett for her involvement and help with individual
   3, Dr. Raj Kapur for his help with interpretation of the biopsy of
   individual 3, Dr. Maila Penttinen for contact information for individual
   1, and Dr. Yujun Han for the mutation-rate-prediction analysis. We thank
   Drs. Pamela Schwartzberg and Harold Varmus for advice and critical
   evaluation of the functional data. We thank Julia Fekecs for
   graphic-design support. The authors thank the Exome Aggregation
   Consortium and the groups that provided exome-variant data for
   comparison. L.G.B. is an uncompensated advisor to Illumina and receives
   royalties from Genentech.
NR 18
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U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD SEP 3
PY 2015
VL 97
IS 3
BP 465
EP 474
DI 10.1016/j.ajhg.2015.07.009
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CR1KW
UT WOS:000361084700009
PM 26279204
ER

PT J
AU Siu, MK
   Tsai, YC
   Chang, YS
   Yin, JJ
   Suau, F
   Chen, WY
   Liu, YN
AF Siu, M. K.
   Tsai, Y-C
   Chang, Y-S
   Yin, J. J.
   Suau, F.
   Chen, W-Y
   Liu, Y-N
TI Transforming growth factor-beta promotes prostate bone metastasis
   through induction of microRNA-96 and activation of the mTOR pathway
SO ONCOGENE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; CANCER; INHIBITION; INVASION;
   PROGRESSION; EXPRESSION; RECEPTOR; CELLS; GENE; AXIS
AB Transforming growth factor-beta (TGF beta) is enriched in the bone matrix and serves as a key factor in promoting bone metastasis in cancer. In addition, TGF beta signaling activates mammalian target of rapamycin (mTOR) functions, which is important for the malignant progression. Here, we demonstrate that TGF beta regulates the level of microRNA-96 (miR-96) through Smad-dependent transcription and that miR-96 promotes the bone metastasis in prostate cancer. The enhanced effects in cellular growth and invasiveness suggest that miR-96 functions as an oncomir/and metastamir. Supporting this idea, we identified a downstream target of the TGF beta-miR-96 signaling pathway to be AKT1S1 mRNA, whose translated protein is a negative regulator of mTOR kinase. Our findings provide a novel mechanism accounting for the TGF beta signaling and bone metastasis.
C1 [Siu, M. K.; Tsai, Y-C; Liu, Y-N] Taipei Med Univ, Coll Med Sci & Technol, Program Canc Biol & Drug Discovery, Taipei 11031, Taiwan.
   [Siu, M. K.; Tsai, Y-C; Liu, Y-N] Acad Sinica, Taipei 115, Taiwan.
   [Siu, M. K.] Taipei Med Univ, Wan Fang Hosp, Dept Anesthesiol, Taipei 11031, Taiwan.
   [Tsai, Y-C; Chang, Y-S; Liu, Y-N] Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, Taipei 11031, Taiwan.
   [Yin, J. J.; Suau, F.] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Chen, W-Y] Taipei Med Univ, Wan Fang Hosp, Dept Pathol, Taipei 11031, Taiwan.
RP Liu, YN (reprint author), Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, 250 Wu Hsing St, Taipei 11031, Taiwan.
EM yuanchin@tmu.edu.tw; liuy@tmu.edu.tw
FU Taipei Medical University-Wan Fang Hospital [102TMU-WFH-05]; Taipei
   Medical University [TMU102-AE1-B30]; Ministry of Science and Technology
   [NSC102-2320-B-038-001, NSC103-2311-B-038-001]
FX This work was jointly supported by grants from the Taipei Medical
   University-Wan Fang Hospital (102TMU-WFH-05) to Y-N Liu, Taipei Medical
   University (TMU102-AE1-B30) to Y-C Tsai, the Ministry of Science and
   Technology (NSC102-2320-B-038-001) of Taiwan to Y-N Liu, and the
   Ministry of Science and Technology (NSC103-2311-B-038-001) of Taiwan to
   Y-C Tsai. We also thank Dr Ji-Hshiung Chen (Tzu Chi University) for
   reading the manuscript and for his comments and helpful suggestions. We
   also thank Dr Orla Casey for reviewing our manuscript and discussion.
NR 36
TC 16
Z9 18
U1 1
U2 5
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 SEP 3
PY 2015
VL 34
IS 36
BP 4767
EP 4776
DI 10.1038/onc.2014.414
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA CQ9JU
UT WOS:000360931500010
PM 25531317
ER

PT J
AU Chowell, G
   Abdirizak, F
   Lee, S
   Lee, J
   Jung, E
   Nishiura, H
   Viboud, C
AF Chowell, Gerardo
   Abdirizak, Fatima
   Lee, Sunmi
   Lee, Jonggul
   Jung, Eunok
   Nishiura, Hiroshi
   Viboud, Cecile
TI Transmission characteristics of MERS and SARS in the healthcare setting:
   a comparative study
SO BMC MEDICINE
LA English
DT Article
DE Coronavirus; Exposure pattern; Hospital transmission; MERS; Middle East;
   Nosocomial; Reproduction number; SARS; South Korea
ID RESPIRATORY SYNDROME CORONAVIRUS; SAUDI-ARABIA; HONG-KONG; NOSOCOMIAL
   OUTBREAK; EPIDEMIOLOGY; COV; SINGAPORE; TORONTO; FACILITIES; DYNAMICS
AB Background: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015.
   Methods: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks.
   Results: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal-Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %.
   Conclusions: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses.
C1 [Chowell, Gerardo; Abdirizak, Fatima] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
   [Chowell, Gerardo; Viboud, Cecile] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Lee, Sunmi] Kyung Hee Univ, Dept Appl Math, Yongin 446701, South Korea.
   [Lee, Jonggul; Jung, Eunok] Konkuk Univ, Dept Math, Seoul 143701, South Korea.
   [Nishiura, Hiroshi] Univ Tokyo, Grad Sch Med, Tokyo, Japan.
   [Nishiura, Hiroshi] Japan Sci & Technol Agcy, CREST, Saitama, Japan.
RP Chowell, G (reprint author), Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
EM gchowell@gsu.edu
OI Nishiura, Hiroshi/0000-0003-0941-8537
FU Division of International Epidemiology and Population Studies, The
   Fogarty International Center, United States National Institutes of
   Health; Office of Pandemics and Emerging Threats at the United States
   Department of Health and Human Services; NSF, NSF-NIH-USDA Ecology and
   Evolution of Infectious Diseases program, United Kingdom Biotechnology
   and Biological Sciences Research Council [1414374, BB/M008894/1]; NSF,
   NSF-IIS Grant [1414374, 1518939]; JSPS KAKENHI [26670308, 26700028];
   Japan Agency for Medical Research and Development; Japan Science and
   Technology Agency (JST) CREST program; RISTEX program for Science of
   Science, Technology and Innovation Policy
FX We thank the Ministry of Health and the Korean Centers for Disease
   Control for making detailed and updated epidemiological data for the
   South Korean outbreak publicly available on a daily basis. GC and CV
   acknowledge financial support from the Division of International
   Epidemiology and Population Studies, The Fogarty International Center,
   United States National Institutes of Health, funded in part by the
   Office of Pandemics and Emerging Threats at the United States Department
   of Health and Human Services. GC also acknowledges support from grants
   NSF grant 1414374 as part of the joint NSF-NIH-USDA Ecology and
   Evolution of Infectious Diseases program, United Kingdom Biotechnology
   and Biological Sciences Research Council grant BB/M008894/1, and NSF-IIS
   Grant# 1518939. HN received funding support from the JSPS KAKENHI Grant
   Numbers 26670308 and 26700028, Japan Agency for Medical Research and
   Development, the Japan Science and Technology Agency (JST) CREST
   program, and RISTEX program for Science of Science, Technology and
   Innovation Policy. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 54
TC 26
Z9 26
U1 5
U2 34
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD SEP 3
PY 2015
VL 13
AR 210
DI 10.1186/s12916-015-0450-0
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA CQ5VV
UT WOS:000360674700001
PM 26336062
ER

PT J
AU Jafri, K
   Taylor, L
   Nezamzadeh, M
   Baker, JF
   Mehta, NN
   Bartels, C
   Williams, CT
   Ogdie, A
AF Jafri, Kashif
   Taylor, Lynne
   Nezamzadeh, Melissa
   Baker, Joshua F.
   Mehta, Nehal N.
   Bartels, Christie
   Williams, Catherine T.
   Ogdie, Alexis
TI Management of hyperlipidemia among patients with rheumatoid arthritis in
   the primary care setting
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
ID POPULATION-BASED COHORT; CORONARY-HEART-DISEASE; CARDIOVASCULAR RISK;
   STATIN DISCONTINUATION; SCORE; RECOMMENDATIONS; EPIDEMIOLOGY;
   PREDICTION; MORTALITY; IMPACT
AB Background: Rheumatoid arthritis (RA) has been associated with an increased risk of cardiovascular morbidity and mortality but this has not translated to optimal management of traditional cardiovascular risk factors such as hyperlipidemia. The objectives of this study were to 1) determine the prevalence of screening for hyperlipidemia in patients with RA followed by primary care practitioners (PCP); 2) examine initiation of lipid-lowering therapy in patients with an indication, and 3) assess whether proposed modifications to cardiovascular risk calculations change the percentage of RA patients with an indication for therapy.
   Methods: We performed a retrospective cohort study using an academic medical center-based medical record database in the United States. Patients with RA defined by the presence of at least one ICD-9 code between 2005-2010 and followed by a PCP within the health care system were included. The positive predictive value of ICD-9 codes for accurately identifying patients with RA was 96.7 %. Descriptive statistics were used to report the prevalence of screening and use of lipid-lowering therapy among those with an indication. Factors associated with not receiving lipid screening were examined using logistic regression models. Indication for and receipt of therapy were then assessed before and after the application of the European Union League Against Rheumatism (EULAR) recommended multiplier to the Framingham risk score.
   Results: Among 1,056 patients with RA followed by PCPs and eligible for lipid screening, lipid screening was ordered for 539 (51 %) within the 3-year follow-up period. Patients with diabetes, hypertension, chronic kidney disease, obesity or age >50 were more likely to be screened. Of those with lipid results (N = 290), 25 (9 %) patients had an indication for lipid-lowering therapy based on Adult Treatment Panel III guidelines. Ten (40 %) patients with an indication for lipid-lowering therapy received therapy did not receive therapy. Applying the EULAR multiplier only changed the indication for lipid-lowering therapy in two patients.
   Conclusions: Screening and management of traditional cardiovascular risk factors, including hyperlipidemia, need to be optimized.
C1 [Jafri, Kashif] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Taylor, Lynne; Williams, Catherine T.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Ctr Clin Epidemiol & Biostat,Biostat Analyt Core, Philadelphia, PA 19104 USA.
   [Nezamzadeh, Melissa] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostatist, Philadelphia, PA 19104 USA.
   [Baker, Joshua F.; Ogdie, Alexis] Univ Penn, Perelman Sch Med, Ctr Pharmacoepidemiol Res & Training, Ctr Clin Epidemiol & Biostat,Div Rheumatol, Philadelphia, PA 19104 USA.
   [Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA.
   [Bartels, Christie] Univ Wisconsin, Sch Med & Publ Hlth, Div Rheumatol, Madison, WI USA.
RP Ogdie, A (reprint author), Univ Penn, Perelman Sch Med, Ctr Pharmacoepidemiol Res & Training, Ctr Clin Epidemiol & Biostat,Div Rheumatol, White Bldg,Room 5024,3400 Spruce St, Philadelphia, PA 19104 USA.
EM alexis.ogdie@uphs.upenn.edu
FU Kynett-FOCUS Junior Faculty Investigator Award for Research in Women's
   Cardiovascular Health - Edna G. Kynett Memorial Foundation; American
   College of Rheumatology Research Foundation; NIH [K23AR063764]; Veterans
   Affairs Clinical Science Research and Development Career Development
   Award [IK2 CX000955]
FX We would like to thank Yihui Connie Jiang for administrative support.
   Funding for this study was provided by the Kynett-FOCUS Junior Faculty
   Investigator Award for Research in Women's Cardiovascular Health
   supported by the Edna G. Kynett Memorial Foundation. Dr. Ogdie was
   supported by the American College of Rheumatology Research Foundation
   and NIH K23AR063764. JFB is supported by a Veterans Affairs Clinical
   Science Research and Development Career Development Award (IK2
   CX000955).
NR 30
TC 0
Z9 0
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD SEP 3
PY 2015
VL 16
AR 237
DI 10.1186/s12891-015-0700-5
PG 8
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA CQ9SM
UT WOS:000360955400001
PM 26336889
ER

PT J
AU Tang, EYH
   Harrison, SL
   Errington, L
   Gordon, MF
   Visser, PJ
   Novak, G
   Dufouil, C
   Brayne, C
   Robinson, L
   Launer, LJ
   Stephan, BCM
AF Tang, Eugene Y. H.
   Harrison, Stephanie L.
   Errington, Linda
   Gordon, Mark F.
   Visser, Pieter Jelle
   Novak, Gerald
   Dufouil, Carole
   Brayne, Carol
   Robinson, Louise
   Launer, Lenore J.
   Stephan, Blossom C. M.
TI Current Developments in Dementia Risk Prediction Modelling: An Updated
   Systematic Review
SO PLOS ONE
LA English
DT Article
ID ALZHEIMERS-DISEASE; NEUROPSYCHOLOGICAL TESTS; INCIDENT DEMENTIA;
   POPULATION; SCORE; INDIVIDUALS; PREVENTION; SAMPLE; COHORT; INDEX
AB Background
   Accurate identification of individuals at high risk of dementia influences clinical care, inclusion criteria for clinical trials and development of preventative strategies. Numerous models have been developed for predicting dementia. To evaluate these models we undertook a systematic review in 2010 and updated this in 2014 due to the increase in research published in this area. Here we include a critique of the variables selected for inclusion and an assessment of model prognostic performance.
   Methods
   Our previous systematic review was updated with a search from January 2009 to March 2014 in electronic databases (MEDLINE, Embase, Scopus, Web of Science). Articles examining risk of dementia in non-demented individuals and including measures of sensitivity, specificity or the area under the curve (AUC) or c-statistic were included.
   Findings
   In total, 1,234 articles were identified from the search; 21 articles met inclusion criteria. New developments in dementia risk prediction include the testing of non-APOE genes, use of non-traditional dementia risk factors, incorporation of diet, physical function and ethnicity, and model development in specific subgroups of the population including individuals with diabetes and those with different educational levels. Four models have been externally validated. Three studies considered time or cost implications of computing the model.
   Interpretation
   There is no one model that is recommended for dementia risk prediction in population-based settings. Further, it is unlikely that one model will fit all. Consideration of the optimal features of new models should focus on methodology (setting/sample, model development and testing in a replication cohort) and the acceptability and cost of attaining the risk variables included in the prediction score. Further work is required to validate existing models or develop new ones in different populations as well as determine the ethical implications of dementia risk prediction, before applying the particular models in population or clinical settings.
C1 [Tang, Eugene Y. H.; Harrison, Stephanie L.; Robinson, Louise; Stephan, Blossom C. M.] Newcastle Univ, Inst Ageing, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
   [Errington, Linda] Newcastle Univ, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Gordon, Mark F.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
   [Visser, Pieter Jelle] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands.
   [Visser, Pieter Jelle] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Alzheimer Ctr, Amsterdam, Netherlands.
   [Novak, Gerald] Janssen Pharmaceut Res & Dev, Titusville, NJ 08560 USA.
   [Dufouil, Carole] Team Neuroepidemiol, INSERM, U897, Res Ctr, F-33000 Bordeaux, France.
   [Brayne, Carol] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England.
   [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Tang, EYH (reprint author), Newcastle Univ, Inst Ageing, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
EM e.y.h.tang@newcastle.ac.uk
RI Visser, Pieter/C-8541-2015; 
OI Visser, Pieter/0000-0001-8008-9727; Robinson,
   Louise/0000-0003-0209-2503; Harrison, Stephanie/0000-0002-8846-0946
FU NIHR Academic Clinical Fellowship; Innovative Medicines Initiative Joint
   Undertaking under EMIF grant [115372]; European Union; EFPIA companies;
   Intramural research Program of the NIH, National institute on Aging
FX Tang EYH is supported by an NIHR Academic Clinical Fellowship. The
   research leading to these results has received support from the
   Innovative Medicines Initiative Joint Undertaking under EMIF grant
   agreement no. 115372, resources of which are composed of financial
   contributions from the European Union's Seventh Framework Programme
   (FP7/2007-2013) and EFPIA companies in kind contribution. This research
   (LJL) was also supported in part by the Intramural research Program of
   the NIH, National institute on Aging. The funders had no role in the
   writing of the manuscript or decision to submit it for publication.
NR 40
TC 9
Z9 9
U1 3
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 3
PY 2015
VL 10
IS 9
AR e0136181
DI 10.1371/journal.pone.0136181
PG 31
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ5AJ
UT WOS:000360615400011
PM 26334524
ER

PT J
AU Manesh, DM
   El-Hoss, J
   Evans, K
   Richmond, J
   Toscan, CE
   Bracken, LS
   Hedrick, A
   Sutton, R
   Marshall, GM
   Wilson, WR
   Kurmasheva, RT
   Billups, C
   Houghton, PJ
   Smith, MA
   Carol, H
   Lock, RB
AF Manesh, Donya Moradi
   El-Hoss, Jad
   Evans, Kathryn
   Richmond, Jennifer
   Toscan, Cara E.
   Bracken, Lauryn S.
   Hedrick, Ashlee
   Sutton, Rosemary
   Marshall, Glenn M.
   Wilson, William R.
   Kurmasheva, Raushan T.
   Billups, Catherine
   Houghton, Peter J.
   Smith, Malcolm A.
   Carol, Hernan
   Lock, Richard B.
TI AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of
   T-cell acute lymphoblastic leukemia
SO BLOOD
LA English
DT Article
ID KETO REDUCTASE 1C3; HYPOXIA-ACTIVATED PRODRUG; HEMATOPOIETIC STEM-CELLS;
   5 17-BETA-HYDROXYSTEROID-DEHYDROGENASE AKR1C3; ACUTE MYELOGENOUS
   LEUKEMIA; BONE-MARROW; INCREASED EXPRESSION; TESTING PROGRAM; PHASE-I;
   CANCER
AB PR-104, a phosphate ester of the nitrogen mustard prodrug PR-104A, has shown evidence of efficacy in adult leukemia clinical trials. Originally designed to target hypoxic cells, PR-104A is independently activated by aldo-keto-reductase 1C3 (AKR1C3). The aim of this study was to test whether AKR1C3 is a predictive biomarker of in vivo PR-104 sensitivity. In a panel of 7 patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts, PR-104 showed significantly greater efficacy against T-lineage ALL (T-ALL) than B-cell-precursor ALL (BCP-ALL) xenografts. Single-agent PR-104 was more efficacious against T-ALL xenografts compared with a combination regimen of vincristine, dexamethasone, and L-asparaginase. Expression of AKR1C3 was significantly higher in T-ALL xenografts compared with BCP-ALL, and correlated with PR-104/PR-104A sensitivity in vivo and in vitro. Overexpression of AKR1C3 in a resistant BCP-ALL xenograft resulted in dramatic sensitization to PR-104 in vivo. Testing leukemic blasts from 11 patients confirmed that T-ALL cells were more sensitive than BCP-ALL to PR-104A in vitro, and that sensitivity correlated with AKR1C3 expression. Collectively, these results indicate that PR-104 shows promise as a novel therapy for relapsed/refractoryT-ALL, and that AKR1C3 expression could be used as a biomarker to select patients most likely to benefit from such treatment in prospective clinical trials.
C1 [Manesh, Donya Moradi; El-Hoss, Jad; Evans, Kathryn; Richmond, Jennifer; Toscan, Cara E.; Bracken, Lauryn S.; Sutton, Rosemary; Carol, Hernan; Lock, Richard B.] Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst, Sydney, NSW, Australia.
   [Hedrick, Ashlee] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia.
   [Marshall, Glenn M.] Sydney Childrens Hosp, Kids Canc Ctr, Randwick, NSW, Australia.
   [Wilson, William R.] Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1, New Zealand.
   [Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
   [Billups, Catherine] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA.
   [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Lock, RB (reprint author), UNSW Australia, Childrens Canc Inst, Lowy Canc Res Ctr, POB 81, Randwick, NSW 2031, Australia.
EM rlock@ccia.unsw.edu.au
RI Lock, Richard/G-4253-2013
FU National Institutes of Health National Cancer Institute [NOI-CM-42216,
   NOI-CM-91001-03]; National Health and Medical Research Council of
   Australia (NHMRC); NHMRC
FX This work was supported by grants from the National Institutes of Health
   National Cancer Institute (NOI-CM-42216 and NOI-CM-91001-03), and the
   National Health and Medical Research Council of Australia (NHMRC).
   R.B.L. is supported by a fellowship from the NHMRC.
NR 47
TC 11
Z9 11
U1 2
U2 11
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 SEP 3
PY 2015
VL 126
IS 10
BP 1193
EP 1202
DI 10.1182/blood-2014-12-618900
PG 10
WC Hematology
SC Hematology
GA CQ3YH
UT WOS:000360540100011
ER

PT J
AU Ying, TL
   Wang, YP
   Feng, Y
   Prabakaran, P
   Gong, R
   Wang, LL
   Crowder, K
   Dimitrov, DS
AF Ying, Tianlei
   Wang, Yanping
   Feng, Yang
   Prabakaran, Ponraj
   Gong, Rui
   Wang, Lili
   Crowder, Karalyne
   Dimitrov, Dimiter S.
TI Engineered antibody domains with significantly increased transcytosis
   and half-life in macaques mediated by FcRn
SO MABS
LA English
DT Article
DE CH2; FcRn; half-life; CH3; macaques; transcytosis; antibody domains
ID MONOMERIC IGG1 FC; BINDING-PROPERTIES; DEVELOPMENT TRENDS;
   CRYSTAL-STRUCTURE; RECEPTOR FCRN; CH2 DOMAINS; THERAPEUTICS; FRAGMENTS;
   PHARMACOKINETICS; PROTEINS
AB Engineered antibody domains (eAds) are promising candidate therapeutics but their half-life is relatively short partly due to weak or absent binding to the neonatal Fc receptor (FcRn). We developed a novel approach to increase the eAd binding to FcRn based on a combination of structure-based design, computational modeling and phage display methodologies. By using this approach, we identified 2 IgG1 CH2-derived eAds fused to a short FcRn-binding motif derived from IgG1 CH3 that exhibited greatly enhanced FcRn binding with strict pH dependency. Importantly, the increased affinity resulted in significantly enhanced FcRn-mediated epithelial transcytosis and prolonged elimination half-life (mean 44.1hours) in cynomolgus macaques. These results demonstrate for the first time that the half-life of isolated eAds can be prolonged (optimized) by increasing their binding to FcRn while maintaining their small size, which has important implications for development of therapeutics, including eAd-drug conjugates with enhanced penetration in solid tissues.
C1 [Ying, Tianlei; Wang, Lili] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Minist Educ, Shanghai 200433, Peoples R China.
   [Ying, Tianlei; Wang, Lili] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Minist Hlth, Shanghai 200433, Peoples R China.
   [Wang, Yanping; Feng, Yang; Prabakaran, Ponraj; Gong, Rui; Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Lab Expt Immunol, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21701 USA.
   [Wang, Yanping] Geneva Fdn, Tacoma, WA USA.
   [Gong, Rui] Chinese Acad Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China.
   [Crowder, Karalyne] SNBL USA, Everett, WA USA.
RP Ying, TL (reprint author), Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Minist Educ, Shanghai 200433, Peoples R China.
EM tlying@fudan.edu.cn
FU NIH, National Cancer Institute, Center for Cancer Research; NIH,
   National Cancer Institute [N01-CO-12400]; Shanghai Pujiang Talent
   Program
FX This work was supported by the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research, Federal funds
   from the NIH, National Cancer Institute, under Contract No.
   N01-CO-12400, and the Shanghai Pujiang Talent Program.
NR 35
TC 4
Z9 4
U1 3
U2 12
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1942-0862
EI 1942-0870
J9 MABS-AUSTIN
JI mAbs
PD SEP 3
PY 2015
VL 7
IS 5
BP 922
EP 930
DI 10.1080/19420862.2015.1067353
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CP9MR
UT WOS:000360218900013
PM 26179052
ER

PT J
AU Nelson, KB
   Blair, E
AF Nelson, Karin B.
   Blair, Eve
TI Prenatal Factors in Singletons with Cerebral Palsy Born at or near Term
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID FETAL THROMBOTIC VASCULOPATHY; PERINATAL BRAIN-INJURY; MAJOR
   BIRTH-DEFECTS; RISK-FACTORS; PRETERM BIRTH; NEURODEVELOPMENTAL
   DISORDERS; CONGENITAL-MALFORMATIONS; NEONATAL ENCEPHALOPATHY;
   INTRAUTERINE GROWTH; 1ST TRIMESTER
C1 [Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA.
   [Nelson, Karin B.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
   [Blair, Eve] Univ Western Australia, Telethon Kids Inst, Subiaco, WA, Australia.
RP Nelson, KB (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM nelsonk@ninds.nih.gov
NR 81
TC 14
Z9 15
U1 2
U2 14
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 SEP 3
PY 2015
VL 373
IS 10
BP 946
EP 953
DI 10.1056/NEJMra1505261
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA CQ2OB
UT WOS:000360439500010
PM 26332549
ER

PT J
AU Yochelis, A
   Ebrahim, S
   Millis, B
   Cui, R
   Kachar, B
   Naoz, M
   Gov, NS
AF Yochelis, A.
   Ebrahim, S.
   Millis, B.
   Cui, R.
   Kachar, B.
   Naoz, M.
   Gov, N. S.
TI Self-organization of waves and pulse trains by molecular motors in
   cellular protrusions
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MYOSIN-X; FILOPODIA FORMATION; PATTERN-FORMATION; STEREOCILIA;
   LOCALIZATION; ELONGATION; ARCHITECTURE; TIP
AB Actin-based cellular protrusions are an ubiquitous feature of cells, performing a variety of critical functions ranging from cell-cell communication to cell motility. The formation and maintenance of these protrusions relies on the transport of proteins via myosin motors, to the protrusion tip. While tip-directed motion leads to accumulation of motors (and their molecular cargo) at the protrusion tip, it is observed that motors also form rearward moving, periodic and isolated aggregates. The origins and mechanisms of these aggregates, and whether they are important for the recycling of motors, remain open puzzles. Motivated by novel myosin-XV experiments, a mass conserving reactiondiffusion- advection model is proposed. The model incorporates a non-linear cooperative interaction between motors, which converts them between an active and an inactive state. Specifically, the type of aggregate formed (traveling waves or pulse-trains) is linked to the kinetics of motors at the protrusion tip which is introduced by a boundary condition. These pattern selection mechanisms are found not only to qualitatively agree with empirical observations but open new vistas to the transport phenomena by molecular motors in general.
C1 [Yochelis, A.] Ben Gurion Univ Negev, Dept Solar Energy & Environm Phys, Swiss Inst Dryland Environm & Energy Res, Blaustein Inst Desert Res, IL-84990 Midreshet Ben Gurion, Israel.
   [Ebrahim, S.; Millis, B.; Cui, R.; Kachar, B.] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
   [Naoz, M.; Gov, N. S.] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
RP Yochelis, A (reprint author), Ben Gurion Univ Negev, Dept Solar Energy & Environm Phys, Swiss Inst Dryland Environm & Energy Res, Blaustein Inst Desert Res, Sede Boqer Campus, IL-84990 Midreshet Ben Gurion, Israel.
EM yochelis@bgu.ac.il; nir.gov@weizmann.ac.il
FU Adelis foundation; NIH intramural research funds [Z01-DC000002]; ISF
   [580/12]
FX This work was supported in part by the Adelis foundation (A.Y.), NIH
   intramural research funds Z01-DC000002 (B.K.), and ISF grant 580/12 for
   support together with the historic generosity of the Perlman family
   (N.S.G.). N.S.G is the incumbent of the Lee and William Abramowitz
   Professorial Chair of Biophysics.
NR 32
TC 3
Z9 3
U1 2
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 SEP 3
PY 2015
VL 5
AR 13521
DI 10.1038/srep13521
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ3VY
UT WOS:000360533300001
PM 26335545
ER

PT J
AU Kupst, MJ
   Butt, Z
   Stoney, CM
   Griffith, JW
   Salsman, JM
   Folkman, S
   Cella, D
AF Kupst, Mary Jo
   Butt, Zeeshan
   Stoney, Catherine M.
   Griffith, James W.
   Salsman, John M.
   Folkman, Susan
   Cella, David
TI Assessment of stress and self-efficacy for the NIH Toolbox for
   Neurological and Behavioral Function
SO ANXIETY STRESS AND COPING
LA English
DT Article
DE perceived stress; self-efficacy; psychometrics; NIH Toolbox
ID EMOTION REGULATION; FIT INDEXES; PSYCHOLOGICAL STRESS; HEALTH;
   POPULATIONS; CRITERIA; DISEASE
AB Background and Objectives: The NIH Toolbox for Neurological and Behavioral Function assessment battery contains measures in the domains of cognitive function, motor function, sensory function, and emotional health. It was designed for use in epidemiological and clinical trials health-related research. Design: This paper describes the first phase of instrument development for the stress and self-efficacy subdomain of emotional health. Based on an extensive literature review and expert consultation, 127 measures were initially considered for inclusion in this subdomain, including measures of stress, self-efficacy, emotion regulation, and coping. Results: Several measures, including emotion regulation and measures of coping strategies, did not meet criteria that were a priori established for inclusion. Psychometric properties of the remaining candidate measures were evaluated using data from five independent samples (combined N = 3175). Confirmatory and exploratory factor analyses indicated the Perceived Stress Scale and the General Self-Efficacy Scale each assessed single dimensions. Conclusions: Based on their psychometric performance, these two instruments were selected for inclusion and subsequent national norming for the NIH Toolbox.
C1 [Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
   [Butt, Zeeshan] Northwestern Univ, Comprehens Transplant Ctr, Dept Med Social Sci, Evanston, IL 60208 USA.
   [Butt, Zeeshan] Northwestern Univ, Inst Healthcare Studies, Evanston, IL 60208 USA.
   [Stoney, Catherine M.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Griffith, James W.; Cella, David] Northwestern Univ, Dept Med Social Sci, Evanston, IL 60208 USA.
   [Salsman, John M.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Dept Med Social Sci, Chicago, IL 60611 USA.
   [Folkman, Susan] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
RP Kupst, MJ (reprint author), Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
EM mkupst@mcw.edu
RI Griffith, James/O-2551-2016
OI Griffith, James/0000-0002-4840-8692
FU Federal funds from Blueprint for Neuroscience Research, National
   Institutes of Health [HHS-N-260-2006-00007-C]
FX This study is funded in whole or in part with Federal funds from the
   Blueprint for Neuroscience Research, National Institutes of Health,
   under Contract No. HHS-N-260-2006-00007-C.
NR 49
TC 0
Z9 0
U1 4
U2 16
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1061-5806
EI 1477-2205
J9 ANXIETY STRESS COPIN
JI Anxiety Stress Coping
PD SEP 3
PY 2015
VL 28
IS 5
BP 531
EP 544
DI 10.1080/10615806.2014.994204
PG 14
WC Neurosciences; Psychiatry; Psychology, Multidisciplinary
SC Neurosciences & Neurology; Psychiatry; Psychology
GA CP2JU
UT WOS:000359704100004
PM 25577948
ER

PT J
AU Burianova, H
   Rich, AN
   Williams, M
   Morgan, M
   Marstaller, L
   Maruff, P
   Baker, CI
   Savage, G
AF Burianova, Hana
   Rich, Anina N.
   Williams, Mark
   Morgan, Michael
   Marstaller, Lars
   Maruff, Paul
   Baker, Chris I.
   Savage, Greg
TI Long-term plasticity in adult somatosensory cortex: functional
   reorganization after surgical removal of an arteriovenous malformation
SO NEUROCASE
LA English
DT Article
DE somatosensory; neuroplasticity; AVM; fMRI; proprioception
ID PARTIAL LEAST-SQUARES; RAT MOTOR CORTEX; CORTICAL REORGANIZATION;
   HORIZONTAL CONNECTIONS; RHESUS-MONKEY; LIMB AMPUTEES; PARIETAL LOBE;
   MEMORY TASK; BRAIN; PAIN
AB The temporal scale of neuroplasticity following acute alterations in brain structure due to neurosurgical intervention is still under debate. We conducted a longitudinal study with the objective of investigating the postoperative changes in a patient who underwent cerebrovascular surgery and who subsequently lost proprioception in the fingers of her right hand. The results show increased activation in contralesional somatosensory areas, additional recruitment of premotor and posterior parietal areas, and changes in functional connectivity with left postcentral gyrus. These findings demonstrate long-term modifications of cortical organization and as such have important implications for treatment strategies for patients with brain injury.
C1 [Burianova, Hana] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia.
   [Burianova, Hana; Rich, Anina N.; Williams, Mark; Marstaller, Lars; Savage, Greg] Macquarie Univ, ARC Ctr Excellence Cognit & Its Disorders, Sydney, NSW 2109, Australia.
   [Rich, Anina N.; Williams, Mark; Marstaller, Lars] Macquarie Univ, Dept Cognit Sci, Sydney, NSW 2109, Australia.
   [Morgan, Michael] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia.
   [Maruff, Paul] CogState Ltd, Melbourne, Vic, Australia.
   [Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
   [Savage, Greg] Macquarie Univ, Dept Psychol, Sydney, NSW 2109, Australia.
RP Burianova, H (reprint author), Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia.
EM hana.burianova@mq.edu.au
RI Marstaller, Lars/F-8434-2014; 
OI Marstaller, Lars/0000-0003-2814-5474; Morgan,
   Michael/0000-0002-9841-9461; Williams, Mark/0000-0002-3897-5167;
   Burianova, Hana/0000-0003-2051-9494; Baker, Chris/0000-0001-6861-8964;
   Maruff, Paul/0000-0002-6947-9537
FU National Health and Medical Research Council; Australian Research
   Council Centre of Excellence for Cognition and its Disorders
   [CE110001021]
FX This work was funded by the National Health and Medical Research Council
   and was also supported by the Australian Research Council Centre of
   Excellence for Cognition and its Disorders [CE110001021]
   (http://www.ccd.edu.au).
NR 55
TC 1
Z9 1
U1 0
U2 9
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1355-4794
EI 1465-3656
J9 NEUROCASE
JI Neurocase
PD SEP 3
PY 2015
VL 21
IS 5
BP 618
EP 627
DI 10.1080/13554794.2014.960429
PG 10
WC Clinical Neurology; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA CK6RE
UT WOS:000356354500010
PM 25265167
ER

PT J
AU Resnik, DB
   Rasmussen, LM
   Kissling, GE
AF Resnik, David B.
   Rasmussen, Lisa M.
   Kissling, Grace E.
TI An International Study of Research Misconduct Policies
SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE
LA English
DT Article
DE policies; research misconduct; international variation; definitions;
   ethics
AB Research misconduct is an international concern. Misconduct policies can play a crucial role in preventing and policing research misconduct, and many institutions have developed their own policies. While institutional policies play a key role in preventing and policing misconduct, national policies are also important to ensure consistent promulgation and enforcement of ethical standards. The purpose of this study was to obtain more information about research misconduct policies across the globe. We found that twenty-two of the top forty research and development funding countries (55%) had a national misconduct policy. Four countries (18.2%) are in the process of developing a policy, and four (18.2%) have a national research ethics code but no misconduct policy. All twenty-two countries (100%) with national policies included fabrication, falsification, and plagiarism in the definition of misconduct, but beyond that there was considerable diversity. Unethical authorship was mentioned in 54.6% of the misconduct definitions, followed by unethical publication practices (36.4%), conflict of interest mismanagement (36.4%), unethical peer review (31.8%), misconduct related to misconduct investigations (27.3%), poor record keeping (27.3%), other deception (27.3%), serious deviations (22.7%), violating confidentiality (22.7%), and human or animal research violations (22.7%). Having a national policy was positively associated with research and development funding ranking and intensiveness. To promote integrity in international research collaborations, countries should seek to harmonize and clarify misconduct definitions and develop procedures for adjudicating conflicts when harmonization does not occur.
C1 [Resnik, David B.; Kissling, Grace E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   [Rasmussen, Lisa M.] Univ N Carolina, Charlotte, NC 28223 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-06]
NR 11
TC 5
Z9 6
U1 6
U2 40
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0898-9621
EI 1545-5815
J9 ACCOUNT RES
JI Account. Res.
PD SEP 3
PY 2015
VL 22
IS 5
BP 249
EP 266
DI 10.1080/08989621.2014.958218
PG 18
WC Medical Ethics
SC Medical Ethics
GA CH1KB
UT WOS:000353779100001
PM 25928177
ER

PT J
AU Tsuda, MC
   Yeung, HM
   Kuo, J
   Usdin, TB
AF Tsuda, Mumeko C.
   Yeung, Ho-Man
   Kuo, Jonathan
   Usdin, Ted B.
TI Incubation of Fear Is Regulated by TIP39 Peptide Signaling in the Medial
   Nucleus of the Amygdala
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE DREADD; fear enhancement; fear incubation; medial amygdala;
   neuropeptide; PTSD
ID POSTTRAUMATIC-STRESS-DISORDER; RECEPTOR-TYPE 2; TUBEROINFUNDIBULAR
   PEPTIDE; CONDITIONED FEAR; 39 RESIDUES; STRIA TERMINALIS; BED NUCLEUS;
   PARATHYROID-HORMONE-2 RECEPTOR; MICE; RESPONSES
AB Fear-related psychopathologies such as post-traumatic stress disorder are characterized by impaired extinction of fearful memories. Recent behavioral evidence suggests that the neuropeptide tuberoinfundibular peptide of 39 residues (TIP39), via its receptor, the parathyroid hormone 2 receptor (PTH2R), modulates fear memory. Here we examined the anatomical and cellular localization of TIP39 signaling that contributes to the increase in fear memory over time following a traumatic event, called fear memory incubation. Contextual freezing, a behavioral sign of fear memory, was significantly greater in PTH2R knock-out than wild-type male mice 2 and 4 weeks after a 2 s 1.5 mA footshock. PTH2R knock-out mice had significantly reduced c-Fos activation in the medial amygdala (MeA) following both footshock and fear recall, but had normal activation in the hypothalamic paraventricular nucleus and the amygdalar central nucleus compared with wild-type. We therefore investigated the contribution of MeA TIP39 signaling to fear incubation. Similar to the effect of global TIP39 signaling loss, blockade of TIP39 signaling in the MeA by lentivirus-mediated expression of a secreted PTH2R antagonist augmented fear incubation. Ablation of MeA PTH2R-expressing neurons also strengthened the fear incubation effect. Using the designer receptor exclusively activated by designer drug pharmacogenetic approach, transient inhibition of MeA PTH2R-expressing neurons before or immediately after the footshock, but not at the time of fear recall, enhanced fear incubation. Collectively, the findings demonstrate that TIP39 signaling within the MeA at the time of an aversive event regulates the increase over time in fear associated with the event context.
C1 [Tsuda, Mumeko C.; Yeung, Ho-Man; Kuo, Jonathan; Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, NIH, Bethesda, MD 20892 USA.
RP Usdin, TB (reprint author), NIMH, Sect Fundamental Neurosci, Bldg 35,Room 1B-215,35 Convent Dr, Bethesda, MD 20892 USA.
EM usdint@mail.nih.gov
OI Yeung, Ho-Man/0000-0002-7188-9738
FU Intramural Research Program of the National Institute of Mental Health
   [ZIA-MH002685]
FX This research was supported by the Intramural Research Program of the
   National Institute of Mental Health (ZIA-MH002685). Technical support
   was provided by Milan Rusnak and Brian Coleman.
NR 50
TC 4
Z9 4
U1 0
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 2
PY 2015
VL 35
IS 35
BP 12152
EP 12161
DI 10.1523/JNEUROSCI.1736-15.2015
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CU6QY
UT WOS:000363658900008
PM 26338326
ER

PT J
AU Jurek, B
   Slattery, DA
   Hiraoka, Y
   Liu, Y
   Nishimori, K
   Aguilera, G
   Neumann, ID
   van den Burg, EH
AF Jurek, Benjamin
   Slattery, David A.
   Hiraoka, Yuichi
   Liu, Ying
   Nishimori, Katsuhiko
   Aguilera, Greti
   Neumann, Inga D.
   van den Burg, Erwin H.
TI Oxytocin Regulates Stress-Induced Crf Gene Transcription through
   CREB-Regulated Transcription Coactivator 3
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Crf; CRTC3/TORC3; intracellular signaling; oxytocin receptor; stress
   response
ID CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RNA EXPRESSION; STRIA
   TERMINALIS; BRAIN OXYTOCIN; BED NUCLEUS; RAT-BRAIN; PARAVENTRICULAR
   NUCLEUS; HORMONE TRANSCRIPTION; MYOMETRIAL CELLS; LACTATING RATS
AB The major regulator of the neuroendocrine stress response in the brain is corticotropin releasing factor (CRF), whose transcription is controlled by CREB and its cofactors CRTC2/3 (TORC2/3). Phosphorylated CRTCs are sequestered in the cytoplasm, but rapidly dephosphorylated and translocated into the nucleus following a stressful stimulus. As the stress response is attenuated by oxytocin (OT), we tested whether OT interferes with CRTC translocation and, thereby, Crf expression. OT(1 nmol, i.c.v.) delayed the stress-induced increase of nuclear CRTC3 and Crf hnRNA levels in the paraventricular nucleus of male rats and mice, but did not affect either parameter in the absence of the stressor. The increase in Crf hnRNA levels at later time points was parallel to elevated nuclear CRTC2/3 levels. A direct effect of Thr(4) Gly(7)-OT (TGOT) on CRTC3 translocation and Crf expression was found in rat primary hypothalamic neurons, amygdaloid (Ar-5), hypothalamic (H32), and human neuroblastoma (Be(2)M17) cell lines. CRTC3, but not CRCT2, knockdown using siRNA in Be(2)M17 cells prevented the effect of TGOT on Crf hnRNA levels. Chromatin-immunoprecipitation demonstrated that TGOT reduced CRTC3, but not CRTC2, binding to the Crf promoter after 10 min of forskolin stimulation. Together, the results indicate that OT modulates CRTC3 translocation, the binding of CRTC3 to the Crf promoter and, ultimately, transcription of the Crf gene.
C1 [Jurek, Benjamin; Slattery, David A.; Neumann, Inga D.; van den Burg, Erwin H.] Univ Regensburg, Dept Behav & Mol Neurobiol, D-93040 Regensburg, Germany.
   [Hiraoka, Yuichi; Nishimori, Katsuhiko] Tohoku Univ, Grad Sch Agr Sci, Mol Biol Lab, Aoba Ku, Sendai, Miyagi 9818555, Japan.
   [Liu, Ying; Aguilera, Greti] Eunice Kennedy Shriver Inst Child Hlth & Human De, Sect Endocrine Physiol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Neumann, ID (reprint author), Univ Regensburg, D-93040 Regensburg, Germany.
EM inga.neumann@biologie.uni-regensburg.de
FU German Research Foundation; Boehringer Ingelheim Foundation; Intramural
   Research Program, NICHD; SRPBS, Japan (MEXT)
FX This work was supported by the German Research Foundation (I.D.N.,
   E.v.d.B.), the Boehringer Ingelheim Foundation (B.J.), the Intramural
   Research Program, NICHD (G.A.), and SRPBS, Japan (MEXT; Y.H., K.N.). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the paper.
NR 70
TC 9
Z9 10
U1 2
U2 8
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 SEP 2
PY 2015
VL 35
IS 35
BP 12248
EP 12260
DI 10.1523/JNEUROSCI.1345-14.2015
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CU6QY
UT WOS:000363658900017
PM 26338335
ER

PT J
AU Reiter, S
   Rodriguez, CC
   Sun, K
   Stopfer, M
AF Reiter, Sam
   Rodriguez, Chelsey Campillo
   Sun, Kui
   Stopfer, Mark
TI Spatiotemporal Coding of Individual Chemicals by the Gustatory System
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE neural coding; taste
ID MOTH HELIOTHIS-VIRESCENS; BITTER TASTE STIMULI; MANDUCA-SEXTA;
   DROSOPHILA-MELANOGASTER; RECEPTOR; NEURONS; LEPIDOPTERA; QUALITY;
   INSECT; CELLS
AB Four of the five major sensory systems (vision, olfaction, somatosensation, and audition) are thought to use different but partially overlapping sets of neurons to form unique representations of vast numbers of stimuli. The only exception is gustation, which is thought to represent only small numbers of basic taste categories. However, using new methods for delivering tastant chemicals and making electrophysiological recordings from the tractable gustatory system of the moth Manduca sexta, we found chemical-specific information is as follows: (1) initially encoded in the population of gustatory receptor neurons as broadly distributed spatiotemporal patterns of activity; (2) dramatically integrated and temporally transformed as it propagates to monosynaptically connected second-order neurons; and (3) observed in tastant-specific behavior. Our results are consistent with an emerging view of the gustatory system: rather than constructing basic taste categories, it uses a spatiotemporal population code to generate unique neural representations of individual tastant chemicals.
C1 [Reiter, Sam; Rodriguez, Chelsey Campillo; Sun, Kui; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA.
   [Reiter, Sam] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
RP Stopfer, M (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA.
EM stopferm@mail.nih.gov
FU National Institute of Child Health and Human Development, National
   Institutes of Health Intramural Grant
FX This work was supported by National Institute of Child Health and Human
   Development, National Institutes of Health Intramural Grant to M.S.
   Light microscopy was performed at the Microscopy and Imaging Core,
   National Institute of Child Health and Human Development, with the
   assistance of V. Schram. Scanning electron microscopy was performed at
   the Electron Microscopy Core Facility, National Heart, Lung, and Blood
   Institute, with the assistance of P.M. Zerfas and C.A. Brantner. We
   thank G. Dold and T. Talbot of the National Institute of Mental Health
   Instrumentation Core Facility for assistance with designing the tastant
   delivery system; J. McFarland for assistance with data analysis; and G.
   Barnea, L. Belluscio, D. Berson, C.-H. Lee, C. McBain, D. Rinberg, and
   the members of the Stopfer laboratory for helpful discussions.
NR 73
TC 5
Z9 5
U1 9
U2 25
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 SEP 2
PY 2015
VL 35
IS 35
BP 12309
EP 12321
DI 10.1523/JNEUROSCI.3802-14.2015
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CU6QY
UT WOS:000363658900023
PM 26338341
ER

PT J
AU Buhnerkempe, MG
   Gostic, K
   Park, M
   Ahsan, P
   Belser, JA
   Lloyd-Smith, JO
AF Buhnerkempe, Michael G.
   Gostic, Katelyn
   Park, Miran
   Ahsan, Prianna
   Belser, Jessica A.
   Lloyd-Smith, James O.
TI Mapping influenza transmission in the ferret model to transmission in
   humans
SO ELIFE
LA English
DT Article
ID A H7N9 VIRUS; AIRBORNE TRANSMISSION; RECEPTOR SPECIFICITY; A/H5N1 VIRUS;
   OSELTAMIVIR; RESISTANT; INFECTION; PATHOGENESIS; ADAPTATION; HOUSEHOLD
AB The controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. However, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. We address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. We demonstrate that estimates of ferret secondary attack rate (SAR) explain 66% of the variation in human SAR estimates at the subtype level. Further analysis shows that ferret transmission experiments have potential to identify influenza viruses of concern for epidemic spread in humans, though small sample sizes and biological uncertainties prevent definitive classification of human transmissibility. Thus, ferret transmission experiments provide valid predictions of pandemic potential of novel influenza strains, though results should continue to be corroborated by targeted virological and epidemiological research.
C1 [Buhnerkempe, Michael G.; Gostic, Katelyn; Park, Miran; Ahsan, Prianna; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Buhnerkempe, Michael G.; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Belser, Jessica A.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Buhnerkempe, MG (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
EM michael.buhnerkempe@ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU National Institutes of Health (NIH)/Fogarty International Center (FIC)
   Research and Policy for Infectious Disease Dynamics (RAPIDD); National
   Institutes of Health (NIH) [T32-GM008185]; National Science Foundation
   (NSF) [DGE-1144087, EF-0928690]; University of California, Los Angeles
   (UCLA)
FX National Institutes of Health (NIH)/Fogarty International Center (FIC)
   Research and Policy for Infectious Disease Dynamics (RAPIDD) Michael G
   Buhnerkempe, James O Lloyd-Smith; National Institutes of Health (NIH)
   Ruth L. Kirschstein National Research Service Award (T32-GM008185)
   Katelyn Gostic; National Science Foundation (NSF) DGE-1144087 Miran
   Park; National Science Foundation (NSF) EF-0928690 James O Lloyd-Smith;
   University of California, Los Angeles (UCLA) De Logi Chair in Biological
   Sciences James O Lloyd-Smith
NR 56
TC 8
Z9 8
U1 2
U2 9
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD SEP 2
PY 2015
VL 4
AR e07969
DI 10.7554/eLife.07969
PG 15
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CS5GM
UT WOS:000362105700001
ER

PT J
AU Song, JB
   Yang, XY
   Jacobson, O
   Huang, P
   Sun, XL
   Lin, LS
   Yan, XF
   Niu, G
   Ma, QJ
   Chen, X
AF Song, Jibin
   Yang, Xiangyu
   Jacobson, Orit
   Huang, Peng
   Sun, Xiaolian
   Lin, Lisen
   Yan, Xuefeng
   Niu, Gang
   Ma, Qingjie
   Chen, Xiaoyuan
TI Ultrasmall Gold Nanorod Vesicles with Enhanced Tumor Accumulation and
   Fast Excretion from the Body for Cancer Therapy
SO ADVANCED MATERIALS
LA English
DT Article
DE biodegradation; nanovesicles; photoacoustic imaging; photothermal
   effects; ultrasmall gold nanorods
ID NEAR-INFRARED LIGHT; DRUG-DELIVERY; PHOTOTHERMAL THERAPY; PLASMONIC
   VESICLES; NANOPARTICLES; RELEASE; NANOMATERIALS; PERSPECTIVES;
   PERFORMANCE; STABILITY
AB A new kind of ultrasmall dissociable AuNR@PEG/PLGA vesicles (approximate to 60 nm) (AuNR = gold nanorod; PEG = poly(ethylene glycol); PLGA = poly(lactic-co-glycolic acid)) assembled from small AuNRs (dimension: approximate to 8 nm x 2 nm) is reported. They exhibit several striking features: prolonged circulation and prominent tumor accumulation; rapid excretion from the body as AuNR@PEG after therapy; enhanced photoacoustic and photo thermal properties; and high photothermal cancer therapy efficacy.
C1 [Song, Jibin; Ma, Qingjie] Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China.
   [Song, Jibin; Yang, Xiangyu; Jacobson, Orit; Huang, Peng; Sun, Xiaolian; Lin, Lisen; Yan, Xuefeng; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Ma, QJ (reprint author), Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China.
EM maqingjiejlu@163.com; shawn.chen@nih.gov
RI Huang, Peng/R-2480-2016
OI Huang, Peng/0000-0003-3651-7813
FU China-Japan Union Hospital of Jilin University; National Institute of
   Biomedical Imaging and Bioengineering (NIBIB); National Institutes of
   Health (NIH)
FX This work was supported by a research program of China-Japan Union
   Hospital of Jilin University and intramural research program of the
   National Institute of Biomedical Imaging and Bioengineering (NIBIB) and
   National Institutes of Health (NIH).
NR 50
TC 32
Z9 32
U1 39
U2 224
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0935-9648
EI 1521-4095
J9 ADV MATER
JI Adv. Mater.
PD SEP 2
PY 2015
VL 27
IS 33
BP 4910
EP 4917
DI 10.1002/adma.201502486
PG 8
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
   Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
   Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
   Physics
GA CQ6NQ
UT WOS:000360721600015
PM 26198622
ER

PT J
AU Al-Hasani, R
   McCall, JG
   Shin, G
   Gomez, AM
   Schmitz, GP
   Bernardi, JM
   Pyo, CO
   Park, SI
   Marcinkiewcz, CM
   Crowley, NA
   Krashes, MJ
   Lowell, BB
   Kash, TL
   Rogers, JA
   Bruchas, MR
AF Al-Hasani, Ream
   McCall, Jordan G.
   Shin, Gunchul
   Gomez, Adrian M.
   Schmitz, Gavin P.
   Bernardi, Julio M.
   Pyo, Chang-O.
   Park, Sung Il
   Marcinkiewcz, Catherine M.
   Crowley, Nicole A.
   Krashes, Michael J.
   Lowell, Bradford B.
   Kash, Thomas L.
   Rogers, John A.
   Bruchas, Michael R.
TI Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive
   Aversion and Reward
SO NEURON
LA English
DT Article
ID KAPPA-OPIOID RECEPTORS; SUBSTANCE-P; MESSENGER-RNA; SEROTONERGIC
   NEURONS; VENTRAL PALLIDUM; DRUG-ADDICTION; BRAIN-REGIONS; RAT-BRAIN;
   STRESS; ACTIVATION
AB The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photo-stimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and realtime aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease.
C1 [Al-Hasani, Ream; McCall, Jordan G.; Gomez, Adrian M.; Schmitz, Gavin P.; Bruchas, Michael R.] Washington Univ, Sch Med, Div Biomed Engn, Div Basic Res Anat & Neurobiol,Dept Anesthesiol, St Louis, MO 63110 USA.
   [Al-Hasani, Ream; McCall, Jordan G.; Gomez, Adrian M.; Schmitz, Gavin P.; Bruchas, Michael R.] Washington Univ, Sch Med, Pain Ctr, St Louis, MO 63110 USA.
   [Shin, Gunchul; Park, Sung Il; Rogers, John A.] Univ Illinois, Frederick Seitz Mat Res Lab, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
   [Bernardi, Julio M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
   [Pyo, Chang-O.; Rogers, John A.] Univ Illinois, Frederick Seitz Mat Res Lab, Dept Elect & Comp Engn, Urbana, IL 61801 USA.
   [Marcinkiewcz, Catherine M.; Crowley, Nicole A.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27516 USA.
   [Marcinkiewcz, Catherine M.; Crowley, Nicole A.] Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27516 USA.
   [Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
   [Krashes, Michael J.] NIDA, NIH, Baltimore, MD USA.
   [Krashes, Michael J.; Lowell, Bradford B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol,Dept Med, Boston, MA 02115 USA.
   [McCall, Jordan G.; Bruchas, Michael R.] Washington Univ, Sch Med, Div Biol & Biomed Sci, St Louis, MO 63110 USA.
RP Al-Hasani, R (reprint author), Washington Univ, Sch Med, Div Biomed Engn, Div Basic Res Anat & Neurobiol,Dept Anesthesiol, St Louis, MO 63110 USA.
EM alhasanir@morpheus.wustl.edu; bruchasm@wustl.edu
RI Rogers, John /L-2798-2016
FU NIDA [R01 DA033396, R01DA037152, K99/R00, DA038725]; NIMH [F31 MH101956,
   TR01NS081707, R01DK075632, R37DK053477, R01DK089044, R01DK071051,
   R01DK096010, P30DK046200]
FX We thank all of the Bruchas Laboratory for their helpful insight and
   discussion throughout the preparation of the manuscript. In particular,
   Edward Siuda for his advice with ELISA analysis. William Planer, Audra
   Foshage, and Lamley Lawson for their technical support. We thank Bryan
   Copits in Professor Gereau's laboratory for his technical assistance and
   advice in the collection of the peptide release data. We also thank the
   HOPE Center viral vector core (NINDS, P30NS057105) and Alafi
   Neuroimaging Lab (NIH, S10RR027552). This work is supported by NIDA R01
   DA033396 (M.R.B.), R01DA037152 (M.R.B.), NIDA K99/R00 Pathway to
   Independence Award DA038725 (R.A.-H.), NIMH F31 MH101956 (J.G.M.),
   TR01NS081707 (M.R.B. and J.A.R.) and R01DK075632 (B.B.L.), R37DK053477
   (B.B.L.), R01DK089044 (B.B.L.), R01DK071051 (B.B.L.), R01DK096010
   (B.B.L.), and P30DK046200 (B.B.L.).
NR 61
TC 29
Z9 29
U1 6
U2 20
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 SEP 2
PY 2015
VL 87
IS 5
BP 1063
EP 1077
DI 10.1016/j.neuron.2015.08.019
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA CR2GZ
UT WOS:000361146300016
PM 26335648
ER

PT J
AU Grady, C
   Eckstein, L
   Berkman, B
   Brock, D
   Cook-Deegan, R
   Fullerton, SM
   Greely, H
   Hansson, MG
   Hull, S
   Kim, S
   Lo, B
   Pentz, R
   Rodriguez, L
   Weil, C
   Wilfond, BS
   Wendler, D
AF Grady, Christine
   Eckstein, Lisa
   Berkman, Ben
   Brock, Dan
   Cook-Deegan, Robert
   Fullerton, Stephanie M.
   Greely, Hank
   Hansson, Mats G.
   Hull, Sara
   Kim, Scott
   Lo, Bernie
   Pentz, Rebecca
   Rodriguez, Laura
   Weil, Carol
   Wilfond, Benjamin S.
   Wendler, David
TI Broad Consent for Research With Biological Samples: Workshop Conclusions
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Article
DE biomedical research; informed consent; regulatory issues; research
   ethics
ID GENETIC RESEARCH; RESEARCH PARTICIPANTS; INFORMED-CONSENT;
   PUBLIC-ATTITUDES; BIOBANK RESEARCH; OPT-OUT; POPULATION; DONORS;
   PERSPECTIVES; HEPATITIS
AB Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The National Institutes of Health (NIH) Clinical Center's Department of Bioethics held a workshop to consider the ethical acceptability of addressing these concerns by using broad consent for future research on stored biospecimens. Multiple bioethics scholars, who have written on these issues, discussed the reasons for consent, the range of consent strategies, and gaps in our understanding, and concluded with a proposal for broad initial consent coupled with oversight and, when feasible, ongoing provision of information to donors. This article describes areas of agreement and areas that need more research and dialogue. Given recent proposed changes to the Common Rule, and new guidance regarding storing and sharing data and samples, this is an important and timely topic.
C1 [Grady, Christine; Hull, Sara; Kim, Scott; Wendler, David] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
   [Eckstein, Lisa] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia.
   [Berkman, Ben] NHGRI, Bethesda, MD USA.
   [Brock, Dan] Harvard Univ, Sch Med, Dept Social Med, Div Med Eth, Cambridge, MA 02138 USA.
   [Cook-Deegan, Robert] Duke Inst Genome Sci & Policy, Durham, NC USA.
   [Fullerton, Stephanie M.] Univ Washington, Sch Med, Genome Eth Law & Policy, Seattle, WA 98195 USA.
   [Greely, Hank] Stanford Law Sch, Crown Quadrangle, Stanford, CA USA.
   [Hansson, Mats G.] Uppsala Univ, Uppsala, Sweden.
   [Hull, Sara] NHGRI, Bioeth Core, Bethesda, MD USA.
   [Lo, Bernie] Greenwall Fdn, New York, NY USA.
   [Pentz, Rebecca] Emory Univ, Ctr Eth, Winship Canc Inst, Atlanta, GA 30322 USA.
   [Rodriguez, Laura] NHGRI, Div Policy Commun & Educ, Bethesda, MD USA.
   [Weil, Carol] NCI, Canc Diag Program, Bethesda, MD 20892 USA.
   [Wilfond, Benjamin S.] Seattle Childrens Hosp, Seattle, WA USA.
RP Grady, C (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118,10 Ctr Dr, Bethesda, MD 20892 USA.
EM cgrady@nih.gov; Lisa.Eckstein@utas.edu.au; berkmanbe@mail.nih.gov;
   dan_brock@hms.harvard.edu; bob.cd@duke.edu; smfllrtn@u.washington.edu;
   hgreely@stanford.edu; mats.hansson@cbg.uu.se; shull@mail.nih.gov;
   scott.kim@nih.gov; bernardlo@greenwall.org; rpentz@emory.edu;
   rodrigla@mail.nih.gov; weilcj@mail.nih.gov;
   benjamin.wilfond@seattlechildrens.org; DWendler@cc.nih.gov
RI Eckstein, Lisa/J-7747-2014; 
OI Eckstein, Lisa/0000-0002-7161-7521; Cook-Deegan,
   Robert/0000-0002-8251-4237
FU NIH CC Department of Bioethics
FX The workshop was funded by the NIH CC Department of Bioethics
NR 41
TC 45
Z9 45
U1 3
U2 18
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD SEP 2
PY 2015
VL 15
IS 9
BP 34
EP 42
DI 10.1080/15265161.2015.1062162
PG 9
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
   Biomedical Social Sciences
GA CQ4DY
UT WOS:000360555700011
PM 26305750
ER

PT J
AU Gunzburg, MJ
   Sivakumaran, A
   Pendini, NR
   Yoon, JH
   Gorospe, M
   Wilce, MCJ
   Wilce, JA
AF Gunzburg, Menachem J.
   Sivakumaran, Andrew
   Pendini, Nicole R.
   Yoon, Je-Hyun
   Gorospe, Myriam
   Wilce, Matthew C. J.
   Wilce, Jacqueline A.
TI Cooperative interplay of let-7 mimic and HuR with MYC RNA
SO CELL CYCLE
LA English
DT Article
DE cooperative binding; c-Myc; HuR; let-7; miRNA; mRNA; RNA-binding protein
   (RBP); surface plasmon resonance (SPR); translational repression; 3
   '-UTR
ID BINDING PROTEIN HUR; MESSENGER-RNA; STABILITY; TRANSLATION; MICRORNAS;
   AUF1
AB Both RNA-binding proteins (RBP) and miRNA play important roles in the regulation of mRNA expression, often acting together to regulate a target mRNA. In some cases the RBP and miRNA have been reported to act competitively, but in other instances they function cooperatively. Here, we investigated HuR function as an enhancer of let-7-mediated translational repression of c-Myc despite the separation of their binding sites. Using an in vitro system, we determined that a let-7 mimic, consisting of single-stranded (ss)DNA complementary to the let-7 binding site, enhanced the affinity of HuR for a 122-nt MYC RNA encompassing both binding sites. This finding supports the biophysical principle of cooperative binding by an RBP and miRNA purely through interactions at distal mRNA binding sites.
C1 [Gunzburg, Menachem J.; Sivakumaran, Andrew; Pendini, Nicole R.; Wilce, Matthew C. J.; Wilce, Jacqueline A.] Monash Univ, Biochem & Mol Biol, Melbourne, Vic 3004, Australia.
   [Yoon, Je-Hyun; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wilce, JA (reprint author), Monash Univ, Biochem & Mol Biol, Melbourne, Vic 3004, Australia.
EM jackie.wilce@monash.edu
OI Wilce, Jacqueline/0000-0002-8344-2626
FU Australian Research Council (ARC); National Health and Medical Research
   Council (NHMRC); National Institute on Aging-Intramural Research Program
   of the National Institutes of Health
FX The current study was funded by an Australian Research Council (ARC)
   Discovery Grant awarded to MCJW, JAW, and MG, and also through a
   National Health and Medical Research Council (NHMRC) Senior Research
   Fellowship awarded to MCJW. JY and MG were supported by the National
   Institute on Aging-Intramural Research Program of the National
   Institutes of Health.
NR 18
TC 3
Z9 3
U1 2
U2 7
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
PD SEP 2
PY 2015
VL 14
IS 17
BP 2729
EP 2733
DI 10.1080/15384101.2015.1069930
PG 5
WC Cell Biology
SC Cell Biology
GA CQ4GB
UT WOS:000360561300009
PM 26177105
ER

PT J
AU Ryu, H
   Yoshida, MM
   Sridharan, V
   Kumagai, A
   Dunphy, WG
   Dasso, M
   Azuma, Y
AF Ryu, Hyunju
   Yoshida, Makoto M.
   Sridharan, Vinidhra
   Kumagai, Akiko
   Dunphy, William G.
   Dasso, Mary
   Azuma, Yoshiaki
TI SUMOylation of the C-terminal domain of DNA topoisomerase II alpha
   regulates the centromeric localization of Claspin
SO CELL CYCLE
LA English
DT Article
DE centromere; Claspin; mitosis; SUMO; topoisomerase II
ID XENOPUS EGG EXTRACTS; REPLICATION CHECKPOINT RESPONSE; CHROMATID
   SEPARATION; MITOTIC CHROMOSOMES; MAMMALIAN-CELLS; CONJUGATION; MITOSIS;
   SUMO; ANAPHASE; BINDING
AB DNA topoisomerase II (TopoII) regulates DNA topology by its strand passaging reaction, which is required for genome maintenance by resolving tangled genomic DNA. In addition, TopoII contributes to the structural integrity of mitotic chromosomes and to the activation of cell cycle checkpoints in mitosis. Post-translational modification of TopoII is one of the key mechanisms by which its broad functions are regulated during mitosis. SUMOylation of TopoII is conserved in eukaryotes and plays a critical role in chromosome segregation. Using Xenopus laevis egg extract, we demonstrated previously that TopoII is modified by SUMO on mitotic chromosomes and that its activity is modulated via SUMOylation of its lysine at 660. However, both biochemical and genetic analyses indicated that TopoII has multiple SUMOylation sites in addition to Lys660, and the functions of the other SUMOylation sites were not clearly determined. In this study, we identified the SUMOylation sites on the C-terminal domain (CTD) of TopoII. CTD SUMOylation did not affect TopoII activity, indicating that its function is distinct from that of Lys660 SUMOylation. We found that CTD SUMOylation promotes protein binding and that Claspin, a well-established cell cycle checkpoint mediator, is one of the SUMOylation-dependent binding proteins. Claspin harbors 2 SUMO-interacting motifs (SIMs), and its robust association to mitotic chromosomes requires both the SIMs and TopoII-CTD SUMOylation. Claspin localizes to the mitotic centromeres depending on mitotic SUMOylation, suggesting that TopoII-CTD SUMOylation regulates the centromeric localization of Claspin. Our findings provide a novel mechanistic insight regarding how TopoII-CTD SUMOylation contributes to mitotic centromere activity.
C1 [Ryu, Hyunju; Yoshida, Makoto M.; Sridharan, Vinidhra; Azuma, Yoshiaki] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
   [Ryu, Hyunju; Dasso, Mary] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD USA.
   [Kumagai, Akiko; Dunphy, William G.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
RP Azuma, Y (reprint author), Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
EM azumay@ku.edu
FU NIH/NIGMS [GM80278, GM043974, GM070891]; University of Kansas; NICHD
   [HD001902]
FX This project was supported by NIH/NIGMS, GM80278 and by bridge funding
   from the University of Kansas. W.G. Dunphy and A. Kumagai are supported
   by NIH/NIGMS (GM043974 and GM070891). M. Dasso is supported by NICHD
   (project no. HD001902).
NR 42
TC 5
Z9 5
U1 0
U2 3
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
PD SEP 2
PY 2015
VL 14
IS 17
BP 2777
EP 2784
DI 10.1080/15384101.2015.1066537
PG 8
WC Cell Biology
SC Cell Biology
GA CQ4GB
UT WOS:000360561300014
PM 26131587
ER

PT J
AU Gao, W
   Kim, H
   Ho, M
AF Gao, Wei
   Kim, Heungnam
   Ho, Mitchell
TI Human Monoclonal Antibody Targeting the Heparan Sulfate Chains of
   Glypican-3 Inhibits HGF-Mediated Migration and Motility of
   Hepatocellular Carcinoma Cells
SO PLOS ONE
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; LIVER-REGENERATION; POOR-PROGNOSIS;
   TUMOR-GROWTH; EXPRESSION; MET; CANCER; ANGIOGENESIS; METASTASIS; PI-88
AB Heparan sulfate proteoglycans (HSPGs) participate in many processes related to tumor development, including tumorigenesis and metastasis. HSPGs contain one or more heparan sulfate (HS) chains that are covalently linked to a core protein. Glypican-3 (GPC3) is a cell surface-associated HSPG that is highly expressed in hepatocellular carcinoma (HCC). GPC3 is involved in Wnt3a-dependent HCC cell proliferation. Our previous study reported that HS20, a human monoclonal antibody targeting the HS chains on GPC3, inhibited Wnt3a/beta-catenin activation. In the current study, we showed that the HS chains of GPC3 could mediate HCC cells' migration and motility. Knocking down GPC3 or targeting the HS chains by HS20 inhibited HCC cell migration and motility. However, HS20 had no effect on GPC3 knockdown cells or GPC3 negative cells. In addition, an antibody that recognizes the core protein of GPC3 did not change the rate of cell motility. HCC cell migration and motility did not respond to either canonical or non-canonical Wnt induction, but did increase under hepatocyte growth factor (HGF) treatment. HS20-treated HCC cells exhibited less ability for HGF-mediated migration and motility. Furthermore, HS20 inhibited in vitro HCC spheroid formation and liver tumor growth in mice. GPC3 interacted with HGF; however, a mutant GPC3 lacking the HS chain showed less interaction with HGF. Blocking the HS chains on GPC3 with HS20 reduced c-Met activation in HGF-treated HCC cells and 3D-cultured spheroids. Taken together, our study suggests that GPC3 is involved in HCC cell migration and motility through HS chain-mediated cooperation with the HGF/Met pathway, showing how HS targeting has potential therapeutic implications for liver cancer.
C1 [Gao, Wei; Kim, Heungnam; Ho, Mitchell] NCI, Antibody Therapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Ho, M (reprint author), NCI, Antibody Therapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
NR 46
TC 9
Z9 9
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 2
PY 2015
VL 10
IS 9
AR e0137664
DI 10.1371/journal.pone.0137664
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ4ZT
UT WOS:000360613800137
PM 26332121
ER

PT J
AU Huang, YD
   Follmann, D
   Nason, M
   Zhang, L
   Huang, Y
   Mehrotra, DV
   Moodie, Z
   Metch, B
   Janes, H
   Keefer, MC
   Churchyard, G
   Robb, ML
   Fast, PE
   Duerr, A
   McElrath, MJ
   Corey, L
   Mascola, JR
   Graham, BS
   Sobieszczyk, ME
   Kublin, JG
   Robertson, M
   Hammer, SM
   Gray, GE
   Buchbinder, SP
   Gilbert, PB
AF Huang, Yunda
   Follmann, Dean
   Nason, Martha
   Zhang, Lily
   Huang, Ying
   Mehrotra, Devan V.
   Moodie, Zoe
   Metch, Barbara
   Janes, Holly
   Keefer, Michael C.
   Churchyard, Gavin
   Robb, Merlin L.
   Fast, Patricia E.
   Duerr, Ann
   McElrath, M. Juliana
   Corey, Lawrence
   Mascola, John R.
   Graham, Barney S.
   Sobieszczyk, Magdalena E.
   Kublin, James G.
   Robertson, Michael
   Hammer, Scott M.
   Gray, Glenda E.
   Buchbinder, Susan P.
   Gilbert, Peter B.
TI Effect of rAd5-Vector HIV-1 Preventive Vaccines on HIV-1 Acquisition: A
   Participant-Level Meta-Analysis of Randomized Trials
SO PLOS ONE
LA English
DT Article
ID DNA CANDIDATE VACCINE; T-CELL RESPONSES; GAG/POL/NEF VACCINE;
   HEALTHY-ADULTS; IMMUNOGENICITY EVALUATION; HVTN 503/PHAMBILI; PHASE-1
   SAFETY; SOUTH-AFRICA; DOUBLE-BLIND; FOLLOW-UP
AB Background
   Three phase 2b, double-blind, placebo-controlled, randomized efficacy trials have tested recombinant Adenovirus serotype-5 (rAd5)-vector preventive HIV-1 vaccines: MRKAd5 HIV-1 gag/pol/nef in Step and Phambili, and DNA/rAd5 HIV-1 env/gag/pol in HVTN505. Due to efficacy futility observed at the first interim analysis in Step and HVTN505, participants of all three studies were unblinded to their vaccination assignments during the study but continued follow-up. Rigorous meta-analysis can provide crucial information to advise the future utility of rAd5-vector vaccines.
   Methods
   We included participant-level data from all three efficacy trials, and three Phase 1-2 trials evaluating the HVTN505 vaccine regimen. We predefined two co-primary analysis cohorts for assessing the vaccine effect on HIV-1 acquisition. The modified-intention-to-treat (MITT) cohort included all randomly assigned participants HIV-1 uninfected at study entry, who received at least the first vaccine/placebo, and the Ad5 cohort included MITT participants who received at least one dose of rAd5-HIV vaccine or rAd5-placebo. Multivariable Cox regression models were used to estimate hazard ratios (HRs) of HIV-1 infection (vaccine vs. placebo) and evaluate HR variation across vaccine regimens, time since vaccination, and subgroups using interaction tests.
   Findings
   Results are similar for the MITT and Ad5 cohorts; we summarize MITT cohort results. Pooled across the efficacy trials, over all follow-up time 403 (n = 224 vaccine; n = 179 placebo) of 6266 MITT participants acquired HIV-1, with a non-significantly higher incidence in vaccine recipients (HR 1.21, 95% CI 0.99-1.48, P = 0.06). The HRs significantly differed by vaccine regimen (interaction P = 0.03; MRKAd5 HR 1.41, 95% CI 1.11-1.78, P = 0.005 vs. DNA/rAd5 HR 0.88, 95% CI 0.61-1.26, P = 0.48). Results were similar when including the Phase 1-2 trials. Exploratory analyses based on the efficacy trials supported that the MRKAd5 vaccine-increased risk was concentrated in Ad5-positive or uncircumcised men early in follow-up, and in Ad5-negative or circumcised men later. Overall, MRKAd5 vaccine-increased risk was evident across subgroups except in circumcised Ad5-negative men (HR 0.97, 95% CI 0.58-1.63, P = 0.91); there was little evidence that the DNA/rAd5 vaccine, that was tested in this subgroup, increased risk (HR 0.88, 95% CI 0.61-1.26, P = 0.48). When restricting the analysis of Step and Phambili to follow-up time before unblinding, 114 (n = 65 vaccine; n = 49 placebo) of 3770 MITT participants acquired HIV-1, with a non-significantly higher incidence in MRKAd5 vaccine recipients (HR 1.30, 95% CI 0.89-1.14, P = 0.18).
   Interpretation and Significance
   The data support increased risk of HIV-1 infection by MRKAd5 over all follow-up time, but do not support increased risk of HIV-1 infection by DNA/rAd5. This study provides a rationale for including monitoring plans enabling detection of increased susceptibility to infection in HIV-1 at-risk populations.
C1 [Huang, Yunda; Zhang, Lily; Huang, Ying; Moodie, Zoe; Metch, Barbara; Janes, Holly; Duerr, Ann; McElrath, M. Juliana; Corey, Lawrence; Kublin, James G.; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
   [Follmann, Dean] NIAID, Bethesda, MD 20892 USA.
   [Follmann, Dean] NIH, Biostat Res Branch, Bethesda, MD 20892 USA.
   [Nason, Martha] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
   [Mehrotra, Devan V.] Merck Res Labs, N Wales, PA USA.
   [Keefer, Michael C.] Univ Rochester, Sch Med & Dent, Div Infect Dis, Rochester, NY USA.
   [Churchyard, Gavin] Aurum Inst Hlth Res, Johannesburg, South Africa.
   [Robb, Merlin L.] US Mil HIV Res Program, HJF HIV Program, Bethesda, MD USA.
   [Fast, Patricia E.] Int AIDS Vaccine Initiat, Res & Dev, New York, NY USA.
   [Mascola, John R.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
   [Graham, Barney S.] NIAID, Viral Pathogenesis Lab, Bethesda, MD 20892 USA.
   [Sobieszczyk, Magdalena E.; Hammer, Scott M.] Columbia Univ, Dept Med, Div Infect Dis, New York, NY USA.
   [Robertson, Michael] Merck, Infect Dis Clin Res, Philadelphia, PA USA.
   [Gray, Glenda E.] Univ Witwatersrand, Johannesburg, South Africa.
   [Buchbinder, Susan P.] San Francisco Dept Publ Hlth, Bridge HIV, San Francisco, CA USA.
RP Gilbert, PB (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
EM pgilbert@scharp.org
FU Division of AIDS; Vaccine Research Center, National Institute of Allergy
   and Infectious Diseases (NIAID), in the US National Institutes of Health
   (NIH); NIH-sponsored HIV Vaccine Trials Network (HVTN); Merck Research
   Laboratories (MRL); NIAID [HVTN505, HVTN204]; HVTN; US Department of
   Health and Human Services (USDHHS) [RV172]; US Military HIV Research
   Program; American people through the United States Agency for
   International Development (USAID) [IAVI001]
FX This meta-analysis was supported by the Division of AIDS and the Vaccine
   Research Center, National Institute of Allergy and Infectious Diseases
   (NIAID), in the US National Institutes of Health (NIH), and the
   NIH-sponsored HIV Vaccine Trials Network (HVTN). The Step and Phambili
   studies were supported by Merck Research Laboratories (MRL), NIAID and
   HVTN; the HVTN505 and HVTN204 studies were supported by NIAID and HVTN;
   the RV172 study was supported by the US Department of Health and Human
   Services (USDHHS), the US Military HIV Research Program and NIAID; and
   the IAVI001 study was made possible by the generous support of the
   American people through the United States Agency for International
   Development (USAID). The contents are the responsibility of the HVTN and
   MRL for Step and Phambili, of HVTN for HVTN505 and HVTN204, of USMHRP
   for RV172, and of IAVI for IAVI001, and do not necessarily reflect the
   views of NIAID, USDHHS, USAID or the United States Government. The
   funder provided support in the form of salaries for authors DVM and MR,
   but did not have any additional role in the study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript. The specific roles of these authors are articulated in the
   'author contributions' section.
NR 31
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SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 2
PY 2015
VL 10
IS 9
AR e0136626
DI 10.1371/journal.pone.0136626
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ4ZT
UT WOS:000360613800063
PM 26332672
ER

PT J
AU Matsui, K
   Adelsberger, JW
   Kemp, TJ
   Baseler, MW
   Ledgerwood, JE
   Pinto, LA
AF Matsui, Ken
   Adelsberger, Joseph W.
   Kemp, Troy J.
   Baseler, Michael W.
   Ledgerwood, Julie E.
   Pinto, Ligia A.
TI Circulating CXCR5(+)CD4(+) T Follicular-Like Helper Cell and Memory B
   Cell Responses to Human Papillomavirus Vaccines
SO PLOS ONE
LA English
DT Article
ID CXC CHEMOKINE RECEPTOR-5; IMMUNE-RESPONSES; TFH CELLS;
   ANTIBODY-RESPONSES; MONONUCLEAR-CELLS; BLOOD; VACCINATION; EXPRESSION;
   DISEASE; SUBSET
AB Through the interaction of T follicular helper (Tfh) cells and B cells, efficacious vaccines can generate high-affinity, pathogen-neutralizing antibodies, and memory B cells. Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1(+)ICOS(+), PD1(+)ICOS(-), or PD1(-)ICOS(-). We used these markers to identify different subsets of CXCR5(+)CD4(+) Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. In this small study, we used PBMC samples from 11 Gardasil recipients, and 8 Cervarix recipients from the Vaccine Research Center 902 Study to examine the induction of circulating Tfh-like cells and IgD-CD38(Hi)CD27(+) memory B cells by flow cytometry. PD1(+)ICOS(+) CXCR3(+)CCR6(-)CXCR5(+)CD4(+) (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not asmuch on D7 post-third vaccination. We also observed a trend toward increase in PD1(+)ICOS(+) CXCR3(-)CCR6(-)CXCR5(+)CD4(+) (Tfh2-like) cells for both vaccines, and PD1(+)ICOS(+) CXCR3(-)CCR6(+)CXCR5(+)CD4(+) (Tfh17-like) subset was induced by Cervarix post-first vaccination. There were alsominimal changes in the other cellular subsets. In addition, Cervarix recipients had more memory B cells post-first vaccination than did Gardasil recipients at D14 and D30. We found frequencies ofmemory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1(+)ICOS(+)Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. Our study showed that induction of circulating CXCR5(+)CD4(+) Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. However, further investigations should be extended to different cohorts with larger sample size to better understand the functions of these T cells, as well as their relationship with B cells and antibodies.
C1 [Matsui, Ken; Kemp, Troy J.; Pinto, Ligia A.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Human Papillomavirus HPV Immunol Lab, Frederick, MD 21702 USA.
   [Adelsberger, Joseph W.; Baseler, Michael W.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, AIDS Monitoring Lab, Clin Serv Program,Appl & Dev Directorate, Frederick, MD USA.
   [Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Pinto, LA (reprint author), Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Human Papillomavirus HPV Immunol Lab, Frederick, MD 21702 USA.
EM pintol@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, National Institutes of Health, under
   Contract No. HHSN261200800001E.
NR 44
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U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 2
PY 2015
VL 10
IS 9
AR e0137195
DI 10.1371/journal.pone.0137195
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ4ZT
UT WOS:000360613800108
PM 26333070
ER

PT J
AU Shah, J
   Mark, O
   Weltman, H
   Barcelo, N
   Lo, W
   Wronska, D
   Kakkilaya, S
   Rao, A
   Bhat, ST
   Sinha, R
   Omar, S
   O'bare, P
   Moro, M
   Gilman, RH
   Harris, N
AF Shah, Jyotsna
   Mark, Olivia
   Weltman, Helena
   Barcelo, Nicolas
   Lo, Wai
   Wronska, Danuta
   Kakkilaya, Srinivas
   Rao, Aravinda
   Bhat, Shalia T.
   Sinha, Ruchi
   Omar, Sabah
   O'bare, Peter
   Moro, Manuel
   Gilman, Robert H.
   Harris, Nick
TI Fluorescence In Situ Hybridization (FISH) Assays for Diagnosing Malaria
   in Endemic Areas
SO PLOS ONE
LA English
DT Article
ID NUCLEIC-ACID PROBES; MYCOBACTERIUM-TUBERCULOSIS; BLOOD SMEAR;
   IDENTIFICATION; SPECIMENS; CULTURE; PCR
AB Malaria is a responsible for approximately 600 thousand deaths worldwide every year. Appropriate and timely treatment of malaria can prevent deaths but is dependent on accurate and rapid diagnosis of the infection. Currently, microscopic examination of the Giemsa stained blood smears is the method of choice for diagnosing malaria. Although it has limited sensitivity and specificity in field conditions, it still remains the gold standard for the diagnosis of malaria. Here, we report the development of a fluorescence in situ hybridization (FISH) based method for detecting malaria infection in blood smears and describe the use of an LED light source that makes the method suitable for use in resource-limited malaria endemic countries. The Plasmodium Genus (P-Genus) FISH assay has a Plasmodium genus specific probe that detects all five species of Plasmodium known to cause the disease in humans. The P. falciparum (PF) FISH assay and P. vivax (PV) FISH assay detect and differentiate between P. falciparum and P. vivax respectively from other Plasmodium species. The FISH assays are more sensitive than Giemsa. The sensitivities of P-Genus, PF and PV FISH assays were found to be 98.2%, 94.5% and 98.3%, respectively compared to 89.9%, 83.3% and 87.9% for the detection of Plasmodium, P. falciparum and P. vivax by Giemsa staining respectively.
C1 [Shah, Jyotsna; Mark, Olivia; Weltman, Helena; Barcelo, Nicolas; Harris, Nick] ID FISH Technol Inc, Palo Alto, CA 94303 USA.
   [Shah, Jyotsna; Mark, Olivia; Weltman, Helena; Lo, Wai; Wronska, Danuta; Harris, Nick] IGeneX Inc, Palo Alto, CA USA.
   [Kakkilaya, Srinivas; Rao, Aravinda] Nova Meditech Pvt Ltd, Mangalore, India.
   [Bhat, Shalia T.; Sinha, Ruchi] Kasturba Med Coll Hosp, Mangalore, India.
   [Omar, Sabah] Kenya Govt Med Res Ctr, Nairobi, Kenya.
   [O'bare, Peter] Walter Reed Project, Kisumu, Kenya.
   [Moro, Manuel] NIH, Bethesda, MD 20892 USA.
   [Gilman, Robert H.] Johns Hopkins Univ, Baltimore, MD USA.
RP Shah, J (reprint author), ID FISH Technol Inc, Palo Alto, CA 94303 USA.
EM jyotsna@aol.com
FU NIH SBIR Phase I and Phase II Grants [A1056785]; ID-FISH Technology
   Inc.; IGeneX Inc.; Nova Meditech Pvt. Ltd.
FX This study was supported by NIH SBIR Phase I and Phase II Grants #
   A1056785. ID-FISH Technology Inc.' and 'IGeneX Inc.' provided support in
   the form of salaries for authors HW, DW and OM and Nova Meditech Pvt.
   Ltd. provided support in the form of salaries for authors AR and SK but
   did not have any additional role in the study design, data collection
   and analysis, decision to publish, or preparation of the manuscript. The
   specific roles of these authors are articulated in the 'author
   contributions' section.
NR 28
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 2
PY 2015
VL 10
IS 9
AR e0136726
DI 10.1371/journal.pone.0136726
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ4ZT
UT WOS:000360613800068
PM 26333092
ER

PT J
AU Smith, CL
   Pivovarova, N
   Reese, TS
AF Smith, Carolyn L.
   Pivovarova, Natalia
   Reese, Thomas S.
TI Coordinated Feeding Behavior in Trichoplax, an Animal without Synapses
SO PLOS ONE
LA English
DT Article
ID RHABDOCALYPTUS-DAWSONI LAMBE; HEXACTINELLID SPONGES; ADHAERENS PLACOZOA;
   FIBER CELLS; GENOME; EVOLUTION; DICKINSONIA; SYSTEMS
AB Trichoplax is a small disk-shaped marine metazoan that adheres to substrates and locomotes by ciliary gliding. Despite having only six cell types and lacking synapses Trichoplax coordinates a complex sequence of behaviors culminating in external digestion of algae. We combine live cell imaging with electron microscopy to show how this is accomplished. When Trichoplax glides over a patch of algae, its cilia stop beating so it ceases moving. A subset of one of the cell types, lipophils, simultaneously secretes granules whose content rapidly lyses algae. This secretion is accurately targeted, as only lipophils located near algae release granules. The animal pauses while the algal content is ingested, and then resumes gliding. Global control of gliding is coordinated with precise local control of lipophil secretion suggesting the presence of mechanisms for cellular communication and integration.
C1 [Smith, Carolyn L.; Pivovarova, Natalia; Reese, Thomas S.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Smith, CL (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM smithca@ninds.nih.gov
FU National Institutes of Neurological Diseases and Stroke, National
   Institutes of Health
FX This work was supported by the National Institutes of Neurological
   Diseases and Stroke, National Institutes of Health.
NR 37
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U1 5
U2 16
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 SEP 2
PY 2015
VL 10
IS 9
AR e0136098
DI 10.1371/journal.pone.0136098
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CQ4ZT
UT WOS:000360613800049
PM 26333190
ER

PT J
AU Li, Q
   Kappil, MA
   Li, A
   Dassanayake, PS
   Darrah, TH
   Friedman, AE
   Friedman, M
   Lambertini, L
   Landrigan, P
   Stodgell, CJ
   Xia, YL
   Nanes, JA
   Aagaard, KM
   Schadt, EE
   Murray, JC
   Clark, EB
   Dole, N
   Culhane, J
   Swanson, J
   Varner, M
   Moye, J
   Kasten, C
   Miller, RK
   Chen, J
AF Li, Qian
   Kappil, Maya A.
   Li, An
   Dassanayake, Priyanthi S.
   Darrah, Thomas H.
   Friedman, Alan E.
   Friedman, Michelle
   Lambertini, Luca
   Landrigan, Philip
   Stodgell, Christopher J.
   Xia, Yulin
   Nanes, Jessica A.
   Aagaard, Kjersti M.
   Schadt, Eric E.
   Murray, Jeff C.
   Clark, Edward B.
   Dole, Nancy
   Culhane, Jennifer
   Swanson, James
   Varner, Michael
   Moye, Jack
   Kasten, Carol
   Miller, Richard K.
   Chen, Jia
TI Exploring the associations between microRNA expression profiles and
   environmental pollutants in human placenta from the National Children's
   Study (NCS)
SO EPIGENETICS
LA English
DT Article
DE environmental pollutants; placenta; birth cohort; microRNA; epigenetics
ID POLYBROMINATED DIPHENYL ETHERS; PERSISTENT ORGANIC POLLUTANTS;
   PREGNANT-WOMEN; LEAD-EXPOSURE; POLYCHLORINATED-BIPHENYLS; MERCURY
   EXPOSURE; IN-UTERO; BLOOD; CELLS; FISH
AB The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188-5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.
C1 [Li, Qian; Kappil, Maya A.; Lambertini, Luca; Landrigan, Philip; Chen, Jia] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
   [Li, Qian; Kappil, Maya A.; Lambertini, Luca; Landrigan, Philip; Chen, Jia] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA.
   [Li, Qian; Kappil, Maya A.; Lambertini, Luca; Landrigan, Philip; Chen, Jia] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA.
   [Li, Qian; Kappil, Maya A.; Lambertini, Luca; Landrigan, Philip; Chen, Jia] Icahn Sch Med Mt Sinai, Dept Obstet Gynecol & Reprod Sci, New York, NY 10029 USA.
   [Li, An; Dassanayake, Priyanthi S.; Xia, Yulin; Nanes, Jessica A.] Univ Illinois, Sch Publ Hlth, Chicago, IL USA.
   [Darrah, Thomas H.; Stodgell, Christopher J.; Miller, Richard K.] Ohio State Univ, Sch Earth Sci, Columbus, OH 43210 USA.
   [Stodgell, Christopher J.; Miller, Richard K.] Univ Rochester, Sch Med & Dent, Dept Obs Gyn, Rochester, NY USA.
   [Stodgell, Christopher J.; Miller, Richard K.] Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY USA.
   [Aagaard, Kjersti M.] Baylor Sch Med, Dept Obs Gyn, Houston, TX USA.
   [Schadt, Eric E.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci & Multiscale Biol, New York, NY 10029 USA.
   [Murray, Jeff C.] Univ Iowa, Dept Genet, Iowa City, IA USA.
   [Clark, Edward B.; Varner, Michael] Univ Utah, Dept Pediat & Obs Gyn, Salt Lake City, UT USA.
   [Dole, Nancy] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
   [Culhane, Jennifer] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Swanson, James] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA.
   [Moye, Jack] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
   [Kasten, Carol] US FDA, Div Pediat & Maternal Hlth, Silver Spring, MD USA.
RP Chen, J (reprint author), Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
EM jia.chen@mssm.edu
RI Darrah, Tom/I-2253-2016; Varner, Michael/K-9890-2013; 
OI Stodgell, Christopher/0000-0002-1666-5299; Varner,
   Michael/0000-0001-9455-3973; moye, john/0000-0001-9976-8586; ,
   Maya/0000-0003-2913-2392
FU National Children's Study Placenta Consortium (NCS formative research
   project) [LOI2-BIO-18]; Eunice Kennedy Shriver National Institute of
   Child Health and Human Development; Office of the Director of the
   National Institutes of Health; NICHD [HHSN267200700027C,
   HHSN275201100002C, HHSN275200503396C]
FX This work is part of the National Children's Study Placenta Consortium
   (NCS formative research project LOI2-BIO-18). This work was supported by
   the Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, and funded, through its appropriation, by the Office of the
   Director of the National Institutes of Health, with NICHD Contracts
   HHSN267200700027C, HHSN275201100002C, and HHSN275200503396C. The
   findings and conclusions in this report are those of the authors and do
   not necessarily represent the views of the National Institutes of Health
   or the US Department of Health and Human Services.
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PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1559-2294
EI 1559-2308
J9 EPIGENETICS-US
JI Epigenetics
PD SEP 2
PY 2015
VL 10
IS 9
BP 793
EP 802
DI 10.1080/15592294.2015.1066960
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CP9NW
UT WOS:000360222200003
PM 26252056
ER

PT J
AU Terashima, M
   Barbour, S
   Ren, JK
   Yu, WS
   Han, YX
   Muegge, K
AF Terashima, Minoru
   Barbour, Samantha
   Ren, Jianke
   Yu, Weishi
   Han, Yixing
   Muegge, Kathrin
TI Effect of high fat diet on paternal sperm histone distribution and male
   offspring liver gene expression
SO EPIGENETICS
LA English
DT Article
DE histone H; epigenetics; epigenetic inheritance, high fat diet; obesity;
   DNA methylation
ID DNA METHYLATION; TRANSGENERATIONAL INHERITANCE; SUBSEQUENT GENERATIONS;
   TRANSCRIPTION FACTOR; METALLOTHIONEIN-I; MOUSE SPERMATOZOA; INDUCED
   OBESITY; CHROMATIN; MICE; SEQUENCES
AB Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined 7 imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers vs. control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.
C1 [Terashima, Minoru; Barbour, Samantha; Ren, Jianke; Yu, Weishi; Han, Yixing; Muegge, Kathrin] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21701 USA.
   [Muegge, Kathrin] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab, Frederick, MD USA.
RP Muegge, K (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21701 USA.
EM Kathrin.Muegge@nih.gov
FU National Cancer Institute, National Institutes of Health
   [HHSN26120080001E]; Intramural Research Program of the NIH, National
   Cancer Institute, Center for Cancer Research; National Library of
   Medicine, NIH
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, National Institutes of Health, under
   contract 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. This
   Research was supported by the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research and the National
   Library of Medicine, NIH.
NR 66
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U2 30
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1559-2294
EI 1559-2308
J9 EPIGENETICS-US
JI Epigenetics
PD SEP 2
PY 2015
VL 10
IS 9
BP 861
EP 871
DI 10.1080/15592294.2015.1075691
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CP9NW
UT WOS:000360222200010
PM 26252449
ER

PT J
AU Nittala, MG
   Hariri, A
   Wong, WT
   Chew, EY
   Ferris, FL
   Sadda, SR
AF Nittala, Muneeswar G.
   Hariri, Amirhossein
   Wong, Wai T.
   Chew, Emily Y.
   Ferris, Frederick L.
   Sadda, Srinivas R.
TI Image Scaling Difference Between a Confocal Scanning Laser
   Ophthalmoscope and a Flash Fundus Camera
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID GEOGRAPHIC ATROPHY; MACULAR DEGENERATION; AUTOFLUORESCENCE
AB BACKGROUND AND OBJECTIVE: To evaluate scaling and measurement differences between flash and scanning laser fundus images.
   PATIENTS AND METHODS: The authors analyzed fundus autofluorescence images of patients with geographic atrophy secondary to age-related macular degeneration imaged with both 30(sic) confocal scanning laser ophthalmoscope (cSLO) and 50(sic) flash fundus camera (FFC). Multiple vessel-crossing points served as landmarks.
   RESULTS: The mean (+/- SD; range) scaling factor between cSLO and FFC images (by GRADOR) for the horizontal dimension was 1.217 (+/- 0.0487; 1.0474-1.272) versus 1.138 (+/- 0.0311; 1.0841-1.193) for the vertical dimension. The mean percentage difference between horizontal and vertical scaling factors was 7.48 (+/- 2.29; 2.30-10.70). Refractive error (focus) and aperture size (or field of view of the image) were positively correlated and aspect ratio was negatively correlated with landmark pair measurements.
   CONCLUSION: Inherent image-scaling differences between fundus autofluorescence imaging systems are not restricted to simple pixel-to-millimeter calibration variances, but appear to vary depending on measurement orientation. Differences should be considered when comparing measurements obtained using different imaging systems, particularly for clinical trials.
C1 [Nittala, Muneeswar G.; Hariri, Amirhossein; Sadda, Srinivas R.] Doheny Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA.
   [Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Wong, Wai T.; Chew, Emily Y.; Ferris, Frederick L.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
   [Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA.
RP Sadda, SR (reprint author), Doheny Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA.
EM ssadda@doheny.org
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU NEI [R01 EY014375]; NIH [EY0304]; Research to Prevent Blindness; DFG [He
   6094/1-1]; Optos plc; Carl Zeiss Meditec
FX Supported in part by NEI Grant R01 EY014375, NIH Grant EY0304, an
   unrestricted grant from Research to Prevent Blindness, and DFG Grant He
   6094/1-1.; Dr. Sadda is a consultant for and receives research support
   from Optos plc and Carl Zeiss Meditec. The remaining authors report no
   relevant financial disclosures.
NR 15
TC 0
Z9 0
U1 2
U2 3
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD SEP
PY 2015
VL 46
IS 8
BP 872
EP 879
DI 10.3928/23258160-20150909-13
PG 8
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA DP9UD
UT WOS:000378842000014
PM 26431304
ER

PT J
AU Keembiyehetty, C
AF Keembiyehetty, Chithra
TI Disruption of O-GlcNAc cycling by deletion of O-GlcNAcase (Oga/Mgea5)
   changed gene expression pattern in mouse embryonic fibroblast (MEF)
   cells
SO GENOMICS DATA
LA English
DT Article
ID TRANSFERASE
AB Adding a single O-GlcNAc moiety to a Ser/Thr molecule of a protein by O-GlcNAc transferase and transiently removing it by O-GlcNAcase is referred to as O-GlcNAc cycling (or O-GlcNAcylation). This O-GlcNAc modification is sensitive to nutrient availability and also shows cross talk with phosphorylation signaling, affecting downstream targets. A mouse model system was developed and evaluated to show genome wide transcriptional changes associated with disruption of O-GlcNAc cycling. Mouse embryonic fibroblast cells derived from O-GlcNAcase (Oga) knock out (KO), heterozygous (Het) and wild type (WT) embryos were used for an Affymetrix based microarray. Results are deposited in GEO dataset GSE52721. Data reveals that Oga KOMEFs had 2534 transcripts differentially expressed at 1.5 fold level while Oga heterozygous MEFs had 959 transcripts changed compared to WT MEFs. There were 1835 transcripts differentially expressed at 1.5 fold Het versus WT comparison group. Gene ontology analysis indicated differentially expressed genes enriched inmetabolic, growth, and cell proliferation categories. (C) 2015 The Author. Published by Elsevier Inc.
C1 [Keembiyehetty, Chithra] NIDDK, Genom Core Facil, NIH, Bethesda, MD 20892 USA.
RP Keembiyehetty, C (reprint author), NIDDK, Genom Core Facil, NIH, Bethesda, MD 20892 USA.
NR 7
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-5960
J9 GENOM DATA
JI Genom. Data
PD SEP
PY 2015
VL 5
BP 30
EP 33
DI 10.1016/j.gdata.2015.04.026
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA DO4MS
UT WOS:000377757800011
PM 26484218
ER

PT J
AU Scheidegger, A
   Burkholder, A
   Abbas, A
   Zarns, K
   Samarakkody, A
   Nechaev, S
AF Scheidegger, Adam
   Burkholder, Adam
   Abbas, Ata
   Zarns, Kris
   Samarakkody, Ann
   Nechaev, Sergei
TI Analysis of paired end Pol II ChIP-seq and short capped RNA-seq in MCF-7
   cells
SO GENOMICS DATA
LA English
DT Article
DE Pol II pausing; Paired end ChIP-sequencing; Short capped RNA
ID POLYMERASE-II; MAMMALIAN PROMOTERS; ALIGNMENT
AB While a role of promoter-proximal RNA Polymerase II (Pol II) pausing in regulation of eukaryotic gene expression is implied, the mechanisms and dynamics of this process are poorly understood. We performed genome-wide analysis of short capped RNAs (scRNAs) and Pol II chromatin immunoprecipitation sequencing (ChIP-seq) in human breast cancer MCF-7 cells to better understand Pol II pausing (Samarakkody, A., Abbas, A., Scheidegger, A., Warns, J., Nnoli, O., Jokinen, B., Zarns, K., Kubat, B., Dhasarathy, A. and Nechaev, S. (2015) RNA polymerase II pausing can be retained or acquired during activation of genes involved in the epithelial to mesenchymal transition. Nucleic Acids Res 43, 3938-3949). The data are available at the NCBI Gene Expression Omnibus under accession number GSE67041. For both ChIP and scRNA samples, we used paired end sequencing on the Illumina MiSeq instrument. For ChIP-seq, the use of paired end sequencing allowed us to avoid ambiguities in center-read definition. For scRNA seq, this allowed us to identify both the 5'-end and the 3'-end in the same run that represent, respectively, the transcription start sites and the locations of Pol II pausing. The sharpening of Pol II ChIP-seq metagene profiles when aligned against 5'-ends of scRNAs indicates that these RNAs can be used to define the start sites for the majority of mRNA transcription events. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Scheidegger, Adam; Abbas, Ata; Samarakkody, Ann; Nechaev, Sergei] Univ N Dakota, Dept Basic Sci, Sch Med, Grand Forks, ND 58202 USA.
   [Zarns, Kris] Univ N Dakota, Dept Comp Sci, Grand Forks, ND 58202 USA.
   [Burkholder, Adam] NIEHS, Ctr Integrat Bioinformat, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Nechaev, S (reprint author), Univ N Dakota, Dept Basic Sci, Sch Med, Grand Forks, ND 58202 USA.
EM sergei.nechaev@med.und.edu
OI Abbas, Ata/0000-0001-8272-1853; Nechaev, Sergei/0000-0002-0803-7188
FU NIGMS NIH HHS [P20 GM104360]
NR 14
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-5960
J9 GENOM DATA
JI Genom. Data
PD SEP
PY 2015
VL 5
BP 263
EP 267
DI 10.1016/j.gdata.2015.06.021
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA DO4MS
UT WOS:000377757800072
PM 26229744
ER

PT J
AU Nakato, G
   Hase, K
   Ohno, H
AF Nakato, Gaku
   Hase, Koji
   Ohno, Hiroshi
TI Distinct microRNA expression profiles in follicle-associated epithelium
   and villous epithelium
SO GENOMICS DATA
LA English
DT Article
DE MicroRNA; Peyer's patch; Follicle-associated epithelium; Villus
   epithelium; M cell
ID DIFFERENTIATION
AB M cells in follicle-associated epithelium(FAE) covering intestinal lymphoid follicles serve as a portal of entry for particulate antigens (Kanaya and Ohno, 2014 [1]). Despite their biological significance, molecular mechanisms that govern M-cell differentiation and function have not been fully elucidated. MicroRNAs (miRNAs) have a role to control host gene expression profiles that modulate cellular physiology and characteristic. Many studies have shown that miRNAs regulate diverse biological processes including developmental timing, differentiation and growth control of cells and tissues (Ivey and Srivastava, 2010 [2]). miRNAs are also relevant to differentiation and function of intestinal epithelium (McKenna et al., 2010 [3]; Runtsch et al., 2014 [4]). Expression profiles and functions of miRNAs in the intestinal epithelium have been examined in jejunal and colonic mucosa [3]. In contrast, those in FAE remain uncharacterized. To address this deficiency, we isolated Peyer's Patch (PP) FAE and villous epithelium (VE) surrounding the FAE, and compared the miRNA expression profiles of FAE and VE by microarray analysis. This revealed that 43 miRNAs were up-regulated, whereas 9 miRNAs were down-regulated, in FAE compared to VE. A unique pattern of miRNA expression by FAE may reflect important diversity in cellular phenotypes and/or functional features of FAE. All microarray data has been deposited at GEO under accession number GSE46264. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Nakato, Gaku; Hase, Koji; Ohno, Hiroshi] RIKEN Ctr Integrat Med Sci IMS, Lab Intestinal Ecosyst, 1-7-22 Suehiro, Tsurumi, Kanagawa 2300045, Japan.
   [Ohno, Hiroshi] Japan Agcy Med Res & Dev, AMED CREST, Tokyo, Japan.
   [Nakato, Gaku] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Hase, Koji] Keio Univ, Fac Pharm, Div Biochem, Tokyo, Japan.
RP Ohno, H (reprint author), RIKEN Ctr Integrat Med Sci IMS, Lab Intestinal Ecosyst, 1-7-22 Suehiro, Tsurumi, Kanagawa 2300045, Japan.
EM hiroshi.ohno@riken.jp
NR 5
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-5960
J9 GENOM DATA
JI Genom. Data
PD SEP
PY 2015
VL 5
BP 388
EP 390
DI 10.1016/j.gdata.2015.07.011
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA DO4MS
UT WOS:000377757800105
PM 26484293
ER

PT J
AU Corona-Villalobos, CP
   Kamel, IR
   Rastegar, N
   Damico, R
   Kolb, TM
   Boyce, DM
   Sager, AES
   Skrok, J
   Shehata, ML
   Vogel-Claussen, J
   Bluemke, DA
   Girgis, RE
   Mathai, SC
   Hassoun, PM
   Zimmerman, SL
AF Corona-Villalobos, Celia P.
   Kamel, Ihab R.
   Rastegar, Neda
   Damico, Rachel
   Kolb, Todd M.
   Boyce, Danielle M.
   Sager, Ala-Eddin S.
   Skrok, Jan
   Shehata, Monda L.
   Vogel-Claussen, Jens
   Bluemke, David A.
   Girgis, Reda E.
   Mathai, Stephen C.
   Hassoun, Paul M.
   Zimmerman, Stefan L.
TI Bidimensional measurements of right ventricular function for prediction
   of survival in patients with pulmonary hypertension: comparison of
   reproducibility and time of analysis with volumetric cardiac magnetic
   resonance imaging analysis
SO PULMONARY CIRCULATION
LA English
DT Article
DE pulmonary arterial hypertension; tricuspid annular plane systolic
   excursion (TAPSE); cardiac MRI; survival
ID PLANE SYSTOLIC EXCURSION; ARTERIAL-HYPERTENSION; ECHOCARDIOGRAPHY; MASS;
   HEMODYNAMICS; PRESSURE; MRI; QUANTIFICATION; DYSFUNCTION; DISEASE
AB We tested the hypothesis that bidimensional measurements of right ventricular (RV) function obtained by cardiac magnetic resonance imaging (CMR) in patients with pulmonary arterial hypertension (PAH) are faster than volumetric measures and highly reproducible, with comparable ability to predict patient survival. CMR-derived tricuspid annular plane systolic excursion (TAPSE), RV fractional shortening (RVFS), RV fractional area change (RVFAC), standard functional and volumetric measures, and ventricular mass index (VMI) were compared with right heart catheterization data. CMR analysis time was recorded. Receiver operating characteristic curves, Kaplan-Meier, Cox proportional hazard (CPH), and Bland-Altman test were used for analysis. Forty-nine subjects with PAH and 18 control subjects were included. TAPSE, RVFS, RVFAC, RV ejection fraction, and VMI correlated significantly with pulmonary vascular resistance and mean pulmonary artery pressure (all P < 0.05). Patients were followed up for a mean (+/- standard deviation) of 2.5 +/- 1.6 years. Kaplan-Meier curves showed that death was strongly associated with TAPSE < 18 mm, RVFS < 16.7%, and RVFAC < 18.8%. In CPH models with TAPSE as dichotomized at 18 mm, TAPSE was significantly associated with risk of death in both unadjusted and adjusted models (hazard ratio, 4.8; 95% confidence interval, 2.0-11.3; P = 0.005 for TAPSE < 18 mm). There was high intra- and interobserver agreement. Bidimensional measurements were faster (1.5 +/- 0.3 min) than volumetric measures (25 +/- 6 min). In conclusion, TAPSE, RVFS, and RVFAC measures are efficient measures of RV function by CMR that demonstrate significant correlation with invasive measures of PAH severity. In patients with PAH, TAPSE, RVFS, and RVFAC have high intra-and interobserver reproducibility and are more rapidly obtained than volumetric measures. TAPSE < 18 mm by CMR was strongly and independently associated with survival in PAH.
C1 [Corona-Villalobos, Celia P.; Kamel, Ihab R.; Rastegar, Neda; Skrok, Jan; Shehata, Monda L.; Zimmerman, Stefan L.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 601 North Caroline St,JHOC 3142,Box 0818, Baltimore, MD 21287 USA.
   [Damico, Rachel; Kolb, Todd M.; Boyce, Danielle M.; Sager, Ala-Eddin S.; Mathai, Stephen C.; Hassoun, Paul M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
   [Vogel-Claussen, Jens] Hannover Med Sch, Dept Radiol, Hannover, Germany.
   [Bluemke, David A.] Natl Inst Hlth Clin Ctr, Radiol & Imaging Sci, Bethesda, MD USA.
   [Girgis, Reda E.] Richard DeVos Heart & Lung Transplant Clin, Grand Rapids, MI USA.
RP Zimmerman, SL (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 601 North Caroline St,JHOC 3142,Box 0818, Baltimore, MD 21287 USA.
EM stefan.zimmerman@jhmi.edu
FU National Institutes of Health/National Heart, Lung, and Blood Institute
   [P01HL84946-01, R01 HL114910]
FX This work was supported by National Institutes of Health/National Heart,
   Lung, and Blood Institute grants P01HL84946-01 and R01 HL114910.
NR 31
TC 4
Z9 4
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 2045-8932
EI 2045-8940
J9 PULM CIRC
JI Pulm. Circ.
PD SEP
PY 2015
VL 5
IS 3
BP 527
EP 537
DI 10.1086/682229
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA DK9BI
UT WOS:000375224400012
PM 26401254
ER

PT J
AU Acosta-Alvear, D
   Cho, MY
   Wild, T
   Buchholz, TJ
   Lerner, AG
   Simakova, O
   Hahn, J
   Korde, N
   Landgren, O
   Maric, I
   Choudhary, C
   Walter, P
   Weissman, JS
   Kampmann, M
AF Acosta-Alvear, Diego
   Cho, Min Y.
   Wild, Thomas
   Buchholz, Tonia J.
   Lerner, Alana G.
   Simakova, Olga
   Hahn, Jamie
   Korde, Neha
   Landgren, Ola
   Maric, Irina
   Choudhary, Chunaram
   Walter, Peter
   Weissman, Jonathan S.
   Kampmann, Martin
TI Paradoxical resistance of multiple myeloma to proteasome inhibitors by
   decreased levels of 19S proteasomal subunits
SO ELIFE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; GENETIC INTERACTION MAPS; CELL-DEATH;
   AGGRESOME FORMATION; FUNCTIONAL-ANALYSIS; MAMMALIAN-CELLS; ER STRESS;
   BORTEZOMIB; PROTEIN; AUTOPHAGY
AB Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM patients invariably acquire resistance to these drugs. Using a next-generation shRNA platform, we found that proteostasis factors, including chaperones and stress-response regulators, controlled the response to carfilzomib. Paradoxically, 19S proteasome regulator knockdown induced resistance to carfilzomib in MM and non-MM cells. 19S subunit knockdown did not affect the activity of the 20S subunits targeted by carfilzomib nor their inhibition by the drug, suggesting an alternative mechanism, such as the selective accumulation of protective factors. In MM patients, lower 19S levels predicted a diminished response to carfilzomib-based therapies. Together, our findings suggest that an understanding of network rewiring can inform development of new combination therapies to overcome drug resistance.
C1 [Acosta-Alvear, Diego; Cho, Min Y.; Walter, Peter] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
   [Acosta-Alvear, Diego; Cho, Min Y.; Walter, Peter; Weissman, Jonathan S.; Kampmann, Martin] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA USA.
   [Cho, Min Y.; Weissman, Jonathan S.; Kampmann, Martin] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
   [Wild, Thomas; Choudhary, Chunaram] Univ Copenhagen, Novo Nordisk Fdn, Ctr Prot Res, Copenhagen, Denmark.
   [Buchholz, Tonia J.; Lerner, Alana G.] Onyx Pharmaceut Inc, San Francisco, CA USA.
   [Simakova, Olga; Hahn, Jamie; Maric, Irina] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
   [Korde, Neha; Landgren, Ola] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
   [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, Dept Med, New York, NY 10021 USA.
RP Walter, P (reprint author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
EM peter@walterlab.ucsf.edu; Jonathan.Weissman@ucsf.edu
FU Howard Hughes Medical Institute Collaborative Innovation Alliance;
   National Institutes of Health [K99/R00 CA181494, U01 CA168370];
   University of California at San Francisco Onyx-Oncology Innovation
   Alliance; Cancer Research Institute; Jane Coffin Childs Memorial Fund
   for Medical Research; Novo Nordisk; Det Frie Forskningsrad
FX Howard Hughes Medical Institute Collaborative Innovation Alliance Peter
   Walter, Jonathan S Weissman; National Institutes of Health Pathway to
   Independence Award K99/R00 CA181494 Martin Kampmann; University of
   California at San Francisco Onyx-Oncology Innovation Alliance Martin
   Kampmann, Diego Acosta-Alvear, Peter Walter, Jonathan S Weissman; Cancer
   Research Institute Irvington Postdoctoral Fellowship Diego
   Acosta-Alvear; Jane Coffin Childs Memorial Fund for Medical Research
   Postdoctoral Fellowship Martin Kampmann; Novo Nordisk Hallas Moller
   Investigator Chunaram Choudhary; Det Frie Forskningsrad Sapere Aude
   research grant Chunaram Choudhary; National Institutes of Health U01
   CA168370 Jonathan S Weissman
NR 52
TC 6
Z9 6
U1 1
U2 1
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD SEP 1
PY 2015
VL 4
AR e08153
DI 10.7554/eLife.08153
PG 19
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9SF
UT WOS:000373842100001
PM 26327694
ER

PT J
AU Gao, B
   Shah, VH
AF Gao, Bin
   Shah, Vijay H.
TI Combination therapy: New hope for alcoholic hepatitis?
SO CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
LA English
DT Review
ID SHORT-TERM SURVIVAL; B-VIRUS INFECTION; LIVER-DISEASE; STAT3 ACTIVATION;
   INTERLEUKIN-22; IL-22; INFLAMMATION; FIBROSIS; INJURY; MICE
AB Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease with high mortality. The pathogenesis of AH is not fully understood, but it is generally believed that inflammation is a key factor leading to liver failure in AH. Steroids, which have broad immunosuppressive effects, have been used for the treatment of AH over the last forty years. Steroids elicit modest improvement in short-term survival rate in patients with severe AH, but also cause severe side effects. Several specific inflammatory targets (e.g., IL-1, LPS, and gut microbiota) are currently under investigation for the treatment of AH with the goal to obviate or reduce steroid administration. In addition to inflammation, impaired liver regeneration is another major cause of liver failure in AH, which deteriorates further after steroid treatment because inflammation plays a key role in promoting liver repair. Interleukin-22 (IL-22) is a promising drug for the treatment of AH because of its hepatoprotective and anti-fibrotic functions and relatively few known side effects. In addition, IL-22 treatment also ameliorates bacterial infection and kidney injury, two major complications associated with severe AH. IL-22 is currently under investigation in preclinical and clinical studies and may hold great promise for AH by providing more beneficial effects and fewer side effects than current therapies. Published by Elsevier Masson SAS.
C1 [Gao, Bin] NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
   [Shah, Vijay H.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
FU NIAAA
FX BG declares that he has no conflict of interest concerning this article.
   Generon Inc (Shanghai, China) will provide recombinant IL-22Fc for an
   upcoming NIAAA funded study to test safety of IL-22 in AH patients. VJ
   is PI of this study.
NR 44
TC 6
Z9 6
U1 1
U2 5
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 2210-7401
EI 2210-741X
J9 CLIN RES HEPATOL GAS
JI Clin. Res. Hepatol. Gastroenterol.
PD SEP
PY 2015
VL 39
SU 1
BP S7
EP S11
DI 10.1016/j.clinre.2015.05.008
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DI0HJ
UT WOS:000373176000003
PM 26193867
ER

PT J
AU Chen, HB
   Zhang, M
   Xi, SC
   Xiong, Y
   Hong, JA
   Schrump, DS
AF Chen, Haobin
   Zhang, Mary
   Xi, Sichuan
   Xiong, Yin
   Hong, Julie A.
   Schrump, David S.
TI Mithramycin Is a Potential Therapeutic Agent for Elimination of
   Stem-Like Cells in Lung Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Stem-like cell; WNT/beta-catenin; Cisplatin; Mithramycin
C1 [Chen, Haobin; Zhang, Mary; Xi, Sichuan; Xiong, Yin; Hong, Julie A.; Schrump, David S.] NCI, Thorac & Gi Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P1.04-098
BP S481
EP S481
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365102255
ER

PT J
AU Daly, ME
   Kelly, K
   Reddy, A
   Sckisel, GD
   Donahue, RN
   Murphy, WJ
   Monjazeb, AM
AF Daly, Megan E.
   Kelly, Karen
   Reddy, Abhinav
   Sckisel, Gail D.
   Donahue, Renee N.
   Murphy, William J.
   Monjazeb, Arta M.
TI Peripheral Blood Immunophenotype Changes Following Thoracic Stereotactic
   Ablative Radiotherapy
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE SBRT; Immunophenotype; biomarker
C1 [Daly, Megan E.; Monjazeb, Arta M.] Univ Calif Davis, Ctr Comprehens Canc, Radiat Oncol, Sacramento, CA 95817 USA.
   [Kelly, Karen] Univ Calif Davis, Ctr Comprehens Canc, Hematol Oncol, Sacramento, CA USA.
   [Reddy, Abhinav; Sckisel, Gail D.; Murphy, William J.] Univ Calif Davis, Dermatol, Sacramento, CA 95817 USA.
   [Donahue, Renee N.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P1.02-036
BP S441
EP S442
PG 2
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365102123
ER

PT J
AU Gandara, DR
   Redman, M
   Herbst, R
   Abrams, J
   Malik, S
   Sigal, E
   Hirsch, FR
   Mack, PC
   Papadimitrakopoulou, V
AF Gandara, David R.
   Redman, Mary
   Herbst, Roy
   Abrams, Jeff
   Malik, Shakun
   Sigal, Ellen
   Hirsch, Fred R.
   Mack, Philip C.
   Papadimitrakopoulou, Vassiliki
TI Lung Master Protocol in Squamous Cell Lung Cancer (Lung-MAP, S1400)
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Master Protocol; squamous cell; Lung-MAP
C1 [Gandara, David R.] UC Davis Comprehens Canc Ctr, Div Hem Oncol, Sacramento, CA USA.
   [Redman, Mary] Fred Hutchinson Canc Res Ctr, Clin Res, Seattle, WA 98104 USA.
   [Herbst, Roy] Yale Canc Ctr, Med Oncol, New Haven, CT USA.
   [Abrams, Jeff; Malik, Shakun] NCI, CTEP, NIH, Rockville, MD USA.
   [Sigal, Ellen] Friends Canc Res, Washington, DC USA.
   [Hirsch, Fred R.] Univ Colorado, Ctr Canc, Aurora, CO USA.
   [Mack, Philip C.] UC Davis Comprehens Canc Ctr, Div Hem Oncol, Sacramento, CA USA.
   [Papadimitrakopoulou, Vassiliki] MD Anderson, Thorac Head & Neck Med Oncol, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA ED07.03
BP S80
EP S80
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100032
ER

PT J
AU Hassan, R
   Bendell, JC
   Blumenschein, G
   Kindler, HL
   Moore, KN
   Santin, AD
   Seward, SM
   Nemunaitis, J
   Rajagopalan, P
   Walter, A
   Sarapa, N
AF Hassan, Raffit
   Bendell, Johanna C.
   Blumenschein, George, Jr.
   Kindler, Hedy Lee
   Moore, Kathleen N.
   Santin, Alessandro D.
   Seward, Shelly M.
   Nemunaitis, John
   Rajagopalan, Prabhu
   Walter, Annette
   Sarapa, Nenad
TI Phase I Study of Anti-Mesothelin Antibody Drug Conjugate Anetumab
   Ravtansine
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE mesothelin; Mesothelioma; antibody drug conjugate
C1 [Hassan, Raffit] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
   [Bendell, Johanna C.] Sarah Canon Canc Ctr, Nashville, TN USA.
   [Blumenschein, George, Jr.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Kindler, Hedy Lee] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA.
   [Moore, Kathleen N.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
   [Santin, Alessandro D.] Yale Univ, Sch Med, New Haven, CT USA.
   [Seward, Shelly M.] Karmanos Canc Inst, Detroit, MI USA.
   [Nemunaitis, John] Mary Crowley Canc Res Ctr, Dallas, TX USA.
   [Rajagopalan, Prabhu; Walter, Annette; Sarapa, Nenad] Bayer Healthcare Pharmaceut, Whippany, NJ USA.
NR 0
TC 1
Z9 1
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA ORAL11.02
BP S195
EP S195
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100269
ER

PT J
AU Hassan, R
AF Hassan, Raffit
TI Immunotoxins and Mesothelin Antibody
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE antibody drug conjugate; anti-mesothelin chimeric antibody; mesothelin;
   Immunotoxin
C1 [Hassan, Raffit] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MS17.02
BP S119
EP S119
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100107
ER

PT J
AU Ji, XM
   Gui, J
   Han, YH
   Brennan, P
   Li, YF
   Mckay, J
   Caporaso, N
   Bertazzi, PA
   Landi, MT
   Amos, CI
AF Ji, Xuemei
   Gui, Jiang
   Han, Younghun
   Brennan, Paul
   Li, Yafang
   Mckay, James
   Caporaso, Neil
   Bertazzi, Pier A.
   Landi, Maria T.
   Amos, Christopher I.
TI The Role of Haplotype in 15q25.1 Locus in Lung Cancer Risk: Results of
   Scanning Chromosome 15
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE genetic factor; lung cancer; haplotype; smoking
C1 [Ji, Xuemei; Gui, Jiang; Han, Younghun; Li, Yafang; Amos, Christopher I.] Dartmouth Coll, Biomed Data Sci, Hanover, NH 03755 USA.
   [Brennan, Paul; Mckay, James] Int Agcy Res Canc, F-69372 Lyon, France.
   [Caporaso, Neil] NIH, Bethesda, MD 20892 USA.
   [Bertazzi, Pier A.] Univ Milan, Milan, Italy.
   [Landi, Maria T.] NCI, Bethesda, NH USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P2.05-008
BP S612
EP S612
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365103040
ER

PT J
AU Khanna, S
   Thomas, A
   Daga, DA
   Morrow, B
   Zhang, JL
   Steinberg, SM
   Orlandi, A
   Ferroni, P
   Schlom, J
   Guadagni, F
   Hassan, R
AF Khanna, Swati
   Thomas, Anish
   Daga, Daniel Abate
   Morrow, Betsy
   Zhang, Jingli
   Steinberg, Seth M.
   Orlandi, Augusto
   Ferroni, Patrizia
   Schlom, Jeffrey
   Guadagni, Fiorella
   Hassan, Raffit
TI PD-L1 Is Highly Expressed in Malignant Mesothelioma and
   PD-1(+)Lymphocytes within Malignant Effusions Induce PD-L1 Expression
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE PD-1; PD-L1; Mesothelioma; Malignant effusions
C1 [Khanna, Swati; Thomas, Anish; Daga, Daniel Abate; Morrow, Betsy; Zhang, Jingli; Hassan, Raffit] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
   [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
   [Orlandi, Augusto] Univ Rome, Dept Biomed & Prevent, Anat Pathol, Rome, Italy.
   [Ferroni, Patrizia; Guadagni, Fiorella] Univ San Raffaele, Sr Res Ctr, Rome & Biodat, Rome, Italy.
   [Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA.
RI Ferroni, Patrizia/C-2705-2017
OI Ferroni, Patrizia/0000-0002-9877-8712
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA ORAL40.01
BP S252
EP S253
PG 2
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100439
ER

PT J
AU Lam, S
   Mandrekar, S
   Ziegler, KA
   Seisler, D
   Midthun, D
   Mao, J
   Aubry, MC
   McWilliams, A
   Sin, D
   Shaipanich, T
   Spira, A
   Ionescu, D
   Mayo, J
   Yi, JE
   Tazelaar, H
   Harmsen, W
   Smith, J
   Limburg, P
   Szabo, E
AF Lam, Stephen
   Mandrekar, Sumithra
   Ziegler, Katie Allen
   Seisler, Drew
   Midthun, David
   Mao, Jenny
   Aubry, Marie Christine
   McWilliams, Annette
   Sin, Don
   Shaipanich, Tawimas
   Spira, Avrum
   Ionescu, Diana
   Mayo, John
   Yi, Joanne Eunhee
   Tazelaar, Henry
   Harmsen, William
   Smith, Judith
   Limburg, Paul
   Szabo, Eva
TI A Randomized Phase IIb Trial of Myo-Inositol in Smokers with Bronchial
   Dysplasia
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE chemoprevention; lung cancer
C1 [Lam, Stephen; McWilliams, Annette; Shaipanich, Tawimas; Ionescu, Diana] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
   [Mandrekar, Sumithra; Ziegler, Katie Allen; Seisler, Drew; Midthun, David; Aubry, Marie Christine; Yi, Joanne Eunhee; Harmsen, William; Limburg, Paul] Mayo Clin, Rochester, MN USA.
   [Mao, Jenny] New Mexico VA Hlth Care, Albuquerque, NM USA.
   [Sin, Don] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada.
   [Spira, Avrum] Boston Univ, Boston, MA 02215 USA.
   [Mayo, John] Vancouver Gen Hosp, Vancouver, BC, Canada.
   [Tazelaar, Henry] Mayo Clin, Scottsdale, AZ USA.
   [Smith, Judith; Szabo, Eva] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA ORAL23.01
BP S218
EP S218
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100339
ER

PT J
AU Linnoila, I
AF Linnoila, Ilona
TI Biology and Pathology of Neuroendocrine Cancers: Small Cell Lung Cancer
   - Call for Action
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE neuroendocrine; small cell lung cancer; ASCL1; Genetically engineered
   mouse models
C1 [Linnoila, Ilona] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MTE20.02
BP S152
EP S152
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100173
ER

PT J
AU Lynch, J
   Berse, B
   Freedman, A
   Filipski, K
   Duvall, S
   Kulich, S
   Kelley, M
AF Lynch, Julie
   Berse, Brygida
   Freedman, Andrew
   Filipski, Kelly
   Duvall, Scott
   Kulich, Scott
   Kelley, Michael
TI Epidermal Growth Factor Receptor (EGFR) Testing among Veterans Diagnosed
   with Lung Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Cancer Registry; reporting actionable mutations; Veterans prevalence of
   EGFR mutations
C1 [Lynch, Julie; Duvall, Scott] Vet Hlth Adm, Salt Lake City, UT USA.
   [Berse, Brygida] Boston Univ, Sch Med, Boston, MA 02215 USA.
   [Freedman, Andrew; Filipski, Kelly] NCI, Washington, DC USA.
   [Kulich, Scott] Vet Healthcare Adm, Philadelphia, PA USA.
   [Kelley, Michael] Vet Hlth Adm, Fayetteville, AR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P2.04-020
BP S584
EP S585
PG 2
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365102599
ER

PT J
AU Malik, S
AF Malik, Shakun
TI Master Protocols
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Malik, Shakun] NCI, CTEP, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MS28.02
BP S139
EP S139
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100147
ER

PT J
AU Moreno, P
   Moody, TW
   Lee, SH
   Mantey, SA
   Jensen, RT
AF Moreno, Paola
   Moody, Terry W.
   Lee, Suk H.
   Mantey, Samuel A.
   Jensen, Robert T.
TI Bombesin Receptor Subtype-3: An Underappreciated Growth Factor in Lung
   Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE growth factor; lung cancer; Bombesin receptor subtype-3; cell signaling
C1 [Moreno, Paola; Lee, Suk H.; Mantey, Samuel A.; Jensen, Robert T.] NIDDK, NIH, Bethesda, MD 20892 USA.
   [Moody, Terry W.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MINI21.08
BP S340
EP S340
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365101236
ER

PT J
AU Rao, M
   Shukla, V
   Straughan, D
   Azoury, S
   Feingold, P
   Atay, SM
   Hong, Y
   Upham, T
   Hong, JA
   Zhang, M
   Li, XM
   Ripley, RT
   Schrump, DS
AF Rao, Mahadev
   Shukla, Vivek
   Straughan, David
   Azoury, Said
   Feingold, Paul
   Atay, Scott M.
   Hong, Young
   Upham, Trevor
   Hong, Julie A.
   Zhang, Mary
   Li, Xinmin
   Ripley, R. T.
   Schrump, David S.
TI RITA Enhances Mithramycin-Mediated Growth Arrest and Apoptosis of
   Malignant Pleural Mesothelioma Cells In-Vitro and In-Vivo
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Mithramycin; RITA; Mesothelioma; apoptosis
C1 [Rao, Mahadev; Shukla, Vivek; Straughan, David; Azoury, Said; Feingold, Paul; Atay, Scott M.; Hong, Young; Upham, Trevor; Hong, Julie A.; Zhang, Mary; Ripley, R. T.; Schrump, David S.] NCI, Thorac & GI Oncol Branch, Bethesda, MD 20892 USA.
   [Li, Xinmin] Univ Calif Los Angeles, Clin Microarray Core, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MINI38.07
BP S403
EP S404
PG 2
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365101428
ER

PT J
AU Sadraei, NH
   Yellu, M
   Fakhrejahani, F
   Sendilnathan, A
   Abdel-Karim, N
   Morris, J
   Latif, T
   Mierzwa, M
   Huth, B
   Redmond, K
   Barrett, W
   Ma, P
   Pennell, N
   Ying, J
   Videtic, GMM
AF Sadraei, Nooshin Hashemi
   Yellu, Mahender
   Fakhrejahani, Farhad
   Sendilnathan, Arun
   Abdel-Karim, Nagla
   Morris, John
   Latif, Tahir
   Mierzwa, Michelle
   Huth, Brdaley
   Redmond, Kevin
   Barrett, William
   Ma, Patrick
   Pennell, Nathan
   Ying, Jun
   Videtic, Gregory M. M.
TI Radiation Dose-Related Lymphopenia as an Outcome Predictor in Stage III
   NSCLC Patients Treated with Chemoradiation
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE lymphopenia; stage III
C1 [Sadraei, Nooshin Hashemi; Yellu, Mahender; Sendilnathan, Arun; Abdel-Karim, Nagla; Morris, John; Latif, Tahir; Mierzwa, Michelle; Huth, Brdaley; Redmond, Kevin; Barrett, William; Ying, Jun] Univ Cincinnati, Cincinnati, OH 20892 USA.
   [Fakhrejahani, Farhad] NCI, Bethesda, MD 44106 USA.
   [Ma, Patrick; Videtic, Gregory M. M.] Cleveland Clin, Radiat Oncol, Cleveland, OH USA.
   [Pennell, Nathan] Univ Cincinnati, Cincinnati, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P1.03-017
BP S448
EP S448
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365102143
ER

PT J
AU Sato, K
   Choyke, PL
   Kobayashi, H
AF Sato, Kazuhide
   Choyke, Peter L.
   Kobayashi, Hisataka
TI Near Infrared Photoimmunotherapy for Pleural Metastases: Preclinical
   Experience
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE photoimmunotherapy; NSCLC; pleural disseminated metastases; fluorescence
   thoracoscopy
C1 [Sato, Kazuhide; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ccr, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P3.01-032
BP S651
EP S651
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365103178
ER

PT J
AU Shukla, V
   Rao, M
   Beers, J
   Zhang, HE
   Wangsa, D
   Wangsa, D
   Reardon, E
   Hong, JA
   Zhang, M
   Davis, S
   Chen, GK
   Ried, T
   Miettinen, MM
   Schrump, DS
AF Shukla, Vivek
   Rao, Mahadev
   Beers, Jeannette
   Zhang, Hongen
   Wangsa, Darawalee
   Wangsa, Danny
   Reardon, Emily
   Hong, Julie A.
   Zhang, Mary
   Davis, Sean
   Chen, Guokai
   Ried, Thomas
   Miettinen, Markku M.
   Schrump, David S.
TI Evaluation of Epigenetic Mechanisms of Pluripotency in Human Respiratory
   Epithelia
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Pluripotency; Epigenetics; Respiratory Epithelia; lung cancer therapy
C1 [Shukla, Vivek; Rao, Mahadev; Reardon, Emily; Hong, Julie A.; Zhang, Mary; Schrump, David S.] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
   [Beers, Jeannette] NHLBI, IPSC Core, Bethesda, MD 20892 USA.
   [Zhang, Hongen; Davis, Sean] NCI, Genet Branch, Bethesda, MD 20892 USA.
   [Wangsa, Darawalee; Wangsa, Danny; Ried, Thomas] NCI, Canc Genom Sect, Bethesda, MD 20892 USA.
   [Chen, Guokai] Univ Macau, Fac Hlth Sci, Macau, Peoples R China.
   [Miettinen, Markku M.] NCI, Lab Pathol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA ORAL07.01
BP S187
EP S187
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100244
ER

PT J
AU Szabo, E
AF Szabo, Eva
TI Chemoprevention Clinical Trials: How Do We Move Forward? How Do We
   Identify Valid End Points?
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE chemoprevention; clinical trials; end points
C1 [Szabo, Eva] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MS14.04
BP S113
EP S113
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100096
ER

PT J
AU Thomas, A
   Hassan, R
   Patel, M
   Nemunaitis, J
   Bennouna, J
   Powderly, J
   Taylor, MH
   Bajars, M
   Von Heydebreck, A
   Gulley, JL
AF Thomas, Anish
   Hassan, Raffit
   Patel, Manish
   Nemunaitis, John
   Bennouna, Jaafar
   Powderly, John
   Taylor, Matthew H.
   Bajars, Marcis
   Von Heydebreck, Anja
   Gulley, James L.
TI Avelumab (MSB0010718C), an Anti-PD-L1 Antibody, Evaluated in a Phase Ib
   Trial in Patients with Advanced Mesothelioma
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Mesothelioma; PD-L1; MSB0010718C; avelumab
C1 [Thomas, Anish; Hassan, Raffit; Gulley, James L.] NCI, NIH, Bethesda, MD 20892 USA.
   [Patel, Manish] Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA.
   [Nemunaitis, John] Mary Crowley Canc Res Ctr, Dallas, TX USA.
   [Bennouna, Jaafar] Ico Site Rene Gauducheau, St Herblain, France.
   [Powderly, John] Carolina Biooncol Inst, Huntersville, NC USA.
   [Taylor, Matthew H.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
   [Bajars, Marcis] Ernd Serono Inc, Global Res & Early Dev Immunooncol, Billerica, MA USA.
   [Von Heydebreck, Anja] Merck Kgaa, R&D Global Biostat, Darmstadt, Germany.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P3.08-011
BP S748
EP S748
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365103519
ER

PT J
AU Thomas, A
   Szabo, E
   Pinsky, P
AF Thomas, Anish
   Szabo, Eva
   Pinsky, Paul
TI Screening for Small Cell Lung Cancer: Analysis of the National Lung
   Cancer Screening Trial Data
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE SCLC; NLST; Screening; Early Detection
C1 [Thomas, Anish] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
   [Szabo, Eva; Pinsky, Paul] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA ORAL25.01
BP S221
EP S221
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100351
ER

PT J
AU Wallin, BA
   Maltzman, JD
   Dmietrienko, A
   Hoffman, K
   Mclaughlin, M
   Hassan, R
AF Wallin, Bruce A.
   Maltzman, Julis D.
   Dmietrienko, Alex
   Hoffman, Kimberly
   Mclaughlin, Megan
   Hassan, Raffit
TI A Randomized, Placebo-Controlled Study of Amatuximab in Combination with
   Pemetrexed and Cisplatin (P/C) in Subjects with Pleural Mesothelioma
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Maligant Pleural Mesothelioma
C1 [Wallin, Bruce A.; Maltzman, Julis D.; Hoffman, Kimberly; Mclaughlin, Megan] Morphotek, Clin Dev, Exton, PA USA.
   [Dmietrienko, Alex] Quintiles, Overland Pk, KS USA.
   [Hassan, Raffit] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P2.08-001
BP S628
EP S628
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365103091
ER

PT J
AU Wigle, D
   Szabo, E
   Spira, A
AF Wigle, Dennis
   Szabo, Eva
   Spira, Avrum
TI Chemoprevention Trials: Past, Present, and Future
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE precision chemoprevention; pre-invasive lesions; novel agents; clinical
   trials
C1 [Wigle, Dennis] Mayo Clin, Thorac Surg, Rochester, MN USA.
   [Szabo, Eva] NIH, Bethesda, MD 20892 USA.
   [Spira, Avrum] Boston Univ, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MTE18.01
BP S151
EP S151
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365100170
ER

PT J
AU Xi, SC
   Shan, JG
   Xu, H
   Xiao, ZX
   Xiong, Y
   Oyetunji, S
   Mercedes, L
   Zhang, M
   Hong, JA
   Schrump, DS
AF Xi, Sichuan
   Shan, Jigui
   Xu, Hong
   Xiao, Zuoxiang
   Xiong, Yin
   Oyetunji, Shakirat
   Mercedes, Leandro
   Zhang, Mary
   Hong, Julie A.
   Schrump, David S.
TI Long Noncoding RNA BC070487 Represses ZNFX1 during Tobacco-Induced Lung
   Carcinogenesis
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE ZNFX1; cigarette smoke; lung cancer; BC070487
C1 [Xi, Sichuan; Xiong, Yin; Oyetunji, Shakirat; Mercedes, Leandro; Zhang, Mary; Hong, Julie A.; Schrump, David S.] NCI, TGIB, CCR, NIH, Bethesda, MD 20892 USA.
   [Shan, Jigui; Xu, Hong] NCI, Frederick, MD 21701 USA.
   [Xiao, Zuoxiang] NCI, Canc & Inflammat Ctr Canc Res, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA MINI34.13
BP S391
EP S391
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365101388
ER

PT J
AU Xiong, Y
   Xi, SC
   Shan, JG
   Zhang, M
   Azoury, S
   Hong, JA
   Schrump, DS
AF Xiong, Yin
   Xi, Sichuan
   Shan, Jigui
   Zhang, Mary
   Azoury, Said
   Hong, Julie A.
   Schrump, David S.
TI Hookah Smoke Mediates Cancer-Associated Alterations in Normal Human
   Respiratory Epithelial Cells
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE Normal Respiratory Epithelial Cells; Cancer-Associated Alterations; lung
   cancer; Hookah Smoke
C1 [Xiong, Yin; Xi, Sichuan; Zhang, Mary; Azoury, Said; Hong, Julie A.; Schrump, David S.] NCI, Tgib, Ccr, NIH, Bethesda, MD 20892 USA.
   [Shan, Jigui] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P3.05-012
BP S732
EP S732
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365103462
ER

PT J
AU Zhang, M
   Xi, SC
   Xiong, Y
   Oyetunji, S
   Hong, JA
   Straughan, D
   Azoury, S
   Reardon, E
   Chen, HB
   Schrump, DS
AF Zhang, Mary
   Xi, Sichuan
   Xiong, Yin
   Oyetunji, Shakirat
   Hong, Julie A.
   Straughan, David
   Azoury, Said
   Reardon, Emily
   Chen, Haobin
   Schrump, David S.
TI The Pluripotency Factor Musashi-2 Is a Potential Target for Lung Cancer
   Therapy
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
DE NSCLC; SCLC; stem cell signaling; Mithramycin
C1 [Zhang, Mary; Xi, Sichuan; Xiong, Yin; Oyetunji, Shakirat; Hong, Julie A.; Straughan, David; Azoury, Said; Reardon, Emily; Chen, Haobin; Schrump, David S.] NCI, Ccr, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2015
VL 10
IS 9
SU 2
MA P2.04-051
BP S594
EP S594
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DE1CX
UT WOS:000370365102630
ER

PT J
AU Martin, M
   Ainsua-Enrich, E
   Serrano-Candelas, E
   Navines-Ferrer, A
   Alvarez-Errico, D
   Picado, C
   Sayos, J
   Rivera, J
AF Martin, M.
   Ainsua-Enrich, E.
   Serrano-Candelas, E.
   Navines-Ferrer, A.
   Alvarez-Errico, D.
   Picado, C.
   Sayos, J.
   Rivera, J.
TI The adaptor 3BP2 is required for human mast cell migration and survival
SO ALLERGY
LA English
DT Meeting Abstract
CT Congress of the European-Academy-of-Allergy-and-Clinical-Immunology
CY JUN 06-10, 2015
CL Barcelona, SPAIN
SP European Acad Allergy & Clin Immunol
C1 [Martin, M.; Ainsua-Enrich, E.; Serrano-Candelas, E.; Navines-Ferrer, A.; Alvarez-Errico, D.] Univ Barcelona, Sch Med, Barcelona, Spain.
   [Martin, M.; Ainsua-Enrich, E.; Serrano-Candelas, E.; Alvarez-Errico, D.; Picado, C.] IDIBAPS, Clin & Expt Resp Immunoallergy, Barcelona, Spain.
   [Picado, C.] Networking Res Ctr Resp Dis CIBERES, Barcelona, Spain.
   [Sayos, J.] Hosp Univ Vall dHebron, Inst Recerca, Barcelona, Spain.
   [Sayos, J.] Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Barcelona, Spain.
   [Rivera, J.] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
EI 1398-9995
J9 ALLERGY
JI Allergy
PD SEP
PY 2015
VL 70
SU 101
SI SI
MA 145
BP 72
EP 72
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DD5GM
UT WOS:000369950700144
ER

PT J
AU Gollner, J
   Andersen, R
   Gollner, K
   Webster, T
AF Gollner, Joe
   Andersen, Rebekka
   Gollner, Kathleen
   Webster, Tenny
TI A Study of the Usefulness of Deploying a Questionnaire to Identify
   Cultural Dynamics Potentially Affecting a Content-Management Project
SO IEEE TRANSACTIONS ON PROFESSIONAL COMMUNICATION
LA English
DT Article
DE Change management; content management; content-management system;
   cultural dynamics; needs assessment; organizational change;
   organizational culture; technological change; technology diffusion;
   technology implementation
ID INFORMATION-TECHNOLOGY; IMPLEMENTATION
AB Background: A content-management project that proceeds with an incomplete understanding of the views, reservations, agendas, and attitudes held by stakeholders could likely encounter problems in implementation. The vast majority of content-management implementation projects proceed with very little visibility into the cultural dynamics that will eventually play such a central role in determining the success or failure of the projects. This case study examines the usefulness of deploying a needs assessment questionnaire to gather qualitative data that could help content-management project leaders understand participant needs, attitudes, and perceptions, and that could potentially improve the implementation of content-management projects. Research questions: How might previously published research questions for assessing cultural dynamics be adapted for a questionnaire intended to gather input from participants in the early stages of the implementation of two separate content-management projects? What kinds of issues does the questionnaire elicit from participants? To what extent is the questionnaire useful in assessing content-management project participant needs and how might it be revised and adapted for other organizational contexts? Situating the case: Implementing a content-management project results in a change to organizational processes; careful attention to managing this change is essential to the success of the project. Specific change-management issues emphasized in literature that addresses organizational and technological change include organizational readiness, stakeholder input, communication of project goals and plans with stakeholders, and training and time to learn and practice new approaches to operations. Organizational culture-a set of beliefs and values that members of an company share in common-plays a role in implementations of technology. Assessing organizational climate and stakeholder values and attitudes-characteristics of organizational culture-as part of a change-management plan can ensure that the culture is addressed when implementing a content-management project. Methodology: This project consisted of three parts: designing a pilot questionnaire based on a previous published methodology for assessing cultural dynamics, conducting the questionnaire within two organizations implementing content-management systems, and assessing the extent to which the questionnaire was useful in the context of the content-management projects. Responses were analyzed using a Grounded Theory approach. About the case: We developed a cultural dynamics needs assessment questionnaire and deployed it within two organizations with the purpose of gathering data about the attitudes and perceptions of project participants toward the impending content-management system implementation. The questionnaires informed the implementations of content management as anticipated. Conclusions: A questionnaire can help understand the cultural dynamics impacting the adoption of new technologies and processes; this method can be included as part of an overall needs assessment for a content-management project. This study also confirms the merit of the research methodology followed; the questionnaire design elicited thoughtful responses from participants and the analysis approach illuminated insights that were then used to engage participants and modify project implementation plans. The constructive outcome of this study suggests the need for more empirical studies and field evaluation studies that build on this one.
C1 [Gollner, Joe] Gnostyx Res Inc, Ottawa, ON KIN 8S7, Canada.
   [Andersen, Rebekka] Univ Calif Davis, Univ Writing Program, Davis, CA 95616 USA.
   [Gollner, Kathleen] Natl Lib Med, Natl Ctr Biotechnol Informat, PubMed, Bethesda, MD 20894 USA.
   [Webster, Tenny] Appalachian Trail Conservancy, Harpers Ferry, WV 25425 USA.
RP Gollner, J (reprint author), Gnostyx Res Inc, Ottawa, ON KIN 8S7, Canada.
EM jag@gnostyx.com; randersen@ucdavis.edu; kathleen.gollner@gmail.com;
   erictwebster@gmail.com
NR 31
TC 1
Z9 1
U1 1
U2 3
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0361-1434
EI 1558-1500
J9 IEEE T PROF COMMUN
JI IEEE Trans. Prof. Commun.
PD SEP
PY 2015
VL 58
IS 3
BP 289
EP 308
DI 10.1109/TPC.2016.2516638
PG 20
WC Communication; Engineering, Multidisciplinary
SC Communication; Engineering
GA DE3IX
UT WOS:000370523100004
ER

PT J
AU Foley, AR
AF Foley, A. R.
TI Next Generation Sequencing in Muscle Disease - A Tale of Two Cities
SO JOURNAL OF PATHOLOGY
LA English
DT Meeting Abstract
CT 8th Joint Meeting of the British-Division of the
   International-Academy-of-Pathology and the
   Pathological-Society-of-Great-Britain-and-Ireland
CY JUN 23-25, 2015
CL Univ Coll D, Dublin, IRELAND
SP Int Acad Pathol, British Div, St Vincents Univ Hosp, Dept Pathol, Pathol Soc Great Britain & Ireland
HO Univ Coll D
C1 [Foley, A. R.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD SEP
PY 2015
VL 237
SU 1
BP S11
EP S11
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA DD5GZ
UT WOS:000369952300048
ER

PT J
AU Hewitt, SM
AF Hewitt, S. M.
TI Digital Pathology - Are We There Yet?
SO JOURNAL OF PATHOLOGY
LA English
DT Meeting Abstract
CT 8th Joint Meeting of the British-Division of the
   International-Academy-of-Pathology and the
   Pathological-Society-of-Great-Britain-and-Ireland
CY JUN 23-25, 2015
CL Univ Coll D, Dublin, IRELAND
SP Int Acad Pathol, British Div, St Vincents Univ Hosp, Dept Pathol, Pathol Soc Great Britain & Ireland
HO Univ Coll D
C1 [Hewitt, S. M.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD SEP
PY 2015
VL 237
SU 1
BP S9
EP S9
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA DD5GZ
UT WOS:000369952300038
ER

PT J
AU Sabayan, B
   van Buchem, MA
   de Craen, AJM
   Sigurdsson, S
   Zhang, Q
   Harris, TB
   Gudnason, V
   Arai, AE
   Launer, LJ
AF Sabayan, Behnam
   van Buchem, Mark A.
   de Craen, Anton J. M.
   Sigurdsson, Sigurdur
   Zhang, Qian
   Harris, Tamara B.
   Gudnason, Vilmundur
   Arai, Andrew E.
   Launer, Lenore J.
TI N-terminal pro-brain natriuretic peptide and abnormal brain aging The
   AGES-Reykjavik Study
SO NEUROLOGY
LA English
DT Article
ID HEART-FAILURE; OLDER-ADULTS; CARDIOVASCULAR RISK; MAGNETIC-RESONANCE;
   GENERAL-POPULATION; BLOOD-FLOW; BIOMARKERS; DISEASE; DEMENTIA; SYSTEM
AB Objective: To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals.
   Methods: In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI.
   Results: In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p 5 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output.
   Conclusions: Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated.
C1 [Sabayan, Behnam; van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RA Leiden, Netherlands.
   [Sabayan, Behnam; de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RA Leiden, Netherlands.
   [Sigurdsson, Sigurdur; Gudnason, Vilmundur] Icelandic Heart Assoc, Reykjavik, Iceland.
   [Zhang, Qian; Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
   [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
   [Arai, Andrew E.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Launer, LJ (reprint author), NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM launerl@nia.nih.gov
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
FU National Institute on Aging (NIA) [N01-AG-12100]; Hjartavernd (the
   Icelandic Heart Association); Althingi (the Icelandic Parliament);
   MedStar Research Institute [2003-145]; NIA [Z01 HL004607-08 CE];
   National Heart, Lung, and Blood Institute [Z01 HL004607-08 CE]
FX The study was funded by the National Institute on Aging (NIA)
   (N01-AG-12100), Hjartavernd (the Icelandic Heart Association), and the
   Althingi (the Icelandic Parliament), with contributions from the
   Intramural Research Programs at the NIA and at the National Heart, Lung,
   and Blood Institute (Z01 HL004607-08 CE). The study was approved by the
   Icelandic National Bioethics Committee (VSN: 00-063) and the MedStar
   Research Institute (project 2003-145).
NR 35
TC 3
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD SEP 1
PY 2015
VL 85
IS 9
BP 813
EP 820
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DE3CL
UT WOS:000370504300015
PM 26231259
ER

PT J
AU Finkle, WD
   Greenland, S
   Ridgeway, GK
   Adams, JL
   Hoover, RN
AF Finkle, William D.
   Greenland, Sander
   Ridgeway, Gregory K.
   Adams, John L.
   Hoover, Robert N.
TI Increased Risk of Non-fatal Myocardial Infarction Following Testosterone
   Therapy Prescription in Men
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Finkle, William D.] Consolidated Res Inc, Los Angeles, CA USA.
   [Greenland, Sander] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA.
   [Greenland, Sander] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA.
   [Ridgeway, Gregory K.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD SEP
PY 2015
VL 24
SU 1
SI SI
MA 68
BP 40
EP 40
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DD5QW
UT WOS:000369980200069
ER

PT J
AU Naples, JG
   Marcum, ZA
   Perera, S
   Gray, SL
   Newman, AB
   Simonsick, EM
   Yaffe, K
   Shorr, RI
   Hanlon, JT
AF Naples, Jennifer G.
   Marcum, Zachary A.
   Perera, Subashan
   Gray, Shelly L.
   Newman, Anne B.
   Simonsick, Eleanor M.
   Yaffe, Kristine
   Shorr, Ronald I.
   Hanlon, Joseph T.
TI Concordance among anticholinergic burden scales
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Naples, Jennifer G.; Perera, Subashan; Hanlon, Joseph T.] Univ Pittsburgh, Med Geriatr, Pittsburgh, PA USA.
   [Marcum, Zachary A.; Gray, Shelly L.] Univ Washington, Pharm, Seattle, WA 98195 USA.
   [Newman, Anne B.] Univ Pittsburgh, Publ Hlth Epidemiol, Pittsburgh, PA USA.
   [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Yaffe, Kristine] Univ Calif San Francisco, Med & Psychiat, San Francisco, CA 94143 USA.
   [Shorr, Ronald I.] North Florida South Georgia Vet Hlth Syst, GRECC, Gainesville, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD SEP
PY 2015
VL 24
SU 1
SI SI
MA 176
BP 99
EP 100
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DD5QW
UT WOS:000369980200171
ER

PT J
AU Rivera, DR
   Filipski, K
   Freedman, AN
AF Rivera, Donna R.
   Filipski, Kelly
   Freedman, Andrew N.
TI Utilization and Trends of Molecularly Targeted Therapies in Cancer
   Treatment: A 2006-2010 NAMCS Analysis
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Rivera, Donna R.; Filipski, Kelly; Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD SEP
PY 2015
VL 24
SU 1
SI SI
MA 207
BP 117
EP 117
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DD5QW
UT WOS:000369980200202
ER

PT J
AU McGlynn, KA
   Hagberg, KW
   Chen, J
   Graubard, BI
   London, WT
   Jick, SS
   Sahasrabuddhe, VV
AF McGlynn, Katherine A.
   Hagberg, Katrina Wilcox
   Chen, Jie
   Graubard, Barry I.
   London, W. Thomas
   Jick, Susan S.
   Sahasrabuddhe, Vikrant V.
TI Statin Use and Risk of Primary Liver Cancer in the UK Clinical Practice
   Research Datalink (CPRD)
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [McGlynn, Katherine A.; Chen, Jie; Graubard, Barry I.; Sahasrabuddhe, Vikrant V.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Hagberg, Katrina Wilcox; Jick, Susan S.] Boston Univ, Sch Publ Hlth, Boston Collaborat Drug Surveillance Program, Lexington, MA USA.
   [London, W. Thomas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
   [London, W. Thomas] Hepatitis B Fdn, Doylestown, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD SEP
PY 2015
VL 24
SU 1
SI SI
MA 755
BP 431
EP 432
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DD5QW
UT WOS:000369980201047
ER

PT J
AU Freedman, AN
   Rivera, DR
   Gail, MH
   Graubard, BI
AF Freedman, Andrew N.
   Rivera, Donna R.
   Gail, Mitchell H.
   Graubard, Barry I.
TI US Women Who Could Benefit from Tamoxifen or Raloxifene for Breast
   Cancer Chemoprevention in 2010
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Freedman, Andrew N.; Rivera, Donna R.; Gail, Mitchell H.; Graubard, Barry I.] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD SEP
PY 2015
VL 24
SU 1
SI SI
MA 815
BP 466
EP 466
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DD5QW
UT WOS:000369980201106
ER

PT J
AU Zou, S
   Nelson, K
   Yu, J
   Glynn, S
   Dhingra-Kumar, N
AF Zou, S.
   Nelson, K.
   Yu, J.
   Glynn, S.
   Dhingra-Kumar, N.
TI Global Estimates of Potential Transfusion-Transmissible Infections of
   Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Zou, S.; Glynn, S.] NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Nelson, K.] Johns Hopkins Univ, Baltimore, MD USA.
   [Yu, J.; Dhingra-Kumar, N.] WHO, CH-1211 Geneva, Switzerland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA S24-020B
BP 16A
EP 16A
PG 1
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500031
ER

PT J
AU Srivastava, K
   Stiles, D
   Wagner, FF
   Flegel, WA
AF Srivastava, K.
   Stiles, D.
   Wagner, F. F.
   Flegel, W. A.
TI Two Large Intergenic Deletions in RHD Involving Either Exon 1 or Exon 10
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Srivastava, K.; Stiles, D.; Flegel, W. A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
   [Wagner, F. F.] Inst Springe, Red Cross Blood Serv NSTOB, Springe, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA S32-020C
BP 19A
EP 19A
PG 1
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500039
ER

PT J
AU Allen, ES
   Cantilena, C
AF Allen, E. S.
   Cantilena, C.
TI Lymphapheresis Yields in the Production of Chimeric Antigen Receptor
   (CAR) T-Cell Therapy
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Allen, E. S.; Cantilena, C.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA SP127
BP 102A
EP 103A
PG 2
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500217
ER

PT J
AU Karafin, MS
   Bruhn, R
   Roubinian, N
   Westlake, M
   Gottschall, J
   Kor, DJ
   Fleischmann, D
   Hauser, R
   Murphy, EL
   Triulzi, D
AF Karafin, M. S.
   Bruhn, R.
   Roubinian, N.
   Westlake, M.
   Gottschall, J.
   Kor, D. J.
   Fleischmann, D.
   Hauser, R.
   Murphy, E. L.
   Triulzi, D.
CA NHLBI Recipient Epidemiology Donor
TI Establishing a Multicenter Transfusion Recipient Database: Feasibility
   and Potential Use
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Karafin, M. S.; Gottschall, J.] BloodCtr Wisconsin, Inst Med Sci, Milwaukee, WI USA.
   [Bruhn, R.] Blood Syst Res Inst, San Francisco, CA USA.
   [Westlake, M.; Fleischmann, D.] RTI Int, Rockville, MD USA.
   [Kor, D. J.] Mayo Clin, Rochester, MN USA.
   [Hauser, R.] Yale Univ, Sch Med, Lab Med, New Haven, CT USA.
   [Triulzi, D.] Inst Transfus Med, Pittsburgh, PA USA.
   [NHLBI Recipient Epidemiology Donor] NIH, Bethesda, MD 20892 USA.
   [Roubinian, N.; Murphy, E. L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA SP273
BP 165A
EP 166A
PG 2
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500363
ER

PT J
AU Vermeulen, M
   Swanevelder, R
   Chowdhury, D
   Ingram, C
   Reddy, V
   Muthivhi, T
   Bloch, E
   Custer, B
   Murphy, EL
AF Vermeulen, M.
   Swanevelder, R.
   Chowdhury, D.
   Ingram, C.
   Reddy, V.
   Muthivhi, T.
   Bloch, E.
   Custer, B.
   Murphy, E. L.
CA NHLBI Recipient Epidemiology Donor
TI Prevalence of HIV and Hepatitis B and C viruses in South African Blood
   Donors, 2012-2014
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Murphy, E. L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Bloch, E.; Custer, B.; Murphy, E. L.] Blood Syst Res Inst, San Francisco, CA USA.
   [Vermeulen, M.; Swanevelder, R.; Ingram, C.; Reddy, V.; Muthivhi, T.] South African Natl Blood Serv, Johannesburg, South Africa.
   [Chowdhury, D.] RTI Int, Rockville, MD USA.
   [NHLBI Recipient Epidemiology Donor] NHLBI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA SP307
BP 181A
EP 182A
PG 2
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500397
ER

PT J
AU Albano, MS
   Ciubotariu, R
   Tarnawski, M
   Scaradavou, A
   Williamson, PC
   Leparc, GF
   Spizman, R
   Caglioti, S
   Williams, JD
   Williams, RC
AF Albano, M. S.
   Ciubotariu, R.
   Tarnawski, M.
   Scaradavou, A.
   Williamson, P. C.
   Leparc, G. F.
   Spizman, R.
   Caglioti, S.
   Williams, J. Dunn
   Williams, R. C.
TI Infectious Disease Markers (IDMs) Assay Performance for Maternal and
   Corresponding Cord Blood Samples
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Williamson, P. C.; Leparc, G. F.; Spizman, R.; Caglioti, S.; Williams, J. Dunn] Creat Testing Solut, Tempe, AZ USA.
   [Albano, M. S.; Ciubotariu, R.; Tarnawski, M.; Scaradavou, A.] New York Blood Ctr, Natl Cord Blood Program, Westbury, NY USA.
   [Williams, R. C.] NIDDK, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA SP310
BP 183A
EP 183A
PG 1
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500400
ER

PT J
AU Zeng, P
   Wang, J
   Liu, J
   Mao, W
   Bi, X
   Li, J
   Zhu, L
   Cao, R
   Liao, D
   Shan, H
AF Zeng, P.
   Wang, J.
   Liu, J.
   Mao, W.
   Bi, X.
   Li, J.
   Zhu, L.
   Cao, R.
   Liao, D.
   Shan, H.
CA Int Component NHLBI Recipient
TI The Staging, Genotypic Distribution, and Drug Resistance Mutation
   Profiles of HIV among Infected Blood Donors from Five Chinese Blood
   Centers, 2012-2014
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Zeng, P.; Wang, J.] CAMS, Inst Blood Transfus, Chengdu, Peoples R China.
   [Liu, J.] Johns Hopkins Univ Hosp, Transfus Med, Baltimore, MD 21287 USA.
   [Mao, W.] Chongqing Blood Ctr, Chongqing, Peoples R China.
   [Bi, X.] Xinyang Blood Ctr, Urumqi, Peoples R China.
   [Li, J.] Guangxi Blood Ctr, Liuzhou, Peoples R China.
   [Zhu, L.] Luoyang Blood Ctr, Luoyang, Peoples R China.
   [Cao, R.] Mianyang Blood Ctr, Mianyang, Peoples R China.
   [Liao, D.] RTI Int, Bethesda, MD USA.
   [Shan, H.] Stanford Univ, Stanford, CA 94305 USA.
   [Int Component NHLBI Recipient] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA SP311
BP 183A
EP 184A
PG 2
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500401
ER

PT J
AU Williams, JD
   Haubert, N
   Phillips, M
   Miller, DL
   Spizman, R
   Ritter, J
   Leparc, GF
   Williamson, PC
   Caglioti, S
   Williams, RC
AF Williams, J. Dunn
   Haubert, N.
   Phillips, M.
   Miller, D. L.
   Spizman, R.
   Ritter, J.
   Leparc, G. F.
   Williamson, P. C.
   Caglioti, S.
   Williams, R. C.
TI Interpretation of Assay Performance in the Detection of Cytomegalovirus
   Antibodies
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting
CY OCT 24-27, 2015
CL Anaheim, CA
SP AABB
C1 [Williams, J. Dunn; Haubert, N.; Phillips, M.; Miller, D. L.; Spizman, R.; Ritter, J.; Leparc, G. F.; Williamson, P. C.; Caglioti, S.] Creat Testing Solut, Tempe, AZ USA.
   [Williams, R. C.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
SU 3
SI SI
MA SP316
BP 185A
EP 186A
PG 2
WC Hematology
SC Hematology
GA DD5GS
UT WOS:000369951500406
ER

PT J
AU Smith, CK
   Kaplan, MJ
AF Smith, Carolyne K.
   Kaplan, Mariana J.
TI The role of neutrophils in the pathogenesis of systemic lupus
   erythematosus
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE bone marrow; low-density granulocytes; neutrophil extracellular traps;
   neutrophils; systemic lupus erythematosus
ID PEPTIDYLARGININE DEIMINASE INHIBITION; GELATINASE-ASSOCIATED LIPOCALIN;
   EXTRACELLULAR TRAPS; APOPTOTIC NEUTROPHILS; RHEUMATOID-ARTHRITIS;
   DISEASE-ACTIVITY; IN-VIVO; NEPHRITIS; DNA; NETOSIS
AB Purpose of review
   Recent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE).
   Recent findings
   Various putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNF alpha) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies.
   Summary
   Recent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.
C1 [Smith, Carolyne K.; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, Intramural Res Program, NIH, Bldg 10,6D47C,10 Ctr Dr,MSC 1560, Bethesda, MD 20892 USA.
RP Kaplan, MJ (reprint author), NIAMSD, Syst Autoimmun Branch, Intramural Res Program, NIH, Bldg 10,6D47C,10 Ctr Dr,MSC 1560, Bethesda, MD 20892 USA.
EM mariana.kaplan@nih.gov
FU Intramural Research Program at NIAMS/NIH; Lupus Research Institute
FX This study was supported by the Intramural Research Program at NIAMS/NIH
   and the Lupus Research Institute.
NR 70
TC 14
Z9 16
U1 4
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD SEP
PY 2015
VL 27
IS 5
BP 448
EP 453
DI 10.1097/BOR.0000000000000197
PG 6
WC Rheumatology
SC Rheumatology
GA DD0PS
UT WOS:000369622500004
PM 26125102
ER

PT J
AU de Jesus, AA
   Goldbach-Mansky, R
AF de Jesus, Adriana Almeida
   Goldbach-Mansky, Raphaela
TI Newly recognized Mendelian disorders with rheumatic manifestations
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE IL-1-mediated autoinflammatory diseases; immune dysregulation;
   interferon-mediated diseases; monogenic autoinflammatory diseases;
   primary immunodeficiencies
ID ADENOSINE-DEAMINASE 2; CONGENITAL SIDEROBLASTIC ANEMIA;
   AICARDI-GOUTIERES SYNDROME; DEVELOPMENTAL DELAY SIFD; HYPER-IGE
   SYNDROME; CAUSES AUTOINFLAMMATION; HUMAN IMMUNODEFICIENCY; IMMUNE
   DYSREGULATION; GERMLINE MUTATIONS; PRKDC MUTATIONS
AB Purpose of review
   We review newly discovered monogenic immune-dysregulatory disorders that were reported in Pubmed over the last year.
   Recent findings
   Fourteen novel monogenic immune-dysregulatory disorders that present with innate and acquired/adaptive immune dysregulation and inflammatory clinical phenotypes were identified. These include autosomal-dominant gain-of function mutations in viral innate immune sensors or their adaptors, TMEM173/STING IFIH1/MDA5 and DDX58/RIG-I that cause complex clinical syndromes distinct from IL-1-mediated diseases and present with a chronic type I interferon (IFN Type I) signature in peripheral blood. Gain-of-function mutations in NLRC4 add a novel inflammasome disorder associated with predisposition to macrophage-activation syndrome and highly elevated IL-18 levels. Mutations in ADA2, TRNT1 and COPA, AP1S3, and TNFRSF11A cause complex syndromes; loss-of-function mutations in enzymes and molecules are linked to the generation of 'cellular stress' and the release of inflammatory mediators that likely cause the inflammatory disease manifestations. A monogenic form of systemic-onset juvenile idiopathic arthritis is caused by homozygous mutations in LACC1. Lastly, mutations in PRKDC (recessive), STAT3, CTLA4, and PIK3R1 (all dominant) lead to impaired central and peripheral T-cell tolerance and present with variable disease manifestations of immunodeficiency and immune dysregulation/autoimmunity.
   Summary
   A number of novel monogenic diseases that present with innate and/or acquired immune dysregulation reveal novel immune pathways that cause human inflammatory diseases and suggest potential novel targets for treatment.
C1 [de Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela] Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA.
RP de Jesus, AA (reprint author), NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bldg 10,Room 6D52,10 Ctr Dr, Bethesda, MD 20892 USA.
EM almeidadejesua@mail.nih.gov
FU NIAMS Intramural Research Program (IRP) NIH; NIAMS
FX This work was funded by the NIAMS Intramural Research Program (IRP) NIH,
   the Clinical Center, and NIAMS.
NR 44
TC 3
Z9 3
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD SEP
PY 2015
VL 27
IS 5
BP 511
EP 519
DI 10.1097/BOR.0000000000000207
PG 9
WC Rheumatology
SC Rheumatology
GA DD0PS
UT WOS:000369622500013
PM 26196376
ER

PT J
AU Mensah, GA
   Norris, KC
AF Mensah, George A.
   Norris, Keith C.
TI ADVANCING HEALTH EQUITY: HONORING THE LEGACY OF DR. ELIJAH B. SAUNDERS
SO ETHNICITY & DISEASE
LA English
DT Editorial Material
ID HYPERTENSION
C1 [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD USA.
   [Norris, Keith C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA.
RP Mensah, GA (reprint author), NHLBI, CTRIS, NIH, Rockledge Ctr 1, 6705 Rockledge Dr,Suite 6070, Bethesda, MD 20892 USA.
EM George.Mensah@nih.gov
NR 6
TC 1
Z9 1
U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
EI 1945-0826
J9 ETHNIC DIS
JI Ethn. Dis.
PD FAL
PY 2015
VL 25
IS 4
BP 381
EP 382
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC9CA
UT WOS:000369517100001
PM 26673125
ER

PT J
AU Downs, JW
   Hakkinen, PJ
AF Downs, John W.
   Hakkinen, Pertti J.
TI What Online Toxicology Resources Are Available at No Cost From the (US)
   National Library of Medicine to Assist Practicing OEM Physicians?
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Editorial Material
ID ENVIRONMENTAL-HEALTH
C1 [Downs, John W.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   [Hakkinen, Pertti J.] Natl Lib Med, Specialized Informat Serv, Off Clin Toxicol, Bethesda, MD 20894 USA.
RP Downs, JW (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
EM john.downs@us.army.mil; hakkinenp@mail.nlm.nih.gov
RI Hakkinen, Pertti/G-4803-2016
OI Hakkinen, Pertti/0000-0002-8295-9738
FU Intramural NIH HHS [Z99 LM999999]
NR 4
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1076-2752
EI 1536-5948
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD SEP
PY 2015
VL 57
IS 9
BP E85
EP E90
DI 10.1097/JOM.0000000000000519
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC8AH
UT WOS:000369441800001
PM 26340294
ER

PT J
AU Meert, KL
   Keele, L
   Morrison, W
   Berg, RA
   Dalton, H
   Newth, CJL
   Harrison, R
   Wessel, DL
   Shanley, T
   Carcillo, J
   Clark, A
   Holubkov, R
   Jenkins, TL
   Doctor, A
   Dean, JM
   Pollack, M
AF Meert, Kathleen L.
   Keele, Linda
   Morrison, Wynne
   Berg, Robert A.
   Dalton, Heidi
   Newth, Christopher J. L.
   Harrison, Rick
   Wessel, David L.
   Shanley, Thomas
   Carcillo, Joseph
   Clark, Amy
   Holubkov, Richard
   Jenkins, Tammara L.
   Doctor, Allan
   Dean, J. Michael
   Pollack, Murray
CA Eunice Kennedy Shriver Natl Inst C
TI End-of-Life Practices Among Tertiary Care PICUs in the United States: A
   Multicenter Study
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE autopsy; death; end-of-life care; organ donation; pediatrics
ID PEDIATRIC INTENSIVE-CARE; SUSTAINING TREATMENTS; RECOMMENDATIONS;
   HOSPITALS; RATES; DEATH
AB Objective: To describe variability in end-of-life practices among tertiary care PICUs in the United States.
   Design: Secondary analysis of data prospectively collected from a random sample of patients (n = 10,078) admitted to PICUs affiliated with the Collaborative Pediatric Critical Care Research Network between December 4, 2011, and April 7, 2013.
   Setting: Seven clinical centers affiliated with the Collaborative Pediatric Critical Care Research Network.
   Patients: Patients included in the primary study were less than 18 years old, admitted to a PICU, and not moribund on PICU admission. Patients included in the secondary analysis were those who died during their hospital stay.
   Interventions: None.
   Measurements and Main Results: Two hundred and seventy-five (2.7%; range across sites, 1.3-5.0%) patients died during their hospital stay; of these, 252 (92%; 76-100%) died in a PICU. Discussions with families about limitation or withdrawal of support occurred during the initial PICU stay for 173 patients (63%; 47-76%; p = 0.27) who died. Of these, palliative care was consulted for 67 (39%; 12-46%); pain service for 11 (6%; 10 of which were at a single site); and ethics committee for six (3%, from three sites). Mode of death was withdrawal of support for 141 (51%; 42-59%), failed cardiopulmonary resuscitation for 53 (19%; 12-28%), limitation of support for 46 (17%; 7-24%), and brain death for 35 (13%; 8-20%); mode of death did not differ across sites (p = 0.58). Organ donation was requested from 101 families (37%; 17-88%; p < 0.001). Of these, 20 donated (20%; 0-64%). Sixty-two deaths (23%; 10-53%; p < 0.001) were medical examiner cases. Of nonmedical examiner cases (n = 213), autopsy was requested for 79 (37%; 17-75%; p < 0.001). Of autopsies requested, 53 (67%; 50-100%) were performed.
   Conclusions: Most deaths in Collaborative Pediatric Critical Care Research Network-affiliated PICUs occur after life support has been limited or withdrawn. Wide practice variation exists in requests for organ donation and autopsy.
C1 [Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
   [Keele, Linda] Valley Childrens Hosp, Dept Anesthesia & Crit Care Med, Madera, CA USA.
   [Morrison, Wynne; Berg, Robert A.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
   [Dalton, Heidi; Pollack, Murray] Phoenix Childrens Hosp, Dept Crit Care Med, Phoenix, AZ USA.
   [Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Anesthesiol & Crit Care Med, Los Angeles, CA 90027 USA.
   [Harrison, Rick] Univ Calif Los Angeles, Dept Pediat, Mattel Childrens Hosp, Los Angeles, CA 90024 USA.
   [Wessel, David L.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
   [Shanley, Thomas] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat, Ann Arbor, MI 48109 USA.
   [Carcillo, Joseph] Childrens Hosp Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA.
   [Clark, Amy; Holubkov, Richard; Dean, J. Michael] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
   [Jenkins, Tammara L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
   [Doctor, Allan] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
RP Meert, KL (reprint author), Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
EM kmeert@med.wayne.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health, Department of Health and
   Human Services [U10HD050096, U10HD049981, U10HD063108, U10HD063106,
   U10HD063114, U10HD049983, U10HD050012, U01HD049934]; National Institutes
   of Health (NIH); NIH
FX Supported, in part, by the following cooperative agreements from the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health, Department of Health and
   Human Services: U10HD050096, U10HD049981, U10HD063108, U10HD063106,
   U10HD063114, U10HD049983, U10HD050012, and U01HD049934.; Dr. Meert is
   employed by the Cincinnati Children's Hospital (one-time consultancy
   visit unrelated to article) and received support for article research
   from the National Institutes of Health (NIH). Her institution received
   grant support from the NIH. Dr. Keele is employed by Pediatric
   Anesthesia Associates
NR 29
TC 7
Z9 7
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1529-7535
EI 1947-3893
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD SEP
PY 2015
VL 16
IS 7
BP E231
EP E238
DI 10.1097/PCC.0000000000000520
PG 8
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA DD1UK
UT WOS:000369707300007
PM 26335128
ER

PT J
AU Komarow, HD
   Eisch, AR
   Young, M
   Nelson, C
   Metcalfe, DD
AF Komarow, Hirsh D.
   Eisch, A. Robin
   Young, Michael
   Nelson, Celeste
   Metcalfe, Dean D.
TI Solar Urticaria
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
LA English
DT Editorial Material
C1 [Komarow, Hirsh D.; Eisch, A. Robin; Nelson, Celeste; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 1C129A1,10 Ctr Dr, Bethesda, MD 20892 USA.
   [Young, Michael] SAIC Frederick Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Clin Res, Frederick, MD USA.
RP Komarow, HD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 1C129A1,10 Ctr Dr, Bethesda, MD 20892 USA.
EM komarowh@niaid.nih.gov
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [ZIA AI000951-05];
   NCI NIH HHS [HHSN261200800001E]; PHS HHS [HHSN261200800001E]
NR 7
TC 1
Z9 1
U1 2
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2198
EI 2213-2201
J9 J ALLER CL IMM-PRACT
JI J. Allergy Clin. Immunol.-Pract.
PD SEP-OCT
PY 2015
VL 3
IS 5
BP 789
EP 790
DI 10.1016/j.jaip.2015.04.006
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA DB6ZX
UT WOS:000368665300023
PM 25982230
ER

PT J
AU Gilbert, PB
   Gabriel, EE
   Huang, Y
   Chan, ISF
AF Gilbert, Peter B.
   Gabriel, Erin E.
   Huang, Ying
   Chan, Ivan S. F.
TI Surrogate Endpoint Evaluation: Principal Stratification Criteria and the
   Prentice Definition
SO JOURNAL OF CAUSAL INFERENCE
LA English
DT Article
DE clinical trial; principal stratification; surrogate paradox; vaccine
   efficacy trial; Zoster
ID VACCINE TRIALS; CLINICAL-TRIALS; BAYESIAN-APPROACH; EFFICACY; OUTCOMES;
   MARKERS; DESIGN; COHORT
AB A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e. assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata subpopulations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect modification analysis and is closely connected to the treatment marker selection problem. The results are illustrated with application to a vaccine efficacy trial, where ACN and ACS for an antibody marker are found to be consistent with the data and hence support the Prentice definition and consistency.
C1 [Gilbert, Peter B.; Huang, Ying] Fred Hutchinson Canc Res Ctr, Vaccine Infect Dis Div, Seattle, WA 98109 USA.
   [Gilbert, Peter B.; Huang, Ying] Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
   [Gabriel, Erin E.] NIAID, Biostat Branch, Bethesda, MD 20817 USA.
   [Chan, Ivan S. F.] Merck & Co Inc, Whitehouse Stn, NJ 08889 USA.
RP Gilbert, PB (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine Infect Dis Div, Seattle, WA 98109 USA.
EM pgilbert@scharp.org; eeg14@uw.edu; yhuang@fhcrc.org; ivan_chan@merck.com
FU NIAID NIH HHS [R37 AI054165, UM1 AI068635]; NIGMS NIH HHS [R01
   GM106177]; NIH HHS [S10 OD020069]
NR 29
TC 1
Z9 1
U1 0
U2 0
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 2193-3677
EI 2193-3685
J9 J CAUSAL INFERENCE
JI J. Causal Inference
PD SEP
PY 2015
VL 3
IS 2
BP 157
EP 175
DI 10.1515/jci-2014-0007
PG 19
WC Mathematics, Interdisciplinary Applications
SC Mathematics
GA DC3DM
UT WOS:000369099500002
PM 26722639
ER

PT J
AU Madhavan, S
   Brooks, A
AF Madhavan, Sangeetha
   Brooks, Alyssa
TI Family Complexity in Rural South Africa: Examining Dynamism in
   Children's Living Arrangement and the Role of Kin
SO JOURNAL OF COMPARATIVE FAMILY STUDIES
LA English
DT Article
ID INVOLVEMENT; FERTILITY; FATHERS; SUPPORT
AB It is well established that Black African children in South Africa live in complex living arrangements. Far less, however, is known about the dynamism in children's living arrangements over the life course or the extent to which kin group characteristics influence the intensity of change in these arrangements. In this article, we draw on data collected on 337 children aged 0-21 embedded in 13 kin groups in Mpumalanga, South Africa to (a) describe the types of living arrangements that children are in at the time of birth and in 2002; (b) examine the extent of change and stability in living arrangements over two points in time; (c) describe the variation in the intensity of change in living arrangements over the life course; and (d) analyze the extent to which kin group characteristics help explain this variation. Our analysis shows that most children are in the same living arrangement at birth and in 2002 but that those born into a nuclear arrangement are most likely to change. Moreover, we also found considerable variation in the number of changes in living arrangements that children experience over the life course. The proportion of dependents in the kin group and the living arrangement at the time of birth explained some of this variation controlling for age and parental attributes.
C1 [Madhavan, Sangeetha] Univ Maryland, 1119 Taliaferro Hall,4280 Chapel Lane, College Pk, MD 20742 USA.
   [Brooks, Alyssa] NIH, 10 Ctr Dr,Room 2B12C, Bethesda, MD 20892 USA.
RP Madhavan, S (reprint author), Univ Maryland, 1119 Taliaferro Hall,4280 Chapel Lane, College Pk, MD 20742 USA.
EM smadhava@umd.edu; alyssa524@gmail.com
FU National Science Foundation [BCS-0109916]
FX We are grateful for comments provided by Natasha Cabrera on earlier
   drafts of the paper. The fieldwork was supported by the National Science
   Foundation (BCS-0109916).
NR 36
TC 0
Z9 0
U1 2
U2 2
PU J COMPARATIVE FAMILY STUDIES
PI CALGARY
PA UNIV CALGARY-DEPT SOCIOLOGY 2500 UNIVERSITY DRIVE NW, CALGARY, AB T2N
   1N4, CANADA
SN 0047-2328
J9 J COMP FAM STUD
JI J. Comp. Fam. Stud.
PD FAL
PY 2015
VL 46
IS 4
BP 483
EP +
PG 17
WC Family Studies
SC Family Studies
GA DC1EW
UT WOS:000368960600004
ER

PT J
AU Vojdeman, FJ
   Kirkby, N
   Herman, SEM
   Wiestner, A
   Veer, MBV
   Tjonnfjord, G
   Remes, MI
   Kimby, E
   Polliack, A
   Wu, KL
   Doorduijn, J
   Alemayehu, WG
   Wittebol, S
   Kozak, T
   Walewski, J
   Abrahamse-Testroote, MCJ
   van Oers, MHJ
   Niemann, CU
   Geisler, CH
AF Vojdeman, Fie Juhl
   Kirkby, Nikolai
   Herman, Sarah E. M.
   Wiestner, Adrian
   Veer, Mars B. van T.
   Tjonnfjord, Geir
   Remes, Maija I.
   Kimby, Eva
   Polliack, Aaron
   Wu, Ka L.
   Doorduijn, Jeanette
   Alemayehu, Wendimagegn G.
   Wittebol, Shulamiet
   Kozak, Tomas
   Walewski, Jan
   Abrahamse-Testroote, Martine C. J.
   van Oers, Marinus H. J.
   Niemann, Carsten U.
   Geisler, Christian H.
TI Soluble Cd52 levels predict time to first treatment for patients with
   chronic lymphocytic leukemia
SO LEUKEMIA & LYMPHOMA
LA English
DT Meeting Abstract
C1 [Vojdeman, Fie Juhl; Niemann, Carsten U.; Geisler, Christian H.] Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark.
   [Kirkby, Nikolai] Rigshosp, Dept Microbiol, DK-2100 Copenhagen, Denmark.
   [Herman, Sarah E. M.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   [Veer, Mars B. van T.] Leiden Univ, Med Ctr, Dept Hematol, Leiden, Netherlands.
   [Tjonnfjord, Geir] Oslo Univ Hosp, Dept Haematol, Oslo, Norway.
   [Remes, Maija I.] Turku Cent Univ Hosp, Turku, Finland.
   [Kimby, Eva] Karolinska Inst, Dept Med Huddinge, Div Hematol, Stockholm, Sweden.
   [Polliack, Aaron] Hebrew Univ Jerusalem, Sch Med, Hadassah Univ Hosp, Dept Hematol, IL-91010 Jerusalem, Israel.
   [Wu, Ka L.] Stuivenberg Hosp, Dept Hematol, Antwerp, Belgium.
   [Doorduijn, Jeanette] Erasmus MC Canc Ctr, Dept Hematol, Rotterdam, Netherlands.
   [Alemayehu, Wendimagegn G.; Wittebol, Shulamiet; Abrahamse-Testroote, Martine C. J.] Erasmus MC, HOVON Data Ctr, Rotterdam, Netherlands.
   [Kozak, Tomas] Charles Univ Hosp Kralovske Vinohrady, Fac Med 3, Dept Clin Hematol, Prague, Czech Republic.
   [Walewski, Jan] Maria Sklodowska Curie Mem Inst & Oncol Ctr, Lymphoid Malignancies, Warsaw, Poland.
   [van Oers, Marinus H. J.] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands.
RI Kozak, Tomas/K-3561-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
EI 1029-2403
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD SEP 1
PY 2015
VL 56
SU 1
SI SI
MA 160
BP 134
EP 136
PG 3
WC Oncology; Hematology
SC Oncology; Hematology
GA DB7QH
UT WOS:000368710200161
ER

PT J
AU Wiestner, A
   Lipsky, A
   Farooqui, M
   Tian, X
   Cullinane, A
   Nghiem, K
   Lozier, J
AF Wiestner, Adrian
   Lipsky, Andrew
   Farooqui, Mohammed
   Tian, Xin
   Cullinane, Ann
   Nghiem, Khanh
   Lozier, Jay
TI Incidence and risk factors of bleedingrelated adverse events in patients
   with chronic lymphocytic leukemia treated with ibrutinib
SO LEUKEMIA & LYMPHOMA
LA English
DT Meeting Abstract
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
   NIH, DLM, CC, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
EI 1029-2403
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD SEP 1
PY 2015
VL 56
SU 1
SI SI
MA 190
BP 163
EP 164
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA DB7QH
UT WOS:000368710200191
ER

PT J
AU Riley, WT
   Nilsen, WJ
   Manolio, TA
   Masys, DR
   Lauer, M
AF Riley, William T.
   Nilsen, Wendy J.
   Manolio, Teri A.
   Masys, Daniel R.
   Lauer, Michael
TI News from the NIH: potential contributions of the behavioral and social
   sciences to the precision medicine initiative
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Editorial Material
DE Precision medicine; Tailored interventions; Personalized medicine;
   Mobile health; Health informatics; Pharmacogenetics; Cohort studies;
   Behavioral risk factors; Environmental risk factors
ID PERSONALIZED MEDICINE; SMOKING-CESSATION; HEALTH; PROMOTION; DISEASE;
   PROJECT; RISK
C1 [Riley, William T.; Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, 30 Ctr Dr, Bethesda, MD USA.
   [Manolio, Teri A.] NHGRI, Div Genom Med, Bethesda, MD 20892 USA.
   [Masys, Daniel R.] Univ Washington, Sch Med, Dept Biomed Informat & Med Educ, Seattle, WA 98109 USA.
   [Lauer, Michael] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Riley, WT (reprint author), NIH, Off Behav & Social Sci Res, 30 Ctr Dr, Bethesda, MD USA.
EM William.Riley@nih.gov
NR 28
TC 5
Z9 5
U1 2
U2 9
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD SEP
PY 2015
VL 5
IS 3
BP 243
EP 246
DI 10.1007/s13142-015-0320-5
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC0LR
UT WOS:000368909300001
PM 26327928
ER

PT J
AU Spruijt-Metz, D
   Hekler, E
   Saranummi, N
   Intille, S
   Korhonen, I
   Nilsen, W
   Rivera, DE
   Spring, B
   Michie, S
   Asch, DA
   Sanna, A
   Salcedo, VT
   Kukakfa, R
   Pavel, M
AF Spruijt-Metz, Donna
   Hekler, Eric
   Saranummi, Niilo
   Intille, Stephen
   Korhonen, Ilkka
   Nilsen, Wendy
   Rivera, Daniel E.
   Spring, Bonnie
   Michie, Susan
   Asch, David A.
   Sanna, Alberto
   Salcedo, Vicente Traver
   Kukakfa, Rita
   Pavel, Misha
TI Building new computational models to support health behavior change and
   maintenance: new opportunities in behavioral research
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Mobile health; mHealth; Connected health; Health-related behavior;
   Just-in-time adaptive interventions; Real-time interventions;
   Computational models of behavior
ID CHANGE INTERVENTIONS; UNITED-STATES; OBESITY; PREVENTION; FRAMEWORK
AB Adverse and suboptimal health behaviors and habits are responsible for approximately 40 % of preventable deaths, in addition to their unfavorable effects on quality of life and economics. Our current understanding of human behavior is largely based on static "snapshots" of human behavior, rather than ongoing, dynamic feedback loops of behavior in response to ever-changing biological, social, personal, and environmental states. This paper first discusses how new technologies (i.e., mobile sensors, smartphones, ubiquitous computing, and cloud-enabled processing/computing) and emerging systems modeling techniques enable the development of new, dynamic, and empirical models of human behavior that could facilitate just-in-time adaptive, scalable interventions. The paper then describes concrete steps to the creation of robust dynamic mathematical models of behavior including: (1) establishing "gold standard" measures, (2) the creation of a behavioral ontology for shared language and understanding tools that both enable dynamic theorizing across disciplines, (3) the development of data sharing resources, and (4) facilitating improved sharing of mathematical models and tools to support rapid aggregation of the models. We conclude with the discussion of what might be incorporated into a "knowledge commons," which could help to bring together these disparate activities into a unified system and structure for organizing knowledge about behavior.
C1 [Spruijt-Metz, Donna] Univ So Calif, 635 Downey Way,Suite 305 Bldg Code VPD 3332, Los Angeles, CA 90089 USA.
   [Hekler, Eric; Rivera, Daniel E.] Arizona State Univ, Tempe, AZ USA.
   [Saranummi, Niilo; Pavel, Misha] VTT Tech Res Ctr Finland, Espoo, Finland.
   [Intille, Stephen] Northeastern Univ, Boston, MA 02115 USA.
   [Korhonen, Ilkka] Tampere Univ Technol, FIN-33101 Tampere, Finland.
   [Nilsen, Wendy] NIH, Bethesda, MD 20892 USA.
   [Spring, Bonnie] Northwestern Univ, Evanston, IL USA.
   [Michie, Susan] UCL, London, England.
   [Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
   [Sanna, Alberto] Hosp San Raffaelle, Inst Sci, Milan, Italy.
   [Salcedo, Vicente Traver] Univ Politecn Valencia, Valencia, Spain.
   [Kukakfa, Rita] Columbia Univ, New York, NY USA.
RP Spruijt-Metz, D (reprint author), Univ So Calif, 635 Downey Way,Suite 305 Bldg Code VPD 3332, Los Angeles, CA 90089 USA.
EM dmetz@usc.edu
RI Korhonen, Ilkka/G-4301-2014; 
OI Korhonen, Ilkka/0000-0002-5322-8469; Spruijt-Metz,
   Donna/0000-0002-3884-4300; Rivera, Daniel/0000-0002-3141-0577
FU National Science Foundation [CISE IIS-1217464]
FX This project was funded by the National Science Foundation (CISE
   IIS-1217464)
NR 87
TC 9
Z9 9
U1 7
U2 19
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD SEP
PY 2015
VL 5
IS 3
BP 335
EP 346
DI 10.1007/s13142-015-0324-1
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC0LR
UT WOS:000368909300012
PM 26327939
ER

PT J
AU Schweitzer, CJ
   Liang, TJ
AF Schweitzer, Cameron J.
   Liang, T. Jake
TI Border Control in Hepatitis C Virus Infection: Inhibiting Viral Entry
SO ACS INFECTIOUS DISEASES
LA English
DT Article
DE viral entry; HCV; antiviral; antibodies; small molecules
ID HUMAN MONOCLONAL-ANTIBODY; B TYPE-I; HUMANIZED MICE; NEUTRALIZING
   ANTIBODIES; ENVELOPE GLYCOPROTEIN; ANTIVIRAL ACTIVITY; HUMAN
   HEPATOCYTES; FUTURE TREATMENT; HCV; CHOLESTEROL
AB A new era has begun in the treatment of hepatitis C virus (HCV) infection with powerful yet expensive therapies. New treatments are emerging that target the entry step of HCV and could potentially block reinfection after liver transplant. These treatments include antibodies, which target the virus or host receptors required by HCV. Additionally, several new and previously approved small-molecule compounds have been described that target unique aspects of HCV entry. Overall, the blocking entry represents an attractive strategy that could yield powerful combination therapies to combat HCV.
C1 [Schweitzer, Cameron J.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Schweitzer, CJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM cameron.schweitzer@nih.gov
NR 33
TC 0
Z9 0
U1 2
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2373-8227
J9 ACS INFECT DIS
JI ACS Infect. Dis.
PD SEP
PY 2015
VL 1
IS 9
SI SI
BP 416
EP 419
DI 10.1021/acsinfecdis.5b00060
PG 4
WC Chemistry, Medicinal; Infectious Diseases
SC Pharmacology & Pharmacy; Infectious Diseases
GA DB4DQ
UT WOS:000368464100004
PM 27617924
ER

PT J
AU Mazoyer, C
   Carlier, J
   Sastre, C
   Di Fazio, V
AF Mazoyer, Cedric
   Carlier, Jeremy
   Sastre, Caroline
   Di Fazio, Vincent
TI Synthetic cannabinoids: Analytical methods
SO TOXICOLOGIE ANALYTIQUE ET CLINIQUE
LA French
DT Review
DE Synthetic cannabinoids; Analytical methods; Mass spectrometry;
   Chromatography; Immunoassay
ID TANDEM MASS-SPECTROMETRY; DESORPTION ELECTROSPRAY-IONIZATION;
   THIN-LAYER-CHROMATOGRAPHY; DESIGNER DRUGS; ORAL FLUID; LC-MS/MS; HUMAN
   URINE; STRUCTURAL-CHARACTERIZATION; JWH-018 METABOLITES; HERBAL INCENSE
AB Considering the growing interest in synthetic cannabinoids, we propose to review the main analytical methods allowing their detection and/or quantification in biological samples (blood, urine, oral fluid and hair) and products (powders, herbal mixtures). The main separation and detection methods are discussed (immunoassay, thin layer chromatography, liquid and gas chromatography, mass spectrometry, infrared spectroscopy, nuclear magnetic resonance). The knowledge of current methods and new analytical perspectives will allow the toxicologist to cope with the problematic of synthetic cannabinoids analysis. (C) 2015 Societe Francaise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.
C1 [Carlier, Jeremy] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Sastre, Caroline] Univ Aix Marseille 2, Fac Med, Serv Med Legale, F-13385 Marseille 05, France.
   [Di Fazio, Vincent] Inst Natl Criminalist & Criminol, Lab Toxicol, B-1120 Brussels, Belgium.
RP Mazoyer, C (reprint author), 19B,2e Impasse Comete, F-26000 Valence, France.
EM mazoyerc@yahoo.fr
OI Mazoyer, Cedric/0000-0002-7086-3261
NR 68
TC 2
Z9 2
U1 8
U2 24
PU ELSEVIER MASSON SAS EDITEUR
PI ISSY LES  MOULINEAUX CEDEX
PA 62, RUE CAMILLE DESMOULINS, ISSY LES  MOULINEAUX CEDEX, 92442, FRANCE
SN 2352-0078
EI 2352-0086
J9 TOXICOL ANAL CLIN
JI Toxicol. Anal. Clin.
PD SEP
PY 2015
VL 27
IS 3
BP 184
EP 194
DI 10.1016/j.toxac.2015.03.112
PG 11
WC Toxicology
SC Toxicology
GA DA0BV
UT WOS:000367462600007
ER

PT J
AU Peuralinna, T
   Myllykangas, L
   Oinas, M
   Nalls, MA
   Keage, HAD
   Isoviita, VM
   Valori, M
   Polvikoski, T
   Paetau, A
   Sulkava, R
   Ince, PG
   Zaccai, J
   Brayne, C
   Traynor, BJ
   Hardy, J
   Singleton, AB
   Tienari, PJ
AF Peuralinna, Terhi
   Myllykangas, Liisa
   Oinas, Minna
   Nalls, Mike A.
   Keage, Hannah A. D.
   Isoviita, Veli-Matti
   Valori, Miko
   Polvikoski, Tuomo
   Paetau, Anders
   Sulkava, Raimo
   Ince, Paul G.
   Zaccai, Julia
   Brayne, Carol
   Traynor, Bryan J.
   Hardy, John
   Singleton, Andrew B.
   Tienari, Pentti J.
TI Genome-wide association study of neocortical Lewy-related pathology
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID SPORADIC PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; BODY
   DISORDERS; RISK-FACTOR; HLA REGION; BODIES DLB; DEMENTIA; BRAIN;
   MUTATIONS
AB Objective: Dementia with Lewy bodies is an alpha-synucleinopathy characterized by neocortical Lewy-related pathology (LRP). We carried out a genome-wide association study (GWAS) on neocortical LRP in a population-based sample of subjects aged 85 or over. Methods: LRP was analyzed in 304 subjects in the Vantaa 85+ sample from Southern Finland. The GWAS included 41 cases with midbrain, hippocampal, and neocortical LRP and 177 controls without midbrain and hippocampal LRP. The Medical Research Council Cognitive Function and Ageing Study (CFAS) material was used for replication (51 cases and 131 controls). Results: By analyzing 327,010 markers the top signal was obtained at the HLA-DPA1/DPB1 locus (P = 1.29 x 10(-7)); five other loci on chromosomes 15q14, 2p21, 2q31, 18p11, and 5q23 were associated with neocortical LRP at P < 10(-5). Two loci were marked by multiple markers, 2p21 (P = 3.9 x 10(-6), upstream of the SPTBN1 gene), and HLA-DPA1/DPB1; these were tested in the CFAS material. Single marker (P = 0.0035) and haplotype (P = 0.04) associations on 2p21 were replicated in CFAS, whereas HLA-DPA1/DPB1 association was not. Bioinformatic analyses suggest functional effects for the HLA-DPA1/DPB1 markers as well as the 15q14 marker rs8037309. Interpretation: We identified suggestive novel risk factors for neocortical LRP. SPTBN1 is the candidate on 2p21, it encodes beta-spectrin, an alpha-synuclein binding protein and a component of Lewy bodies. The HLA-DPA1/DPB1 association suggests a role for antigen presentation or alternatively, cis-regulatory effects, one of the regulated neighboring genes identified here (vacuolar protein sorting 52) plays a role in vesicular trafficking and has been shown to interact with alpha-synuclein in a yeast model.
C1 [Peuralinna, Terhi; Isoviita, Veli-Matti; Valori, Miko; Tienari, Pentti J.] Univ Helsinki, Biomedicum, Mol Neurol, Res Program Unit, FIN-00290 Helsinki, Finland.
   [Myllykangas, Liisa; Oinas, Minna; Paetau, Anders] Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00290 Helsinki, Finland.
   [Myllykangas, Liisa; Oinas, Minna; Paetau, Anders] HUSLAB, Helsinki, Finland.
   [Myllykangas, Liisa] Folkhalsan Inst Genet, Helsinki, Finland.
   [Oinas, Minna] Helsinki Univ Cent Hosp, Dept Neurosurg, Helsinki, Finland.
   [Nalls, Mike A.; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Keage, Hannah A. D.] Univ S Australia, Sch Psychol Social Work & Social Policy, Adelaide, SA 5001, Australia.
   [Keage, Hannah A. D.; Zaccai, Julia; Brayne, Carol] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Polvikoski, Tuomo] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Sulkava, Raimo] Univ Eastern Finland, Sch Publ Hlth & Clin Nutr, Kuopio, Finland.
   [Ince, Paul G.] Univ Sheffield, Dept Neurosci, Sheffield, S Yorkshire, England.
   [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Hardy, John] UCL Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London, England.
   [Hardy, John] UCL Inst Neurol, Reta Lila Weston Res Labs, Dept Clin Neurosci, London, England.
   [Tienari, Pentti J.] Helsinki Univ Cent Hosp, Dept Neurol, Helsinki, Finland.
RP Tienari, PJ (reprint author), Univ Helsinki, Biomedicum, Mol Neurol, Res Program Unit, Haartmaninkatu 8, FIN-00290 Helsinki, Finland.
EM pentti.tienari@hus.fi
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; 
OI Keage, Hannah/0000-0002-6814-4997
FU Medical Research Council [MR/L016451/1, G0400074, G0900652, G0502157,
   G0900582, G1100540]; NIA NIH HHS [Z01 AG000950, ZIA AG000932]
NR 40
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD SEP
PY 2015
VL 2
IS 9
BP 920
EP 931
DI 10.1002/acn3.231
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CZ6VD
UT WOS:000367238200005
PM 26401513
ER

PT J
AU Diaz, A
   Enomoto, S
   Romagosa, A
   Sreevatsan, S
   Nelson, M
   Culhane, M
   Torremorell, M
AF Diaz, Andres
   Enomoto, Shinichiro
   Romagosa, Anna
   Sreevatsan, Srinand
   Nelson, Martha
   Culhane, Marie
   Torremorell, Montserrat
TI Genome plasticity of triple-reassortant H1N1 influenza A virus during
   infection of vaccinated pigs
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID EVOLUTIONARY DYNAMICS; ANTIGENIC DRIFT; MUTANT SPECTRUM; DNA-POLYMERASE;
   UNITED-STATES; SEQUENCE DATA; US SWINE; TRANSMISSION; IMMUNITY; PCR
AB To gain insight into the evolution of influenza A viruses (IAVs) during infection of vaccinated pigs, we experimentally infected a 3-week-old naive pig with a triple-reassortant H1N1 IAV and placed the seeder pig in direct contact with a group of age-matched vaccinated pigs (n=10). We indexed the genetic diversity and evolution of the virus at an intra-host level by deep sequencing the entire genome directly from nasal swabs collected at two separate samplings during infection. We obtained 13 IAV metagenomes from 13 samples, which included the virus inoculum and two samples from each of the six pigs that tested positive for IAV during the study. The infection produced a population of heterogeneous alleles (sequence variants) that was dynamic over time. Overall, 794 polynnorphisms were identified amongst all samples, which yielded 327 alleles, 214 of which were unique sequences. A total of 43 distinct haemagglutinin proteins were translated, two of which were observed in multiple pigs, whereas the neuraminidase (NA) was conserved and only one dominant NA was found throughout the study. The genetic diversity of IAVs changed dynamically within and between pigs. However, most of the substitutions observed in the internal gene segments were synonymous. Our results demonstrated remarkable IAV diversity, and the complex, rapid and dynamic evolution of IAV during infection of vaccinated pigs that can only be appreciated with repeated sampling of individual animals and deep sequence analysis.
C1 [Diaz, Andres; Romagosa, Anna; Sreevatsan, Srinand; Culhane, Marie; Torremorell, Montserrat] Univ Minnesota St Paul, Coll Vet Med, St Paul, MN 55108 USA.
   [Enomoto, Shinichiro] Univ Utah, Dept Biol, South Lake City, UT USA.
   [Nelson, Martha] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Torremorell, M (reprint author), Univ Minnesota St Paul, Coll Vet Med, St Paul, MN 55108 USA.
EM torr003@umn.edu
OI Sreevatsan, Srinand/0000-0002-5162-2403
FU National Institutes of Health [HHSN266200700007C]; US Department of
   Agriculture Discretionary GAR Funds as part of Signature Program at
   College of Veterinary Medicine University of Minnesota [AES0060014];
   COLCIENCIAS: Departamento Administrativo de Ciencia, Tecnologia e
   Innovacion
FX This work was supported in whole or in part by federal funds from the
   National Institutes of Health (contract HHSN266200700007C), the US
   Department of Agriculture Discretionary GAR Funds (AES0060014) as part
   of the Signature Program Funding at the College of Veterinary Medicine
   University of Minnesota and COLCIENCIAS: Departamento Administrativo de
   Ciencia, Tecnologia e Innovacion. The authors would like to acknowledge
   Dr Douglas Marthaler from the University of Minnesota Veterinary
   Diagnostic Laboratory for his technical assistance, and the Minnesota
   Supercomputing Institute at the University of Minnesota.
NR 64
TC 0
Z9 0
U1 0
U2 3
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
   BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD SEP
PY 2015
VL 96
BP 2982
EP 2993
DI 10.1099/jgv.0.000258
PN 10
PG 12
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA CZ6LL
UT WOS:000367212700005
PM 26251306
ER

PT J
AU Devine, K
   Mumford, SL
   Wu, M
   DeCherney, AH
   Hill, MJ
   Propst, A
AF Devine, Kate
   Mumford, Sunni L.
   Wu, Mae
   DeCherney, Alan H.
   Hill, Micah J.
   Propst, Anthony
TI Diminished ovarian reserve in the United States assisted reproductive
   technology population: diagnostic trends among 181,536 cycles from the
   Society for Assisted Reproductive Technology Clinic Outcomes Reporting
   System
SO FERTILITY AND STERILITY
LA English
DT Article
DE Diminished ovarian reserve; poor ovarian response; live birth;
   diagnosis; FSH
ID IN-VITRO FERTILIZATION; ANTRAL FOLLICLE COUNT; RANDOMIZED
   CONTROLLED-TRIAL; LIVE BIRTH-RATES; BOLOGNA CRITERIA; POOR RESPONDERS;
   STIMULATING-HORMONE; PREDICTIVE-VALUE; WOMEN; IVF
AB Objective: To evaluate trends in diminished ovarian reserve (DOR) assignment in the Society for Assisted Reproductive Technology (SART) Clinic Outcomes Reporting System database and to evaluate its accuracy in predicting poor ovarian response (POR) as defined in European Society of Human Reproduction and Embryology's Bologna criteria (2011).
   Design: Retrospective cohort study.
   Setting: Not applicable.
   Patient(s): A total of 181,536 fresh, autologous ART cycles reported to SART by U.S. clinics in 2004 and 2011 (earliest and most recent available reporting years).
   Intervention(s): None.
   Main Outcome Measure(s): DOR assignment was the primary exposure. POR, defined as cycle cancellation for poor response or less than 4 oocytes retrieved after conventional gonadotropin stimulation (>149 IU FSH daily), was the primary outcome. Secondary outcomes were live birth and number of oocytes retrieved. DOR prevalence, power of DOR and FSH (</>= 12 mIU/mL) to predict POR, and live birth in POR cycles were also calculated.
   Result(s): DOR prevalence increased from 19% to 26% from 2004 to 2011. Among cycles clinically assigned as DOR, incidence of POR decreased from 32% to 30%, and live birth improved from 15% to 17%. Comparing basal FSH >= 12 versus clinical assignment of DOR, basal FSH had a higher specificity (92.2% vs. 81.6%) and positive predictive value (38.3% vs. 30.9%) for predicting POR. Live birth among POR cycles was 4%.
   Conclusion(s): DOR diagnosis is increasing, and accuracy remains poor, despite the availability of additional diagnostic parameters such as antral follicle count and antimullerian hormone. POR entailed poor outcomes, but the majority of patients clinically assigned as DOR did not experience POR. Development and use of more accurate predictors of POR are needed to minimize patient distress resulting from overdiagnosis. (C) 2015 by American Society for Reproductive Medicine.
C1 [Devine, Kate; Wu, Mae; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
   [Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
   [Hill, Micah J.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
   [Propst, Anthony] Texas Fertil Ctr, Austin, TX USA.
RP Devine, K (reprint author), 10 Ctr Dr,MSC 1109,Rm 1-3140, Bethesda, MD 20892 USA.
EM kate.devine@nih.gov
FU Program in Reproductive and Adult Endocrinology; Intramural Research
   Program, National Institute of Child Health and Human Development,
   National Institutes of Health
FX Supported by the Program in Reproductive and Adult Endocrinology and the
   Intramural Research Program, National Institute of Child Health and
   Human Development, National Institutes of Health.
NR 43
TC 5
Z9 6
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2015
VL 104
IS 3
BP 612
EP +
DI 10.1016/j.fertnstert.2015.05.017
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CY5YP
UT WOS:000366484100023
PM 26049057
ER

PT J
AU Bennuru, S
AF Bennuru, Sasisekhar
TI Understanding Hidden Antigens and Targeting Parasitic Nematodes
SO EBIOMEDICINE
LA English
DT Editorial Material
ID PROTEINS
C1 [Bennuru, Sasisekhar] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
RP Bennuru, S (reprint author), NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD SEP
PY 2015
VL 2
IS 9
BP 1010
EP 1011
DI 10.1016/j.ebiom.2015.09.021
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX8MK
UT WOS:000365957600004
PM 26501090
ER

PT J
AU Ryerson, LZ
   Kister, I
   Foley, J
   Remington, G
   Weinstock-Guttman, B
   Pandey, K
   Pawate, S
   Bomprezzi, R
   Smith, D
   Hojnacki, D
   Kolb, C
   Okuda, D
   Frohman, T
   Kalina, J
   Hoyt, T
   Green, R
   Fox, M
   Donnelly, S
   Chamot, E
   Major, E
   Frohman, E
AF Ryerson, L. Zhovtis
   Kister, I.
   Foley, J.
   Remington, G.
   Weinstock-Guttman, B.
   Pandey, K.
   Pawate, S.
   Bomprezzi, R.
   Smith, D.
   Hojnacki, D.
   Kolb, C.
   Okuda, D.
   Frohman, T.
   Kalina, J.
   Hoyt, T.
   Green, R.
   Fox, M.
   Donnelly, S.
   Chamot, E.
   Major, E.
   Frohman, E.
TI Extending natalizumab treatment up to eight weeks shown safe and
   effective in patients with multiple sclerosis: updated analysis from an
   ongoing multicenter study
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Ryerson, L. Zhovtis; Kister, I.; Kalina, J.; Fox, M.] NYU, Langone Med Ctr, New York, NY USA.
   [Foley, J.; Hoyt, T.] Rocky Mt MS Clin, Salt Lake City, UT USA.
   [Remington, G.; Okuda, D.; Frohman, T.; Frohman, E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Weinstock-Guttman, B.; Hojnacki, D.; Kolb, C.] SUNY Buffalo, Buffalo, NY 14260 USA.
   [Pandey, K.; Green, R.] Barnabas Hlth Syst, Livingston, NJ USA.
   [Pawate, S.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
   [Bomprezzi, R.] Univ Massachusetts, Sch Med, Wilcox, MA USA.
   [Smith, D.] Multiple Sclerosis Ctr Connecticut, Norwich, CT USA.
   [Donnelly, S.] CUNY, Grad Ctr, New York, NY USA.
   [Chamot, E.] Univ Alabama Birmingham, Birmingham, AL USA.
   [Major, E.] NINDS, Bethesda, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA 57
BP 13
EP 14
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400015
ER

PT J
AU Muraro, PA
   Pasquini, M
   Atkins, H
   Bowen, J
   Farge, D
   Fassas, A
   Freedman, MS
   Georges, GE
   Gualandi, F
   Hamerschlak, N
   Havrdova, E
   Kimiskidis, VK
   Kozak, T
   Mancardi, GL
   Massacesi, L
   Moraes, D
   Nash, RA
   Pavletic, S
   Ouyang, J
   Rovira, M
   Saiz, A
   Simoes, B
   Trneny, M
   Zhu, L
   Zhong, X
   Badoglio, M
   Sormani, MP
   Saccardi, R
AF Muraro, P. A.
   Pasquini, M.
   Atkins, H.
   Bowen, J.
   Farge, D.
   Fassas, A.
   Freedman, M. S.
   Georges, G. E.
   Gualandi, F.
   Hamerschlak, N.
   Havrdova, E.
   Kimiskidis, V. K.
   Kozak, T.
   Mancardi, G. L.
   Massacesi, L.
   Moraes, D.
   Nash, R. A.
   Pavletic, S.
   Ouyang, J.
   Rovira, M.
   Saiz, A.
   Simoes, B.
   Trneny, M.
   Zhu, L.
   Zhong, X.
   Badoglio, M.
   Sormani, M. P.
   Saccardi, R.
CA MS-AHSCT Long-Term Outcomes Study
TI Long term outcomes after autologous hematopoietic stem cell
   transplantation for treatment of MS
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Muraro, P. A.] Univ London Imperial Coll Sci Technol & Med, Div Brain Sci, London, England.
   [Pasquini, M.; Zhong, X.] Med Coll Wisconsin, CIBMTR Milwaukee, Dept Med, Div Hematol Oncol, Milwaukee, WI 53226 USA.
   [Atkins, H.] Univ Ottawa, Clin Hematol, Ottawa, ON, Canada.
   [Atkins, H.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
   [Bowen, J.] Swedish Neurosci Inst, MS Ctr, Seattle, WA USA.
   [Farge, D.] Hop St Louis, AP HP, INSERM UMRS 1160, Internal Med & Vasc Dis Unit, Paris, France.
   [Fassas, A.] Aristotle Univ Thessaloniki, Dept Hematol, GR-54006 Thessaloniki, Greece.
   [Freedman, M. S.] Univ Ottawa, Dept Neurol, Ottawa, ON, Canada.
   [Freedman, M. S.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
   [Georges, G. E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Georges, G. E.] Univ Washington, Seattle, WA 98195 USA.
   [Gualandi, F.] San Martino Hosp, Bone Marrow Transplantat Unit, Genoa, Italy.
   [Hamerschlak, N.] Hosp Israelita Albert Einstein, Bone Marrow Transplant Unit, Sao Paulo, Brazil.
   [Havrdova, E.] Charles Univ Prague, Med Fac 1, Dept Neurol, Prague, Czech Republic.
   [Kimiskidis, V. K.] Aristotle Univ Thessaloniki, Lab Clin Neurophysiol, GR-54006 Thessaloniki, Greece.
   [Kozak, T.] Charles Univ Prague, Fac Med 3, Dept Internal Med & Haematol, Prague, Czech Republic.
   [Kozak, T.] Fac Hosp Kralovske Vinohrady, Prague, Czech Republic.
   [Mancardi, G. L.] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy.
   [Massacesi, L.] Univ Florence, Dept Neurosci, Florence, Italy.
   [Moraes, D.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Clin Med, Sao Paulo, Brazil.
   [Nash, R. A.] Colorado Blood Canc Inst, Denver, CO USA.
   [Pavletic, S.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Ouyang, J.] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Hematol, Nanjing 210008, Jiangsu, Peoples R China.
   [Rovira, M.] Hosp Clin Barcelona, Hematol Serv, Barcelona, Spain.
   [Saiz, A.] Hosp Clin Barcelona, Neurol Serv, Barcelona, Spain.
   [Saiz, A.] Univ Barcelona, Inst Invest August Pi & Sunyer IDIBAPS, Barcelona, Spain.
   [Simoes, B.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Clin Med, Ribeirao Preto, Brazil.
   [Trneny, M.] Charles Univ Prague, Gen Hosp, Dept Med, Prague, Czech Republic.
   [Zhu, L.] Nanjing Med Univ, Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China.
   [Badoglio, M.] Hop St Antoine, EBMT Paris Off, F-75571 Paris, France.
   [Sormani, M. P.] Univ Genoa, Biostat Unit, Genoa, Italy.
   [Saccardi, R.] Careggi Univ Hosp, Haematol Dept, Florence, Italy.
RI Kozak, Tomas/K-3561-2012
NR 0
TC 0
Z9 0
U1 0
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA 193
BP 63
EP 64
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400107
ER

PT J
AU Solomon, AJ
   Schindler, MK
   Watts, R
   Sati, P
   Nickerson, JP
   Reich, DS
AF Solomon, A. J.
   Schindler, M. K.
   Watts, R.
   Sati, P.
   Nickerson, J. P.
   Reich, D. S.
TI The "central vessel sign" on 3T FLAIR* MRI differentiates multiple
   sclerosis from migraine
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Solomon, A. J.; Watts, R.; Nickerson, J. P.] Univ Vermont, Burlington, VT USA.
   [Schindler, M. K.; Sati, P.; Reich, D. S.] NINDS, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA 198
BP 67
EP 67
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400112
ER

PT J
AU Xia, Z
   White, C
   Reich, D
   Chibnik, L
   De Jager, P
AF Xia, Z.
   White, C.
   Reich, D.
   Chibnik, L.
   De Jager, P.
TI Genes and environment in multiple sclerosis: an integrated study of
   multiple sclerosis risk factors in first-degree relatives
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Xia, Z.; White, C.; Chibnik, L.; De Jager, P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
   [Reich, D.] NINDS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P361
BP 144
EP 144
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400252
ER

PT J
AU Sethi, VV
   Dewey, BE
   Sati, P
   Reich, DS
AF Sethi, V. V.
   Dewey, B. E.
   Sati, P.
   Reich, D. S.
TI 7T MP2RAGE for detection of cortical lesions
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Sethi, V. V.; Dewey, B. E.; Sati, P.; Reich, D. S.] NINDS, TNU, NIH, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P461
BP 199
EP 200
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400352
ER

PT J
AU Datta, R
   Sethi, V
   Waldman, AT
   Narula, S
   Dewey, BE
   Sati, P
   Reich, DS
   Banwell, BL
AF Datta, R.
   Sethi, V.
   Waldman, A. T.
   Narula, S.
   Dewey, B. E.
   Sati, P.
   Reich, D. S.
   Banwell, B. L.
TI Cortical lesions in pediatric-onset multiple sclerosis: a preliminary 7
   tesla view
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Datta, R.; Waldman, A. T.; Narula, S.; Banwell, B. L.] Childrens Hosp Philadelphia, Neurol, Philadelphia, PA 19104 USA.
   [Datta, R.; Waldman, A. T.; Narula, S.; Banwell, B. L.] Univ Penn, Neurol, Philadelphia, PA 19104 USA.
   [Sethi, V.; Dewey, B. E.; Sati, P.; Reich, D. S.] NINDS, Translat Neurol Unit, Div Neuroimmunol & Neurovirol, NIH, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P481
BP 210
EP 211
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400372
ER

PT J
AU Vuolo, L
   Dewey, B
   Sati, P
   Massacesi, L
   Reich, DS
AF Vuolo, L.
   Dewey, B.
   Sati, P.
   Massacesi, L.
   Reich, D. S.
TI Efficiency of FLAIR* at 1.5T, 3T, and 7T for detecting perivenular
   lesions in multiple sclerosis (MS)
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Vuolo, L.; Massacesi, L.] Univ Florence, Florence, Italy.
   [Dewey, B.; Sati, P.; Reich, D. S.] NINDS, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P479
BP 210
EP 210
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400370
ER

PT J
AU Bermel, RA
   Yankey, J
   Novalis, C
   Schneebaum, J
   Kaiser, P
   Coffey, C
   Cudkowicz, ME
   Gleason, T
   Goodman, A
   Klawiter, EC
   Matsuda, K
   McGovern, MM
   McNeil, E
   Naismith, R
   Fox, RJ
AF Bermel, R. A.
   Yankey, J.
   Novalis, C.
   Schneebaum, J.
   Kaiser, P.
   Coffey, C.
   Cudkowicz, M. E.
   Gleason, T.
   Goodman, A.
   Klawiter, E. C.
   Matsuda, K.
   McGovern, M. M.
   McNeil, E.
   Naismith, R.
   Fox, R. J.
TI OCT characteristics at baseline in the SPRINT-MS/NN 102 phase II trial
   of ibudilast in progressive MS
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Bermel, R. A.; Kaiser, P.; Fox, R. J.] Cleveland Clin, Cleveland, OH 44106 USA.
   [Yankey, J.; Coffey, C.] Univ Iowa, Iowa City, IA USA.
   [Novalis, C.; Schneebaum, J.] Digital Angiog Reading Ctr, Great Neck, NY USA.
   [Cudkowicz, M. E.; Klawiter, E. C.; McGovern, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Goodman, A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
   [Matsuda, K.] Medicinova Inc, San Diego, CA USA.
   [McNeil, E.] NINDS, Bethesda, MD 20892 USA.
   [Naismith, R.] Washington Univ, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P498
BP 219
EP 220
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400389
ER

PT J
AU Khoury, SJ
   Rochon, J
   Ding, L
   Byron, M
   Arnold, DL
   Cook, S
   Gao, W
   Tosta, P
   Sayre, PH
   Smilek, D
AF Khoury, S. J.
   Rochon, J.
   Ding, L.
   Byron, M.
   Arnold, D. L.
   Cook, S.
   Gao, W.
   Tosta, P.
   Sayre, P. H.
   Smilek, D.
CA ACCLAIM Study Grp
TI Costimulatory blockade with abatacept (CTLA4-Ig) in relapsing-remitting
   multiple sclerosis: results from the ACCLAIM trial
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Khoury, S. J.; Cook, S.] Brigham & Womens Hosp, Partners MS Ctr, Boston, MA 02115 USA.
   [Khoury, S. J.] AUBMC, Abu Haidar Neurosci Inst, Beirut, Lebanon.
   [Rochon, J.; Byron, M.] Rho Inc, Chapel Hill, NC USA.
   [Ding, L.; Gao, W.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
   [Arnold, D. L.] McGill Univ, Montreal, PQ, Canada.
   [Tosta, P.; Sayre, P. H.; Smilek, D.] Immune Tolerance Network, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P573
BP 269
EP 269
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400464
ER

PT J
AU Wundes, A
   Griffith, LM
   Georges, GE
   McLaughlin, BA
   Kane, CE
   Von Geldern, G
   Maravilla, KR
   Bowen, JD
   Kraft, GH
   Nash, RA
AF Wundes, A.
   Griffith, L. M.
   Georges, G. E.
   McLaughlin, B. A.
   Kane, C. E.
   Von Geldern, G.
   Maravilla, K. R.
   Bowen, J. D.
   Kraft, G. H.
   Nash, R. A.
TI The concept of no evidence of disease activity in multiple sclerosis
   after autologous hematopoietic stem cell transplantation - assessing
   outcome parameters across trials
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Wundes, A.; Von Geldern, G.; Maravilla, K. R.; Kraft, G. H.] Univ Washington, Seattle, WA 98195 USA.
   [Griffith, L. M.] NIAID, DAIT, Bethesda, MD 20892 USA.
   [Griffith, L. M.] NIAID, Bethesda, MD 20892 USA.
   [Griffith, L. M.] NIH, Bethesda, MD 20892 USA.
   [Georges, G. E.; McLaughlin, B. A.; Kane, C. E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Bowen, J. D.] Swedish Neurosci Inst, Seattle, WA USA.
   [Nash, R. A.] Colorado Blood Canc Inst, Denver, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P576
BP 271
EP 272
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729400467
ER

PT J
AU Leibovitch, E
   Caruso, B
   Sati, P
   Billioux, BJ
   Guy, J
   Li, X
   Lefeuvre, J
   Schindler, M
   Silva, A
   Reich, D
   Jacobson, S
AF Leibovitch, E.
   Caruso, B.
   Sati, P.
   Billioux, B. J.
   Guy, J.
   Li, X.
   Lefeuvre, J.
   Schindler, M.
   Silva, A.
   Reich, D.
   Jacobson, S.
TI Human herpesvirus 6 accelerates clinical and radiological disease in a
   nonhuman primate model of multiple sclerosis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Leibovitch, E.; Caruso, B.; Sati, P.; Billioux, B. J.; Guy, J.; Li, X.; Lefeuvre, J.; Schindler, M.; Silva, A.; Jacobson, S.] NINDS, NIH, Bethesda, MD 20892 USA.
   [Leibovitch, E.] George Washington Univ, Washington, DC USA.
   [Reich, D.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P862
BP 433
EP 433
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729401240
ER

PT J
AU Tiwari, H
   Patki, A
   Cofield, SS
   Gustafson, T
   Duggan, D
   Jacobson, S
   Wolinsky, JS
   Lublin, FD
   Cutter, GR
AF Tiwari, H.
   Patki, A.
   Cofield, S. S.
   Gustafson, T.
   Duggan, D.
   Jacobson, S.
   Wolinsky, J. S.
   Lublin, F. D.
   Cutter, G. R.
CA CombiRx Investigator Grp
TI GWAS on relapse outcomes in CombiRx trial
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Tiwari, H.; Patki, A.; Cofield, S. S.; Cutter, G. R.] Univ Alabama Birmingham, Biostat, Birmingham, AL USA.
   [Gustafson, T.; Lublin, F. D.] Mt Sinai Sch Med, Corinne Goldsmith Dickinson Ctr MS, New York, NY USA.
   [Duggan, D.] TGen, Phoenix, AZ USA.
   [Jacobson, S.] NIH, Bethesda, MD 20892 USA.
   [Wolinsky, J. S.] Univ Texas Hlth Sci Ctr Houston, Neurol, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P875
BP 440
EP 441
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729401253
ER

PT J
AU Sousa, ADA
   Jonhson, KR
   Nicholas, R
   Darko, S
   Price, D
   Douek, D
   Muraro, P
   Jacobson, S
AF Sousa, A. De Paula Alves
   Jonhson, K. R.
   Nicholas, R.
   Darko, S.
   Price, D.
   Douek, D.
   Muraro, P.
   Jacobson, S.
TI Expanded T-cell clonotype sequences showed specificity relatedness in
   the peripheral blood of MS patients by phylogenetic tree analysis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Sousa, A. De Paula Alves; Jonhson, K. R.; Jacobson, S.] NINDS, Bethesda, MD 20892 USA.
   [Nicholas, R.; Muraro, P.] Univ London Imperial Coll Sci Technol & Med, London, England.
   [Darko, S.; Douek, D.] NIAID, Bethesda, MD 20892 USA.
   [Price, D.] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales.
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P878
BP 442
EP 442
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729401256
ER

PT J
AU von Geldern, G
   Smith, B
   Reich, D
   Nath, A
   Cortese, I
AF von Geldern, G.
   Smith, B.
   Reich, D.
   Nath, A.
   Cortese, I.
TI A functional scale for progressive multifocal leukoencephalopathy: the
   NIH PML scale
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [von Geldern, G.] Univ Washington, Neurol, Seattle, WA 98195 USA.
   [Smith, B.; Reich, D.; Nath, A.; Cortese, I.] NINDS, Bethesda, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P1118
BP 580
EP 580
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729401495
ER

PT J
AU von Geldern, G
   Ryschkewitsch, C
   Monaco, MC
   Jensen, P
   Major, EO
AF von Geldern, G.
   Ryschkewitsch, C.
   Monaco, M. C.
   Jensen, P.
   Major, E. O.
TI The importance of low JC virus copy numbers in CSF in the diagnosis of
   progressive multifocal leukoencephalopathy in MS patients
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [von Geldern, G.] Univ Washington, Neurol, Seattle, WA 98195 USA.
   [Ryschkewitsch, C.; Monaco, M. C.; Jensen, P.; Major, E. O.] NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA P1122
BP 582
EP 582
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729401499
ER

PT J
AU Fox, RJ
   Coffey, C
   Cudkowicz, ME
   Gleason, T
   Goodman, A
   Klawiter, EC
   Matsuda, K
   McGovern, MM
   McNeil, E
   Naismith, R
   Yankey, J
AF Fox, R. J.
   Coffey, C.
   Cudkowicz, M. E.
   Gleason, T.
   Goodman, A.
   Klawiter, E. C.
   Matsuda, K.
   McGovern, M. M.
   McNeil, E.
   Naismith, R.
   Yankey, J.
TI SPRINT-MS/NN 102 phase II trial of ibudilast in progressive MS: baseline
   characteristics
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 31st Congress of the
   European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
   (ECTRIMS)
CY OCT 07-10, 2015
CL Barcelona, SPAIN
SP European Comm Treatment & Res Multiple Sclerosis
C1 [Fox, R. J.] Cleveland Clin, Cleveland, OH 44106 USA.
   [Coffey, C.; Yankey, J.] Univ Iowa, Iowa City, IA USA.
   [Cudkowicz, M. E.; Klawiter, E. C.; McGovern, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Goodman, A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
   [Matsuda, K.] Medicinova Inc, San Diego, CA USA.
   [McNeil, E.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
   [Naismith, R.] Washington Univ, Sch Med, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2015
VL 21
SU 11
MA EP1475
BP 769
EP 770
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX5GF
UT WOS:000365729402339
ER

PT J
AU Callicott, J
   Ihne, J
   Ursini, G
   Blasi, G
   Berman, KF
   Bertolino, A
   Weinberger, DR
AF Callicott, J.
   Ihne, J.
   Ursini, G.
   Blasi, G.
   Berman, K. F.
   Bertolino, A.
   Weinberger, D. R.
TI Gene-environment interaction and prefrontal cortical function as
   measured by fMRI
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP)
CY AUG 29-SEP 01, 2015
CL Amsterdam, NETHERLANDS
SP European Coll Neuropsychopharmacol
C1 [Callicott, J.] Clin & Translat Neurosci Branch, Bethesda, MD USA.
   [Ihne, J.; Berman, K. F.] NIMH, Clin & Translat Neurosci Branch, Bethesda, MD 20892 USA.
   [Ursini, G.; Blasi, G.; Bertolino, A.] Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.
   [Weinberger, D. R.] Leiber Inst Dev Disorders, Clin, Baltimore, MD USA.
NR 4
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2015
VL 25
SU 2
MA S.11.01
BP S125
EP S126
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CX2HR
UT WOS:000365518200045
ER

PT J
AU Hallett, M
AF Hallett, M.
TI Psychogenic movement disorders
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP)
CY AUG 29-SEP 01, 2015
CL Amsterdam, NETHERLANDS
SP European Coll Neuropsychopharmacol
C1 [Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2015
VL 25
SU 2
MA E.01.01
BP S153
EP S153
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CX2HR
UT WOS:000365518200113
ER

PT J
AU Hilbert, K
   Pine, DS
   Lueken, U
   Beesdo-Baum, K
AF Hilbert, K.
   Pine, D. S.
   Lueken, U.
   Beesdo-Baum, K.
TI Clustering of emotional processing data in subjects with generalised
   anxiety disorder and major depression
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP)
CY AUG 29-SEP 01, 2015
CL Amsterdam, NETHERLANDS
SP European Coll Neuropsychopharmacol
C1 [Hilbert, K.; Beesdo-Baum, K.] Tech Univ Dresden, Behav Epidemiol, Inst Clin Psychol & Psychotherapy, Dresden, Germany.
   [Pine, D. S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
   [Lueken, U.] Univ Hosp Wuerzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany.
RI Lueken, Ulrike/A-8109-2014
OI Lueken, Ulrike/0000-0003-1564-4012
NR 4
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2015
VL 25
SU 2
MA P.1.b.018
BP S188
EP S188
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CX2HR
UT WOS:000365518200170
ER

PT J
AU Kellner, C
   Geduldig, E
   Knapp, R
   Young, R
   Weiner, R
   Greenberg, R
   Prudic, J
   McCall, WV
   Petrides, G
   Husain, M
   Rudorfer, M
   Lisanby, S
AF Kellner, C.
   Geduldig, E.
   Knapp, R.
   Young, R.
   Weiner, R.
   Greenberg, R.
   Prudic, J.
   McCall, W. V.
   Petrides, G.
   Husain, M.
   Rudorfer, M.
   Lisanby, S.
TI Prolonging remission in depressed elderly (PRIDE; NCT01028508)
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP)
CY AUG 29-SEP 01, 2015
CL Amsterdam, NETHERLANDS
SP European Coll Neuropsychopharmacol
C1 [Kellner, C.; Geduldig, E.] Icahn Sch Med Mt Sinai, Psychiat, New York, NY 10029 USA.
   [Knapp, R.] Med Univ S Carolina, Publ Hlth Sci, Charleston, SC USA.
   [Young, R.] Cornell Univ, Weill Med Coll, Psychiat, New York, NY 10021 USA.
   [Weiner, R.; Husain, M.; Lisanby, S.] Duke Univ, Sch Med Psychiat & Behav Sci, Durham, NC 27706 USA.
   [Greenberg, R.] Lutheran Med Ctr, Geriatr Psychiat, Brooklyn, NY USA.
   [Prudic, J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
   [Prudic, J.] Columbia Univ Coll Phys & Surg, Psychiat, New York, NY 10032 USA.
   [McCall, W. V.] Georgia Regents Univ, Psychiat & Hlth Behav, Augusta, GA USA.
   [Petrides, G.] Hofstra Unviers, Hofstra North Shore LIJ Sch Med, Hempstead, Hempstead, NY USA.
   [Rudorfer, M.] NIMH, Somat Treatments Program, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2015
VL 25
SU 2
MA S.05.04
BP S117
EP S117
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CX2HR
UT WOS:000365518200024
ER

PT J
AU Leibenluft, E
AF Leibenluft, E.
TI Irritability and DSM-5 disruptive mood dysregulation disorder:
   correlates, predictors, and outcome in children
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP)
CY AUG 29-SEP 01, 2015
CL Amsterdam, NETHERLANDS
SP European Coll Neuropsychopharmacol
C1 [Leibenluft, E.] Georgetown Univ, Dept Psychiat, Natl Inst Mental Hlth, Washington, DC USA.
NR 2
TC 0
Z9 0
U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2015
VL 25
SU 2
MA E.03.01
BP S153
EP S154
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CX2HR
UT WOS:000365518200115
ER

PT J
AU Kim, ES
   Bernstein, D
   Hilsenbeck, SG
   Chung, CH
   Dicker, AP
   Ersek, JL
   Stein, S
   Khuri, FR
   Burgess, E
   Hunt, K
   Ivy, P
   Bruinooge, SS
   Meropol, N
   Schilsky, RL
AF Kim, Edward S.
   Bernstein, David
   Hilsenbeck, Susan G.
   Chung, Christine H.
   Dicker, Adam P.
   Ersek, Jennifer L.
   Stein, Steven
   Khuri, Fadlo R.
   Burgess, Earle
   Hunt, Kelly
   Ivy, Percy
   Bruinooge, Suanna S.
   Meropol, Neal
   Schilsky, Richard L.
TI Modernizing Eligibility Criteria for Molecularly Driven Trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CELL LUNG-CANCER; PHASE-III TRIAL; METASTATIC MELANOMA; CLINICAL-TRIALS;
   CHEMOTHERAPY; DOCETAXEL; CISPLATIN; BRAF
AB As more clinical trials of molecularly targeted agents evolve, the number of eligibility criteria seems to be increasing. The importance and utility of eligibility criteria must be considered in the context of the fundamental goal of a clinical trial: to understand the risks and benefits of a treatment in the intended-use patient population. Although eligibility criteria are necessary to define the population under study and conduct trials safely, excessive requirements may severely restrict the population available for study, and often, this population is not reflective of the general population for which the drug would be prescribed. The American Society of Clinical Oncology Cancer Research Committee, which comprises academic faculty, industry representatives, and patient advocates, evaluated this issue. Evaluation results were mixed. Most physicians agreed that excessive eligibility criterias slow study enrollment rates and prolong the duration of enrollment; however, this hypothesis was difficult to validate with the data examined. We propose the organization of a public workshop, with input from regulatory bodies and key stakeholders, with the goal of developing an algorithmic approach to determining eligibility criteria for individual study protocols, which may help guide future investigators and companies in streamlining eligibility criteria in the era of molecularly driven therapy. (C) 2015 by American Society of Clinical Oncology
C1 [Kim, Edward S.; Ersek, Jennifer L.; Burgess, Earle] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC 28204 USA.
   [Bernstein, David; Hilsenbeck, Susan G.; Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA USA.
   [Hilsenbeck, Susan G.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Hunt, Kelly] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Chung, Christine H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   [Ivy, Percy] NCI, Bethesda, MD 20892 USA.
   [Dicker, Adam P.] Thomas Jefferson Univ, Sidney Kimmel Med Coll & Canc Ctr, Philadelphia, PA 19107 USA.
   [Stein, Steven] Novartis, E Hanover, NJ USA.
   [Khuri, Fadlo R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
   [Meropol, Neal] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
RP Kim, ES (reprint author), Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC 28204 USA.
EM edward.kim@carolinashealthcare.org
FU Eli Lilly; Immunogen; Boehringer Ingelheim; Pfizer
FX Eli Lilly; Immunogen, Boehringer Ingelheim; Pfizer
NR 23
TC 10
Z9 10
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 1
PY 2015
VL 33
IS 25
BP 2815
EP U139
DI 10.1200/JCO.2015.62.1854
PG 7
WC Oncology
SC Oncology
GA CX4ST
UT WOS:000365691300017
PM 26195710
ER

PT J
AU Thomas, A
   Lopez-Chavez, A
   Giaccone, G
AF Thomas, Anish
   Lopez-Chavez, Ariel
   Giaccone, Giuseppe
TI Basket Trials: Just the End of the First Quarter Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Thomas, Anish] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Lopez-Chavez, Ariel] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA.
   [Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Thomas, A (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU Intramural NIH HHS
NR 3
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 1
PY 2015
VL 33
IS 25
BP 2824
EP U147
DI 10.1200/JCO.2015.62.7323
PG 2
WC Oncology
SC Oncology
GA CX4ST
UT WOS:000365691300020
PM 26169619
ER

PT J
AU Gail, MH
   Pfeiffer, RM
AF Gail, Mitchell H.
   Pfeiffer, Ruth M.
TI Is the Benign Breast Disease Breast Cancer Model Well Calibrated?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID RISK
C1 [Gail, Mitchell H.; Pfeiffer, Ruth M.] NCI, Rockville, MD 20852 USA.
RP Gail, MH (reprint author), NCI, Rockville, MD 20852 USA.
FU Intramural NIH HHS
NR 6
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 1
PY 2015
VL 33
IS 25
BP 2829
EP U157
DI 10.1200/JCO.2015.61.6177
PG 3
WC Oncology
SC Oncology
GA CX4ST
UT WOS:000365691300025
PM 26215936
ER

PT J
AU Edwards, JK
   Kleine, C
   Munster, V
   Giuliani, R
   Massaquoi, M
   Sprecher, A
   Chertow, DS
AF Edwards, Jeffrey K.
   Kleine, Christian
   Munster, Vincent
   Giuliani, Ruggero
   Massaquoi, Moses
   Sprecher, Armand
   Chertow, Daniel S.
TI Interpretation of Negative Molecular Test Results in Patients With
   Suspected or Confirmed Ebola Virus Disease: Report of Two Cases
SO OPEN FORUM INFECTIOUS DISEASES
LA English
DT Article
DE Ebola; hemorrhagic fever; Liberia; PCR; West Africa
ID CASE-DEFINITION; WEST-AFRICA; OUTBREAK
AB Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) is the most sensitive quantitative diagnostic assay for detection of Ebola virus in multiple body fluids. Despite the strengths of this assay, we present 2 cases of Ebola virus disease (EVD) and highlight the potential for false-negative results during the early and late stages of EVD. The first case emphasizes the low negative-predictive value of qR-TPCR during incubation and the early febrile stage of EVD, and the second case emphasizes the potential for false-negative results during recovery and late neurologic complications of EVD. Careful interpretation of test results are needed to guide difficult admission and discharge decisions in suspected or confirmed EVD.
C1 [Edwards, Jeffrey K.; Kleine, Christian; Giuliani, Ruggero; Sprecher, Armand; Chertow, Daniel S.] Medecins Sans Frontieres, Operat Ctr Brussels, B-1050 Brussels, Belgium.
   [Edwards, Jeffrey K.] Johns Hopkins Univ, Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
   [Kleine, Christian] JW Goethe Univ Hosp, Dept Infect Dis & Trop Med, Frankfurt, Germany.
   [Munster, Vincent] NIAID, Virol Lab, NIH, Rocky Mt Labs, Hamilton, MT USA.
   [Massaquoi, Moses] Clinton Hlth Initiat, Monrovia, CA, Liberia.
   [Chertow, Daniel S.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Edwards, JK (reprint author), Medecins Sans Frontieres, Dept Med, Rue Arbre Benit 46, B-1050 Brussels, Belgium.
EM jeffrey.edwards@brussels.msf.org
OI Munster, Vincent/0000-0002-2288-3196
NR 16
TC 2
Z9 2
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 2328-8957
J9 OPEN FORUM INFECT DI
JI Open Forum Infect. Dis.
PD FAL
PY 2015
VL 2
IS 4
DI 10.1093/ofid/ofv137
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA CX6BY
UT WOS:000365787400008
ER

PT J
AU Ostrowski, M
   Benko, E
   Yue, FY
   Kim, CJ
   Huibner, S
   Lee, T
   Singer, J
   Pankovich, J
   Laeyendecker, O
   Kaul, R
   Kandel, G
   Kovacs, C
AF Ostrowski, Mario
   Benko, Erika
   Yue, Feng Yun
   Kim, Connie J.
   Huibner, Sanja
   Lee, Terry
   Singer, Joel
   Pankovich, Jim
   Laeyendecker, Oliver
   Kaul, Rupert
   Kandel, Gabor
   Kovacs, Colin
TI Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc
   During Early Human Immunodeficiency Virus (HIV) Infection Does Not
   Accelerate HIV Reservoir Reduction
SO OPEN FORUM INFECTIOUS DISEASES
LA English
DT Article
DE acute; early; HIV; intensive cART; reservoir
ID CD4(+) T-CELLS; LATENT RESERVOIR; VIRAL LOAD; ERADICATION;
   INTENSIFICATION; ESTABLISHMENT; COMBINATION; VIREMIA; TRIAL
AB Background. Persistent human immunodeficiency virus (HIV) within the CD4(+) T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication.
   Methods. A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (<6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4(+) T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection.
   Results. Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was -1.03 log DNA copies/10(6) CD4(+) T cells versus -. 84 log in the standard and intensive groups, respectively (P = .056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4(+) T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent.
   Conclusions. Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.
C1 [Ostrowski, Mario; Kaul, Rupert] Univ Toronto, Dept Immunol, Toronto, ON, Canada.
   [Ostrowski, Mario; Yue, Feng Yun; Kim, Connie J.; Huibner, Sanja; Kaul, Rupert; Kandel, Gabor; Kovacs, Colin] Univ Toronto, Dept Med, Toronto, ON, Canada.
   [Benko, Erika; Kovacs, Colin] St Michaels Hosp, Maple Leaf Clin, Toronto, ON M5B 1W8, Canada.
   [Ostrowski, Mario; Kandel, Gabor] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON M5B 1W8, Canada.
   [Laeyendecker, Oliver] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
   [Laeyendecker, Oliver] Johns Hopkins Univ, Baltimore, MD USA.
   [Lee, Terry; Singer, Joel; Pankovich, Jim] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
   [Lee, Terry; Singer, Joel; Pankovich, Jim] CIHR Canadian HIV Trials Network, Vancouver, BC, Canada.
RP Ostrowski, M (reprint author), Room 6271,Med Sci Bldg,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.
EM mario.ostrowski@gmail.com
NR 23
TC 2
Z9 2
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 2328-8957
J9 OPEN FORUM INFECT DI
JI Open Forum Infect. Dis.
PD FAL
PY 2015
VL 2
IS 4
DI 10.1093/ofid/ofv138
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA CX6BY
UT WOS:000365787400025
ER

PT J
AU Huppmann, AR
   Leiding, JW
   Hsu, AP
   Raffeld, M
   Uzel, G
   Pittaluga, S
   Holland, SM
AF Huppmann, Alison R.
   Leiding, Jennifer W.
   Hsu, Amy P.
   Raffeld, Mark
   Uzel, Gulbu
   Pittaluga, Stefania
   Holland, Steven M.
TI Pathologic Findings in NEMO Deficiency: A Surgical and Autopsy Survey
SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY
LA English
DT Article
DE autopsy; immunodeficiency; mycobacteria; NEMO; NF-kappa B; pathology
ID FACTOR-KAPPA-B; NONTUBERCULOUS MYCOBACTERIAL INFECTION; ESSENTIAL
   MODULATOR MUTATION; ECTODERMAL DYSPLASIA; RECEPTOR ACTIVATOR;
   IMMUNE-DEFICIENCY; IMMUNODEFICIENCY; GAMMA; RANK
AB Hypomorphic mutations in nuclear factor kappa B (NF-kappa B) essential modulator (NEMO), encoded by IKBKG, lead to a variable combined immunodeficiency, which puts patients at risk of early death from infectious complications. The spectrum of clinical manifestations includes inflammatory disorders, especially colitis. Because of the multiple complications of NEMO deficiency, a variety of biopsy, excisional, and autopsy materials from these patients may be subject to pathologic examination. Therefore, using samples from a cohort of patients with this disorder, we aimed to survey the pathologic spectrum of NEMO deficiency and search for correlations between specific genotypes and phenotypes. Clinical and laboratory data, mutation analysis, and pathology from 13 patients were examined, including 6 autopsies. No specific genotype-pathology correlation was identified. However, we confirmed an association between ectodermal dysplasia and inflammatory conditions. We found no characteristic pathology to identify patients with NEMO deficiency; therefore, history, physical examination, and specific infections must remain the clues to suggest the diagnosis. Variability among patients and by infection makes the pathologic recognition of NEMO deficiency challenging.
C1 [Huppmann, Alison R.; Raffeld, Mark; Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   [Leiding, Jennifer W.; Hsu, Amy P.; Uzel, Gulbu; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Leiding, Jennifer W.] Univ S Florida, Dept Pediat, Div Allergy Immunol & Rheumatol, St Petersburg, FL 33701 USA.
RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM smh@nih.gov
NR 26
TC 2
Z9 2
U1 0
U2 0
PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS
PI LAWRENCE
PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA
SN 1093-5266
EI 1615-5742
J9 PEDIATR DEVEL PATHOL
JI Pediatr. Dev. Pathol.
PD SEP-OCT
PY 2015
VL 18
IS 5
BP 387
EP 400
DI 10.2350/15-05-1631-OA.1
PG 14
WC Pathology; Pediatrics
SC Pathology; Pediatrics
GA CX6NJ
UT WOS:000365817500008
PM 26230867
ER

PT J
AU Zeidner, JF
   Foster, MC
   Blackford, AL
   Litzow, MR
   Morris, LE
   Strickland, SA
   Lancet, JE
   Bose, P
   Levy, MY
   Tibes, R
   Gojo, I
   Gocke, CD
   Rosner, GL
   Little, RF
   Wright, JJ
   Doyle, LA
   Smith, BD
   Karp, JE
AF Zeidner, Joshua F.
   Foster, Matthew C.
   Blackford, Amanda L.
   Litzow, Mark R.
   Morris, Lawrence E.
   Strickland, Stephen A.
   Lancet, Jeffrey E.
   Bose, Prithviraj
   Levy, M. Yair
   Tibes, Raoul
   Gojo, Ivana
   Gocke, Christopher D.
   Rosner, Gary L.
   Little, Richard F.
   Wright, John J.
   Doyle, L. Austin
   Smith, B. Douglas
   Karp, Judith E.
TI Randomized multicenter phase II study of flavopiridol (alvocidib),
   cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3)
   in newly diagnosed acute myeloid leukemia
SO HAEMATOLOGICA
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TIMED SEQUENTIAL THERAPY; ACUTE
   MYELOGENOUS LEUKEMIA; ACUTE MYELOCYTIC-LEUKEMIA; TUMOR LYSIS SYNDROME;
   BONE-MARROW BIOPSY; INDUCTION THERAPY; ADULT PATIENTS; EUROPEAN
   LEUKEMIANET; CYTOSINE-ARABINOSIDE
AB Serial studies have demonstrated that induction therapy with FLAM [flavopiridol 50 mg/m(2) days 1-3, cytarabine 667 mg/m(2)/day continuous infusion days 6-8, and mitoxantrone 40 mg/m(2) day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011-July 2013, 165 newly diagnosed acute myeloid leukemia patients (18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m(2)/day continuous infusion days 1-7 and daunorubicin 90 mg/m(2) days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m(2)/day continuous infusion days 1-5 and daunorubicin 45 mg/m(2) days 1-2), whereas patients on FLAM were not retreated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between 1 cycle of FLAM and 1 cycle of 7+3. Secondary endpoints included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%, p=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%, p=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase 3 study is currently in development.
C1 [Zeidner, Joshua F.; Blackford, Amanda L.; Gojo, Ivana; Gocke, Christopher D.; Rosner, Gary L.; Smith, B. Douglas; Karp, Judith E.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
   [Zeidner, Joshua F.; Foster, Matthew C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Litzow, Mark R.] Mayo Clin, Rochester, MN USA.
   [Morris, Lawrence E.] Northside Hosp, Bone Marrow Transplant Grp Georgia, Blood & Marrow Transplant Program, Atlanta, GA USA.
   [Strickland, Stephen A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
   [Lancet, Jeffrey E.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
   [Bose, Prithviraj] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
   [Levy, M. Yair] Baylor Charles A Simmons Canc Ctr, Texas Oncol, Dallas, TX USA.
   [Tibes, Raoul] Mayo Clin, Scottsdale, AZ USA.
   [Gojo, Ivana] Univ Maryland, Med Ctr, Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
   [Little, Richard F.; Wright, John J.; Doyle, L. Austin] NCI, Rockville, MD USA.
RP Zeidner, JF (reprint author), Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
EM joshua_zeidner@med.unc.edu
FU NCI [U01 CA70095]; NCI Cancer Center Support Grant [2P30 CA06973-46];
   Conquer Cancer Foundation
FX This study was supported in part by NCI Cooperative Agreement U01
   CA70095 and NCI Cancer Center Support Grant 2P30 CA06973-46.; JFZ
   recieved a 2013 Conquer Cancer Foundation Young Investigator Award, in
   memory of Dr. John R, Durant, and is a 2014-2017 Leukemia and Lymphoma
   Society Special Fellow in Clinical Research.
NR 34
TC 9
Z9 9
U1 2
U2 5
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD SEP
PY 2015
VL 100
IS 9
BP 1172
EP 1179
DI 10.3324/haemato1.2015.125849
PG 8
WC Hematology
SC Hematology
GA CW6BH
UT WOS:000365081500027
PM 26022709
ER

PT J
AU Curtis, LM
   Datiles, MB
   Steinberg, SM
   Mitchell, SA
   Bishop, RJ
   Cowen, EW
   Mays, J
   McCarty, JM
   Kuzmina, Z
   Pirsl, F
   Fowler, DH
   Gress, RE
   Pavletic, SZ
AF Curtis, Lauren M.
   Datiles, Manuel B., III
   Steinberg, Seth M.
   Mitchell, Sandra A.
   Bishop, Rachel J.
   Cowen, Edward W.
   Mays, Jacqueline
   McCarty, John M.
   Kuzmina, Zoya
   Pirsl, Filip
   Fowler, Daniel H.
   Gress, Ronald E.
   Pavletic, Steven Z.
TI Predictive models for ocular chronic graft-versus-host disease diagnosis
   and disease activity in transplant clinical practice
SO HAEMATOLOGICA
LA English
DT Article
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; MEASURING
   THERAPEUTIC RESPONSE; BONE-MARROW-TRANSPLANTATION; CHRONIC GVHD; DRY
   EYE; RISK-FACTORS; CRITERIA; TRIALS; CONJUNCTIVA
AB Ocular chronic graft-versus-host disease is one of the most bothersome common complications following allogeneic hematopoietic stem cell transplantation. The National Institutes of Health Chronic Graft-versus-Host Disease Consensus Project provided expert recommendations for diagnosis and organ severity scoring. However, ocular chronic graft-versus-host disease can be diagnosed only after examination by an ophthalmologist. There are no currently accepted definitions of ocular chronic graft-versus-host disease activity. The goal of this study was to identify predictive models of diagnosis and activity for use in clinical transplant practice. A total of 210 patients with moderate or severe chronic graft-versus-host disease were enrolled in a prospective, cross-sectional, observational study (clinicaltrials.gov identifier: 00092235). Experienced ophthalmologists determined presence of ocular chronic graft-versus-host disease, diagnosis and activity. Measures gathered by the transplant clinician included Schirmers tear test and National Institutes of Health 03 Eye Score. Patient-reported outcome measures were the ocular subscale of the Lee Chronic Graft-versus-Host Disease Symptom Scale and Chief Eye Symptom Intensity Score. Altogether, 157 (75%) patients were diagnosed with ocular chronic graft-versus-host disease; 133 of 157 patients (85%) had active disease. In a multivariable model, the National Institutes of Health Eye Score (P<0.0001) and Schirmers tear test (P<0.0001) were independent predictors of ocular chronic graft-versus-host disease (sensitivity 93.0%, specificity 92.2%). The Lee ocular subscale was the strongest predictor of active ocular chronic graft-versus-host disease (P<0.0001) (sensitivity 68.5%, specificity 82.6%). Ophthalmology specialist measures that were most strongly predictive of diagnosis in a multivariate model were Oxford grand total staining (P<0.0001) and meibomian score (P=0.027). These results support the use of selected transplant clinician- and patient-reported outcome measures for ocular chronic graft-versus-host disease screening when providing care to allogeneic hematopoietic stem cell transplantation survivors with moderate to severe chronic graft-versus-host disease. Prospective studies are needed to determine if the Lee ocular subscale demonstrates adequate responsiveness as a disease activity outcome measure.
C1 [Curtis, Lauren M.; Kuzmina, Zoya; Pirsl, Filip; Fowler, Daniel H.; Gress, Ronald E.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Datiles, Manuel B., III; Bishop, Rachel J.] NEI, NIH, Bethesda, MD 20892 USA.
   [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Rockville, MD USA.
   [Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
   [Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
   [Mays, Jacqueline] NIDR, NIH, Bethesda, MD 20892 USA.
   [McCarty, John M.] Virginia Commonwealth Univ, Med Ctr, Massey Canc Ctr, Bone Marrow Transplant Program, Richmond, VA USA.
RP Pavletic, SZ (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM pavletis@mail.nih.gov
NR 29
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U1 2
U2 3
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD SEP
PY 2015
VL 100
IS 9
BP 1228
EP 1236
DI 10.3324/haematol.2015.124131
PG 9
WC Hematology
SC Hematology
GA CW6BH
UT WOS:000365081500034
PM 26088932
ER

PT J
AU Alter, BP
   Rosenberg, PS
AF Alter, Blanche P.
   Rosenberg, Philip S.
TI Comment on: "The impact of category, cytopathology and cytogenetics on
   development and progression of clonal and malignant myeloid
   transformation in inherited bone marrow failure syndromes"
SO HAEMATOLOGICA
LA English
DT Letter
DE inherited bone marrow failure syndromes; CCC classification;
   transformation; precision medicine
C1 [Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM alterb@mail.nih.gov
NR 5
TC 1
Z9 1
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD SEP
PY 2015
VL 100
IS 9
BP E378
EP E378
DI 10.3324/haematol.2015.128066
PG 1
WC Hematology
SC Hematology
GA CW6BH
UT WOS:000365081500014
PM 26341527
ER

PT J
AU Thompson, CN
   Zelner, JL
   Nhu, TDH
   Phan, MVT
   Phuc, HL
   Hung, NT
   Duong, VT
   Ngoc, MN
   Tuan, HM
   Tu, VHM
   Vi, LL
   Chauh, NVV
   Hien, TT
   von Clemm, E
   Storch, H
   Thwaites, G
   Grenfell, BT
   Baker, S
AF Thompson, Corinne N.
   Zelner, Jonathan L.
   Tran Do Hoang Nhu
   My VT Phan
   Hoang Le Phuc
   Nguyen Thanh Hung
   Vu Thuy Duong
   Minh Nguyen Ngoc
   Ha Manh Tuan
   Van Hoang Minh Tu
   Lu Lan Vi
   Nguyen Van Vinh Chauh
   Tran Tinh Hien
   von Clemm, Emmiliese
   Storch, Harry
   Thwaites, Guy
   Grenfell, Bryan T.
   Baker, Stephen
TI The impact of environmental and climatic variation on the spatiotemporal
   trends of hospitalized pediatric diarrhea in Ho Chi Minh City, Vietnam
SO HEALTH & PLACE
LA English
DT Article
DE Diarrhea; Climate change; Environment; Spatial risk; Mixed effects
ID SOUTHERN VIETNAM; VARIABILITY; DISEASE; CHOLERA
AB It is predicted that the integration of climate-based early warning systems into existing action plans will facilitate the timely provision of interventions to diarrheal disease epidemics in resource-poor settings. Diarrhea remains a considerable public health problem in Ho Chi Minh City (HCMC), Vietnam and we aimed to quantify variation in the impact of environmental conditions on diarrheal disease risk across the city. Using all inpatient diarrheal admissions data from three large hospitals within HCMC, we developed a mixed effects regression model to differentiate district-level variation in risk due to environmental conditions from the overarching seasonality of diarrheal disease hospitalization in HCMC. We identified considerable spatial heterogeneity in the risk of all-cause diarrhea across districts of HCMC with low elevation and differential responses to flooding, air temperature, and humidity driving further spatial heterogeneity in diarrheal disease risk. The incorporation of these results into predictive forecasting algorithms will provide a powerful resource to aid diarrheal disease prevention and control practices in HCMC and other similar settings. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
C1 [Thompson, Corinne N.; Tran Do Hoang Nhu; Tran Tinh Hien; Thwaites, Guy; Baker, Stephen] Univ Oxford, Climat Res Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
   [Thompson, Corinne N.; Tran Tinh Hien; Thwaites, Guy; Baker, Stephen] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford OX1 2JD, England.
   [Thompson, Corinne N.; Baker, Stephen] London Sch Hyg & Trop Med, London, England.
   [Zelner, Jonathan L.] Columbia Univ, Robert Wood Johnson Fdn, Hlth & Soc Scholars Program, New York, NY 10027 USA.
   [My VT Phan] Wellcome Trust Sanger Inst, Hinxton, Cambs, England.
   [Hoang Le Phuc; Nguyen Thanh Hung; Vu Thuy Duong] Childrens Hosp 1, Ho Chi Minh City, Vietnam.
   [Minh Nguyen Ngoc; Ha Manh Tuan; Van Hoang Minh Tu] Childrens Hosp 2, Ho Chi Minh City, Vietnam.
   [Lu Lan Vi; Nguyen Van Vinh Chauh] Hosp Trop Dis, Ho Chi Minh City, Vietnam.
   [von Clemm, Emmiliese; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [Storch, Harry] Brandenburg Tech Univ Cottbus, D-03044 Cottbus, Germany.
   [Grenfell, Bryan T.] NIH, RAPIDD Program, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Zelner, JL (reprint author), Columbia Univ, Robert Wood Johnson Fdn, Hlth & Soc Scholars Program, 701A Knox Hall, New York, NY 10027 USA.
EM cthompson@oucru.org; jlz2115@columbia.edu; nhutdh@oucru.org;
   mp21@sanger.ac.uk; drphuc.ph1@gmail.com; hungnt@oucru.org;
   duongvt@oucru.org; mngocnd2@yahoo.com; manhtuanzu@yahoo.com;
   vanhmt@oucru.org; drluvi@yahoo.com.vn; chaunvv@oucru.org;
   hientt@oucru.org; emmiliese.von.clemm@gmail.com; harry.storch@gmail.com;
   gthwaites@oucru.org; grenfell@princeton.edu; sbaker@oucru.org
OI Thwaites, Guy/0000-0002-2858-2087; Phan, My VT/0000-0002-6905-8513
FU Wellcome Trust [WT1093824, 100087/Z/12/Z]; Royal Society
   [100087/Z/12/Z]; Research and Policy for Infectious Disease Dynamics
   program of the Science and Technology Directorate, Department of
   Homeland Security; Fogarty International Center, National Institutes of
   Health; Bill and Melinda Gates Foundation
FX This work was supported through the Wellcome Trust Vizions strategic
   award (WT1093824). SB is a Sir Henry Dale Fellow, jointly funded by the
   Wellcome Trust and the Royal Society (100087/Z/12/Z). JLZ and BTG were
   supported by the Research and Policy for Infectious Disease Dynamics
   program of the Science and Technology Directorate, Department of
   Homeland Security and the Fogarty International Center, National
   Institutes of Health. BTG was funded by the Bill and Melinda Gates
   Foundation. The sponsors of the study had no role in the study design,
   data collection, data analysis, data interpretation, or writing of the
   report.
NR 39
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U1 3
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8292
EI 1873-2054
J9 HEALTH PLACE
JI Health Place
PD SEP
PY 2015
VL 35
BP 147
EP 154
DI 10.1016/j.healthplace.2015.08.001
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CW8GN
UT WOS:000365237600018
PM 26402922
ER

PT J
AU Davis, JM
   Ramsden, CE
AF Davis, John M.
   Ramsden, Christopher E.
TI Do Antipsychotics Cause Hip Fractures? Promise and Pitfalls of Big Data
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Editorial Material
DE psychotics; Schizophrenia
ID BONE-MINERAL DENSITY; SCHIZOPHRENIA; RISK
C1 [Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
   [Ramsden, Christopher E.] NIAAA, NIH, Bethesda, MD USA.
RP Davis, JM (reprint author), Univ Illinois, Psychiat Inst MC 912, 1601 W Taylor St, Chicago, IL 60612 USA.
EM jdavis@psych.uic.edu
NR 11
TC 0
Z9 0
U1 1
U2 2
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD SEP
PY 2015
VL 76
IS 9
BP E1155
EP E1156
DI 10.4088/JCP.14com09551
PG 2
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA CX0UM
UT WOS:000365412500020
PM 26455690
ER

PT J
AU Pena-Munzenmayer, G
   Jaramillo, Y
   Melvin, JE
   Catalan, MA
AF Pena-Muenzenmayer, Gaspar
   Jaramillo, Yasna
   Melvin, James E.
   Catalan, Marcelo A.
TI Ae4 (S1c4a9) is an Electroneutral Cl-/Na+-HCO3- Exchanger .
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Meeting Abstract
CT 69th Annual Meeting of the Society-of-General-Physiologists -
   Macromolecular Local Signaling Complexes
CY SEP 16-20, 2015
CL Woods Hole, MA
SP Soc Gen Physiologists, Marine Biol Lab
C1 [Pena-Muenzenmayer, Gaspar; Jaramillo, Yasna; Melvin, James E.; Catalan, Marcelo A.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1295
EI 1540-7748
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD SEP
PY 2015
VL 146
IS 3
MA 25
BP 13A
EP 13A
PG 1
WC Physiology
SC Physiology
GA CW7OK
UT WOS:000365188500034
ER

PT J
AU Tong, XH
   Lopez, W
   Ramachandran, J
   Ayad, WA
   Liu, Y
   Lopez-Rodriguez, A
   Harris, AL
   Contreras, JE
AF Tong, Xuhui
   Lopez, William
   Ramachandran, Jayalakshmi
   Ayad, Wafaa A.
   Liu, Yu
   Lopez-Rodriguez, Angelica
   Harris, Andrew L.
   Contreras, Jorge E.
TI Glutathione release through connexin hemichannels: Implications for
   chemical modification of pores permeable to large molecules
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID 1ST EXTRACELLULAR LOOP; P2X RECEPTOR CHANNELS; LINING RESIDUES; CX46
   HEMICHANNELS; CA2+ REGULATION; CYSTEINE; PATHWAY; CELLS; HOMOCYSTEINE;
   INVOLVEMENT
AB Cysteine-scanning mutagenesis combined with thiol reagent modification is a powerful method with which to define the pore-lining elements of channels and the changes in structure that accompany channel gating. Using the Xenopus laevis oocyte expression system and two-electrode voltage clamp, we performed cysteine-scanning mutagenesis of several pore-lining residues of connexin 26 (Gx26) hemichannels, followed by chemical modification using a methanethiosulfonate (MIS) reagent, to help identify the position of the gate. Unexpectedly, we observed that the effect of NITS modification on the currents was reversed within minutes of washout. Such a reversal should not occur unless reducing agents, which can break the disulfide thiol MTS linkage, have access to the site of modification. Given the permeability to large metabolites of connexin channels, we tested whether cytosolic glutathione (GSH), the primary cell reducing agent, was reaching ifie modified sites through the connexin pore. Inhibition of gamm a-glutamylcysteine synthetase by buthionine sulfoximine decreased the cytosolic GSH concentration in Xenopus oocytes and reduced reversibility of NTT'S modification, as did acute treatment with tert-butyl hydroperoxide, which oxidizes GSH. Cysteine modification based on thioether linkages (e.g., maleimides) cannot be reversed by reducing agents and did not reverse with w;:tshout. Using reconstituted hemichannels in a liposome-based transport-specific fractionation assay, we confirmed that homomeric Cx26 and Cx32 and heteromeric Cx26/Cx32 are permeable to GSII and other endogenous reductants. These results show that, for wide pores, accessibility of cytosolic reductants can lead to reversal of MTS-based thiol modifications. 't his potential for reversibility of thiol modification applies to on-cell accessibility studies of connexin channels and other channels that are permeable to large molecules, such as pannexin, CALHM, and VRAC.
C1 [Tong, Xuhui; Lopez, William; Ramachandran, Jayalakshmi; Ayad, Wafaa A.; Liu, Yu; Harris, Andrew L.; Contreras, Jorge E.] Rutgers State Univ, New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 USA.
   [Tong, Xuhui] Bengbu Med Coll, Dept Pharmacol, Bengbu 233000, Anhui, Peoples R China.
   [Lopez-Rodriguez, Angelica] NIH, Porter Neurosci Res Ctr, Mol Neurophysiol Sect, Bethesda, MD 20892 USA.
RP Contreras, JE (reprint author), Rutgers State Univ, New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 USA.
EM contrejo@njms.rutgers.edu
RI Ramachandran, Jayalakshmi/D-8278-2013
FU National Institutes of Health/National Institute of General Medical
   Sciences [RO1-GM099490, RO1-R01GM101950, RO1GM36044]
FX This work was supported by National Institutes of Health/National
   Institute of General Medical Sciences (grants RO1-GM099490 to J.E.
   Contreras, RO1-R01GM101950 to A.L. Harris and J.E. Contreras, and
   RO1GM36044 to A.L. Harris).
NR 39
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Z9 4
U1 1
U2 5
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1295
EI 1540-7748
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD SEP
PY 2015
VL 146
IS 3
BP 245
EP 254
DI 10.1085/jpg.201511375
PG 10
WC Physiology
SC Physiology
GA CW7OK
UT WOS:000365188500007
PM 26324677
ER

PT J
AU Hwang, BS
   Chen, Z
AF Hwang, Beom Seuk
   Chen, Zhen
TI An Integrated Bayesian Nonparametric Approach for Stochastic and
   Variability Orders in ROC Curve Estimation: An Application to
   Endometriosis Diagnosis
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Area under the curve; Dirichlet process mixture; Gold standard; Order
   restricted analysis
ID OPERATING CHARACTERISTIC CURVES; CHAIN MONTE-CARLO; SEMIPARAMETRIC
   ESTIMATION; GOLD STANDARD; DIRICHLET; INFERENCE; MIXTURES; TESTS; AREA
AB In estimating ROC curves of multiple tests, some a priori constraints may exist, either between the healthy and diseased populations within a test or between tests within a population. In this article, we proposed an integrated modeling approach for ROC curves that jointly accounts for stochastic and variability orders. The stochastic order constrains the distributional centers of the diseased and healthy populations within a test, while the variability order constrains the distributional spreads of the tests within each of the populations. Under a Bayesian nonparametric framework, we used features of the Dirichlet process mixture to incorporate these order constraints in a natural way. We applied the proposed approach to data from the Physician Reliability Study that investigated the accuracy of diagnosing endometriosis using different clinical information. To address the issue of no gold standard in the real data, we used a sensitivity analysis approach that exploited diagnosis from a panel of experts. To demonstrate the performance of the methodology, we conducted simulation studies with varying sample sizes, distributional assumptions, and order constraints. Supplementary materials for this article are available online.
C1 [Hwang, Beom Seuk; Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Bethesda, MD 20892 USA.
RP Hwang, BS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Bethesda, MD 20892 USA.
EM beomseuk.hwang@nih.gov; chenzhe@mail.nih.gov
FU Intramural Research Program of the 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 of the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health. This study used the
   high-performance computational capabilities of the Biowulf Linux cluster
   at the National Institutes of Health, Bethesda, MD
   (http://biowulf.nih.gov). The authors thank Athanasios Kottas, Paul S.
   Albert, the editor, associate editor, and two anonymous reviewers for
   insightful and helpful comments.
NR 39
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Z9 0
U1 4
U2 5
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
EI 1537-274X
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD SEP
PY 2015
VL 110
IS 511
BP 923
EP 934
DI 10.1080/01621459.2015.1023806
PG 12
WC Statistics & Probability
SC Mathematics
GA CW6YO
UT WOS:000365144600006
PM 26839441
ER

PT J
AU Fee, E
   Blum, N
AF Fee, Elizabeth
   Blum, Nava
TI The Air We Breathe
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Fee, Elizabeth; Blum, Nava] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Fee, E (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM feee@mail.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD SEP
PY 2015
VL 105
IS 9
BP 1751
EP 1751
DI 10.2105/AJPH.2015.302700
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CV5PG
UT WOS:000364322600027
PM 26180966
ER

PT J
AU McCarthy, JF
   Bossarte, RM
   Katz, IR
   Thompson, C
   Kemp, J
   Hannemann, CM
   Nielson, C
   Schoenbaum, M
AF McCarthy, John F.
   Bossarte, Robert M.
   Katz, Ira R.
   Thompson, Caitlin
   Kemp, Janet
   Hannemann, Claire M.
   Nielson, Christopher
   Schoenbaum, Michael
TI Predictive Modeling and Concentration of the Risk of Suicide:
   Implications for Preventive Interventions in the US Department of
   Veterans Affairs
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID PROGNOSTIC MODELS; HEALTH SYSTEM; VA PATIENTS; SELF-HARM; SERVICES;
   RECORDS; VIOLENT; CARE
AB Objectives. The Veterans Health Administration (VHA) evaluated the use of predictive modeling to identify patients at risk for suicide and to supplement ongoing care with risk-stratified interventions.
   Methods. Suicide data came from the National Death Index. Predictors were measures from VHA clinical records incorporating patient-months from October 1, 2008, to September 30, 2011, for all suicide decedents and 1% of living patients, divided randomly into development and validation samples. We used data on all patients alive on September 30, 2010, to evaluate predictions of suicide risk over 1 year.
   Results. Modeling demonstrated that suicide rates were 82 and 60 times greater than the rate in the overall sample in the highest 0.01% stratum for calculated risk for the development and validation samples, respectively; 39 and 30 times greater in the highest 0.10%; 14 and 12 times greater in the highest 1.00%; and 6.3 and 5.7 times greater in the highest 5.00%.
   Conclusions. Predictive modeling can identify high-risk patients who were not identified on clinical grounds. VHA is developing modeling to enhance clinical care and to guide the delivery of preventive interventions.
C1 [McCarthy, John F.; Hannemann, Claire M.] Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Off Mental Hlth Operat, Washington, DC USA.
   [Nielson, Christopher] Dept Vet Affairs, Off Business Intelligence & Analyt, Predict Analyt, Canandaigua, NY USA.
   [Kemp, Janet] Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY USA.
   [Schoenbaum, Michael] NIMH, Off Sci Policy Planning & Commun, Rockville, MD 20857 USA.
RP Bossarte, RM (reprint author), 810 Vermont Ave,Mailstop 10P3A, Washington, DC 20420 USA.
EM Robert.Bossarte@va.gov
NR 36
TC 9
Z9 9
U1 4
U2 9
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD SEP
PY 2015
VL 105
IS 9
BP 1935
EP 1942
DI 10.2105/AJPH.2015.302737
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CV5PG
UT WOS:000364322600052
PM 26066914
ER

PT J
AU Fenton, SE
   Birnbaum, LS
AF Fenton, Suzanne E.
   Birnbaum, Linda S.
TI Timing of Environmental Exposures as a Critical Element in Breast Cancer
   Risk
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID SEVESO WOMENS HEALTH; MAMMARY-GLAND; IN-UTERO; ENDOCRINE DISRUPTORS;
   DIOXIN EXPOSURE; FOLLOW-UP; DIETHYLSTILBESTROL; MORTALITY; LIFE; RAT
AB Objective: The role of the chemical environment in disease initiation or progression is becoming more evident. Endocrine disruption via environmental chemicals is now well documented in humans, rodent research models, and wildlife. Breast cancer is an endocrine-based disease whose risk may be modified by environmental exposures. Our purpose is to encourage more investigation into early life environmental exposures as they relate to breast cancer risk factors and disease over a lifetime.
   Evidence: The 2009 President's Cancer Panel, 2012 Institute of Medicine, 2013 Interagency Breast Cancer and the Environment Research Coordinating Committee reports, and research publications dated >2012 in PubMed were used to inform our perspective.
   Consensus Process: Literature was reviewed and evidence gathered on the effects of the environment on risk of breast cancer or mammary tumor development in animal research models as it pertained to the influence of timing of exposure on later-life outcomes.
   Conclusions: Evidence has accumulated for several chemicals that environmental factors have a stronger effect on breast cancer risk when exposure occurred early in life. The insecticide, dichlorodiphenyltrichloroethane, is an excellent example and is just one of several chemicals for which there seems to be both animal and human evidence for the developmental basis of adult disease. The developing breast undergoes many changes in early life, leaving it vulnerable to the effects of epigenetic marks, endocrine disruption, and carcinogens. More research is needed in the area of early beginnings of breast cancer, with prevention of the disease as the ultimate goal.
C1 [Fenton, Suzanne E.] NIEHS, Natl Toxicol Program NTP Lab, Div NTP, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   [Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Fenton, SE (reprint author), NIEHS, 111 TW Alexander Dr,MDE1-08, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
FU National Institutes of Health
FX This work was supported by the National Institutes of Health.
NR 50
TC 3
Z9 3
U1 1
U2 7
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 SEP
PY 2015
VL 100
IS 9
BP 3245
EP 3250
DI 10.1210/jc.2015-2848
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3BV
UT WOS:000364867800028
PM 26214118
ER

PT J
AU Carhill, AA
   Litofsky, DR
   Ross, DS
   Jonklaas, J
   Cooper, DS
   Brierley, JD
   Ladenson, PW
   Ain, KB
   Fein, HG
   Haugen, BR
   Magner, J
   Skarulis, MC
   Steward, DL
   Xing, MX
   Maxon, HR
   Sherman, SI
AF Carhill, Aubrey A.
   Litofsky, Danielle R.
   Ross, Douglas S.
   Jonklaas, Jacqueline
   Cooper, David S.
   Brierley, James D.
   Ladenson, Paul W.
   Ain, Kenneth B.
   Fein, Henry G.
   Haugen, Bryan R.
   Magner, James
   Skarulis, Monica C.
   Steward, David L.
   Xing, Mingxhao
   Maxon, Harry R.
   Sherman, Steven I.
TI Long-Term Outcomes Following Therapy in Differentiated Thyroid
   Carcinoma: NTCTCS Registry Analysis 1987-2012
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID THYROTROPIN-SUPPRESSIVE THERAPY; QUALITY-OF-LIFE; SERUM THYROTROPIN;
   STIMULATING HORMONE; EXERCISE CAPACITY; INITIAL THERAPY; RISK PAPILLARY;
   CANCER; DISEASE; LEVOTHYROXINE
AB Context: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer.
   Objective: The objective was to examine effects of initial therapies on outcomes.
   Design/Setting: This was a prospective multi-institutional registry.
   Patients: A total of 4941 patients, median follow-up, 6 years, participated.
   Intervention: Interventions included total/near-total thyroidectomy (T/NTT), postoperative radioiodine (RAI), and thyroid hormone suppression therapy (THST).
   Main Outcome Measure: Main outcome measures were overall survival (OS) and disease-free survival using product limit and proportional hazards analyses.
   Results: Improved OS was noted in NTCTCS stage III patients who received RAI (risk ratio [RR], 0.66; P =.04) and stage IV patients who received both T/NTT and RAI (RR, 0.66 and 0.70; combined P =.049). In all stages, moderate THST (TSH maintained subnormal-normal) was associated with significantly improved OS (RR stages I-IV: 0.13, 0.09, 0.13, 0.33) and disease-free survival (RR stages I-III: 0.52, 0.40, 0.18); no additional survival benefit was achieved with more aggressive THST (TSH maintained undetectable-subnormal). This remained true, even when distant metastatic disease was diagnosed during follow-up. Lower initial stage and moderate THST were independent predictors of improved OS during follow-up years 1-3.
   Conclusions: We confirm previous findings that T/NTT followed by RAI is associated with benefit in high-risk patients, but not in low-risk patients. In contrast with earlier reports, moderate THST is associated with better outcomes across all stages, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow-up. Moderate THST continued at least 3 years after diagnosis may be indicated in high-risk patients.
C1 [Carhill, Aubrey A.; Litofsky, Danielle R.; Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA.
   [Litofsky, Danielle R.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA.
   [Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Dept Med, Div Endocrinol, Washington, DC 20057 USA.
   [Cooper, David S.; Ladenson, Paul W.; Xing, Mingxhao] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD 21205 USA.
   [Brierley, James D.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada.
   [Ain, Kenneth B.] Vet Affairs Med Ctr, Dept Internal Med, Lexington, KY 40502 USA.
   [Ain, Kenneth B.] Univ Kentucky, Lexington, KY 40502 USA.
   [Fein, Henry G.] Sinai Hosp, Div Endocrinol & Metab, Baltimore, MD 21215 USA.
   [Haugen, Bryan R.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA.
   [Magner, James] Genzyme, Cambridge, MA 02142 USA.
   [Skarulis, Monica C.] NIH, Diabet, Endocrinol, Obes Branch, Bethesda, MD 20892 USA.
   [Steward, David L.] Univ Cincinnati, Med Ctr, Dept Head & Neck Surg, Cincinnati, OH 45219 USA.
   [Maxon, Harry R.] Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45219 USA.
RP Sherman, SI (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, 1400 Pressler,Unit 1461, Houston, TX 77030 USA.
EM sisherma@mdanderson.org
OI Sherman, Steven/0000-0002-3079-5153
FU Genzyme, a Sanofi company; Pfizer; University of Texas MD Anderson
   Cancer Center Support Grant (NCI) [P30 CA016672]
FX The NTCTCS has been supported in part by research grants from Genzyme, a
   Sanofi company, and Pfizer, and by the University of Texas MD Anderson
   Cancer Center Support Grant (NCI Grant P30 CA016672).
NR 40
TC 5
Z9 7
U1 0
U2 4
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 SEP
PY 2015
VL 100
IS 9
BP 3270
EP 3279
DI 10.1210/JC.2015-1346
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3BV
UT WOS:000364867800031
PM 26171797
ER

PT J
AU Hernandez-Ramirez, LC
   Gabrovska, P
   Denes, J
   Stals, K
   Trivellin, G
   Tilley, D
   Ferrau, F
   Evanson, J
   Ellard, S
   Grossman, AB
   Roncaroli, F
   Gadelha, MR
   Korbonits, M
AF Hernandez-Ramirez, Laura C.
   Gabrovska, Plamena
   Denes, Judit
   Stals, Karen
   Trivellin, Giampaolo
   Tilley, Daniel
   Ferrau, Francesco
   Evanson, Jane
   Ellard, Sian
   Grossman, Ashley B.
   Roncaroli, Federico
   Gadelha, Monica R.
   Korbonits, Marta
CA Int FIPA Consortium
TI Landscape of Familial Isolated and Young-Onset Pituitary Adenomas:
   Prospective Diagnosis in AIP Mutation Carriers
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID INTERACTING-PROTEIN GENE; CLINICAL CHARACTERISTICS; SOMATOSTATIN
   ANALOGS; SOMATOTROPH ADENOMAS; ACROMEGALIC PATIENTS; GERMLINE MUTATIONS;
   ADENYLYL-CYCLASE; ALPHA MUTATIONS; LARGE COHORT; TUMORS
AB Context: Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (Alp) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.
   Objective: To determine the A/Pmutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AlPmut carrier family members.
   Design: This was an observational, longitudinal study conducted over 7 years.
   Setting: International collaborative study conducted at referral centers for pituitary diseases.
   Participants: FIPA families (n = 216) and sporadic young-onset y) pituitary adenoma patients (n = 404) participated in the study.
   Interventions: We performed genetic screening of patients for A/Pmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant.
   Main Outcome Measure(s): We assessed clinical disease in mutation carriers, comparison of characteristics of A/Pmut positive and negative patients, results of GNAS1, and FGFR4 analysis.
   Results: Thirty-seven FIPA families and 34 sporadic patients had A/Pmuts. Patients with truncating A/Pmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating A/Pmuts. Somatic GNAS1 mutations were absent in tumors from A/Pmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in A/Pmut-positive individuals. A total of 164 A/Pmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening.
   Conclusions: A quarter of the A/Pmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for A/Pmut-positive pituitary adenomas.
C1 [Hernandez-Ramirez, Laura C.; Gabrovska, Plamena; Denes, Judit; Trivellin, Giampaolo; Tilley, Daniel; Ferrau, Francesco; Evanson, Jane; Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Ctr Endocrinol, London EC1M 6BQ, England.
   [Stals, Karen; Ellard, Sian] Royal Devon & Exeter Natl Hlth Serv Fdn Trust, Dept Mol Genet, Exeter EX2 5DW, Devon, England.
   [Trivellin, Giampaolo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
   [Grossman, Ashley B.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Dept Endocrinol, Oxford OX3 7LE, England.
   [Roncaroli, Federico] Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, Fac Med, Div Brain Sci, London W6 8RP, England.
   [Gadelha, Monica R.] Univ Fed Rio de Janeiro, Clementino Fraga Filho Univ Hosp, Endocrinol Unit, Ilha Fundao, BR-21941913 Rio De Janeiro, Brazil.
RP Korbonits, M (reprint author), Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Endocrinol & Metab,Ctr Endocrinol, Charterhouse Sq, London EC1M 6BQ, England.
EM m.korbonits@qmul.ac.uk
RI Trivellin, Giampaolo/J-6583-2016; Ferrao, Francesco/P-8852-2015; Badiu,
   Corin/C-5783-2012; 
OI Trivellin, Giampaolo/0000-0003-2384-4153; Ferrao,
   Francesco/0000-0002-7472-6598; Badiu, Corin/0000-0002-8087-8125; Eeles,
   Rosalind/0000-0002-3698-6241; Street, Maria
   Elisabeth/0000-0001-8427-8971; Korbonits, Marta/0000-0002-4101-9432;
   Hernandez-Ramirez, Laura C./0000-0002-6599-6406; Pearce,
   Simon/0000-0001-8384-8063; KARAVITAKI, NIKI/0000-0002-4696-0643
FU Medical Research Council of the United Kingdom [G0701307]; Wellcome
   Trust [097970/Z/11/Z]; National Institute of Health Research; Barts and
   The London Charity; Royal Society; Pfizer; National Council of Science
   and Technology; Secretariat of Public Education from the Mexican
   Government
FX This work was supported by the Medical Research Council of the United
   Kingdom (G0701307), the Wellcome Trust (097970/Z/11/Z), the National
   Institute of Health Research, the Barts and The London Charity, the
   Royal Society, and Pfizer. L.C.H.-R. is supported by grants from the
   National Council of Science and Technology and the Secretariat of Public
   Education from the Mexican Government.
NR 40
TC 18
Z9 18
U1 0
U2 2
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 SEP
PY 2015
VL 100
IS 9
BP E1242
EP E1254
DI 10.1210/jc.2015-1869
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3BV
UT WOS:000364867800023
PM 26186299
ER

PT J
AU Batycka-Baran, A
   Hattinger, E
   Zwicker, S
   Summer, B
   Howard, OMZ
   Thomas, P
   Szepietowski, JC
   Ruzicka, T
   Prinz, JC
   Wolf, R
AF Batycka-Baran, Aleksandra
   Hattinger, Eva
   Zwicker, Stephanie
   Summer, Burkhard
   Howard, O. M. Zack
   Thomas, Peter
   Szepietowski, Jacek C.
   Ruzicka, Thomas
   Prinz, Joerg C.
   Wolf, Ronald
TI Leukocyte-derived koebnerisin (S100A15) and psoriasin (S100A7) are
   systemic mediators of inflammation in psoriasis
SO JOURNAL OF DERMATOLOGICAL SCIENCE
LA English
DT Article
DE S100; Psoriasin; Koebnerisin; Psoriasis; UVB; Leukocytes
ID NECROSIS-FACTOR-ALPHA; MOLECULAR-CLONING; PROTEIN PSORIASIN;
   GENE-EXPRESSION; SKIN; PATHOGENESIS; ULTRAVIOLET; INTERFERES; CYTOKINES;
   DISEASES
AB Background: Psoriasis is a systemic immune-mediated chronic inflammatory disease. In the skin, the antimicrobial proteins koebnerisin (S100A15) and psoriasin (S100A7) are overexpressed in the epidermis of psoriatic lesions and mediate inflammation as chemoattractants for immune cells. Their role for systemic inflammation in circulating leukocytes is unknown.
   Objective: The aim of the study was to identify circulating leukocyte populations as a source of koebnerisin and psoriasin. Further, immune-stimulatory effects of these S100A proteins on circulating leukocytes were evaluated and their role as therapeutic response markers in patients with psoriasis was analyzed upon UVB treatment.
   Methods: The expression and production of koebnerisin and psoriasin by leukocytes were assessed by quantitative real-time PCR (qRT-PCR) and immunoblotting.The S100A protein mediated regulation of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs) was measured with qRT-PCR and cytometric bead assay.
   Results: We identified circulating leukocytes as novel sources of koebnerisin (S100A15) and psoriasin (S100A7). Circulating leukocytes (PBMCs) of patients with psoriasis produced increased levels of koebnerisin and psoriasin compared to healthy individuals. Both S100A proteins further acted as 'alarmins' on PBMC to induce proinflammatory cytokines implicated in the pathogenesis of psoriasis, such as IL-1 beta TNF-alpha, IL-6 and IL-8. Koebnerisin levels were suppressed in PBMC of psoriatic patients when effectively treated with narrow-band UVB.
   Conclusions: Data suggest that koebnerisin and psoriasin are systemic pro-inflammatory mediators and koebnerisin acts as a therapeutic response marker in psoriasis. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Batycka-Baran, Aleksandra; Szepietowski, Jacek C.] Wroclaw Med Univ, Dept Dermatol Venereol & Allergol, Wroclaw, Poland.
   [Batycka-Baran, Aleksandra; Hattinger, Eva; Zwicker, Stephanie; Summer, Burkhard; Thomas, Peter; Ruzicka, Thomas; Prinz, Joerg C.; Wolf, Ronald] Univ Munich, Dept Dermatol & Allergol, Munich, Germany.
   [Howard, O. M. Zack] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Wolf, R (reprint author), Univ Munich, Dept Dermatol & Allergol, Munich, Germany.
EM ronald.wolf@med.uni-muenchen.de
FU Almirall Research Award; German Research Foundation [WO 843/3-1]; Otto
   Braun-Falco Scholarship;  [ST-672]
FX We would like to thank Daniela Bureik for her skillful support. This
   work was supported by the the Almirall Research Award (R.W.), the German
   Research Foundation (R.W., WO 843/3-1), Otto Braun-Falco Scholarship
   (A.B.-B.) and ST-672.
NR 33
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0923-1811
EI 1873-569X
J9 J DERMATOL SCI
JI J. Dermatol. Sci.
PD SEP
PY 2015
VL 79
IS 3
BP 214
EP 221
DI 10.1016/j.jdermsci.2015.05.007
PG 8
WC Dermatology
SC Dermatology
GA CV8BN
UT WOS:000364501600004
PM 26055798
ER

PT J
AU Gan, C
   Jenkins, M
   Win, A
   Macrae, F
AF Gan, C.
   Jenkins, M.
   Win, A.
   Macrae, F.
CA Colon Canc Family Registry
TI Spectrum of cancer phenotypes in Asian Lynch syndrome families
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Meeting Abstract
ID CLINICAL-FEATURES
C1 [Gan, C.; Jenkins, M.; Win, A.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
   [Gan, C.; Macrae, F.] Familial Canc Clin, Dept Colorectal Med & Genet, Parkville, Vic, Australia.
   [Gan, C.; Macrae, F.] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Parkville, Vic 3052, Australia.
   [Colon Canc Family Registry] NIH, Washington, DC USA.
RI Jenkins, Mark/P-7803-2015
OI Jenkins, Mark/0000-0002-8964-6160
NR 3
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0815-9319
EI 1440-1746
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD SEP
PY 2015
VL 30
SU 3
SI SI
BP 77
EP 77
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CV8CZ
UT WOS:000364505900154
ER

PT J
AU Aksyuk, AA
   Newcomb, WW
   Cheng, NQ
   Winkler, DC
   Fontana, J
   Heymann, JB
   Steven, AC
AF Aksyuk, Anastasia A.
   Newcomb, William W.
   Cheng, Naiqian
   Winkler, Dennis C.
   Fontana, Juan
   Heymann, J. Bernard
   Steven, Alasdair C.
TI Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus
   Procapsid
SO MBIO
LA English
DT Article
ID MAJOR CAPSID PROTEIN; RECOMBINANT BACULOVIRUSES; CRYOELECTRON
   MICROSCOPY; CONFORMATIONAL-CHANGES; MATURATION; TYPE-1; BINDING;
   MECHANISM; DYNAMICS; BACTERIOPHAGE-T4
AB The herpes simplex virus 1 (HSV-1) capsid is a massive particle (similar to 200 MDa; 1,250-angstrom diameter) with T = 16 icosahedral symmetry. It initially assembles as a procapsid with similar to 4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a process driven by proteolysis and expulsion of the internal scaffolding protein. Assembly also relies on an external scaffolding protein, the triplex, an alpha(2)beta heterotrimer that coordinates neighboring capsomers in the procapsid and becomes a stabilizing clamp in the mature capsid. To investigate the mechanisms that regulate its assembly, we developed a novel isolation procedure for the metastable procapsid and collected a large set of cryo-electron microscopy data. In addition to procapsids, these preparations contain maturation intermediates, which were distinguished by classifying the images and calculating a three-dimensional reconstruction for each class. Appraisal of the procapsid structure led to a new model for assembly; in it, the protomer (assembly unit) consists of one triplex, surrounded by three major capsid protein (MCP) subunits. The model exploits the triplexes' departure from 3-fold symmetry to explain the highly skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T = 16 architecture. These observations also yielded new insights into maturation.
   IMPORTANCE This paper addresses the molecular mechanisms that govern the self-assembly of large, structurally complex, macromolecular particles, such as the capsids of double-stranded DNA viruses. Although they may consist of thousands of protein subunits of many different kinds, their assembly is precise, ranking them among the largest entities in the biosphere whose structures are uniquely defined to the atomic level. Assembly proceeds in two stages: formation of a precursor particle (procapsid) and maturation, during which major changes in structure and composition take place. Our analysis of the HSV procapsid by cryo-electron microscopy suggests a hierarchical pathway in which multisubunit "protomers" are the building blocks of the procapsid but their subunits are redistributed into different subcomplexes upon being incorporated into a nascent procapsid and are redistributed again in maturation. Assembly is a highly virus-specific process, making it a potential target for antiviral intervention.
C1 [Aksyuk, Anastasia A.; Newcomb, William W.; Cheng, Naiqian; Winkler, Dennis C.; Fontana, Juan; Heymann, J. Bernard; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
RI Fontana, Juan/A-9138-2009
OI Fontana, Juan/0000-0002-9084-2927
FU NIAMS; NIGMS PRAT fellowship
FX This work was supported by the Intramural Research Program of NIAMS,
   with additional support from an NIGMS PRAT fellowship (to A.A.A.).
NR 45
TC 3
Z9 3
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD SEP-OCT
PY 2015
VL 6
IS 5
AR e01525-15
DI 10.1128/mBio.01525-15
PG 11
WC Microbiology
SC Microbiology
GA CV8HK
UT WOS:000364523100068
PM 26443463
ER

PT J
AU Baz, M
   Boonnak, K
   Paskel, M
   Santos, C
   Powell, T
   Townsend, A
   Subbarao, K
AF Baz, Mariana
   Boonnak, Kobporn
   Paskel, Myeisha
   Santos, Celia
   Powell, Timothy
   Townsend, Alain
   Subbarao, Kanta
TI Nonreplicating Influenza A Virus Vaccines Confer Broad Protection
   against Lethal Challenge
SO MBIO
LA English
DT Article
ID NEURAMINIDASE ANTIBODY; PANDEMIC INFLUENZA; CROSS-PROTECTION; LIVE
   VACCINE; T-CELLS; MICE; INFECTION; IMMUNITY; GENERATION; HEMAGGLUTININ
AB New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding H1N1 and H5N1 cold-adapted (ca) live attenuated influenza virus vaccines in mice and ferrets. Administration of two doses of H1 or H5 S-FLU vaccines protected mice and ferrets from lethal challenge with homologous, heterologous, and heterosubtypic influenza viruses, and two doses of S-FLU and ca vaccines yielded comparable effects. Importantly, when ferrets immunized with one dose of H1 S-FLU or ca vaccine were challenged with the homologous H1N1 virus, the challenge virus failed to transmit to naive ferrets by the airborne route. S-FLU technology can be rapidly applied to any emerging influenza virus, and the promising preclinical data support further evaluation in humans.
   IMPORTANCE Influenza viruses continue to represent a global public health threat, and cross-protective vaccines are needed to prevent seasonal and pandemic influenza. Currently licensed influenza vaccines are based on immunity to the hemagglutinin protein that is highly variable. However, T cell responses directed against highly conserved viral proteins contribute to clearance of the virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses. In this study, two nonreplicating pseudotyped influenza virus vaccines were compared with their corresponding live attenuated influenza virus vaccines, and both elicited robust protection against homologous and heterosubtypic challenge in mice and ferrets, making them promising candidates for further evaluation in humans.
C1 [Baz, Mariana; Boonnak, Kobporn; Paskel, Myeisha; Santos, Celia; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Powell, Timothy; Townsend, Alain] Univ Oxford, John Radcliffe Hosp, Weatherall Inst, Human Immunol Unit,Mol Immunol Grp, Oxford OX3 9DU, England.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU NIAID, NIH; Townsend-Jeantet Prize Charitable Trust [1011770]; Human
   Immunology Unit of Oxford University
FX This work was supported by the Intramural Research Program of the NIAID,
   NIH, the Townsend-Jeantet Prize Charitable Trust (registered charity
   1011770), and the Human Immunology Unit of Oxford University.
NR 36
TC 1
Z9 1
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD SEP-OCT
PY 2015
VL 6
IS 5
AR e01487-15
DI 10.1128/mBio.01487-15
PG 13
WC Microbiology
SC Microbiology
GA CV8HK
UT WOS:000364523100063
PM 26489862
ER

PT J
AU Chesebro, B
   Striebel, J
   Rangel, A
   Phillips, K
   Hughson, A
   Caughey, B
   Race, B
AF Chesebro, Bruce
   Striebel, James
   Rangel, Alejandra
   Phillips, Katie
   Hughson, Andrew
   Caughey, Byron
   Race, Brent
TI Early Generation of New PrPSc on Blood Vessels after Brain
   Microinjection of Scrapie in Mice
SO MBIO
LA English
DT Article
ID PATHOLOGICAL ALPHA-SYNUCLEIN; PRION PROTEIN ACCUMULATION;
   KAINATE-INDUCED SEIZURES; CEREBROSPINAL-FLUID; MOUSE SCRAPIE; IN-VIVO;
   DISEASE; HAMSTERS; CELLS; MODEL
AB Aggregation of misfolded host proteins in the central nervous system is believed to be important in the pathogenic process in several neurodegenerative diseases of humans, including prion diseases, Alzheimer's disease, and Parkinson's disease. In these diseases, protein misfolding and aggregation appear to expand through a process of seeded polymerization. Prion diseases occur in both humans and animals and are experimentally transmissible orally or by injection, thus providing a controllable model of other neurodegenerative protein misfolding diseases. In rodents and ruminants, prion disease has a slow course, lasting months to years. Although prion infectivity has been detected in brain tissue at 3 to 4 weeks postinfection (p.i.), the details of early prion replication in the brain are not well understood. Here we studied the localization and quantitation of PrPSc generation in vivo starting at 30 min postmicroinjection of scrapie into the brain. In C57BL mice at 3 days p.i., generation of new PrPSc was detected by immunohistochemistry and immunoblot assays, and at 7 days p.i., new generation was confirmed by real-time quaking-induced conversion assay. The main site of new PrPSc generation was near the outer basement membrane of small and medium blood vessels. The finding and localization of replication at this site so early after injection have not been reported previously. This predominantly perivascular location suggested that structural components of the blood vessel basement membrane or perivascular astrocytes might act as cofactors in the initial generation of PrPSc. The location of PrPSc replication at the basement membrane also implies a role for the brain interstitial fluid drainage in the early infection process.
   IMPORTANCE Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and prion diseases, of humans are characterized by misfolding and aggregation of certain proteins, resulting in the destruction of brain tissue. In these diseases, the damage process spreads progressively within the central nervous system, but only prion diseases are known to be transmissible between individuals. Here we used microinjection of infectious prion protein (PrPSc) into the mouse brain to model early events of iatrogenic prion transmission via surgical instruments or tissue grafts. At 3 and 7 days postinjection, we detected the generation of new PrPSc, mostly on the outer walls of blood vessels near the injection site. This location and very early replication were surprising and unique. Perivascular prion replication suggested the transport of injected PrPSc via brain interstitial fluid to the basement membranes of blood vessels, where interactions with possible cofactors made by astrocytes or endothelia might facilitate the earliest cycles of prion infection.
C1 [Chesebro, Bruce; Striebel, James; Rangel, Alejandra; Phillips, Katie; Hughson, Andrew; Caughey, Byron; Race, Brent] NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA.
RP Chesebro, B (reprint author), NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA.
EM bchesebro@nih.gov
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
   NIH, NIAID.
NR 60
TC 3
Z9 3
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD SEP-OCT
PY 2015
VL 6
IS 5
AR e01419-15
DI 10.1128/mBio.01419-15
PG 10
WC Microbiology
SC Microbiology
GA CV8HK
UT WOS:000364523100050
PM 26396245
ER

PT J
AU Gallichotte, EN
   Widman, DG
   Yount, BL
   Wahala, WM
   Durbin, A
   Whitehead, S
   Sariol, CA
   Crowe, JE
   de Silva, AM
   Baric, RS
AF Gallichotte, E. N.
   Widman, D. G.
   Yount, B. L.
   Wahala, W. M.
   Durbin, A.
   Whitehead, S.
   Sariol, C. A.
   J. E. Crowe, Jr.
   de Silva, A. M.
   Baric, R. S.
TI A New Quaternary Structure Epitope on Dengue Virus Serotype 2 Is the
   Target of Durable Type-Specific Neutralizing Antibodies
SO MBIO
LA English
DT Article
ID RESPIRATORY SYNDROME CORONAVIRUS; LENGTH INFECTIOUS CDNA; REVERSE
   GENETICS; VACCINE; FLAVIVIRUSES; RECOGNITION; MATURATION; MECHANISM;
   REVEALS; VIRIONS
AB Dengue virus serotype 2 (DENV2) is widespread and responsible for severe epidemics. While primary DENV2 infections stimulate serotype-specific protective responses, a leading vaccine failed to induce a similar protective response. Using human monoclonal antibodies (hMAbs) isolated from dengue cases and structure-guided design of a chimeric DENV, here we describe the major site on the DENV2 envelope (E) protein targeted by neutralizing antibodies. DENV2-specific neutralizing hMAb 2D22 binds to a quaternary structure epitope. We engineered and recovered a recombinant DENV4 that displayed the 2D22 epitope. DENV2 neutralizing antibodies in people exposed to infection or a live vaccine tracked with the 2D22 epitope on the DENV4/2 chimera. The chimera remained sensitive to DENV4 antibodies, indicating that the major neutralizing epitopes on DENV2 and -4 are at different sites. The ability to transplant a complex epitope between DENV serotypes demonstrates a hitherto underappreciated structural flexibility in flaviviruses, which could be harnessed to develop new vaccines and diagnostics.
   IMPORTANCE Dengue virus causes fever and dengue hemorrhagic fever. Dengue serotype 2 (DENV2) is widespread and frequently responsible for severe epidemics. Natural DENV2 infections stimulate serotype-specific neutralizing antibodies, but a leading DENV vaccine did not induce a similar protective response. While groups have identified epitopes of single monoclonal antibodies (MAbs), the molecular basis of DENV2 neutralization by polyclonal human immune sera is unknown. Using a recombinant DENV displaying serotype 2 epitopes, here we map the main target of DENV2 polyclonal neutralizing antibodies induced by natural infection and a live DENV2 vaccine candidate. Proper display of the epitope required the assembly of viral envelope proteins into higher-order structures present on intact virions. Despite the complexity of the epitope, it was possible to transplant the epitope between DENV serotypes. Our findings have immediate implications for evaluating dengue vaccines in the pipeline as well as designing next-generation vaccines.
C1 [Gallichotte, E. N.; Wahala, W. M.; de Silva, A. M.; Baric, R. S.] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
   [Widman, D. G.; Yount, B. L.; Baric, R. S.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
   [Durbin, A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Whitehead, S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Sariol, C. A.] Univ Puerto Rico Med Sci Campus, Caribbean Primate Res Ctr, San Juan, PR USA.
   [Sariol, C. A.] Univ Puerto Rico Med Sci Campus, Dept Microbiol & Med Zool, San Juan, PR USA.
   [Sariol, C. A.] Univ Puerto Rico Med Sci Campus, Dept Internal Med, San Juan, PR USA.
   [J. E. Crowe, Jr.] Vanderbilt Univ, Dept Pediat, Nashville, TN 37235 USA.
   [J. E. Crowe, Jr.] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Nashville, TN 37235 USA.
RP de Silva, AM (reprint author), Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
EM aravinda_desilva@med.unc.edu; rbasric@email.unc.edu
FU United States National Institute of Allergy and Infectious Diseases [R01
   AI107731, U19 AI109761 CETR]; NIAID [5UO1-AI078060, P40 OD012217]
FX This research was supported by the extramural (R01 AI107731 [principal
   investigator, Aravinda de Silva]; U19 AI109761 CETR [principal
   investigator, Ralph Baric]) and intramural research programs of the
   United States National Institute of Allergy and Infectious Diseases
   (principal investigators, S. Whitehead and A. P. Durbin). This work was
   also partially supported by NIAID grant 5UO1-AI078060 and grant P40
   OD012217 (principal investigator, Carlos Sariol).
NR 31
TC 9
Z9 9
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD SEP-OCT
PY 2015
VL 6
IS 5
AR e01461-15
DI 10.1128/mBio.01461-15
PG 8
WC Microbiology
SC Microbiology
GA CV8HK
UT WOS:000364523100060
PM 26463165
ER

PT J
AU Kapoor, A
   Kumar, A
   Simmonds, P
   Bhuva, N
   Chauhan, LS
   Lee, B
   Sall, AA
   Jin, ZZ
   Morse, SS
   Shaz, B
   Burbelo, PD
   Lipkin, WI
AF Kapoor, Amit
   Kumar, Arvind
   Simmonds, Peter
   Bhuva, Nishit
   Chauhan, Lokendra Singh
   Lee, Bohyun
   Sall, Amadou Alpha
   Jin, Zhezhen
   Morse, Stephen S.
   Shaz, Beth
   Burbelo, Peter D.
   Lipkin, W. Ian
TI Virome Analysis of Transfusion Recipients Reveals a Novel Human Virus
   That Shares Genomic Features with Hepaciviruses and Pegiviruses
SO MBIO
LA English
DT Article
ID HEPATITIS-C VIRUS; ORDERED RNA STRUCTURE; NON-A; HUMAN-IMMUNODEFICIENCY;
   INFECTION; IDENTIFICATION; HEMOPHILIACS; TRANSLATION; EVOLUTION;
   DISCOVERY
AB To investigate the transmission of novel infectious agents by blood transfusion, we studied changes in the virome composition of blood transfusion recipients pre- and posttransfusion. Using this approach, we detected and genetically characterized a novel human virus, human hepegivirus 1 (HHpgV-1), that shares features with hepatitis C virus (HCV) and human pegivirus (HPgV; formerly called GB virus C or hepatitis G virus). HCV and HPgV belong to the genera Hepacivirus and Pegivirus of the family Flaviviridae. HHpgV-1 was found in serum samples from two blood transfusion recipients and two hemophilia patients who had received plasma-derived clotting factor concentrates. In the former, the virus was detected only in the posttransfusion samples, indicating blood-borne transmission. Both hemophiliacs were persistently viremic over periods of at least 201 and 1,981 days. The 5' untranslated region (UTR) of HHpgV-1 contained a type IV internal ribosome entry site (IRES), structurally similar to although highly divergent in sequence from that of HCV and other hepaciviruses. However, phylogenetic analysis of nonstructural genes (NS3 and NS5B) showed that HHpgV-1 forms a branch within the pegivirus clade distinct from HPgV and homologs infecting other mammalian species. In common with some pegivirus variants infecting rodents and bats, the HHpgV-1 genome encodes a short, highly basic protein upstream of E1, potentially possessing a core-like function in packaging RNA during assembly. Identification of this new human virus, HHpgV-1, expands our knowledge of the range of genome configurations of these viruses and may lead to a reevaluation of the original criteria by which the genera Hepacivirus and Pegivirus are defined.
   IMPORTANCE More than 30 million blood components are transfused annually in the United States alone. Surveillance for infectious agents in the blood supply is key to ensuring the safety of this critical resource for medicine and public health. Here, we report the identification of a new and highly diverse HCV/GB virus (GBV)-like virus from human serum samples. This new virus, human hepegivirus 1 (HHpgV-1), was found in serum samples from blood transfusion recipients, indicating its potential for transmission via transfusion products. We also found persistent long-term HHpgV-1 viremia in two hemophilia patients. HHpgV-1 is unique because it shares genetic similarity with both highly pathogenic HCV and the apparently nonpathogenic HPgV (GBV-C). Our results add to the list of human viruses and provide data to develop reagents to study virus transmission and disease association and for interrupting virus transmission and new human infections.
C1 [Kapoor, Amit; Kumar, Arvind; Bhuva, Nishit; Chauhan, Lokendra Singh; Lee, Bohyun; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
   [Simmonds, Peter] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.
   [Sall, Amadou Alpha] Inst Pasteur, Dakar, Senegal.
   [Jin, Zhezhen] Columbia Univ, Dept Biostat, MSPH, New York, NY USA.
   [Morse, Stephen S.] Columbia Univ, Dept Epidemiol, MSPH, New York, NY USA.
   [Shaz, Beth] New York Blood Ctr, New York, NY USA.
   [Burbelo, Peter D.] Natl Inst Dent & Cranofacial Res, Dent Clin Res Core, NIH, Bethesda, MD USA.
RP Kapoor, A (reprint author), Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
EM ak3117@columbia.edu
FU NIH [HL119485, AI107631, AI109761]; National Institute of Dental and
   Craniofacial Research, NIH
FX The study was supported by NIH grants HL119485 (A. Kapoor), AI107631 (A.
   Kapoor) and AI109761 (Lipkin). P. D. B. was supported by the Intramural
   Research Program of National Institute of Dental and Craniofacial
   Research, NIH.
NR 47
TC 15
Z9 16
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD SEP-OCT
PY 2015
VL 6
IS 5
AR e01466-15
DI 10.1128/mBio.01466-15
PG 12
WC Microbiology
SC Microbiology
GA CV8HK
UT WOS:000364523100061
PM 26396247
ER

PT J
AU Nightingale, S
AF Nightingale, Stuart
TI Dual-Use Research of Concern (DURC) Review at American Society for
   Microbiology Journals and Its Effect on Other Organizations
SO MBIO
LA English
DT Editorial Material
C1 [Nightingale, Stuart] NIH, Bethesda, MD 20892 USA.
RP Nightingale, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM nightins@od.nih.gov
NR 7
TC 0
Z9 0
U1 2
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD SEP-OCT
PY 2015
VL 6
IS 5
AR e01512-15
DI 10.1128/mBio.01512-15
PG 1
WC Microbiology
SC Microbiology
GA CV8HK
UT WOS:000364523100066
PM 26463166
ER

PT J
AU Yang, J
   Bennett, BD
   Luo, SJ
   Inoue, K
   Grimm, SA
   Schroth, GP
   Bushel, PR
   Kinyamu, HK
   Archer, TK
AF Yang, Jun
   Bennett, Brian D.
   Luo, Shujun
   Inoue, Kaoru
   Grimm, Sara A.
   Schroth, Gary P.
   Bushel, Pierre R.
   Kinyamu, H. Karimi
   Archer, Trevor K.
TI LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer
   Cells
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID EMBRYONIC STEM-CELLS; PYRUVATE-KINASE; MESSENGER-RNA; LET-7 MICRORNA;
   HNRNP PROTEINS; GLUCOCORTICOID-RECEPTOR; HMENA ENAH; LIN-28;
   TRANSFORMATION; REVEALS
AB LIN28 is an evolutionarily conserved RNA-binding protein with critical functions in developmental timing and cancer. However, the molecular mechanisms underlying LIN28's oncogenic properties are yet to be described. RNA-protein immunoprecipitation coupled with genome-wide sequencing (RIP-Seq) analysis revealed significant LIN28 binding within 843 mRNAs in breast cancer cells. Many of the LIN28-bound mRNAs are implicated in the regulation of RNA and cell metabolism. We identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein with multiple roles in mRNA metabolism, as a LIN28-interacting partner. Subsequently, we used a custom computational method to identify differentially spliced gene isoforms in LIN28 and hnRNP A1 small interfering RNA (siRNA)-treated cells. The results reveal that these proteins regulate alternative splicing and steady-state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of the ENAH exon 11a isoform. The expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. Intriguingly, analysis of publicly available array data from the Cancer Genome Atlas (TCGA) reveals that LIN28 expression in the HER2 subtype is significantly different from that in other breast cancer subtypes. Collectively, our data suggest that LIN28 may regulate splicing and gene expression programs that drive breast cancer subtype phenotypes.
C1 [Yang, Jun; Inoue, Kaoru; Kinyamu, H. Karimi; Archer, Trevor K.] Natl Inst Environm Hlth Sci, Chromatin & Gene Express Sect, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC USA.
   [Bennett, Brian D.; Grimm, Sara A.] Natl Inst Environm Hlth Sci, Integrat Bioinformat, NIH, Res Triangle Pk, NC USA.
   [Luo, Shujun; Schroth, Gary P.] Illumina Inc, Res & Dev, Hayward, CA 94545 USA.
   [Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC USA.
RP Kinyamu, HK (reprint author), Illumina Inc, Res & Dev, Hayward, CA 94545 USA.
EM kinyamu@niehs.nih.gov; archer1@niehs.nih.gov
FU Intramural Research Program of the National Institute of Environmental
   Health Sciences, NIH [Z01 ES071006-15]
FX This research was supported by the Intramural Research Program of the
   National Institute of Environmental Health Sciences, NIH (project number
   Z01 ES071006-15).
NR 62
TC 4
Z9 4
U1 1
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD SEP
PY 2015
VL 35
IS 18
BP 3225
EP 3243
DI 10.1128/MCB.00426-15
PG 19
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CV8AT
UT WOS:000364499600011
PM 26149387
ER

PT J
AU Ghosh, MC
   Zhang, DL
   Rouault, TA
AF Ghosh, Manik C.
   Zhang, De-Liang
   Rouault, Tracey A.
TI Iron misregulation and neurodegenerative disease in mouse models that
   lack iron regulatory proteins
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Iron; Iron regulatory protein; Polycythemia; Pulmonary hypertension;
   Anemia; Neurodegeneration; Axonal degeneration; Amino cupric silver
   stain; Erythropoietic protoporphyria; Motor neuron
ID NONTRANSFERRIN-BOUND IRON; METAL-ION TRANSPORTER; MESSENGER-RNA;
   RESPONSIVE ELEMENT; KNOCKOUT MICE; IN-VIVO; MITOCHONDRIAL ACONITASE;
   ALZHEIMERS-DISEASE; INTRACELLULAR IRON; TARGETED DELETION
AB Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are two cytosolic proteins that maintain cellular iron homeostasis by binding to RNA stem loops known as iron responsive elements (IREs) that are found in the untranslated regions of target mRNAs that encode proteins involved in iron metabolism. IRPs modify the expression of iron metabolism genes, and global and tissue-specific knockout mice have been made to evaluate the physiological significance of these iron regulatory proteins (Irps). Here, we will discuss the results of the studies that have been performed with mice engineered to lack the expression of one or both Irps and made in different strains using different methodologies. Both Irp1 and Irp2 knockout mice are viable, but the double knockout (Irp1(-/-)Irp2(-/-)) mice die before birth, indicating that these Irps play a crucial role in maintaining iron homeostasis. Irp1 mice develop polycythemia and pulmonary hypertension, and when these mice are challenged with a low iron diet, they die early of abdominal hemorrhages, suggesting that Irp1 plays an essential role in erythropoiesis and in the pulmonary and cardiovascular systems. Irp2(-/-) mice develop microcytic anemia, etythropoietic protoporphyria and a progressive neurological disorder, indicating that Irp2 has important functions in the nervous system and erythropoietic homeostasis. Several excellent review articles have recently been published on Irp knockout mice that mainly focus on Irp1(-/-) mice (referenced in the introduction). In this review, we will briefly describe the phenotypes and physiological implications of Itp1(-/-) mice and discuss the phenotypes observed for Irp2(-/-) mice in detail with a particular emphasis on the neurological problems of these mice. Published by Elsevier Inc.
C1 [Ghosh, Manik C.; Zhang, De-Liang; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Human Iron Metab, NIH, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Human Iron Metab, NIH, Bethesda, MD 20892 USA.
EM rouault@mail.nih.gov
FU intramural program of the Eunice Kennedy Shriver National Institute of
   Child Health and Human Development
FX This work was supported by the intramural program of the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development. We
   thank Dan Crooks for making the HIF2 alpha IRE.
NR 79
TC 5
Z9 5
U1 4
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD SEP
PY 2015
VL 81
SI SI
BP 66
EP 75
DI 10.1016/j.nbd.2015.02.026
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CV9LC
UT WOS:000364607700008
PM 25771171
ER

PT J
AU Mosquera, A
   Braun, M
   Hulett, M
   Ryszka, L
AF Mosquera, Alexis
   Braun, Michelle
   Hulett, Melissa
   Ryszka, Lauren
TI US Public Health Service Response to the 2014-2015 Ebola Epidemic in
   West Africa: A Nursing Perspective
SO PUBLIC HEALTH NURSING
LA English
DT Article
DE epidemic; epidemiology; ethics; infectious diseases; public health
   nursing practice
AB The 2014-2015 Ebola epidemic in West Africa has been the deadliest Ebola epidemic to date. In response to this deadly epidemic, the U.S. government declared this a top national security priority and members of the Commissioned Corps of the United States Public Health Service were tasked to provide direct patient care to Ebola virus disease patients. Commissioned Corps nurses provided the highest level of care under the most austere conditions. This article discusses the training, ethical dilemmas, and constant risk for potential exposure while working in an Ebola Treatment Unit.
C1 [Mosquera, Alexis] USAMRMC, Congressionally Directed Med Res Programs, Ft Detrick, MD 21702 USA.
   [Braun, Michelle] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
   [Hulett, Melissa] US FDA, CDER OMP OMPI DMPP, Silver Spring, MD USA.
   [Ryszka, Lauren] US Marshals Serv Headquarters, Prisoner Operat Div, Washington, DC USA.
RP Mosquera, A (reprint author), USAMRMC, Congressionally Directed Med Res Programs, 1077 Patchel St, Ft Detrick, MD 21702 USA.
EM alexis.mosquera.mil@mail.mil
NR 4
TC 1
Z9 1
U1 4
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0737-1209
EI 1525-1446
J9 PUBLIC HEALTH NURS
JI Public Health Nurs.
PD SEP-OCT
PY 2015
VL 32
IS 5
BP 550
EP 554
DI 10.1111/phn.12217
PG 5
WC Public, Environmental & Occupational Health; Nursing
SC Public, Environmental & Occupational Health; Nursing
GA CV4EA
UT WOS:000364217600019
PM 26207646
ER

PT J
AU Mueller, C
   Marx, A
   Epp, SW
   Zhong, Y
   Kuo, A
   Balo, AR
   Soman, J
   Schotte, F
   Lemke, HT
   Owen, RL
   Pai, EF
   Pearson, AR
   Olson, JS
   Anfinrud, PA
   Ernst, OP
   Miller, RJD
AF Mueller, C.
   Marx, A.
   Epp, S. W.
   Zhong, Y.
   Kuo, A.
   Balo, A. R.
   Soman, J.
   Schotte, F.
   Lemke, H. T.
   Owen, R. L.
   Pai, E. F.
   Pearson, A. R.
   Olson, J. S.
   Anfinrud, P. A.
   Ernst, O. P.
   Miller, R. J. Dwayne
TI Fixed target matrix for femtosecond time-resolved and in situ serial
   micro-crystallography
SO Structural Dynamics
LA English
DT Article
ID FREE-ELECTRON LASERS; SPERM-WHALE MYOGLOBIN; MACROMOLECULAR
   CRYSTALLOGRAPHY; LAUE CRYSTALLOGRAPHY; SYNTHETIC GENE; PROTEIN;
   CRYSTALS; DYNAMICS
AB We present a crystallography chip enabling in situ room temperature crystallography at microfocus synchrotron beamlines and X-ray free-electron laser (X-FEL) sources. Compared to other in situ approaches, we observe extremely low background and high diffraction data quality. The chip design is robust and allows fast and efficient loading of thousands of small crystals. The ability to load a large number of protein crystals, at room temperature and with high efficiency, into prescribed positions enables high throughput automated serial crystallography with microfocus synchrotron beamlines. In addition, we demonstrate the application of this chip for femtosecond time-resolved serial crystallography at the Linac Coherent Light Source (LCLS, Menlo Park, California, USA). The chip concept enables multiple images to be acquired from each crystal, allowing differential detection of changes in diffraction intensities in order to obtain high signal-to-noise and fully exploit the time resolution capabilities of XFELs. (C) 2015 Author(s).
C1 [Mueller, C.; Miller, R. J. Dwayne] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada.
   [Mueller, C.; Miller, R. J. Dwayne] Univ Toronto, Dept Phys, Toronto, ON M5S 3H6, Canada.
   [Marx, A.; Epp, S. W.; Zhong, Y.; Miller, R. J. Dwayne] Max Planck Inst Struct & Dynam Matter, Atom Resolved Dynam Div, D-22761 Hamburg, Germany.
   [Kuo, A.; Balo, A. R.; Pai, E. F.; Ernst, O. P.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Soman, J.; Olson, J. S.] Rice Univ, Dept Biosci, Houston, TX 77251 USA.
   [Schotte, F.; Anfinrud, P. A.] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Lemke, H. T.] SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.
   [Owen, R. L.] Diamond Light Source, Didcot OX11 0DE, Oxon, England.
   [Pai, E. F.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
   [Pai, E. F.] Univ Hlth Network, Campbell Family Inst Canc Res, Toronto, ON M5G 1L7, Canada.
   [Pai, E. F.; Ernst, O. P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Pearson, A. R.] Univ Hamburg, Hamburg Ctr Ultrafast Imaging, CFEL, D-22761 Hamburg, Germany.
   [Pearson, A. R.] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England.
RP Anfinrud, PA (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM anfinrud@nih.gov; oliver.ernst@utoronto.ca; dwayne.miller@mpsd.mpg.de
RI Lemke, Henrik Till/N-7419-2016; 
OI Lemke, Henrik Till/0000-0003-1577-8643; Epp, Sascha/0000-0001-6366-9113;
   Pai, Emil/0000-0002-1162-7242; Owen, Robin/0000-0002-2104-7057
FU Natural Sciences and Engineering Research Council of Canada; Max Planck
   Society; Canadian Institute for Advanced Research; Canada Excellence
   Research Chair program; Canada Research Chairs Program; USA NIH Grant
   [P01-HL110900]; Robert A. Welch Foundation [C-0612]; NIH Intramural
   Research Program of the National Institute of Diabetes and Digestive and
   Kidney Diseases
FX This research was supported by the Natural Sciences and Engineering
   Research Council of Canada (R.J.D.M. and E.F.P.), the Max Planck Society
   (R.J.D.M.), the Canadian Institute for Advanced Research (R.J.D.M. and
   O.P.E.), the Canada Excellence Research Chair program (O.P.E.), the
   Canada Research Chairs Program (E.F.P.), USA NIH Grant No. P01-HL110900
   (J.S.O.), Grant No. C-0612 from the Robert A. Welch Foundation (J.S.O.),
   and the NIH Intramural Research Program of the National Institute of
   Diabetes and Digestive and Kidney Diseases (P.A.A.). We thank Diamond
   Light Source for access to beamline I24 (Proposal No. mx-8367) that
   contributed to the results presented here. We also acknowledge the EPSRC
   Dynamic Structural Science Consortium at the Research Complex at Harwell
   (EPSRC EP/I01974X/1) for access to facilities for sample preparation and
   mounting prior to Diamond beam time. We also thank Pedram Mehrabi and
   Natasha Kruglyak (University of Toronto) for supplying defluorinase and
   CorA sample crystals and Anna Polyakova (University of Leeds) for the
   Mhp1 crystals used in initial testing of the crystallography chip.
   Portions of this research were carried out at the Linac Coherent Light
   Source (LCLS) at the SLAC National Accelerator Laboratory. LCLS is an
   Office of Science User Facility operated for the U.S. Department of
   Energy Office of Science by Stanford University. We thank Matthieu
   Chollet and James Michael Glownia for their help with the facilities of
   the LCLS beamline XPP.
NR 34
TC 9
Z9 9
U1 4
U2 17
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 2329-7778
J9 STRUCT DYNAM-US
JI Struct. Dyn.-US
PD SEP
PY 2015
VL 2
IS 5
AR 054302
DI 10.1063/1.4928706
PG 16
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA CV6UJ
UT WOS:000364406300006
PM 26798825
ER

PT J
AU Apolo, AB
   Burger, M
AF Apolo, Andrea B.
   Burger, Maximilian
TI A precision, personalized approach to the management of bladder cancer
SO CURRENT OPINION IN UROLOGY
LA English
DT Editorial Material
C1 [Apolo, Andrea B.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Burger, Maximilian] Univ Regensburg, Caritas St Josef Med Ctr, Dept Urol, D-93053 Regensburg, Germany.
RP Apolo, AB (reprint author), 10 Ctr Dr,Rm 12N226,MSC 1906, Bethesda, MD 20892 USA.
EM andrea.apolo@nih.gov
NR 3
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0963-0643
EI 1473-6586
J9 CURR OPIN UROL
JI Curr. Opin. Urol.
PD SEP
PY 2015
VL 25
IS 5
BP 416
EP 417
DI 10.1097/MOU.0000000000000195
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA CV3BD
UT WOS:000364132200009
PM 26153639
ER

PT J
AU Malayeri, AA
   Pattanayak, P
   Apolo, AB
AF Malayeri, Ashkan A.
   Pattanayak, Puskar
   Apolo, Andrea B.
TI Imaging muscle-invasive and metastatic urothelial carcinoma
SO CURRENT OPINION IN UROLOGY
LA English
DT Review
DE bladder cancer; diffusion-weighted-MRI; muscle-invasive; PET; computed
   tomography; ultra-small superparamagnetic iron oxide
ID POSITRON-EMISSION-TOMOGRAPHY; URINARY-BLADDER CANCER; ULTRASMALL
   SUPERPARAMAGNETIC PARTICLES; TRANSITIONAL-CELL CARCINOMA;
   COMPUTED-TOMOGRAPHY; RADICAL CYSTECTOMY; PROSTATE-CANCER; LYMPH-NODES;
   CLINICAL-VALUE; MRI
AB Purpose of reviewMuscle-invasive bladder cancer (MIBC) comprises approximately one-third of bladder cancers and is associated with significant morbidity and mortality. Accurate staging of bladder cancer is essential because of significantly different treatment options and the consequences of inaccurate staging. The current recommended method for staging is transurethral resection of the bladder tumor followed by contrast-enhanced computed tomography (CT). In this review, we discuss cross-sectional imaging approaches used to assess local, nodal, and distant metastases in MIBC.Recent findingsDetermining the most accurate imaging method for staging MIBC is a contentious issue. CT with contrast is a practical approach; however, there is potential for understaging of small lymph nodes or foci of metastasis. Multiparametric MRI is emerging as the imaging modality of choice in tumor staging, with a reported accuracy of more than 90%. Locoregional lymph node metastasis can also be accurately evaluated using functional MRI and specific contrast agents with paramagnetic characteristics. PET/CT with conventional radiotracers is a common imaging modality for staging distant metastases.SummaryConventional imaging methods for evaluating MIBC are of limited use. However, recent advances in molecular imaging, targeted contrast agents, and functional MRI have shown promising results for the staging of bladder cancer.
C1 [Malayeri, Ashkan A.; Pattanayak, Puskar] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
   [Apolo, Andrea B.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Apolo, AB (reprint author), 10 Ctr Dr 12N226,MSC 1906, Bethesda, MD 20892 USA.
EM andrea.apolo@nih.gov
NR 52
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0963-0643
EI 1473-6586
J9 CURR OPIN UROL
JI Curr. Opin. Urol.
PD SEP
PY 2015
VL 25
IS 5
BP 441
EP 448
DI 10.1097/MOU.0000000000000208
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CV3BD
UT WOS:000364132200013
PM 26222929
ER

PT J
AU DiBianco, JM
   George, AK
   Su, D
   Agarwal, PK
AF DiBianco, John Michael
   George, Arvin K.
   Su, Daniel
   Agarwal, Piyush K.
TI Managing noninvasive recurrences after definitive treatment for
   muscle-invasive bladder cancer or high-grade upper tract urothelial
   carcinoma
SO CURRENT OPINION IN UROLOGY
LA English
DT Review
DE bladder cancer; cancer recurrence; upper tract urothelial carcinoma;
   urothelial carcinoma
ID TRANSITIONAL-CELL CARCINOMA; RADICAL CYSTECTOMY; SURGICAL RESECTION;
   TUMOR LOCATION; NEPHROURETERECTOMY; MANAGEMENT; THERAPY; SURVIVAL;
   OUTCOMES; RADIOTHERAPY
AB Purpose of reviewApproximately 50% of patients with muscle invasive urothelial carcinoma will relapse with distant recurrence. Though rates of local recurrence after definitive therapy have improved, management remains a challenge. In this review, treatment strategies for this cohort are re-examined in an effort to enhance patient outcomes.Recent findingsUrothelial carcinoma continues to demonstrate high rates of recurrence and low rates of survival. Similarly to the treatment of primary urothelial cancer, treatment of recurrence focuses on cytology, stage, and clinical characteristics. Current areas of interest have focused on identification and causes/predictors of recurrence.SummaryLimited progress has been achieved in differentiating management of recurrent urothelial carcinoma from the treatment of primary urothelial carcinoma. However, there may be an increasing role for endoscopic and organ conserving therapies for carefully selected patients with recurrent noninvasive urothelial carcinoma. Identifying those at risk for early recurrence and early diagnosis of recurrence may be the most beneficial future strategies. The treatment regimen for noninvasive bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma should include intravesical chemotherapy or Bacillus Calmette-Guerin to prevent further bladder recurrence or tumor progression. We do not advocate diversion sparing techniques for local recurrence after radical cystectomy. Metastasectomy for distant/metastatic urothelial carcinoma recurrence represents a promising area of future study.
C1 [DiBianco, John Michael; George, Arvin K.; Su, Daniel; Agarwal, Piyush K.] NCI, Urol Oncol Branch, Ctr Canc Res, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Agarwal, PK (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,2950-W,Bldg 10,CRC Room 2W-5940, Bethesda, MD 20892 USA.
EM piyush.agarwal@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
   NIH, National Cancer Institute, Center for Cancer Research.
NR 48
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 0963-0643
EI 1473-6586
J9 CURR OPIN UROL
JI Curr. Opin. Urol.
PD SEP
PY 2015
VL 25
IS 5
BP 468
EP 475
DI 10.1097/MOU.0000000000000201
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CV3BD
UT WOS:000364132200016
PM 26125507
ER

PT J
AU Pfaender, S
   Walter, S
   Todt, D
   Behrendt, P
   Doerrbecker, J
   Wolk, B
   Engelmann, M
   Gravemann, U
   Seltsam, A
   Steinmann, J
   Burbelo, PD
   Klawonn, F
   Feige, K
   Pietschmann, T
   Cavalleri, JMV
   Steinmann, E
AF Pfaender, Stephanie
   Walter, Stephanie
   Todt, Daniel
   Behrendt, Patrick
   Doerrbecker, Juliane
   Woelk, Benno
   Engelmann, Michael
   Gravemann, Ute
   Seltsam, Axel
   Steinmann, Joerg
   Burbelo, Peter D.
   Klawonn, Frank
   Feige, Karsten
   Pietschmann, Thomas
   Cavalleri, Jessika-M. V.
   Steinmann, Eike
TI Assessment of cross-species transmission of hepatitis C virus-related
   non-primate hepacivirus in a population of humans at high risk of
   exposure
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID IDENTIFICATION; PEGIVIRUSES; PROTEIN; INNATE; HORSES
AB The recent discovery of hepatitis C virus (HCV)-related viruses in different animal species has raised new speculations regarding the origin of HCV and the possibility of a zoonotic source responsible for the endemic HCV transmission. As a consequence, these new findings prompt questions regarding the potential for cross-species transmissions of hepaciviruses. The closest relatives to HCV discovered to date are the non-primate hepaciviruses (NPHVs), which have been described to infect horses. To evaluate the risk of a potential zoonotic transmission, we analysed NPHV RNA and antibodies in humans with occupational exposure to horses in comparison with a low-risk group. Both groups were negative for NPHV RNA, even though low seroreactivities against various NPHV antigens could be detected irrespective of the group. In conclusion, we did not observe evidence of NPHV transmission between horses and humans.
C1 [Pfaender, Stephanie; Walter, Stephanie; Todt, Daniel; Behrendt, Patrick; Doerrbecker, Juliane; Engelmann, Michael; Pietschmann, Thomas; Steinmann, Eike] Twincore Ctr Expt & Clin Infect Res, Inst Expt Virol, D-30625 Hannover, Germany.
   [Woelk, Benno] Hannover Med Sch, Inst Virol, Hannover, Germany.
   [Woelk, Benno] LADR Med Lab Dr Kramer & Colleagues, Geesthacht, Germany.
   [Gravemann, Ute; Seltsam, Axel] Inst Springe, German Red Cross Blood Serv NSTOB, Springe, Germany.
   [Steinmann, Joerg] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Microbiol, Essen, Germany.
   [Burbelo, Peter D.] Natl Inst Dent Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD USA.
   [Klawonn, Frank] Helmholtz Ctr Infect Res HZI, Dept Cellular Prote, Bioinformat & Stat Res Grp, Braunschweig, Germany.
   [Klawonn, Frank] Ostfalia Univ Appl Sci, Dept Comp Sci, Wolfenbuettel, Germany.
   [Feige, Karsten; Cavalleri, Jessika-M. V.] Univ Vet Med Hannover, Clin Horses, Hannover, Germany.
RP Steinmann, E (reprint author), Twincore Ctr Expt & Clin Infect Res, Inst Expt Virol, Feodor Lynen Str 7, D-30625 Hannover, Germany.
EM Eike.Steinmann@twincore.de
FU international research training group 1273 by the DFG [IRTG 1273];
   Helmholtz Centre for Infection Research; Hannover Biomedical Research
   School (HBRS); Centre for Infection Biology (ZIB); DFG [STE 1954/1-1];
   Division of Intramural Research, NIH; Helmholtz Association [SO-024];
   European Research Council [ERC-2011-StG_281473-VIRAFRONT]
FX We are grateful to all volunteers who contributed the serum samples,
   Annett Kessler and the German Red Cross blood service NSTOB for
   technical support in acquiring serum samples and all members of the
   Institute of Experimental Virology, Twincore, for helpful suggestions
   and discussions. S. P. was supported by a stipend from the international
   research training group 1273 (IRTG 1273) provided by the DFG. S. W. was
   supported by a stipend from the Helmholtz Centre for Infection Research
   and supported by Hannover Biomedical Research School (HBRS) and the
   Centre for Infection Biology (ZIB). E. S. was supported by the DFG (STE
   1954/1-1) and intramural young investigator award of the Helmholtz
   Centre for Infection Research. Support for P. D. B. came from the
   Division of Intramural Research, NIH. T. P. was supported by a grant
   from the Helmholtz Association (SO-024) and by a grant from the European
   Research Council (ERC-2011-StG_281473-VIRAFRONT).
NR 24
TC 6
Z9 7
U1 0
U2 3
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
   BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD SEP
PY 2015
VL 96
BP 2636
EP 2642
DI 10.1099/vir.0.000208
PN 9
PG 7
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA CV0CQ
UT WOS:000363915400016
PM 26041875
ER

PT J
AU Nakano, Y
   Matsuda, K
   Yoshikawa, R
   Yamada, E
   Misawa, N
   Hirsch, VM
   Koyanagi, Y
   Sato, K
AF Nakano, Yusuke
   Matsuda, Kenta
   Yoshikawa, Rokusuke
   Yamada, Eri
   Misawa, Naoko
   Hirsch, Vanessa M.
   Koyanagi, Yoshio
   Sato, Kei
TI Down-modulation of primate lentiviral receptors by Nef proteins of
   simian immunodeficiency virus (SIV) of chimpanzees (SIVcpz) and related
   SIVs: implication for the evolutionary event at the emergence of SIVcpz
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID CELL-SURFACE RECEPTORS; RED-CAPPED MANGABEY; HIV-1 NEF; TYPE-1 NEF;
   CHEMOKINE RECEPTORS; NONPANDEMIC HIV-1; MAJOR CORECEPTOR; T-LYMPHOCYTES;
   VPU GENE; CD4
AB It has been estimated that human immunodeficiency virus type 1 originated from the zoonotic transmission of simian immunodeficiency virus (SIV) of chimpanzees, SIVcpz, and that SIVcpz emerged by the recombination of two lineages of SIVs in Old World monkeys (SIVgsn/mon/mus in guenons and SIVrcm in red-capped mangabeys) and SIVcpz Nef is most closely related to SIVrcnn Nef. These observations suggest that SIVrcm Nef had an advantage over SIVgsn/nnon/mus during the evolution of SIVcpz in chimpanzees, although this advantage remains uncertain. Nef is a multifunctional protein which downregulates CD4 and coreceptor proteins from the surface of infected cells, presumably to limit superinfection. To assess the possibility that SIVrcm Net was selected by its superior ability to downregulate viral entry receptors in chimpanzees, we compared its ability to down-modulate viral receptor proteins from humans, chimpanzees and red-capped mangabeys with Net proteins from eight other different strains of SIVs. Surprisingly, the ability of SIVrcm Net to downregulate CCR5, CCR2B and CXCR6 was comparable to or lower than SIVgsn/mon/mus Net, indicating that ability to down-modulate chennokine receptors was not the selective pressure. However, SIVrcm Nef significantly downregulates chimpanzee CD4 over SIVgsn/mon/mus Nets. Our findings suggest the possibility that the selection of SIVrcm Nef by ancestral SIVcpz is due to its superior capacity to down-modulate chimpanzees CD4 rather than coreceptor proteins.
C1 [Nakano, Yusuke; Yoshikawa, Rokusuke; Yamada, Eri; Misawa, Naoko; Koyanagi, Yoshio; Sato, Kei] Kyoto Univ, Inst Virus Res, Lab Viral Pathogenesis, Kyoto 6068507, Japan.
   [Nakano, Yusuke] Kumamoto Univ, Fac Life Sci, Dept Med Virol, Kumamoto 8608556, Japan.
   [Matsuda, Kenta; Hirsch, Vanessa M.] NIAID, Lab Mol Microbiol, NIH, Bethesda, MD 20892 USA.
   [Sato, Kei] Japan Sci & Technol Agcy, CREST, Saitama 3220012, Japan.
RP Sato, K (reprint author), Kyoto Univ, Inst Virus Res, Lab Viral Pathogenesis, Kyoto 6068507, Japan.
EM ksato@virus.kyoto-u.ac.jp
FU CREST, Japan Science and Technology Agency; Ministry of Health, Labor
   and Welfare of Japan Health Labor Sciences Research Grant [26361601];
   Takeda Science Foundation; Sumitomo Foundation Research Grant; Senshin
   Medical Research Foundation; Imai Memorial Trust for AIDS Research;
   Ichiro Kanehara Foundation; Kanae Foundation for the Promotion of
   Medical Science; Suzuken Memorial Foundation; Uehara Memorial
   Foundation; National Institute of Allergy and Infectious Diseases; Japan
   Society for the Promotion of Science (JSPS) [C15K07166, B24390112,
   S22220007]; Ministry of Education, Culture, Sports, Science and
   Technology of Japan [24115008]; Japan Agency for Medical Research and
   Development Research on HIV/AIDS AMED [15Afk0410013h0001]; JSPS
FX We would like to thank Dr Frank Kirchhoff (University of Ulm, Germany)
   for pCGCG plasmid and Dr Takamasa Ueno (Kumamoto University, Japan) for
   lively discussion. This study was supported in part by: CREST, Japan
   Science and Technology Agency (to K. S.); Ministry of Health, Labor and
   Welfare of Japan Health Labor Sciences Research Grant (26361601) (to K.
   S.); Takeda Science Foundation (to K. S.); Sumitomo Foundation Research
   Grant (to K. S.); Senshin Medical Research Foundation (to K. S.); Imai
   Memorial Trust for AIDS Research (to K. S.); Ichiro Kanehara Foundation
   (to K. S.); Kanae Foundation for the Promotion of Medical Science (to K.
   S.); Suzuken Memorial Foundation (to K. S.); Uehara Memorial Foundation
   (to K. S.); National Institute of Allergy and Infectious Diseases
   intramural research program (to K. M. and V. M. H.); Japan Society for
   the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research
   C15K07166 (to K. S.), B24390112 (to Y. K.) and S22220007 (to Y. K.);
   Ministry of Education, Culture, Sports, Science and Technology of Japan
   Grant-in-Aid for Scientific Research on Innovative Areas 24115008 (to Y.
   K.); Japan Agency for Medical Research and Development Research on
   HIV/AIDS AMED 15Afk0410013h0001 (to Y. K.); and JSPS Core-to-Core
   Program, A: Advanced Research Networks (to K. M., V. M. H. and Y. K.).
NR 59
TC 1
Z9 1
U1 0
U2 1
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
   BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD SEP
PY 2015
VL 96
BP 2867
EP 2877
DI 10.1099/vir.0.000207
PN 9
PG 11
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA CV0CQ
UT WOS:000363915400040
PM 26041873
ER

PT J
AU Menazza, S
   Aponte, A
   Sun, JH
   Gucek, M
   Steenbergen, C
   Murphy, E
AF Menazza, Sara
   Aponte, Angel
   Sun, Junhui
   Gucek, Marjan
   Steenbergen, Charles
   Murphy, Elizabeth
TI Molecular Signature of Nitroso-Redox Balance in Idiopathic Dilated
   Cardiomyopathies
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE heart failure; nitroso-redox signaling; oxidation; S-nitrosylation
ID PROTEIN S-NITROSYLATION; NITRIC-OXIDE SYNTHASE; HUMAN HEART-FAILURE;
   CARDIOVASCULAR-SYSTEM; CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; OXIDATIVE
   STRESS; NADPH OXIDASE; CARDIOPROTECTION; DISEASE
AB Background-Idiopathic dilated cardiomyopathy is one of the most common types of cardiomyopathy. It has been proposed that an increase in oxidative stress in heart failure leads to a decrease in nitric oxide signaling, leading to impaired nitroso-redox signaling. To test this hypothesis, we investigated the occurrence of protein S-nitrosylation (SNO) and oxidation in biopsies from explanted dilated cardiomyopathy and nonfailing donor male and female human hearts.
   Methods and Results-Redox-based resin-assisted capture for oxidation and SNO proteomic analysis was used to measure protein oxidation and SNO, respectively. In addition, 2-dimensional difference gel electrophoresis using maleimide sulfhydryl-reactive fluors was used to identify the SNO proteins. Protein oxidation increased in dilated cardiomyopathy biopsies in comparison with those from healthy donors. Interestingly, we did not find a consistent decrease in SNO in failing hearts; we found that some proteins showed an increase in SNO and others showed a decrease, and there were sex-specific differences in the response. We found 10 proteins with a significant decrease in SNO and 4 proteins with an increase in SNO in failing female hearts. Comparing nonfailing and failing male hearts, we found 9 proteins with a significant decrease and 12 proteins with a significant increase. We also found an increase in S-glutathionylation of endothelial nitric oxide synthase in failing female versus male hearts, suggesting an increase in uncoupled nitric oxide synthase in female hearts.
   Conclusion-These findings highlight the importance of nitroso-redox signaling in both physiological and pathological conditions, suggesting a potential target to treat heart failure.
C1 [Menazza, Sara; Sun, Junhui; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Aponte, Angel; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
   [Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
RP Murphy, E (reprint author), NHLBI, NIH, Bldg 10,Rm 8N202,10 Ctr Dr, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
FU NHLBI-NIH Intramural Program [ZO1HL006059, ZO1HL002066, HL005903-08];
   NIH [5R01HL039752]
FX This work was supported by the NHLBI-NIH Intramural Program (ZO1HL006059
   and ZO1HL002066, Menazza, and Murphy; HL005903-08, Aponte and Gucek) and
   NIH grant 5R01HL039752 (Steenbergen).
NR 47
TC 1
Z9 1
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD SEP
PY 2015
VL 4
IS 9
AR e002251
DI 10.1161/JAHA.115.002251
PG 27
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CV3IH
UT WOS:000364152100023
PM 26396203
ER

PT J
AU Tsao, CW
   Gona, PN
   Salton, CJ
   Chuang, ML
   Levy, D
   Manning, WJ
   O'Donnell, CJ
AF Tsao, Connie W.
   Gona, Philimon N.
   Salton, Carol J.
   Chuang, Michael L.
   Levy, Daniel
   Manning, Warren J.
   O'Donnell, Christopher J.
TI Left Ventricular Structure and Risk of Cardiovascular Events: A
   Framingham Heart Study Cardiac Magnetic Resonance Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cardiovascular disease; cardiovascular magnetic resonance; epidemiology;
   left ventricular geometry; left ventricular mass
ID EJECTION FRACTION; ECHOCARDIOGRAPHIC PREDICTORS; SYSTEMIC HYPERTENSION;
   PROGNOSTIC VALUE; ELDERLY COHORT; FAILURE; GEOMETRY; MASS; HYPERTROPHY;
   MORTALITY
AB Background-Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized.
   Methods and Results-Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65 +/- 9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002-2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m(2) increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness).
   Conclusions-Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation.
C1 [Tsao, Connie W.; Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
   [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Div Radiol, Boston, MA 02215 USA.
   [Gona, Philimon N.] Univ Massachusetts, Dept Exercise & Hlth Sci, Boston, MA 02125 USA.
   [O'Donnell, Christopher J.] Boston Vet Adm Healthcare Syst, Cardiol Sect, Dept Med, Boston, MA USA.
   [Gona, Philimon N.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
   [Tsao, Connie W.; Gona, Philimon N.; Chuang, Michael L.; Levy, Daniel; O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
RP Tsao, CW (reprint author), 330 Brookline Ave,RW 453, Boston, MA 02215 USA.
EM ctsao1@bidmc.harvard.edu
FU National Heart, Lung and Blood Institute [NO1-HC-25195,
   HHSN268201500001I]; NHLBI [R01-HL70279, 1K23 HL118259]; Harvard Medical
   School Fellowship
FX The Framingham Heart Study is supported by the National Heart, Lung and
   Blood Institute (NO1-HC-25195 and HHSN268201500001I). This work was also
   supported by NHLBI R01-HL70279 (to Manning), 1K23 HL118259 (to Tsao),
   and the Harvard Medical School Fellowship (to Tsao).
NR 32
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Z9 8
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD SEP
PY 2015
VL 4
IS 9
AR e002188
DI 10.1161/JAHA.115.002188
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CV3IH
UT WOS:000364152100020
PM 26374295
ER

PT J
AU Henderson, MJ
   Wires, ES
   Trychta, KA
   Yan, XK
   Harvey, BK
AF Henderson, Mark J.
   Wires, Emily S.
   Trychta, Kathleen A.
   Yan, Xiaokang
   Harvey, Brandon K.
TI Monitoring Endoplasmic Reticulum Calcium Homeostasis Using a Gaussia
   Luciferase SERCaMP
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Cellular Biology; Issue 103; SERCaMP; calcium; endoplasmic reticulum; ER
   stress; reporter protein; MANF; Gaussia luciferase; liver; neuroscience;
   rat
ID IN-VIVO; AAV VECTORS; CULTURE; CA2+; VITRO
AB The endoplasmic reticulum (ER) contains the highest level of intracellular calcium, with concentrations approximately 5,000-fold greater than cytoplasmic levels. Tight control over ER calcium is imperative for protein folding, modification and trafficking. Perturbations to ER calcium can result in the activation of the unfolded protein response, a three-prong ER stress response mechanism, and contribute to pathogenesis in a variety of diseases. The ability to monitor ER calcium alterations during disease onset and progression is important in principle, yet challenging in practice. Currently available methods for monitoring ER calcium, such as calcium-dependent fluorescent dyes and proteins, have provided insight into ER calcium dynamics in cells, however these tools are not well suited for in vivo studies. Our lab has demonstrated that a modification to the carboxy-terminus of Gaussia luciferase confers secretion of the reporter in response to ER calcium depletion. The methods for using a luciferase based, secreted ER calcium monitoring protein (SERCaMP) for in vitro and in vivo applications are described herein. This video highlights hepatic injections, pharmacological manipulation of GLuc-SERCaMP, blood collection and processing, and assay parameters for longitudinal monitoring of ER calcium.
C1 [Henderson, Mark J.; Wires, Emily S.; Trychta, Kathleen A.; Yan, Xiaokang; Harvey, Brandon K.] NIDA, NIH, North Bethesda, MD 74739 USA.
RP Harvey, BK (reprint author), NIDA, NIH, North Bethesda, MD 74739 USA.
EM bharvey@mail.nih.gov
FU Intramural Research Program at National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program at the
   National Institute on Drug Abuse. We thank Doug Howard, Chris Richie,
   Lowella Fortuno, and Josh Hinkle for their contributions to developing
   this method.
NR 22
TC 0
Z9 0
U1 3
U2 5
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD SEP
PY 2015
IS 103
AR e53199
DI 10.3791/53199
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV4FL
UT WOS:000364222300047
ER

PT J
AU Wentzensen, N
   de Gonzalez, AB
AF Wentzensen, Nicolas
   de Gonzalez, Amy Berrington
TI The Pill's gestation: from birth control to cancer prevention
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID ORAL-CONTRACEPTIVES; HORMONAL CONTRACEPTION; WOMEN
C1 [Wentzensen, Nicolas; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Dr, Bethesda, MD 20892 USA.
EM wentzenn@mail.nih.gov
NR 10
TC 0
Z9 0
U1 6
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 9
BP 1004
EP 1006
DI 10.1016/S1470-2045(15)00211-9
PG 4
WC Oncology
SC Oncology
GA CV0TL
UT WOS:000363966100033
PM 26254029
ER

PT J
AU Strauss, J
   Figg, WD
AF Strauss, Julius
   Figg, William D.
TI Epigenetic approaches to overcoming chemotherapy resistance
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID DRUG-RESISTANCE; OVARIAN-CANCER; DEMETHYLATION; METHYLATION; EXPRESSION;
   PROMOTER
C1 [Strauss, Julius; Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 10
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 9
BP 1013
EP 1015
DI 10.1016/S1470-2045(15)00231-4
PG 4
WC Oncology
SC Oncology
GA CV0TL
UT WOS:000363966100039
PM 26296953
ER

PT J
AU Bear, HD
   Tang, G
   Rastogi, P
   Geyer, CE
   Liu, Q
   Robidoux, A
   Baez-Diaz, L
   Brufsky, AM
   Mehta, RS
   Fehrenbacher, L
   Young, JA
   Senecal, FM
   Gaur, R
   Margolese, RG
   Adams, PT
   Gross, HM
   Costantino, JP
   Paik, S
   Swain, SM
   Mamounas, EP
   Wolmark, N
AF Bear, Harry D.
   Tang, Gong
   Rastogi, Priya
   Geyer, Charles E., Jr.
   Liu, Qing
   Robidoux, Andre
   Baez-Diaz, Luis
   Brufsky, Adam M.
   Mehta, Rita S.
   Fehrenbacher, Louis
   Young, James A.
   Senecal, Francis M.
   Gaur, Rakesh
   Margolese, Richard G.
   Adams, Paul T.
   Gross, Howard M.
   Costantino, Joseph P.
   Paik, Soonmyung
   Swain, Sandra M.
   Mamounas, Eleftherios P.
   Wolmark, Norman
TI Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40
   [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled
   trial
SO LANCET ONCOLOGY
LA English
DT Article
ID PATHOLOGICAL COMPLETE RESPONSE; TUMOR-GROWTH; PREOPERATIVE CHEMOTHERAPY;
   ENDOGENOUS INHIBITOR; ANGIOGENESIS; PACLITAXEL; THERAPY;
   CYCLOPHOSPHAMIDE; TRASTUZUMAB; DOXORUBICIN
AB Background Highly emetogenic chemotherapy induces emesis in almost all patients in the absence of prophylaxis. Guidelines recommend use of a neurokinin-1 (NK-1) receptor antagonist in conjunction with a 5-HT 3 receptor antagonist and corticosteroid in patients receiving highly emetogenic chemotherapy. We aimed to assess rolapitant, an NK-1 receptor antagonist, for prevention of chemotherapy-induced nausea and vomiting in patients with cancer after administration of cisplatin-based highly emetogenic chemotherapy.
   Methods We conducted two global, randomised, double-blind, active-controlled, phase 3 trials (HEC-1 and HEC-2) at 155 cancer centres (76 in HEC-1 and 79 in HEC-2) in 26 countries (17 in HEC-1 and 14 in HEC-2). We enrolled patients with cancer aged 18 years or older, who had not previously been treated with cisplatin, with a Karnofsky performance score of 60 or higher, and a predicted life expectancy of 4 months or longer. We used an interactive web-based randomisation system to randomly assign patients to treatment. Patients were stratified by sex and randomly allocated to either oral rolapitant (180 mg dose; rolapitant group) or a placebo that was identical in appearance (active control group) about 1-2 h before administration of highly emetogenic chemotherapy. All patients received granisetron (10 mu g/kg intravenously) and dexamethasone (20 mg orally) on day 1, and dexamethasone (8 mg orally) twice daily on days 2-4. Every cycle was a minimum of 14 days. In up to five subsequent cycles, patients were allowed to receive the same study drug they were assigned in cycle 1, unless removed at the clinician's discretion. Patients could also choose to leave the study at any point. Efficacy analysis was done in the modified intention-to-treat population (comprising all patients who received at least one dose of study drug at a cancer centre compliant with Good Clinical Practice [GCP]). The primary endpoint was the proportion of patients achieving a complete response (no emesis or use of rescue medication) in the delayed phase (>24-120 h after initiation of chemotherapy) in cycle 1. These studies are registered with ClinicalTrials.gov, numbers NCT01499849 and NCT01500213. Both studies have been completed.
   Findings Between Feb 21, 2012, and March 12, 2014, 532 patients in HEC-1 and 555 patients in HEC-2 were randomly assigned to treatment. 526 patients in HEC-1 (264 rolapitant and 262 active control) and 544 in HEC-2 (271 rolapitant and 273 active control) received at least one dose of study drug at a GCP-compliant site and were included in the modified intention-to-treat population. A significantly greater proportion of patients in the rolapitant group had complete responses in the delayed phase than did patients in the active control group (HEC-1: 192 [73%] vs 153 [58%]; odds ratio 1.9, 95% CI 1.3-2.7; p=0.0006; HEC-2: 190 [70%] vs 169 [62%]; 1.4, 1.0-2.1; p=0.0426; pooled studies: 382 [71%] vs 322 [60%]; 1.6, 1.3-2.1; p=0.0001). The incidence of adverse events was similar across treatment groups. The most commonly reported treatment-related treatment-emergent adverse events in the rolapitant versus active control groups were headache (three [<1%] vs two [<1%]), hiccups (three [<1%] vs four [<1%]), constipation (two [<1%] vs three [<1%]), and dyspepsia (two [<1%] vs three [<1%]). For cycle 1, the most common grade 3-5 adverse events in patients allocated rolapitant versus active control were neutropenia (HEC-1: nine [3%] vs 14 [5%]; HEC-2: 16 [6%] vs 14 [ 5%]), anaemia (HEC-1: one [<1%] vs one [<1%]; HEC-2: seven [ 3%] vs two [<1%]), and leucopenia (HEC-1: six [2%] vs two [<1%]; HEC-2: two [<1%] vs two [<1%]). No serious treatment-emergent adverse events were treatment related, and no treatment-related treatment-emergent adverse events resulted in death.
   Interpretation Rolapitant in combination with a 5-HT 3 receptor antagonist and dexamethasone is well-tolerated and shows superiority over active control for the prevention of chemotherapy-induced nausea and vomiting during the at-risk period (120 h) after administration of highly emetogenic cisplatin-based chemotherapy.
C1 [Bear, Harry D.; Rastogi, Priya; Geyer, Charles E., Jr.; Robidoux, Andre; Baez-Diaz, Luis; Brufsky, Adam M.; Mehta, Rita S.; Fehrenbacher, Louis; Young, James A.; Senecal, Francis M.; Gaur, Rakesh; Margolese, Richard G.; Adams, Paul T.; Gross, Howard M.; Paik, Soonmyung; Swain, Sandra M.; Mamounas, Eleftherios P.; Wolmark, Norman] NSABP NRG Oncol, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
   [Bear, Harry D.; Geyer, Charles E., Jr.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA.
   [Bear, Harry D.; Geyer, Charles E., Jr.] Massey Canc Ctr, Richmond, VA USA.
   [Tang, Gong; Liu, Qing; Costantino, Joseph P.] NRG Oncol, Pittsburgh, PA USA.
   [Tang, Gong; Liu, Qing; Costantino, Joseph P.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Rastogi, Priya] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
   [Robidoux, Andre] Univ Montreal CHUM, Ctr Hosp, Montreal, PQ, Canada.
   [Baez-Diaz, Luis] Minority Based CCOP, San Juan, PR USA.
   [Brufsky, Adam M.] Univ Pittsburgh, Inst Canc, Magee Womens Hosp, Pittsburgh, PA USA.
   [Mehta, Rita S.] Univ Calif Irvine, Div Hematol Oncol, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA.
   [Fehrenbacher, Louis] KaiserPermanente Oncol Clin Trials, Northern Calif, Vallejo, CA USA.
   [Young, James A.] Colorado Canc Res Program, Colorado Springs, CO USA.
   [Senecal, Francis M.] Northwest Med Specialties, Tacoma, WA USA.
   [Gaur, Rakesh] CCOP, Kansas City, MO USA.
   [Margolese, Richard G.] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
   [Adams, Paul T.] Genesys Reg Med Ctr, Grand Blanc, MI USA.
   [Gross, Howard M.] CCOP, Dayton, OH USA.
   [Paik, Soonmyung] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea.
   [Paik, Soonmyung] Yonsei Univ, Coll Med, Dept Med Oncol, Seoul, South Korea.
   [Swain, Sandra M.] MedStar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA.
   [Mamounas, Eleftherios P.] UF Hlth Canc Ctr, Orlando Hlth, Orlando, FL USA.
   [Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
RP Bear, HD (reprint author), VCUHS, Div Surg Oncol, Box 980011, Richmond, VA 23298 USA.
EM hdbear@vcu.edu
OI , Gong/0000-0002-6247-4338; Swain, Sandra/0000-0002-1320-3830
FU National Institute of Health (NIH), National Cancer Institute,
   Department of Health and Human Services, Public Health Service
   [U10-CA-12027, U10CA-69651, U10-CA-37377, U10-CA-69974, U10-CA-44066,
   U-10-CA-180868, U-10-CA-180822]; Genentech, a full member of the Roche
   Group of companies; Roche Laboratories; Lilly Research Laboratories, a
   division of Eli Lilly Company; Precision Therapeutics
FX This study was supported by grant numbers U10-CA-12027, U10CA-69651,
   U10-CA-37377, U10-CA-69974 (NSABP), and U10-CA-44066 (AR),
   U-10-CA-180868 and U-10-CA-180822 (NRG Oncology), and UG1CA-189867
   (NCORP) from the National Institute of Health (NIH), National Cancer
   Institute, Department of Health and Human Services, Public Health
   Service; Genentech, a full member of the Roche Group of companies; Roche
   Laboratories; Lilly Research Laboratories, a division of Eli Lilly &
   Company; and Precision Therapeutics. The funding sources had no further
   role. We thank Barbara C Good, Wendy L Rea, and Christine I Rudock with
   NSABP (NRG Oncology) for editorial assistance. They were not compensated
   beyond their normal salary for this work.
NR 53
TC 18
Z9 19
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 9
BP 1037
EP 1048
DI 10.1016/S1470-2045(15)00041-8
PG 12
WC Oncology
SC Oncology
GA CV0TL
UT WOS:000363966100046
PM 26272770
ER

PT J
AU Kreimer, AR
   Struyf, F
   Hildesheim, A
   David, MP
   Wheeler, CM
AF Kreimer, Aimee R.
   Struyf, Frank
   Hildesheim, Allan
   David, Marie-Pierre
   Wheeler, Cosette M.
TI Fewer than three doses of HPV vaccine reply
SO LANCET ONCOLOGY
LA English
DT Letter
C1 [Kreimer, Aimee R.; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Struyf, Frank; David, Marie-Pierre] GSK Vaccines, Wavre, Belgium.
   [Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA.
   [Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
RP Kreimer, AR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM kreimera@mail.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 9
BP E424
EP E425
PG 3
WC Oncology
SC Oncology
GA CV0TL
UT WOS:000363966100004
PM 26370346
ER

PT J
AU Knobf, MT
   Cooley, ME
   Duffy, S
   Doorenbos, A
   Eaton, L
   Given, B
   Mayer, DK
   McCorkle, R
   Miaskowski, C
   Mitchell, S
   Sherwood, P
   Bender, C
   Cataldo, J
   Hershey, D
   Katapodi, M
   Menon, U
   Schumacher, K
   Sun, V
   Von Ah, D
   LoBiondo-Wood, G
   Mallory, G
AF Knobf, M. Tish
   Cooley, Mary E.
   Duffy, Sonia
   Doorenbos, Ardith
   Eaton, Linda
   Given, Barbara
   Mayer, Deborah K.
   McCorkle, Ruth
   Miaskowski, Christine
   Mitchell, Sandra
   Sherwood, Paula
   Bender, Catherine
   Cataldo, Janine
   Hershey, Denise
   Katapodi, Maria
   Menon, Usha
   Schumacher, Karen
   Sun, Virginia
   Von Ah, Diane
   LoBiondo-Wood, Geri
   Mallory, Gail
TI The 2014-2018 Oncology Nursing Society Research Agenda
SO ONCOLOGY NURSING FORUM
LA English
DT Article
DE oncology; nursing; research
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-CANCER-SOCIETY;
   CELL LUNG-CANCER; COGNITIVE-BEHAVIORAL INTERVENTION; SMOKING-CESSATION
   INTERVENTIONS; INDUCED PERIPHERAL NEUROPATHY; CYTOKINE GENE VARIATIONS;
   HEALTH INTERVIEW SURVEY; SELF-CARE INTERVENTION
AB Purpose/Objectives: To identify priority areas of research for the Oncology Nursing Society (ONS) Research Agenda for 2014-2018, consistent with ONS's mission to promote excellence in oncology nursing and quality cancer care.
   Data Sources: Review of the literature, 2013 ONS Research Priorities Survey, National Institute of Nursing Research, and the National Cancer Institute research foci.
   Data Synthesis: Multimethod consensus-building approach by content leaders and content experts of the ONS Research Agenda Project Team.
   Conclusions: The 2014-2018 Research Agenda Project Team identified eight high-priority research areas: symptoms, late effects of cancer treatment and survivorship care, palliative and end-of-life care, self-management, aging, family and caregivers, improving healthcare systems, and risk reduction. In addition, four cross-cutting themes were identified: biomarkers, bioinformatics, comparative effectiveness research, and dissemination and implementation science.
   Implications for Nursing: The Research Agenda is a synthesis of the state of the science in cancer and identifies gaps and directions for the conduct and dissemination of research. Oncology nurses can use the agenda to inform clinical practice, develop research proposals, inform policy makers, support interdisciplinary research efforts, and promote scientist and clinician collaborations in targeted patient-centered research.
C1 [Knobf, M. Tish; McCorkle, Ruth] Yale Univ, Sch Nursing, Orange, CT 06477 USA.
   [Cooley, Mary E.] Dana Farber Canc Ctr Nursing Res, Boston, MA USA.
   [Duffy, Sonia] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA.
   [Doorenbos, Ardith; Eaton, Linda] Univ Washington, Sch Nursing, Seattle, WA 98195 USA.
   [Eaton, Linda] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA.
   [Given, Barbara; Hershey, Denise] Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA.
   [Mayer, Deborah K.] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA.
   [Miaskowski, Christine] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA USA.
   [Mitchell, Sandra] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA.
   [Sherwood, Paula] Univ Pittsburgh, Sch Nursing, Res, Pittsburgh, PA 15260 USA.
   [Bender, Catherine] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15260 USA.
   [Cataldo, Janine] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA.
   [Katapodi, Maria] Univ Basel, Inst Nursing Sci, CH-4003 Basel, Switzerland.
   [Menon, Usha] Ohio State Univ, Coll Nursing, Nursing, Columbus, OH 43210 USA.
   [Schumacher, Karen] Univ Nebraska Med Ctr, Coll Nursing, Omaha, NE 68198 USA.
   [Sun, Virginia] City Hope Natl Med Ctr, Nursing Educ & Res Dept, Duarte, CA 91010 USA.
   [Von Ah, Diane] Indiana Univ, Coll Nursing, Indianapolis, IN 46204 USA.
   [LoBiondo-Wood, Geri] Univ Texas Houston, Hlth Sci Sch Nursing, Doctoral Programs, Houston, TX USA.
   [Mallory, Gail] Oncol Nursing Soc, Res, Pittsburgh, PA USA.
RP Knobf, MT (reprint author), Yale Univ, Sch Nursing, Orange, CT 06477 USA.
EM tish.knobf@yale.edu
NR 326
TC 3
Z9 3
U1 6
U2 9
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
EI 1538-0688
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD SEP
PY 2015
VL 42
IS 5
BP 450
EP 465
DI 10.1188/15.ONF.450-465
PG 16
WC Oncology; Nursing
SC Oncology; Nursing
GA CU9VA
UT WOS:000363892900008
PM 26302275
ER

PT J
AU Aon, MA
   Cortassa, S
AF Aon, Miguel A.
   Cortassa, Sonia
TI Systems Biology of the Fluxome
SO PROCESSES
LA English
DT Review
DE systems biology; metabolic disorders; diabetes; cancer; metabolomics;
   multi-scale modeling
ID SACCHAROMYCES-CEREVISIAE; INDIVIDUAL MITOCHONDRIA; ESCHERICHIA-COLI;
   METABOLIC FLUXES; CELL BIOLOGY; MODEL; TIME; OSCILLATIONS; NETWORK;
   ARRHYTHMIAS
AB The advent of high throughput -omics has made the accumulation of comprehensive data sets possible, consisting of changes in genes, transcripts, proteins and metabolites. Systems biology-inspired computational methods for translating metabolomics data into fluxomics provide a direct functional, dynamic readout of metabolic networks. When combined with appropriate experimental design, these methods deliver insightful knowledge about cellular function under diverse conditions. The use of computational models accounting for detailed kinetics and regulatory mechanisms allow us to unravel the control and regulatory properties of the fluxome under steady and time-dependent behaviors. This approach extends the analysis of complex systems from description to prediction, including control of complex dynamic behavior ranging from biological rhythms to catastrophic lethal arrhythmias. The powerful quantitative metabolomics-fluxomics approach will help our ability to engineer unicellular and multicellular organisms evolve from trial-and-error to a more predictable process, and from cells to organ and organisms.
C1 [Aon, Miguel A.; Cortassa, Sonia] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
RP Aon, MA (reprint author), NIA, NIH, BRC BG Rm 09B119,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maon1@jhmi.edu; scortas1@jhmi.edu
RI Aon, Miguel/A-6564-2008; 
OI Aon, Miguel/0000-0002-4355-5431; Cortassa, Sonia/0000-0001-7224-9858
NR 69
TC 3
Z9 3
U1 3
U2 10
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2227-9717
J9 PROCESSES
JI Processes
PD SEP
PY 2015
VL 3
IS 3
BP 607
EP 618
DI 10.3390/pr3030607
PG 12
WC Engineering, Chemical
SC Engineering
GA CV0YY
UT WOS:000363981100006
ER

PT J
AU Tijssen, JA
   Prince, DK
   Morrison, LJ
   Atkins, DL
   Austin, MA
   Berg, R
   Brown, SP
   Christenson, J
   Egan, D
   Fedor, PJ
   Fink, EL
   Meckler, GD
   Osmond, MH
   Sims, KA
   Hutchison, JS
AF Tijssen, Janice A.
   Prince, David K.
   Morrison, Laurie J.
   Atkins, Dianne L.
   Austin, Michael A.
   Berg, Robert
   Brown, Siobhan P.
   Christenson, Jim
   Egan, Debra
   Fedor, Preston J.
   Fink, Ericka L.
   Meckler, Garth D.
   Osmond, Martin H.
   Sims, Kathryn A.
   Hutchison, James S.
CA Resuscitation Outcomes Consortium
TI Time on the scene and interventions are associated with improved
   survival in pediatric out-of-hospital cardiac arrest
SO RESUSCITATION
LA English
DT Article
DE Cardiac arrest; Pediatric; Emergency medical services
ID ADVANCED LIFE-SUPPORT; CARDIOPULMONARY ARREST; YOUNG-ADULTS;
   EPIDEMIOLOGY; RESUSCITATION; CHILDREN; OUTCOMES; AGE; NATIONWIDE;
   QUALITY
AB Background: Survival is less than 10% for pediatric patients following out-of-hospital cardiac arrest. It is not known if more time on the scene of the cardiac arrest and advanced life support interventions by emergency services personnel are associated with improved survival.
   Aim: This study was performed to determine which times on the scene and which prehospital interventions were associated with improved survival.
   Methods: We studied patients aged 3 days to 19 years old with out-of-hospital cardiac arrest, using the Resuscitation Outcomes Consortium cardiac arrest database from 11 North American regions, from 2005 to 2012. We evaluated survival to hospital discharge according to on-scene times (<10, 10 to 35 and >35 min).
   Results: Data were available for 2244 patients (1017 infants, 594 children and 633 adolescents). Infants had the lowest rate of survival (3.7%) compared to children (9.8%) and adolescents (16.3%). Survival improved over the 7 year study period especially among adolescents. Survival was highest in the 10 to 35 min onscene time group (10.2%) compared to the > 35 min. group (6.9%) and the <10 min. group (5.3%, p = 0.01). Intravenous or intra-osseous access attempts and fluid administration were associated with improved survival, whereas advanced airway attempts were not associated with survival and resuscitation drugs were associated with worse survival.
   Conclusions: In this observational study, a scene time of 10 to 35 min was associated with the highest survival, especially among adolescents. Access for fluid resuscitation was associated with increased survival but advanced airway and resuscitation drugs were not. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Tijssen, Janice A.] Univ Western Ontario, Dept Pediat, London Hlth Sci Ctr, Div Pediat Crit Care Med, London, ON N6A 3K7, Canada.
   [Tijssen, Janice A.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
   [Prince, David K.; Brown, Siobhan P.; Sims, Kathryn A.] Univ Washington, Resuscitat Outcomes Consortium, Data Coordinating Ctr, Seattle, WA 98195 USA.
   [Morrison, Laurie J.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
   [Morrison, Laurie J.] Univ Toronto, Dept Med, Div Emergency Med, Toronto, ON, Canada.
   [Atkins, Dianne L.] Univ Iowa, Carver Coll Med, Stead Dept Pediat, Iowa City, IA USA.
   [Austin, Michael A.] Univ Ottawa, Ottawa Hosp, Dept Emergency Med, Ottawa, ON, Canada.
   [Berg, Robert] Childrens Hosp Philadelphia, Dept Anesthesiol, Philadelphia, PA 19104 USA.
   [Berg, Robert] Childrens Hosp Philadelphia, Dept Crit Care Med, Philadelphia, PA 19104 USA.
   [Berg, Robert] Univ Penn, Philadelphia, PA 19104 USA.
   [Christenson, Jim] Univ British Columbia, Fac Med, Dept Emergency Med, Vancouver, BC, Canada.
   [Egan, Debra] NHLBI, Div Cardiovasc Sci, Heart Failure & Arrhythmias Branch, NIH, Bethesda, MD 20892 USA.
   [Fedor, Preston J.] Univ Texas Southwestern, Dept Surg, Div Emergency Med, Dallas, TX USA.
   [Fink, Ericka L.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA 15213 USA.
   [Meckler, Garth D.] Univ British Columbia, Dept Pediat, Div Emergency Med, Vancouver, BC V6T 1W5, Canada.
   [Meckler, Garth D.] British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada.
   [Osmond, Martin H.] Univ Ottawa, Dept Pediat, Div Emergency Med, Ottawa, ON K1N 6N5, Canada.
   [Osmond, Martin H.] Univ Ottawa, Childrens Hosp Eastern Ontario, Ottawa, ON, Canada.
   [Hutchison, James S.] Hosp Sick Children, Dept Crit Care & Neurosci, Toronto, ON M5G 1X8, Canada.
   [Hutchison, James S.] Hosp Sick Children, Mental Hlth Res Program, Toronto, ON M5G 1X8, Canada.
   [Hutchison, James S.] Univ Toronto, Fac Med, Interdept Div Crit Care Med, Toronto, ON, Canada.
   [Hutchison, James S.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada.
RP Tijssen, JA (reprint author), London Hlth Sci Ctr, Childrens Hosp, 800 Commissioners Rd East, London, ON N6A 5W9, Canada.
EM Janice.Tijssen@lhsc.on.ca; Jamie.Hutchison@sickkids.ca
RI morrison, laurie/A-6325-2012; 
OI morrison, laurie/0000-0001-8369-9774; Brown, Siobhan/0000-0002-4774-3122
FU University of Washington Data Coordinating Center from the National
   Heart, Lung and Blood Institute [5U01 HL077863]; Medical College of
   Wisconsin from the National Heart, Lung and Blood Institute [HL077866];
   University of Washington from the National Heart, Lung and Blood
   Institute [HL077867]; University of Pittsburgh from the National Heart,
   Lung and Blood Institute [HL077871]; St. Michael's Hospital from the
   National Heart, Lung and Blood Institute [HL077872]; Oregon Health and
   Science University from the National Heart, Lung and Blood Institute
   [HL077873]; University of Alabama at Birmingham from the National Heart,
   Lung and Blood Institute [HL077881]; Ottawa Hospital Research Institute
   from the National Heart, Lung and Blood Institute [HL077885]; University
   of Texas SW Medical Ctr/Dallas from the National Heart, Lung and Blood
   Institute [HL077887]; University of California San Diego from the
   National Heart, Lung and Blood Institute [HL077908]; National Institute
   of Neurological Disorders and Stroke; U.S. Army Medical Research &
   Material Command; Canadian Institutes of Health Research
   (CIHR)-Institute of Circulatory and Respiratory Health; Defence Research
   and Development Canada; Heart, Stroke Foundation of Canada; American
   Heart Association
FX The authors would like to thank Umberto Lenzi for organizing and
   providing technical assistance for writing group teleconference sessions
   and to Dr. M. Drake for helping to review the literature. We thank Dr.
   Brian Kavanagh for his critical review of the manuscript. The ROC is
   supported by a series of cooperative agreements to nine regional
   clinical centers and one Data Coordinating Center (5U01
   HL077863-University of Washington Data Coordinating Center,
   HL077866-Medical College of Wisconsin, HL077867-University of
   Washington, HL077871-University of Pittsburgh, HL077872-St. Michael's
   Hospital, HL077873-Oregon Health and Science University,
   HL077881-University of Alabama at Birmingham, HL077885-Ottawa Hospital
   Research Institute, HL077887-University of Texas SW Medical Ctr/Dallas,
   HL077908-University of California San Diego) from the National Heart,
   Lung and Blood Institute in partnership with the National Institute of
   Neurological Disorders and Stroke, U.S. Army Medical Research & Material
   Command, The Canadian Institutes of Health Research (CIHR)-Institute of
   Circulatory and Respiratory Health, Defence Research and Development
   Canada and the Heart, Stroke Foundation of Canada and the American Heart
   Association. The studys ponsors were not involved in the study design,
   data collection, analysis or interpretation, in the writing of the
   manuscript, nor in the decision to submit the manuscript for
   publication.
NR 40
TC 7
Z9 7
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0300-9572
J9 RESUSCITATION
JI Resuscitation
PD SEP
PY 2015
VL 94
BP 1
EP 7
DI 10.1016/j.resuscitation.2015.06.012
PG 7
WC Critical Care Medicine; Emergency Medicine
SC General & Internal Medicine; Emergency Medicine
GA CV0UC
UT WOS:000363967900010
PM 26095301
ER

PT J
AU Webb, JR
   Addington, J
   Perkins, DO
   Bearden, CE
   Cadenhead, KS
   Cannon, TD
   Cornblatt, BA
   Heinssen, RK
   Seidman, LJ
   Tarbox, SI
   Tsuang, MT
   Walker, EF
   McGlashan, TH
   Woods, SW
AF Webb, Jadon R.
   Addington, Jean
   Perkins, Diana O.
   Bearden, Carrie E.
   Cadenhead, Kristin S.
   Cannon, Tyrone D.
   Cornblatt, Barbara A.
   Heinssen, Robert K.
   Seidman, Larry J.
   Tarbox, Sarah I.
   Tsuang, Ming T.
   Walker, Elaine F.
   McGlashan, Thomas H.
   Woods, Scott W.
TI Specificity of Incident Diagnostic Outcomes in Patients at Clinical High
   Risk for Psychosis
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE validity; bipolar disorder; nonbipolar mood disorder; anxiety disorder
ID RANDOMIZED CONTROLLED-TRIAL; ULTRA-HIGH RISK; GROUP COGNITIVE
   INTERVENTION; PSYCHIATRIC-DISORDERS; YOUNG-ADULTS; DEPRESSIVE DISORDER;
   1ST-EPISODE SCHIZOPHRENIA; PREVENTIVE INTERVENTION; INTERRATER
   RELIABILITY; STRUCTURED INTERVIEW
AB It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2-45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis.
C1 [Webb, Jadon R.] Yale Univ, Child Study Ctr, New Haven, CT 06519 USA.
   [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
   [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
   [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
   [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
   [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
   [Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT 06519 USA.
   [Cannon, Tyrone D.; Tarbox, Sarah I.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06519 USA.
   [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA.
   [Heinssen, Robert K.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
   [Seidman, Larry J.; Tsuang, Ming T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
   [Tarbox, Sarah I.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA.
   [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
   [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA.
RP Woods, SW (reprint author), Yale Univ, Sch Med, Dept Psychiat, PRIME Prodromal Res Clin, 34 Pk St, New Haven, CT 06519 USA.
EM scott.woods@yale.edu
FU National Institute of Mental Health [U01 MH066160, U01 MH066134, R01
   MH066069, P50 MH064065, R01 MH065079, MH60720, K24 MH76191, R01
   MH061523, U01 MH065562, P50 MH080272, R21 MH075027, RO1 MH062066, K05
   MH01654]; Donaghue Foundation; Eli Lilly Co
FX National Institute of Mental Health (U01 MH066160 to S.W.W., U01
   MH066134 to J.A., R01 MH066069 and P50 MH064065 to D.O.P., R01 MH065079
   to T.D.C., MH60720 and K24 MH76191 to K.S.C., R01 MH061523 to B.A.C.,
   U01 MH065562 and P50 MH080272 to L.J.S., R21 MH075027 to M.T.T., RO1
   MH062066 to E.F.W., K05 MH01654 to T.H.M.); Donaghue Foundation (to
   S.W.W.); Eli Lilly & Co (to T.H.M., J.A., and D.O.P.).
NR 80
TC 4
Z9 4
U1 2
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
EI 1745-1701
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD SEP
PY 2015
VL 41
IS 5
BP 1066
EP 1075
DI 10.1093/schbul/sbv091
PG 10
WC Psychiatry
SC Psychiatry
GA CV0YM
UT WOS:000363979800011
PM 26272875
ER

PT J
AU Waltz, JA
   Brown, JK
   Gold, JM
   Ross, TJ
   Salmeron, BJ
   Stein, EA
AF Waltz, James A.
   Brown, Jaime K.
   Gold, James M.
   Ross, Thomas J.
   Salmeron, Betty J.
   Stein, Elliot A.
TI Probing the Dynamic Updating of Value in Schizophrenia Using a
   Sensory-Specific Satiety Paradigm
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE schizophrenia; satiety; value; anhedonia; avolition
ID HUMAN ORBITOFRONTAL CORTEX; NEGATIVE SYMPTOMS; NEURONAL-ACTIVITY;
   DECISION-MAKING; BRAIN ACTIVITY; REWARD VALUE; ABNORMALITIES; SCALE;
   FOOD; REPRESENTATIONS
AB It has been proposed that both positive and negative symptoms in schizophrenia (SZ) may derive, at least in part, from a disrupted ability to accurately and flexibly represent the value of stimuli and actions. To assess relationships between dimensions of psychopathology in SZ, and the tendency to devalue food stimuli, on which subjects were fed to satiety, we administered a sensory-specific satiety (SSS) paradigm to 42 SZ patients and 44 controls. In each of 2 sessions, subjects received 16 0.7-ml squirts of each of 2 rewarding foods and 32 squirts of a control solution, using syringes. In between the 2 sessions, each subject was instructed to drink one of the foods until he/she felt "full, but not uncomfortable." At 10 regular intervals, interspersed throughout the 2 sessions, subjects rated each liquid for pleasantness, using a Likert-type scale. Mann-Whitney U-tests revealed group differences in SSS effects. Within-group tests revealed that, while controls showed an effect of satiety that was sensory specific, patients showed an effect of satiety that was not, devaluing the sated and unsated foods similarly. In SZ patients, we observed correlations between the magnitude of SSS effects and measures of both positive and negative symptoms. We argue that the ability to flexibly and rapidly update representations of the value of stimuli and actions figures critically in the ability of patients with psychotic illness to process salient events and adaptively engage in goal-directed behavior.
C1 [Waltz, James A.; Brown, Jaime K.; Gold, James M.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA.
   [Ross, Thomas J.; Salmeron, Betty J.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD USA.
RP Waltz, JA (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA.
EM jwaltz@mprc.umaryland.edu
RI Salmeron, Betty Jo/M-1793-2016; 
OI Salmeron, Betty Jo/0000-0003-1699-9333; Ross, Thomas/0000-0002-7745-3572
FU National Institutes of Health (NIH) [R21 MH086739, R01 MH080066, K12
   RR023250]; National Institute on Drug Abuse - Intramural Research
   Program (NIDA-IRP)
FX This work supported by National Institutes of Health (NIH) grants R21
   MH086739, R01 MH080066, K12 RR023250 and by the National Institute on
   Drug Abuse - Intramural Research Program (NIDA-IRP).
NR 47
TC 0
Z9 0
U1 2
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
EI 1745-1701
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD SEP
PY 2015
VL 41
IS 5
BP 1115
EP 1122
DI 10.1093/schbul/sbv034
PG 8
WC Psychiatry
SC Psychiatry
GA CV0YM
UT WOS:000363979800016
PM 25834028
ER

PT J
AU Ganapathi, KA
   Schafernak, KT
   Rao, VK
   Calvo, KR
AF Ganapathi, Karthik A.
   Schafernak, Kristian T.
   Rao, V. Koneti
   Calvo, Katherine R.
TI Pediatric myelodysplastic/myeloproliferative neoplasms and related
   diseases
SO JOURNAL OF HEMATOPATHOLOGY
LA English
DT Article
DE Myelodysplastic/myeloproliferative neoplasms (MDS/MPN); Juvenile
   myelomonocytic leukemia (JMML); RAS-associated autoimmune
   leukoproliferative disorder (RALD)
ID JUVENILE MYELOMONOCYTIC LEUKEMIA; AUTOIMMUNE LYMPHOPROLIFERATIVE
   SYNDROME; GENOTYPE-PHENOTYPE CORRELATION; NOONAN-SYNDROME; RAS
   MUTATIONS; NEUROFIBROMATOSIS TYPE-1; MYELOID DISORDERS; PTPN11
   MUTATIONS; MOUSE MODEL; CHILDREN
AB Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal hematopoietic disorders with myeloproliferative features, varying degrees of dysplasia and cytopenias, and increased propensity for progression to acute myeloid leukemia (AML). MDS/MPN are uncommon in the pediatric age group, and best exemplified by Juvenile myelomonocytic leukemia (JMML), a rare but aggressive leukemia of early childhood. Remarkable progress has been made in understanding the genetic basis of JMML leading to improved diagnostic criteria and better management. It is now understood that JMML is associated with somatic or germ line mutations in NF1, NRAS, KRAS, PTPN11, and CBL in greater than 90 % of cases with the common downstream mechanism being uncontrolled activation of the RAS/MAPK pathway. More recently, KRAS and NRAS mutations have also been identified in RAS-associated autoimmune leukoproliferative disorder (RALD), which shares some clinical, hematopathological, and genetic features with JMML, but has an indolent clinical course. Hematopoietic stem cell transplant (HSCT) is currently the only curative therapy for JMML, although newer therapeutic agents are currently in clinical trials. This review will focus primarily on the current clinical features, diagnostic criteria, pathologic features, and therapy of JMML and provide a brief description of RALD.
C1 [Ganapathi, Karthik A.] Columbia Univ, Dept Pathol & Cell Biol, Div Hematopathol, Med Ctr, New York, NY USA.
   [Schafernak, Kristian T.] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pathol & Lab Med, Chicago, IL 60611 USA.
   [Rao, V. Koneti] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Calvo, Katherine R.] Natl Inst Hlth Clin Ctr, Hematol Sect, Dept Lab Med, Bethesda, MD 20892 USA.
RP Calvo, KR (reprint author), Natl Inst Hlth Clin Ctr, Hematol Sect, Dept Lab Med, 10 Ctr Dr,Bldg 10-2C306, Bethesda, MD 20892 USA.
EM calvok@mail.nih.gov
OI Calvo, Katherine/0000-0002-0771-4191; Schafernak,
   Kristian/0000-0003-3052-8925
FU Intramural Research Program of the National Institutes of Health of the
   USA
FX The Intramural Research Program of the National Institutes of Health of
   the USA supported this work.
NR 41
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1868-9256
EI 1865-5785
J9 J HEMATOP
JI J. Hematop.
PD SEP
PY 2015
VL 8
IS 3
BP 159
EP 167
DI 10.1007/s12308-015-0250-7
PG 9
WC Hematology; Pathology
SC Hematology; Pathology
GA CU8AJ
UT WOS:000363762800006
ER

PT J
AU Fabbri, E
   Tanaka, T
   An, Y
   Zoli, M
   Bandinelli, S
   Guralnik, JM
   Simonsick, EM
   Boyd, CM
   Studenski, SA
   Harris, TB
   Ferrucci, L
AF Fabbri, Elisa
   Tanaka, Toshiko
   An, Yang
   Zoli, Marco
   Bandinelli, Stefania
   Guralnik, Jack M.
   Simonsick, Eleanor M.
   Boyd, Cynthia M.
   Studenski, Stephanie A.
   Harris, Tamara B.
   Ferrucci, Luigi
TI Loss of Weight in Obese Older Adults: A Biomarker of Impending Expansion
   of Multimorbidity?
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE multimorbidity; BMI; weight loss; obesity; older adults
ID ALL-CAUSE MORTALITY; BODY-MASS INDEX; PRIMARY-CARE; CHRONIC DISEASES;
   HEALTH; PREVALENCE; ASSOCIATION; RISK; POPULATION; COHORT
AB OBJECTIVES: To determine whether weight loss in older adults may be a marker of impending burden of multimorbidity regardless of initial weight, testing the hypotheses that obesity but not overweight in elderly adults is associated with greater number of diseases than normal weight and that obese older adults who lose weight over time have the greatest burden of multimorbidity.
   DESIGN: Longitudinal cohort study (Invecchiare in Chianti Study).
   SETTING: Community.
   PARTICIPANTS: Individuals aged 60 and older at baseline followed for an average of 4 years (N = 1,025).
   MEASUREMENTS: Multimorbidity was measured as number of diagnosed diseases. Baseline body mass index (BMI) was categorized as normal weight (< 25.0 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (>= 30.0 kg/m(2)). Loss of weight was defined as decrease over time in BMI of at least 0.15 kg/m(2) per year. Age, sex, and education were covariates.
   RESULTS: Baseline obesity was cross-sectionally associated with high multimorbidity and greater longitudinal increase of multimorbidity than normal weight (P = .005) and overweight (P < .001). Moreover, obese participants who lost weight over follow-up had a significantly greater increase in multimorbidity than other participants, including obese participants who maintained or gained weight over time (P = .005). In nonobese participants, changes in weight had no effect on changes in multimorbidity over time. Sensitivity analyses confirmed that one specific disease did not drive the association and that competing mortality did not bias the association.
   CONCLUSION: Loss of weight in obese older persons is a strong biomarker of impending expansion of multimorbidity. Older obese individuals who lose weight should receive thoughtful medical attention.
C1 [Fabbri, Elisa; Tanaka, Toshiko; An, Yang; Simonsick, Eleanor M.; Studenski, Stephanie A.; Ferrucci, Luigi] NIA, Intramural Res Branch, NIH, Baltimore, MD 21224 USA.
   [Fabbri, Elisa; Zoli, Marco] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy.
   [Bandinelli, Stefania] Azienda Sanit Firenze, Dept Geriatr Med, Florence, Italy.
   [Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
   [Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.
   [Harris, Tamara B.] NIH, Geriatr Epidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Fabbri, E (reprint author), NIA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM elisa.fabbri@nih.gov
FU NIA NIH HHS [K23 AG032910]
NR 39
TC 3
Z9 3
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD SEP
PY 2015
VL 63
IS 9
BP 1791
EP 1797
DI 10.1111/jgs.13608
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CU8PI
UT WOS:000363804800008
PM 26311068
ER

PT J
AU Bigelow, RT
   Semenov, YR
   Trevino, C
   Ferrucci, L
   Resnick, SM
   Simonsick, EM
   Xue, QL
   Agrawal, Y
AF Bigelow, Robin T.
   Semenov, Yevgeniy R.
   Trevino, Carolina
   Ferrucci, Luigi
   Resnick, Susan M.
   Simonsick, Eleanor M.
   Xue, Qian-Li
   Agrawal, Yuri
TI Association Between Visuospatial Ability and Vestibular Function in the
   Baltimore Longitudinal Study of Aging
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE vestibular function; cognition; aging; visuospatial ability
ID EVOKED MYOGENIC POTENTIALS; AGE-RELATED-CHANGES; VIRTUAL ENVIRONMENT;
   SPATIAL MEMORY; NAVIGATION; STIMULATION; CONNECTIVITY; RELIABILITY;
   PERFORMANCE; DISORDERS
AB OBJECTIVES: To investigate the relationship between vestibular loss associated with aging and age-related decline in visuospatial function.
   DESIGN: Cross-sectional analysis within a prospective cohort study.
   SETTING: Baltimore Longitudinal Study of Aging (BLSA).
   PARTICIPANTS: Community-dwelling BLSA participants with a mean age of 72 (range 26-91) (N = 183).
   MEASUREMENTS: Vestibular function was measured using vestibular-evoked myogenic potentials. Visuospatial cognitive tests included Card Rotations, Purdue Pegboard, Benton Visual Retention Test, and Trail-Making Test Parts A and B. Tests of executive function, memory, and attention were also considered.
   RESULTS: Participants underwent vestibular and cognitive function testing. In multiple linear regression analyses, poorer vestibular function was associated with poorer performance on Card Rotations (P = .001), Purdue Pegboard (P = .005), Benton Visual Retention Test (P = 0.008), and Trail-Making Test Part B (P = .04). Performance on tests of executive function and verbal memory were not significantly associated with vestibular function. Exploratory factor analyses in a subgroup of participants who underwent all cognitive tests identified three latent cognitive abilities: visuospatial ability, verbal memory, and working memory and attention. Vestibular loss was significantly associated with lower visuospatial and working memory and attention factor scores.
   CONCLUSION: Significant consistent associations between vestibular function and tests of visuospatial ability were observed in a sample of community-dwelling adults. Impairment in visuospatial skills is often one of the first signs of dementia and Alzheimer's disease. Further longitudinal studies are needed to evaluate whether the relationship between vestibular function and visuospatial ability is causal.
C1 [Bigelow, Robin T.; Semenov, Yevgeniy R.; Trevino, Carolina; Xue, Qian-Li; Agrawal, Yuri] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA.
   [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
   [Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Simonsick, Eleanor M.] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
   [Xue, Qian-Li] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
   [Xue, Qian-Li] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
RP Bigelow, RT (reprint author), Dept Otolaryngol Head & Neck Surg, 601 N Caroline St, Baltimore, MD 21287 USA.
EM rbigelow@jhmi.edu
FU NIA NIH HHS [P30 AG021334, P50 AG005146]; NIDCD NIH HHS [5T32
   DC000023-30, K23 DC013056, T32 DC000023]
NR 47
TC 10
Z9 10
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD SEP
PY 2015
VL 63
IS 9
BP 1837
EP 1844
DI 10.1111/jgs.13609
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CU8PI
UT WOS:000363804800014
PM 26311169
ER

PT J
AU Di Francesco, A
   de Cabo, R
AF Di Francesco, Andrea
   de Cabo, Rafael
TI Two-Year Trial of Human Caloric Restriction
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Editorial Material
ID RHESUS-MONKEYS
C1 [Di Francesco, Andrea; de Cabo, Rafael] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
RP de Cabo, R (reprint author), NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
EM decabora@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016; 
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU National Institute on Aging, National Institutes of Health
FX This work is funded by the Intramural Research Program of the National
   Institute on Aging, National Institutes of Health.
NR 13
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD SEP
PY 2015
VL 70
IS 9
BP 1095
EP 1096
DI 10.1093/gerona/glv100
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CU4FK
UT WOS:000363482300006
PM 26187232
ER

PT J
AU Ravussin, E
   Redman, LM
   Rochon, J
   Das, SK
   Fontana, L
   Kraus, WE
   Romashkan, S
   Williamson, DA
   Meydani, SN
   Villareal, DT
   Smith, SR
   Stein, RI
   Scott, TM
   Stewart, TM
   Saltzman, E
   Klein, S
   Bhapkar, M
   Martin, CK
   Gilhooly, CH
   Holloszy, JO
   Hadley, EC
   Roberts, SB
AF Ravussin, Eric
   Redman, Leanne M.
   Rochon, James
   Das, Sai Krupa
   Fontana, Luigi
   Kraus, William E.
   Romashkan, Sergei
   Williamson, Donald A.
   Meydani, Simin N.
   Villareal, Dennis T.
   Smith, Steven R.
   Stein, Richard I.
   Scott, Tammy M.
   Stewart, Tiffany M.
   Saltzman, Edward
   Klein, Samuel
   Bhapkar, Manju
   Martin, Corby K.
   Gilhooly, Cheryl H.
   Holloszy, John O.
   Hadley, Evan C.
   Roberts, Susan B.
CA CALERIE Study Grp
TI A 2-Year Randomized Controlled Trial of Human Caloric Restriction:
   Feasibility and Effects on Predictors of Health Span and Longevity
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Metabolism; Nutrition; Risk factors; Biomarkers; Caloric restriction
ID RHESUS-MONKEYS; COMPREHENSIVE ASSESSMENT; ENERGY-EXPENDITURE; REDUCING
   INTAKE; MORTALITY; CALERIE; EXERCISE; BIOMARKERS; INTERVENTIONS;
   TEMPERATURE
AB Background. Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR.
   Methods. To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. Outcomes were change from baseline resting metabolic rate adjusted for weight change ("RMR residual") and core temperature (primary); plasma triiodothyronine (T3) and tumor necrosis factor-alpha (secondary); and exploratory physiological and psychological measures.
   Results. Body mass index averaged 25.1 (range: 21.9-28.0 kg/m(2)). Eighty-two percent of CR and 95% of AL participants completed the protocol. The CR group achieved 11.7 +/- 0.7 % CR (mean +/- standard error) and maintained 10.4 +/- 0.4% weight loss. Weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p =.04) but not 24 months (M24). Core temperature change differed little between groups. T3 decreased more in CR at M12 and M24 (p <.001), while tumor necrosis factor-alpha decreased significantly more only at M24 (p =.02). CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life.
   Conclusions. Sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.
C1 [Ravussin, Eric; Redman, Leanne M.; Williamson, Donald A.; Smith, Steven R.; Stewart, Tiffany M.; Martin, Corby K.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
   [Rochon, James; Kraus, William E.; Bhapkar, Manju] Duke Clin Res Inst, Durham, NC USA.
   [Rochon, James; Kraus, William E.; Bhapkar, Manju] Duke Univ, Sch Med, Durham, NC USA.
   [Rochon, James] Rho Fed Syst, Chapel Hill, NC USA.
   [Das, Sai Krupa; Meydani, Simin N.; Scott, Tammy M.; Saltzman, Edward; Gilhooly, Cheryl H.; Roberts, Susan B.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Fontana, Luigi; Villareal, Dennis T.; Stein, Richard I.; Klein, Samuel; Holloszy, John O.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Fontana, Luigi] Univ Brescia, Sch Med, Dept Clin & Expt Sci, I-25121 Brescia, Italy.
   [Fontana, Luigi] CEINGE Biotecnol Avanzate, Naples, Italy.
   [Romashkan, Sergei; Hadley, Evan C.] NIA, Bethesda, MD 20892 USA.
   [Smith, Steven R.] Florida Hosp, Translat Res Inst Metab & Diabet, Orlando, FL USA.
   [Smith, Steven R.] Sanford Burnham Med Res Inst, Orlando, FL USA.
RP Hadley, EC (reprint author), NIA, Gateway Bldg,Suite 3C307, Bethesda, MD 20892 USA.
EM ehadley@nih.gov
RI John, Speakman/A-9494-2008; 
OI John, Speakman/0000-0002-2457-1823; Schram, Miranda/0000-0003-0515-4124
FU National Institute on Aging; National Institute of Diabetes and
   Digestive and Kidney Diseases; National Institutes of Health
   [U01AG022132, U01AG020478, U01AG020487, U01AG020480]
FX This study was supported by the National Institute on Aging; National
   Institute of Diabetes and Digestive and Kidney Diseases; National
   Institutes of Health Cooperative Agreements (U01AG022132, U01AG020478,
   U01AG020487, and U01AG020480).
NR 37
TC 34
Z9 34
U1 14
U2 29
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD SEP
PY 2015
VL 70
IS 9
BP 1097
EP 1104
DI 10.1093/gerona/glv057
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CU4FK
UT WOS:000363482300007
PM 26187233
ER

PT J
AU Cauley, JA
   Fluharty, L
   Ellenberg, SS
   Gill, TM
   Ensrud, KE
   Barrett-Connor, E
   Cifelli, D
   Cunningham, GR
   Matsumoto, AM
   Bhasin, S
   Pahor, M
   Farrar, JT
   Cella, D
   Rosen, RC
   Resnick, SM
   Swerdloff, RS
   Lewis, CE
   Molitch, ME
   Crandall, JP
   Stephens-Shields, AJ
   Strorer, TW
   Wang, C
   Anton, S
   Basaria, S
   Diem, S
   Tabatabaie, V
   Dougar, D
   Hou, X
   Snyder, PJ
AF Cauley, Jane A.
   Fluharty, Laura
   Ellenberg, Susan S.
   Gill, Thomas M.
   Ensrud, Kristine E.
   Barrett-Connor, Elizabeth
   Cifelli, Denise
   Cunningham, Glenn R.
   Matsumoto, Alvin M.
   Bhasin, Shalender
   Pahor, Marco
   Farrar, John T.
   Cella, David
   Rosen, Raymond C.
   Resnick, Susan M.
   Swerdloff, Ronald S.
   Lewis, Cora E.
   Molitch, Mark E.
   Crandall, Jill P.
   Stephens-Shields, Alisa J.
   Strorer, Thomas W.
   Wang, Christina
   Anton, Stephen
   Basaria, Shehzad
   Diem, Susan
   Tabatabaie, Vafa
   Dougar, Darlene
   Hou, Xiaoling
   Snyder, Peter J.
TI Recruitment and Screening for the Testosterone Trials
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Testosterone treatment; Recruitment; Hypogonadal men; Physical function;
   Vitality; Sexual function; Randomized clinical trials
ID OLDER-ADULTS; UNITED-STATES; MEN; EXPERIENCE; SPEED
AB Background. We describe the recruitment of men for The Testosterone (T) Trials, which were designed to determine the efficacy of T treatment.
   Methods. Men were eligible if they were >= 65 years, had an average of two morning total T values <275 ng/dL with neither value >300 ng/mL, and had symptoms and objective evidence of mobility limitation, sexual dysfunction, and/or low vitality. Men had to be eligible for and enroll in at least one of these three main trials (physical function, sexual function, vitality).
   Results. Men were recruited primarily through mass mailings in 12 U.S. communities: 82% of men who contacted the sites did so in response to mailings. Men who responded were screened by telephone to ascertain eligibility. Of 51,085 telephone screens, 53.5% were eligible for further screening. Of 23,889 initial screening visits (SV1), 2,781 (11.6%) men were eligible for the second screening visit (SV2), which 2,261 (81.3%) completed. At SV2, 931 (41.2%) men met the criteria for one or more trials, the T level criterion and had no other exclusions. Of these, 790 (84.6%) were randomized; 99 (12.5%) in all three trials and 348 (44%) in two trials. Their mean age was 72 years and mean body mass index (BMI) was 31.0 kg/m(2). Mean (standard deviation) total T (ng/dL) was 212.0 (40.0).
   Conclusion: Despite the telephone screening to enrollment ratio of 65 to 1, we met the recruitment goals for each trial. Recruitment of symptomatic older men with low testosterone levels is difficult but feasible.
C1 [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
   [Fluharty, Laura; Cifelli, Denise; Dougar, Darlene] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Ellenberg, Susan S.; Farrar, John T.; Stephens-Shields, Alisa J.; Hou, Xiaoling] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Gill, Thomas M.] Yale Univ, Sch Med, Div Geriatr Med, New Haven, CT USA.
   [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
   [Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA.
   [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, San Diego Sch Med, La Jolla, CA 92093 USA.
   [Cunningham, Glenn R.] Baylor Coll Med, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA.
   [Cunningham, Glenn R.] Baylor St Lukes Med Ctr, Houston, TX USA.
   [Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA.
   [Matsumoto, Alvin M.] Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Internal Med, Seattle, WA 98195 USA.
   [Bhasin, Shalender] Harvard Univ, Sch Med, Brigham & Womens Hosp, Res Program Mens Health Aging & Metab, Boston, MA 02115 USA.
   [Pahor, Marco] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
   [Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL USA.
   [Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA.
   [Resnick, Susan M.] NIA, NIH, Lab Behav Neurosci, Baltimore, MD 21224 USA.
   [Swerdloff, Ronald S.] Harbor Univ Calif Los Angeles, Div Endocrinol, Med Ctr, Torrance, CA USA.
   [Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA.
   [Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35487 USA.
   [Molitch, Mark E.] Northwestern Univ, Div Endocrinol Metab & Mol Med, Feinberg Sch Med, Chicago, IL USA.
   [Crandall, Jill P.; Tabatabaie, Vafa] Albert Einstein Coll Med, Div Endocrinol & Geriatr, Bronx, NY 10467 USA.
   [Strorer, Thomas W.] Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA USA.
   [Snyder, Peter J.] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
RP Cauley, JA (reprint author), Univ Pittsburgh, 130 DeSoto St,Crabtree A510, Pittsburgh, PA 15261 USA.
EM jcauley@edc.pitt.edu
RI Cauley, Jane/N-4836-2015
OI Cauley, Jane/0000-0003-0752-4408
FU National Institute on Aging, National Institutes of Health [U01
   AG030644, U01 AG034661]; National Heart, Lung and Blood Institute;
   National Institute of Neurological Diseases and Stroke; National
   Institute of Child Health and Human Development; National Institute on
   Aging [R01 AG037679, K24-AG021507]; AbbVie; Department of Veterans
   Affairs Puget Sound Health Care System; Claude D. Pepper Older Americans
   Independence Center [P30-AG021342]; Yale CTSA [UL1 TR000142]; National
   Institute on Aging, National Institutes of Health; National Institute
   for Diabetes, Digestive and Kidney Diseases, National Institutes of
   Health [DK079626]
FX The Testosterone Trials were supported by a grant from the National
   Institute on Aging, National Institutes of Health (U01 AG030644),
   supplemented by funds from the National Heart, Lung and Blood Institute,
   National Institute of Neurological Diseases and Stroke, and National
   Institute of Child Health and Human Development. The Bone Trial was
   supported by a grant from the National Institute on Aging (R01
   AG037679). The Anemia Trial was supported by a grant from the National
   Institute on Aging, National Institutes of Health (U01 AG034661) to the
   Partnership for Anemia Clinical and Translational Trials in the Elderly
   consortium. AbbVie (formerly Solvay and Abbott Laboratories) generously
   provided funding, AndroGel and placebo gel. AMM was supported by the
   Department of Veterans Affairs Puget Sound Health Care System. TMG is
   the recipient of an Academic Leadership Award (K24-AG021507) from the
   National Institute on Aging. The Yale Field Center was partially
   supported by the Claude D. Pepper Older Americans Independence Center
   (P30-AG021342) and Yale CTSA (UL1 TR000142). SMR was supported by the
   Intramural Research Program, National Institute on Aging, National
   Institutes of Health. CEL was supported by the National Institute for
   Diabetes, Digestive and Kidney Diseases, National Institutes of Health
   (DK079626) to the UAB Diabetes Research and Training Center.
NR 14
TC 8
Z9 8
U1 3
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD SEP
PY 2015
VL 70
IS 9
BP 1105
EP 1111
DI 10.1093/gerona/glv031
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CU4FK
UT WOS:000363482300008
PM 25878029
ER

PT J
AU Urpi-Sarda, M
   Andres-Lacueva, C
   Rabassa, M
   Ruggiero, C
   Zamora-Ros, R
   Bandinelli, S
   Ferrucci, L
   Cherubini, A
AF Urpi-Sarda, Mireia
   Andres-Lacueva, Cristina
   Rabassa, Montserrat
   Ruggiero, Carmelinda
   Zamora-Ros, Raul
   Bandinelli, Stefania
   Ferrucci, Luigi
   Cherubini, Antonio
TI The Relationship Between Urinary Total Polyphenols and the Frailty
   Phenotype in a Community-Dwelling Older Population: The InCHIANTI Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Frailty; Nutrition; Biomarkers; Polyphenols; Elderly people; InCHIANTI
ID SERUM MICRONUTRIENT CONCENTRATIONS; MEDITERRANEAN DIET; ADULTS; WOMEN;
   CAROTENOIDS; BIOMARKER; DECLINE; MEN; ATHEROSCLEROSIS; ASSOCIATIONS
AB Background. Frailty, an age-related state of increased vulnerability, is associated with a higher risk of multiple adverse events. Studies have suggested that the quality of dietary intake may affect the development of frailty. We hypothesized that frailty in older subjects would be associated with dietary total polyphenols (DTP) intake and its biomarker, urinary total polyphenols (UTP).
   Methods. The Invecchiare in Chianti (InCHIANTI) Study is a prospective cohort study set in the Chianti area (Italy). We used data at baseline from 811 participants aged 65 years and older. UTP was determined using the Folin-Ciocalteu assay after solid-phase extraction. DTP was estimated using a validated Food Frequency Questionnaire and our own polyphenol database. The frailty, prefrailty, and nonfrailty states were defined according to the Fried and colleagues' criteria. Multinomial logistic regressions adjusted for potential confounders were used to assess the relationship between polyphenols and frailty.
   Results. Both DTP and UTP concentrations progressively decrease from nonfrail to frail participants. Participants in the highest UTP tertile compared to those in the lowest tertile were significantly less likely to be both frail (odds ratio [OR] = 0.36 [0.14-0.88], p =.025) and prefrail (OR = 0.64 [0.42-0.98], p =.038). Exhaustion and slowness were the only individual frailty criteria significantly associated with UTP tertiles. No significant association was observed between frailty and DTP, after adjustment for covariates.
   Conclusions. High concentrations of UTP were associated with lower prevalence of frailty and prefrailty in an older community-dwelling population. A polyphenol-rich diet may protect against frailty in older persons. Our findings should be confirmed in longitudinal studies.
C1 [Urpi-Sarda, Mireia; Andres-Lacueva, Cristina; Rabassa, Montserrat] Univ Barcelona, Biomarkers & Nutrimetabol Lab, Nutr & Food Sci Dept, XaRTA,INSA,Pharm Sch, E-08007 Barcelona, Spain.
   [Urpi-Sarda, Mireia; Andres-Lacueva, Cristina; Rabassa, Montserrat] FUN C FOOD, Ingenio CONSOLIDER Program, Barcelona, Spain.
   [Ruggiero, Carmelinda] Univ Perugia, Dept Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
   [Zamora-Ros, Raul] Int Agcy Res Canc, Biomarkers Grp, Nutr & Metab Sect, F-69372 Lyon, France.
   [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
   [Ferrucci, Luigi] NIA, Intramural Program, Baltimore, MD 21224 USA.
   [Cherubini, Antonio] IRCCS INRCA, Geriatr & Geriatr Emergency Room, Ancona, Italy.
RP Andres-Lacueva, C (reprint author), Univ Barcelona, Fac Pharm, Dept Nutr & Food Sci, E-08028 Barcelona, Spain.
EM candres@ub.edu
RI Andres-Lacueva, Cristina/J-3377-2012; 
OI Andres-Lacueva, Cristina/0000-0002-8494-4978; Cherubini,
   Antonio/0000-0003-0261-9897; urpi, mireia/0000-0002-4064-5175
FU Italian Ministry of Health; U.S. National Institute on Aging [263 MD
   916413, 263 MD 821336]; MAPFRE FOUNDATION grant; Spanish National Grants
   from the Ministry of Economy and Competitiveness (MINECO); Bosch i
   Gimpera Foundation [FBG306776]; FEDER (Fondo Europeo de Desarrollo
   Regional) [AGL2009-13906-C02-01]; CONSOLIDER INGENIO Programme,
   FUN-C-FOOD [CSD2007-063]; Project (Plan N de I+D+i) by
   ISCII-Subdireccion General de Evaluacion y Fomento de la Investigacion
   [PI13/01172]; Generalitat de Catalunya's Agency AGAUR [2014SGR1566]
FX The InCHIANTI study was supported by the Italian Ministry of Health and
   by the U.S. National Institute on Aging (contracts 263 MD 916413 and 263
   MD 821336). Special thanks to the MAPFRE FOUNDATION grant in
   collaboration with the Bosch i Gimpera Foundation (FBG306776). This
   research was also supported by the Spanish National Grants from the
   Ministry of Economy and Competitiveness (MINECO) and co-founded by FEDER
   (Fondo Europeo de Desarrollo Regional): AGL2009-13906-C02-01, the
   CONSOLIDER INGENIO 2010 Programme, FUN-C-FOOD (CSD2007-063), as well as
   the PI13/01172 Project (Plan N de I+D+i 2013-2016) by ISCII-Subdireccion
   General de Evaluacion y Fomento de la Investigacion. We thank the award
   of 2014SGR1566 from the Generalitat de Catalunya's Agency AGAUR.
NR 33
TC 5
Z9 5
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD SEP
PY 2015
VL 70
IS 9
BP 1141
EP 1147
DI 10.1093/gerona/glv026
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CU4FK
UT WOS:000363482300013
PM 25838546
ER

PT J
AU Shardell, M
   Semba, RD
   Kalyani, RR
   Hicks, GE
   Bandinelli, S
   Ferrucci, L
AF Shardell, Michelle
   Semba, Richard D.
   Kalyani, Rita R.
   Hicks, Gregory E.
   Bandinelli, Stefania
   Ferrucci, Luigi
TI Serum 25-Hydroxyvitamin D, Plasma Klotho, and Lower-Extremity Physical
   Performance Among Older Adults: Findings From the InCHIANTI Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Biomarkers; Epidemiology; Physical function; Metabolism; Physical
   performance
ID COMMUNITY-DWELLING ADULTS; BONE-MINERAL DENSITY; VITAMIN-D STATUS;
   POSTMENOPAUSAL WOMEN; HORMONE KLOTHO; GAIT SPEED; ASSOCIATION; GENE;
   DISABILITY; MORTALITY
AB Background. The hormone klotho is encoded by aging-suppressor gene klotho and has multiple roles, including regulating mineral (calcium and phosphate) homeostasis. Vitamin D also regulates mineral homeostasis and upregulates klotho expression. Klotho positively relates to longevity, upper-extremity strength, and reduced disability in older adults; however, it is unknown whether circulating klotho relates to lower-extremity physical performance or whether the relation of vitamin D with physical performance is mediated by klotho.
   Methods. Klotho and 25-hydroxyvitamin D [25(OH)D] were measured in 860 participants aged >= 55 years in Invecchiare in Chianti, "Aging in Chianti" (InCHIANTI), a prospective cohort study comprising Italian adults. Lower-extremity physical performance was measured using the Short Physical Performance Battery, a summary score of balance, chair stand ability, and walking speed. Weighted estimating equations related plasma klotho and serum 25(OH)D concentrations measured at one visit to Short Physical Performance Battery measured longitudinally at multiple visits.
   Results. Each additional natural log of klotho (pg/mL) was associated with 0.47 higher average Short Physical Performance Battery scores (95% confidence interval: 0.08 to 0.86, p value =.02) after adjustment for covariates, including 25(OH)D. Each natural log of 25(OH)D (ng/mL) was associated with 0.61 higher average Short Physical Performance Battery scores (95% confidence interval: 0.35 to 0.88, p value <.001) after adjustment for covariates, a result that changed little after adjustment for klotho.
   Conclusions. Plasma klotho and 25(OH)D both positively related to lower-extremity physical performance. However, the findings did not support the hypothesis that klotho mediates the relation of 25(OH)D with physical performance.
C1 [Shardell, Michelle; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
   [Semba, Richard D.] Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Kalyani, Rita R.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
   [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA.
   [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy.
RP Shardell, M (reprint author), NIA, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM michelle.shardell@nih.gov
FU National Institutes of Health [R01AG027012, R01HL094507, K23DK093583,
   R01AG041202]; Italian Ministry of Health [ICS110.1/RF97.71]; National
   Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1,
   N.1-AG-1-2111, N01-AG-5-0002]; National Institute on Aging
FX This work was supported by the National Institutes of Health grants
   (R01AG027012 and R01HL094507 to R. D. S., K23DK093583 to R. R. K.,
   R01AG041202 to G. E. H.); the Italian Ministry of Health
   (ICS110.1/RF97.71); National Institute on Aging contracts (263 MD 9164,
   263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002); and the
   Intramural Research Program of the National Institute on Aging.
NR 40
TC 2
Z9 2
U1 3
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD SEP
PY 2015
VL 70
IS 9
BP 1156
EP 1162
DI 10.1093/gerona/glv017
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CU4FK
UT WOS:000363482300015
PM 25748032
ER

PT J
AU Tosh, DK
   Padia, J
   Salvemini, D
   Jacobson, KA
AF Tosh, Dilip K.
   Padia, Janak
   Salvemini, Daniela
   Jacobson, Kenneth A.
TI Efficient, large-scale synthesis and preclinical studies of MRS5698, a
   highly selective A(3) adenosine receptor agonist that protects against
   chronic neuropathic pain
SO PURINERGIC SIGNALLING
LA English
DT Article
DE Nucleoside; Purines; G protein-coupled receptor; ADME-toxicity;
   Preclinical development
ID INDUCED PERIPHERAL NEUROPATHY; STEREOSELECTIVE-SYNTHESIS; NUCLEOSIDES;
   ACTIVATION; OPIOIDS; RAT
AB We reported that 2-(3,4-difluorophenylethynyl)-N-6-3-chlorobenzyl (N)-methanocarba adenosine derivative 1 (MRS5698) binds selectively to human and mouse A3 adenosine receptors (A(3)ARs, K-i 3 nM). It is becoming an important pharmacological tool for defining A(3)AR effects and is orally active in a chronic neuropathic pain model. Here, we introduce a new synthetic route for MRS5698 from D-ribose, suitable for a scale-up on a multi-gram scale, and we measure in vitro and in vivo ADME-Tox parameters. MRS5698 was very stable in vitro, failed to inhibit CYPs at <10 mu M, and was largely bound to plasma proteins. It was well tolerated in the rat at doses of <= 200 mg/kg i.p. A 1 mg/kg i.p. dose in the mouse displayed t(1/2) of 1.09 h and plasma C-max of 204 nM at 1 h with an AUC of 213 ngxh/mL. CACO-2 bidirectional transport studies suggested intestinal efflux of MRS5698 (efflux ratio 86). Although the oral % F is only 5 %, the beneficial effect to reverse pain lasted for at least 2 h in the CCI model in rats, using the same vehicle for oral administration of a high dose. The stability, low toxicity, lack of CYP interaction, pharmacokinetic half-life, and in vivo efficacy suggest that MRS5698 is a preferred compound for further consideration as a treatment for neuropathic pain.
C1 [Tosh, Dilip K.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Padia, Janak] PrimeTime Life Sci, Germantown, MD USA.
   [Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural Research Program of the NIH, National Institute of Diabetes
   and Digestive and Kidney Diseases [Z01 DK031117-27]; National Cancer
   Institute [R01CA169519]; National Institute of Mental Health's
   Psychoactive Drug Screening Program [HHSN-271-2008-00025-C]
FX This research was supported in part by the Intramural Research Program
   of the NIH, National Institute of Diabetes and Digestive and Kidney
   Diseases (Z01 DK031117-27), and National Cancer Institute (R01CA169519).
   We thank Dr. Bryan L. Roth (University of North Carolina at Chapel Hill)
   and the National Institute of Mental Health's Psychoactive Drug
   Screening Program (Contract # HHSN-271-2008-00025-C) for hERG screening
   data.
NR 30
TC 8
Z9 8
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
EI 1573-9546
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD SEP
PY 2015
VL 11
IS 3
BP 371
EP 387
DI 10.1007/s11302-015-9459-2
PG 17
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CU7NN
UT WOS:000363727600009
PM 26111639
ER

PT J
AU Poschau, M
   Dickreuter, E
   Singh-Muller, J
   Zscheppang, K
   Eke, I
   Liersch, T
   Cordes, N
AF Poschau, Mandy
   Dickreuter, Ellen
   Singh-Mueller, Jenny
   Zscheppang, Katja
   Eke, Iris
   Liersch, Torsten
   Cordes, Nils
TI EGFR and beta 1-integrin targeting differentially affect colorectal
   carcinoma cell radiosensitivity and invasion
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 14th International Wolfsberg Meeting on Molecular Radiation
   Biology/Oncology
CY JUL 20-22, 2015
CL Wolfsberg, AUSTRIA
SP ESTRO
DE beta 1 integrin; EGFR; Colorectal carcinoma; Ionizing radiation;
   Invasion
ID RECTAL-CANCER; COLON-CANCER; PHASE-3 TRIAL; OPEN-LABEL; CETUXIMAB;
   RADIOTHERAPY; RESISTANCE; ADHESION; THERAPY; CAPECITABINE
AB Background and purpose: Simultaneous targeting of in integrin receptor and epidermal growth factor receptor (EGFR) showed higher level of radiosensitization in head and neck cancers than monotherapies. As EGFR inhibition is similarly performed in colorectal cancer (CRC), we investigated the radiosensitizing and anti-invasive potential of beta 1-integrin/EGFR inhibition in CRC cell lines grown in more physiological three-dimensional (3D) matrix-based cell cultures.
   Materials and methods: DLD-1 and HT-29 cells were used for 3D-colony formation, invasion and proliferation assays and Western blotting. beta 1 integrin, focal adhesion kinase and EGFR were inhibited by AIIB2, TAE226 and Cetuximab, respectively. KRAS and BRAF knockdown were accomplished using small-interfering RNA technology. Single doses of X-rays ranged from 2 Gy to 6 Gy and 5-fluorouracil (5-FU) concentration was 10 mu M.
   Results: Neither beta 1-integrin/EGFR inhibition nor KRAS or BRAF depletion nor 5-FU significantly modified CRC cell radiosensitivity. Cetuximab, AIIB2 and Cetuximab/AIIB2 differentially modulated MAPK, JNK and AICT phosphorylation. AIIB2 and TAE226 significantly decreased cell invasion.
   Conclusions: Our data show inefficiency of Cetuximab and AIIB2 on top of radiochemotherapy. The functions of KRAS and BRAF in therapy resistance remain unanswered and warrant further preclinical molecular-driven investigations. One promising approach might be beta 1 integrin targeting for reducing metastatic CRC cell spread. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Poschau, Mandy; Dickreuter, Ellen; Singh-Mueller, Jenny; Zscheppang, Katja; Eke, Iris; Cordes, Nils] Tech Univ Dresden, Fac Med, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany.
   [Poschau, Mandy; Dickreuter, Ellen; Singh-Mueller, Jenny; Zscheppang, Katja; Eke, Iris; Cordes, Nils] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany.
   [Poschau, Mandy; Dickreuter, Ellen; Singh-Mueller, Jenny; Zscheppang, Katja; Eke, Iris; Cordes, Nils] Helmholtz Zentrum Dresden Rossendorf, Dresden, Germany.
   [Cordes, Nils] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Radiat Oncol, D-01307 Dresden, Germany.
   [Cordes, Nils] Helmholtz Zentrum Dresden Rossendorf, Inst Radiooncol, Dresden, Germany.
   [Eke, Iris] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Liersch, Torsten] Univ Gottingen, Univ Med Ctr, Gen Visceral & Paediat Surg, Gottingen, Germany.
   [Cordes, Nils] German Canc Consortium DKTK, Dresden, Germany.
   [Cordes, Nils] German Canc Res Ctr, Heidelberg, Germany.
RP Cordes, N (reprint author), Tech Univ Dresden, Med Fak Carl Gustav Carus, OncoRay Natl Ctr Radiat Res Oncol, Fetscherstr 74-PF 41, D-01307 Dresden, Germany.
EM Nils.Cordes@OncoRay.de
RI Eke, Iris/B-9251-2016
OI Eke, Iris/0000-0002-3591-019X
FU BMBF [03ZIK041]; Medizinische Fakultat Carl Gustav Carus, Technische
   Universitat Dresden, Germany (MeDDrive grant)
FX The research and authors are in part supported by a grant from the BMBF
   (BMBF contract 03ZIK041 to NC) and the Medizinische Fakultat Carl Gustav
   Carus, Technische Universitat Dresden, Germany (MeDDrive grant to I.E.).
   We thank Novartis (Basel, Switzerland) of TAE226 and I. Lange for
   excellent technical assistance.
NR 33
TC 2
Z9 3
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD SEP
PY 2015
VL 116
IS 3
BP 510
EP 516
DI 10.1016/j.radonc.2015.06.005
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CU8UN
UT WOS:000363819700028
PM 26096850
ER

PT J
AU Correia-Pinto, JF
   Csaba, N
   Schiller, JT
   Alonso, MJ
AF Correia-Pinto, Jorge F.
   Csaba, Noemi
   Schiller, John T.
   Alonso, Maria J.
TI Chitosan-Poly (I:C)-PADRE Based Nanoparticles as Delivery Vehicles for
   Synthetic Peptide Vaccines
SO VACCINES
LA English
DT Article
DE peptide-based antigens; nanoparticle; adjuvant; chitosan; poly (I:C);
   HPV; T-Helper peptide
ID CROSS-NEUTRALIZING EPITOPE; NONVIRAL GENE DELIVERY; I-C; TLR LIGANDS;
   PROTEIN; RESPONSES; CARRIERS; FORMULATIONS; IMMUNIZATION; CHALLENGE
AB The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C) (pIC) and a T-Helper peptide (PADRE), integrated into a chitosan (CS) based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa) derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm), a high positive surface charge (>40 mV) and high pIC association efficiency (>96%). They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed) on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.
C1 [Correia-Pinto, Jorge F.; Csaba, Noemi; Alonso, Maria J.] Univ Santiago de Compostela, Sch Pharm, Dept Pharm & Pharmaceut Technol, Santiago De Compostela 15782, Spain.
   [Correia-Pinto, Jorge F.; Csaba, Noemi; Alonso, Maria J.] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CIMUS, Santiago De Compostela 15707, Spain.
   [Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Alonso, MJ (reprint author), Univ Santiago de Compostela, Sch Pharm, Dept Pharm & Pharmaceut Technol, Santiago De Compostela 15782, Spain.
EM jo.pinto84@gmail.com; noemi.csaba@usc.es; schillej@dc37a.nci.nih.gov;
   mariaj.alonso@usc.es
RI Csaba, Noemi/C-7621-2014
OI Csaba, Noemi/0000-0002-6187-7717
NR 42
TC 2
Z9 2
U1 2
U2 6
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2076-393X
J9 VACCINES
JI Vaccines
PD SEP
PY 2015
VL 3
IS 3
BP 730
EP 750
DI 10.3390/vaccines3030730
PG 21
WC Immunology
SC Immunology
GA CU2SM
UT WOS:000363373600013
PM 26378586
ER

PT J
AU Schiffman, M
   Boyle, S
   Raine-Bennett, T
   Katki, HA
   Gage, JC
   Wentzensen, N
   Kornegay, JR
   Apple, R
   Aldrich, C
   Erlich, HA
   Tam, T
   Befano, B
   Burk, RD
   Castle, PE
AF Schiffman, Mark
   Boyle, Sean
   Raine-Bennett, Tina
   Katki, Hormuzd A.
   Gage, Julia C.
   Wentzensen, Nicolas
   Kornegay, Janet R.
   Apple, Raymond
   Aldrich, Carrie
   Erlich, Henry A.
   Tam, Thanh
   Befano, Brian
   Burk, Robert D.
   Castle, Philip E.
TI The Role of Human Papillomavirus Genotyping in Cervical Cancer
   Screening: A Large-Scale Evaluation of the cobas HPV Test
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID POPULATION; GUIDELINES; MANAGEMENT; CYTOLOGY; WOMEN; RISK; PERFORMANCE;
   INFECTION; SPECIMENS; PCR
AB Background: The cobas HPV Test ("cobas"; Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for (i) atypical squamous cells of undetermined significance (ASC-US) triage to determine need for colposcopy, (ii) combined screening with cytology ("cotesting"), and (iii) primary HPV screening.
   Methods: To assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared with those of an established method, the Linear Array HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+.
   Results: Grouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the k statistic for agreement between cobas and LA was 0.86 [95% confidence interval (CI), 0.86-0.87]. In all three scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women ages 21 and older with ASC-US (14.5%; 95% CI, 13.5%-15.5% vs. 3.5%; 95% CI, 3.3-3.6); women ages 30 years and older that were HPV-positive cytology-negative (10.3%; 95% CI, 9.6-11.1 vs. 2.3%; 95% CI, 2.2-2.4); and all women 25 years and older that were HPV-positive (18.5%; 95% CI, 17.8-19.2 vs. 4.3%; 95% CI, 4.2-4.4).
   Conclusion: The cobas and LA results show excellent agreement. The data support HPV16 typing.
   Impact: HPV16 typing is useful in the management of HPV-positive/cytology-negative women in cotesting, of allHPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US. (C) 2015 AACR.
C1 [Schiffman, Mark; Katki, Hormuzd A.; Gage, Julia C.; Wentzensen, Nicolas] NCI, Bethesda, MD 20892 USA.
   [Boyle, Sean; Kornegay, Janet R.; Apple, Raymond; Aldrich, Carrie; Erlich, Henry A.; Tam, Thanh] Roche Mol Syst, Pleasanton, CA USA.
   [Raine-Bennett, Tina] Kaiser Permanente No Calif, Oakland, CA USA.
   [Befano, Brian] Informat Management Serv Inc, Calverton, MD USA.
   [Burk, Robert D.] Albert Einstein Coll Med, The Bronx, NY USA.
   [Castle, Philip E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, The Bronx, NY USA.
   [Castle, Philip E.] Global Coalit Cerv Canc, Arlington, VA USA.
RP Schiffman, M (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Shady Grove Room 6E544, Bethesda, MD 20892 USA.
EM schiffmm@mail.nih.gov
FU Kaiser Permanente Northern California; Intramural Research Program of
   the NCI, NIH (Bethesda, MD); NCI
FX Kaiser Permanente Northern California funded its own clinical and
   laboratory activities. Specific study costs were funded by the
   Intramural Research Program of the NCI, NIH (Bethesda, MD). Roche
   Molecular Systems performed HPV typing at no cost to NCI. R.D. Burk
   laboratory efforts were partly supported by NCI grants.
NR 21
TC 11
Z9 13
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2015
VL 24
IS 9
BP 1304
EP 1310
DI 10.1158/1055-9965.EPI-14-1353
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CU3CK
UT WOS:000363401000003
PM 26088703
ER

PT J
AU Wang, J
   Figueroa, JD
   Wallstrom, G
   Barker, K
   Park, JG
   Demirkan, G
   Lissowska, J
   Anderson, KS
   Qiu, J
   LaBaer, J
AF Wang, Jie
   Figueroa, Jonine D.
   Wallstrom, Garrick
   Barker, Kristi
   Park, Jin G.
   Demirkan, Gokhan
   Lissowska, Jolanta
   Anderson, Karen S.
   Qiu, Ji
   LaBaer, Joshua
TI Plasma Autoantibodies Associated with Basal-like Breast Cancers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ASSEMBLING PROTEIN MICROARRAYS; ACUTE MYELOID-LEUKEMIA; RISK-FACTORS;
   TUMOR CHARACTERISTICS; MOLECULAR PORTRAITS; HORMONE-RECEPTOR;
   OVARIAN-CANCER; LUNG-CANCER; BIOMARKERS; EXPRESSION
AB Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease.
   Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed.
   Results: We identified 13 AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (P = 0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival [MN1 AAb marker HR = 2.25, 95% confidence interval (CI), 1.03-4.91; P = 0.04; TP53, HR = 2.02, 95% CI, 1.06-3.85; P = 0.03]. We found limited evidence that AAb levels differed by demographic characteristics.
   Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection.
   Impact: Our study identifies 13 AAb markers associated specifically with BLBC and may improve detection or management of this deadly disease. (C) 2015 AACR.
C1 [Wang, Jie; Wallstrom, Garrick; Barker, Kristi; Park, Jin G.; Demirkan, Gokhan; Anderson, Karen S.; Qiu, Ji; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA.
   [Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
RP LaBaer, J (reprint author), Arizona State Univ, 1001 S McAllister Ave, Tempe, AZ 85287 USA.
EM Ji.Qiu@asu.edu; Joshua.LaBaer@asu.edu
FU Early Detection Research Network [5U01CA117374-02]; Intramural Research
   Funds of the NCI, Department of Health and Human Services
FX J. Wang, G. Wallstrom, K. Barker, J. G. Park, G. Demirkan, K.S.
   Anderson, J. Qiu, and J. LaBaer were supported by a grant from the Early
   Detection Research Network (5U01CA117374-02; to J. LaBaer and K.S.
   Anderson). J.D. Figueroa and J. Lissowska were supported by the
   Intramural Research Funds of the NCI, Department of Health and Human
   Services (to J.D. Figueroa).
NR 57
TC 7
Z9 7
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2015
VL 24
IS 9
BP 1332
EP 1340
DI 10.1158/1055-9965.EPI-15-0047
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CU3CK
UT WOS:000363401000007
PM 26070530
ER

PT J
AU Petrick, JL
   Freedman, ND
   Graubard, BI
   Sahasrabuddhe, VV
   Lai, GY
   Alavanja, MC
   Beane-Freeman, LE
   Boggs, DA
   Buring, JE
   Chan, AT
   Chong, DQ
   Fuchs, CS
   Gapstur, SM
   Gaziano, JM
   Giovannucci, EL
   Hollenbeck, AR
   King, LY
   Koshiol, J
   Lee, IM
   Linet, MS
   Palmer, JR
   Poynter, JN
   Purdue, MP
   Robien, K
   Schairer, C
   Sesso, HD
   Sigurdson, AJ
   Zeleniuch-Jacquotte, A
   Wactawski-Wende, J
   Campbell, PT
   McGlynn, KA
AF Petrick, Jessica L.
   Freedman, Neal D.
   Graubard, Barry I.
   Sahasrabuddhe, Vikrant V.
   Lai, Gabriel Y.
   Alavanja, Michael C.
   Beane-Freeman, Laura E.
   Boggs, Deborah A.
   Buring, Julie E.
   Chan, Andrew T.
   Chong, Dawn Q.
   Fuchs, Charles S.
   Gapstur, Susan M.
   Gaziano, John Michael
   Giovannucci, Edward L.
   Hollenbeck, Albert R.
   King, Lindsay Y.
   Koshiol, Jill
   Lee, I-Min
   Linet, Martha S.
   Palmer, Julie R.
   Poynter, Jenny N.
   Purdue, Mark P.
   Robien, Kim
   Schairer, Catherine
   Sesso, Howard D.
   Sigurdson, Alice J.
   Zeleniuch-Jacquotte, Anne
   Wactawski-Wende, Jean
   Campbell, Peter T.
   McGlynn, Katherine A.
TI Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic
   Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BASE-LINE CHARACTERISTICS; UNITED-STATES; WOMENS HEALTH; LARGE COHORT;
   ASSOCIATION; EPIDEMIOLOGY; METAANALYSIS; DISEASE; DESIGN; JAPAN
AB Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer.
   Methods: In the Liver Cancer Pooling Project, a consortium of U. S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression.
   Results: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; P-trend cups/day = <0.0001). More notable reduced risk was seen among women than men (P-interaction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no association between coffee consumption and ICC.
   Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC.
   Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. (C) 2015 AACR.
C1 [Petrick, Jessica L.; Freedman, Neal D.; Graubard, Barry I.; Sahasrabuddhe, Vikrant V.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Koshiol, Jill; Linet, Martha S.; Schairer, Catherine; Sigurdson, Alice J.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Lai, Gabriel Y.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Boggs, Deborah A.; Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
   [Buring, Julie E.; Chan, Andrew T.; Gaziano, John Michael; King, Lindsay Y.; Lee, I-Min; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Buring, Julie E.; Giovannucci, Edward L.; Lee, I-Min; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Chan, Andrew T.; King, Lindsay Y.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
   [Chan, Andrew T.; Chong, Dawn Q.; King, Lindsay Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
   [Fuchs, Charles S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
   [Gapstur, Susan M.; Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
   [Hollenbeck, Albert R.] AARP, Washington, DC USA.
   [Poynter, Jenny N.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
   [Purdue, Mark P.] Ontario Inst Canc Res, Toronto, ON, Canada.
   [Robien, Kim] George Washington Univ, Milken Inst Sch Publ Hlth, Exercise & Nutr Sci, Washington, DC USA.
   [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
   [Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA.
RP Petrick, JL (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-232, Bethesda, MD 20892 USA.
EM jessica.petrick@nih.gov
RI Purdue, Mark/C-9228-2016; Beane Freeman, Laura/C-4468-2015; 
OI Purdue, Mark/0000-0003-1177-3108; Beane Freeman,
   Laura/0000-0003-1294-4124; Robien, Kim/0000-0002-2120-2280;
   Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303
FU NIH Intramural Research Program, NCI; NCI [CA39742, CA047988, HL043851,
   HL080467, HL099355, DK098311, CA186107, CA87969, CA167552]
FX NIH Intramural Research Program, NCI (to J.L. Petrick, N.D. Freedman,
   B.I. Graubard, M.C. Alavanja, L.E. Beane-Freeman, J. Koshiol, M.S.
   Linet, M. Purdue, C. Schairer, A.J. Sigurdson, V.V. Sahasrabuddhe, and
   K.A. McGlynn). NCI Grants CA39742 (to J.N. Poynter and K. Robien),
   CA047988(to I.-M. Lee and J.E. Buring), HL043851 (to I.-M. Lee and J.E.
   Buring), HL080467 (to I.-M. Lee and J.E. Buring), HL099355(to I.-M. Lee
   and J.E. Buring), DK098311(to A.T. Chan), CA186107(to A.T. Chan),
   CA87969 (to A.T. Chan), and CA167552 (to A.T. Chan).
NR 50
TC 4
Z9 4
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2015
VL 24
IS 9
BP 1398
EP 1406
DI 10.1158/1055-9965.EPI-15-0137
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CU3CK
UT WOS:000363401000015
PM 26126626
ER

PT J
AU Falk, RT
   Dallal, CM
   Lacey, JV
   Bauer, DC
   Buist, DSM
   Cauley, JA
   Hue, TF
   LaCroix, AZ
   Tice, JA
   Pfeiffer, RM
   Xu, X
   Veenstra, TD
   Brinton, LA
AF Falk, Roni T.
   Dallal, Cher M.
   Lacey, James V.
   Bauer, Douglas C.
   Buist, Diana S. M.
   Cauley, Jane A.
   Hue, Trisha F.
   LaCroix, Andrea Z.
   Tice, Jeffrey A.
   Pfeiffer, Ruth M.
   Xu, Xia
   Veenstra, Timothy D.
   Brinton, Louise A.
CA B Fit Res Grp
TI Estrogen Metabolites Are Not Associated with Colorectal Cancer Risk in
   Postmenopausal Women
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SEX-HORMONES
AB Background: A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women.
   Methods: We followed 15,595 women (ages 55-80 years) enrolled in the Breast and Bone Follow-up to the Fracture Intervention Trial (B similar to FIT) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 colorectal cancer cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position) and by ratios of the groupings using Cox proportional hazards regression models.
   Results: No significant associations were seen for estrone (HRQ4 vs. Q1 = 1.15; 95% CI, 0.69-1.93; P-trend = 0.54), estradiol (HRQ4 vs. Q1 = 0.98; 95% CI, 0.58-1.64; P-trend > 0.99), or total EM (the sum of all EM; HRQ4 vs. Q1 = 1.35; 95% CI, 0.81-2.24; P-trend = 0.33). Most metabolites in the 2-, 4-, or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol.
   Conclusion: Circulating estrogens and their metabolites were generally unrelated to colorectal cancer risk in postmenopausal women.
   Impact: Additional studies are needed to understand how exogenous estrogen may prevent colorectal cancer. (C) 2015 AACR.
C1 [Falk, Roni T.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Dallal, Cher M.] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA.
   [Lacey, James V.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
   [Bauer, Douglas C.; Tice, Jeffrey A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
   [Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA USA.
   [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
   [Hue, Trisha F.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [LaCroix, Andrea Z.] Univ Calif San Diego, Div Epidemiol, La Jolla, CA 92093 USA.
   [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Xu, Xia] Frederick Natl Lab Canc Res, Leidos Frederick, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD USA.
   [Veenstra, Timothy D.] C2N Diagnost, St Louis, MO USA.
RP Falk, RT (reprint author), NCI, 96096 Med Ctr Dr,Room 7-E224, Bethesda, MD 20892 USA.
EM falkr@mail.nih.gov
RI Cauley, Jane/N-4836-2015
OI Cauley, Jane/0000-0003-0752-4408
FU Merck Research Laboratories; National Cancer Institute [N02-CP]
FX The original FIT study was supported by Merck Research Laboratories. B
   similar to FIT was supported by the National Cancer Institute (contract
   # N02-CP; D.C. Bauer and J.A. Tice).
NR 8
TC 3
Z9 3
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2015
VL 24
IS 9
BP 1419
EP 1422
DI 10.1158/1055-9965.EPI-15-0541
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CU3CK
UT WOS:000363401000018
PM 26104910
ER

PT J
AU Carrick, DM
   Chaturvedi, AK
   Shiels, MS
   Divi, RL
   Filipski, KK
   Hebert, EF
   Verma, M
   Hildesheim, A
AF Carrick, Danielle M.
   Chaturvedi, Anil K.
   Shiels, Meredith S.
   Divi, Rao L.
   Filipski, Kelly K.
   Hebert, Elizabeth F.
   Verma, Mukesh
   Hildesheim, Allan
TI Using Immune Marker Panels to Evaluate the Role of Inflammation in
   Cancer: Summary of an NCI-Sponsored Workshop
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; C-REACTIVE PROTEIN; PREDIAGNOSTIC SERUM-LEVELS;
   LARGE GENE LISTS; OVARIAN-CANCER; CIRCULATING CYTOKINES; PLASMA
   CYTOKINES; SCREENING TRIAL; GASTRIC-CANCER; SOLUBLE CD30
AB Chronic inflammation is recognized to play a role in the development of several cancers. Past investigations of inflammation and cancer have typically been small, used varied assay platforms, and included a narrow range of analytes. Multiplex technologies have now been developed to measure larger numbers of inflammatory markers using small volumes of specimens. This has created an opportunity for systematic, large-scale epidemiologic studies to evaluate the role of inflammation in cancer. However, lack of consensus on the approach to these studies, the technologies/assays to be used, and the most adequate analysis/interpretation of findings have thus far hindered progress. In June 2014, the National Cancer Institute (Bethesda, MD) convened a workshop involving epidemiologists, immunologists, statisticians, and laboratory biologists to share their experiences with new inflammation marker technologies and findings from association studies using such methods and technologies (http://epi.grants.cancer.gov/workshops/). Consensus and gaps in our understanding of the role of chronic inflammation in cancer were identified and recommendations were made to improve future efforts in this area. These recommendations are summarized herein, along with specific suggestions for how they may be implemented. By facilitating discussions among various groups and encouraging interdisciplinary collaborations, we anticipate that the pace of research in this field will be accelerated and duplication of efforts can be minimized. (C) 2015 AACR.
C1 [Carrick, Danielle M.; Divi, Rao L.; Filipski, Kelly K.; Hebert, Elizabeth F.; Verma, Mukesh] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
   [Chaturvedi, Anil K.; Shiels, Meredith S.; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
RP Carrick, DM (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E224, Rockville, MD 20850 USA.
EM Danielle.Carrick@nih.gov
RI Chaturvedi, Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
NR 59
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 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2015
VL 24
IS 9
BP 1427
EP 1433
DI 10.1158/1055-9965.EPI-14-1419
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CU3CK
UT WOS:000363401000020
ER

PT J
AU Wang, TC
   Szabo, E
AF Wang, Timothy C.
   Szabo, Eva
TI Implications of the "Bad Luck" Explanation of Cancer Risk for the Field
   of Cancer Prevention
SO CANCER PREVENTION RESEARCH
LA English
DT Editorial Material
C1 [Wang, Timothy C.] Columbia Univ, Dept Med, Div Digest & Liver Dis, New York, NY 10032 USA.
   [Szabo, Eva] NCI, Div Canc Prevent, Rockville, MD USA.
RP Wang, TC (reprint author), Columbia Univ, Irving Canc Res Ctr 9 925, Div Digest & Liver Dis, Dept Med, 1130 St Nicholas Ave, New York, NY 10032 USA.
EM tcw21@columbia.edu
NR 8
TC 0
Z9 0
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD SEP
PY 2015
VL 8
IS 9
BP 761
EP 761
DI 10.1158/1940-6207.CAPR-15-0264
PG 1
WC Oncology
SC Oncology
GA CU3BL
UT WOS:000363398400001
PM 26174321
ER

PT J
AU Manna, SK
   Golla, S
   Golla, JP
   Tanaka, N
   Cai, Y
   Takahashi, S
   Krausz, KW
   Matsubara, T
   Korboukh, I
   Gonzalez, FJ
AF Manna, Soumen K.
   Golla, Srujana
   Golla, Jaya Prakash
   Tanaka, Naoki
   Cai, Yan
   Takahashi, Shogo
   Krausz, Kristopher W.
   Matsubara, Tsutomu
   Korboukh, Ilia
   Gonzalez, Frank J.
TI St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through
   Suppression of Inflammatory Signaling
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID NF-KAPPA-B; PREGNANE-X-RECEPTOR; TNF-ALPHA; MATRIX METALLOPROTEINASES;
   GENE-EXPRESSION; CANCER; ACTIVATION; PATHWAY; CELLS; AZOXYMETHANE
AB Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-kappa B) and extracellular signal-regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes. (C) 2015 AACR.
C1 [Manna, Soumen K.; Golla, Srujana; Golla, Jaya Prakash; Tanaka, Naoki; Cai, Yan; Takahashi, Shogo; Krausz, Kristopher W.; Matsubara, Tsutomu; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Korboukh, Ilia] Syncon Inc, Atwood, CA USA.
RP Gonzalez, FJ (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Cai, Yan/P-4383-2015
FU National Cancer Institute Intramural Research Program; Office of Dietary
   Supplements Research grant
FX This work was supported by the National Cancer Institute Intramural
   Research Program to F.J. Gonzalez and an Office of Dietary Supplements
   Research grant received by S.K. Manna.
NR 39
TC 0
Z9 0
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD SEP
PY 2015
VL 8
IS 9
BP 786
EP 795
DI 10.1158/1940-6207.CAPR-14-0113
PG 10
WC Oncology
SC Oncology
GA CU3BL
UT WOS:000363398400005
PM 26069204
ER

PT J
AU Yanik, EL
   Katki, HA
   Silverberg, MJ
   Manos, MM
   Engels, EA
   Chaturvedi, AK
AF Yanik, Elizabeth L.
   Katki, Hormuzd A.
   Silverberg, Michael J.
   Manos, M. Michele
   Engels, Eric A.
   Chaturvedi, Anil K.
TI Leukoplakia, Oral Cavity Cancer Risk, and Cancer Survival in the US
   Elderly
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID POTENTIALLY MALIGNANT DISORDERS; FOLLOW-UP; PREMALIGNANT LESIONS;
   TRANSFORMATION; POPULATION; MORTALITY; KERALA; TRIAL; INDIA
AB Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case-cohort study of U.S. adults ages >= 65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer registries. Weighted Cox regression was used to estimate leukoplakia associations with OCC incidence, and the absolute OCC risk following leukoplakia diagnosis was calculated. Among OCC cases, we compared OCC stage and OCC survival between cases with a prior leukoplakia diagnosis versus those without prior leukoplakia. Among 470,266 individuals in the SEER-Medicare subcohort, 1,526 (0.3%) had a leukoplakia diagnosis. Among people with leukoplakia, the cumulative OCC incidence was 0.7% at 3 months and 2.5% at 5 years. OCC risk was most increased <3 months after leukoplakia diagnosis (HR, 115), likely representing the diagnosis of prevalent cancers. Nonetheless, risk remained substantially increased in subsequent follow-up [HR >= 3 months, 24; 95% confidence interval (CI), 22-27; HR >= 12 months, 22, 95% CI, 20-25]. Among OCC cases (N = 8,927), those with prior leukoplakia were less likely to be diagnosed at regional/distant stage (OR, 0.36; 95% CI, 0.30-0.43), and had lower mortality (HR, 0.74; 95% CI, 0.65-0.84) when compared with OCC cases without a prior leukoplakia. Individuals with leukoplakia have substantially elevated risk of OCC. Lower stage and better survival after OCC diagnosis suggest that leukoplakia identification can lead to earlier OCC detection and reduced mortality. (C) 2015 AACR.
C1 [Yanik, Elizabeth L.; Katki, Hormuzd A.; Engels, Eric A.; Chaturvedi, Anil K.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Silverberg, Michael J.; Manos, M. Michele] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
RP Yanik, EL (reprint author), NCI, 9609 Med Ctr Dr,Room 6E-216, Rockville, MD 20850 USA.
EM elizabeth.yanik@nih.gov
RI Chaturvedi, Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
FU National Cancer Institute at the NIH
FX E.L. Yanik, H.A. Katki, E.A. Engels, and A.K. Chaturvedi were supported
   by the Intramural Research Program of the National Cancer Institute at
   the NIH.
NR 28
TC 4
Z9 4
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD SEP
PY 2015
VL 8
IS 9
BP 857
EP 863
DI 10.1158/1940-6207.CAPR-15-0091
PG 7
WC Oncology
SC Oncology
GA CU3BL
UT WOS:000363398400012
PM 26159805
ER

PT J
AU Morgan, TR
   Osann, K
   Bottiglieri, T
   Pimstone, N
   Hoefs, JC
   Hu, KQ
   Hassanein, T
   Boyer, TD
   Kong, L
   Chen, WP
   Richmond, E
   Gonzalez, R
   Rodriguez, LM
   Meyskens, FL
AF Morgan, Timothy R.
   Osann, Kathryn
   Bottiglieri, Teodoro
   Pimstone, Neville
   Hoefs, John C.
   Hu, Ke-Qin
   Hassanein, Tarek
   Boyer, Thomas D.
   Kong, Lorene
   Chen, Wen-Pin
   Richmond, Ellen
   Gonzalez, Rachel
   Rodriguez, Luz M.
   Meyskens, Frank L.
TI A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in
   Reducing Serum alpha-Fetoprotein in Patients with Hepatitis C Cirrhosis
   and Elevated AFP
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID ADENOSYL-L-METHIONINE; RAT-LIVER CARCINOGENESIS; QUALITY-OF-LIFE;
   HEPATOCELLULAR-CARCINOMA; PRENEOPLASTIC LESIONS; PLASMA HOMOCYSTEINE;
   DNA METHYLATION; CLINICAL-TRIAL; RISK-FACTORS; DOUBLE-BLIND
AB In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum alpha-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential. (C) 2015 AACR.
C1 [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Med Healthcare Grp, Long Beach, CA USA.
   [Morgan, Timothy R.; Hu, Ke-Qin] Univ Calif Irvine, Dept Med, Div Gastroenterol, Irvine, CA 92717 USA.
   [Osann, Kathryn] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92717 USA.
   [Bottiglieri, Teodoro] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA.
   [Pimstone, Neville] VA Greater Los Angeles Healthcare Syst, Med Healthcare Grp, Los Angeles, CA USA.
   [Hoefs, John C.; Meyskens, Frank L.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
   [Hassanein, Tarek] Univ Calif San Diego, Dept Med, Div Hepatol, San Diego, CA 92103 USA.
   [Boyer, Thomas D.] Univ Arizona, Liver Res Inst, Tucson, AZ USA.
   [Boyer, Thomas D.] Univ Arizona, Dept Med, Tucson, AZ USA.
   [Kong, Lorene] Univ Calif Irvine, Res Pharm, Irvine, CA USA.
   [Chen, Wen-Pin; Meyskens, Frank L.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA.
   [Richmond, Ellen; Rodriguez, Luz M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Gonzalez, Rachel] VA Long Beach Healthcare Syst, Res Healthcare Grp, Long Beach, CA USA.
   [Rodriguez, Luz M.] Walter Reed Natl Mil Med Ctr, Dept Surg, Bethesda, MD USA.
   [Meyskens, Frank L.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA.
   [Meyskens, Frank L.] Univ Calif Irvine, Dept Publ Hlth, Irvine, CA USA.
   [Meyskens, Frank L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
RP Morgan, TR (reprint author), VA Long Beach Healthcare Syst GI 11, 5901 East Seventh St, Long Beach, CA 90822 USA.
EM timothy.morgan@va.gov
FU NCI [N01-CN-35160]; National Center for Research Resources, NIH;
   National Center for Advancing Translational Sciences, NIH [UL1 TR000153]
FX The study was supported by contract N01-CN-35160 from the NCI to F.L.
   Meyskens. The project described was supported by the National Center for
   Research Resources and the National Center for Advancing Translational
   Sciences, NIH, through Grant UL1 TR000153 to D.M. Cooper.
NR 41
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD SEP
PY 2015
VL 8
IS 9
BP 864
EP 872
DI 10.1158/1940-6207.CAPR-15-0029
PG 9
WC Oncology
SC Oncology
GA CU3BL
UT WOS:000363398400013
PM 26130251
ER

PT J
AU Ferrannini, G
   Hach, T
   Crowe, S
   Sanghvi, A
   Hall, KD
   Ferrannini, E
AF Ferrannini, Giulia
   Hach, Thomas
   Crowe, Susanne
   Sanghvi, Arjun
   Hall, Kevin D.
   Ferrannini, Ele
TI Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition
SO DIABETES CARE
LA English
DT Article
ID INADEQUATE GLYCEMIC CONTROL; TYPE-2 DIABETES-MELLITUS;
   PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RANDOMIZED-TRIAL; WEIGHT-LOSS;
   SGLT2 INHIBITION; BODY-WEIGHT; ADD-ON; DAPAGLIFLOZIN
AB OBJECTIVE
   Sodium-glucose cotransporter 2 (SGLT2) inhibitors cause substantially less weight loss than expected from the energy excreted via glycosuria. Our aim was to analyze this phenomenon quantitatively.
   RESEARCH DESIGN AND METHODS
   Eighty-six patients with type 2 diabetes (HbA(1c) 7.8 +/- 0.8% [62 +/- 9 mmol/mol], estimated glomerular filtration rate [eGFR] 89 +/- 19 mL . min(-1) . 1.73 m(-2)) received empagliflozin (25 mg/day) for 90 weeks with frequent (n = 11) assessments of body weight, eGFR, and fasting plasma glucose (FPG). Time-dependent glucose filtration was calculated as the product of eGFR and FPG; time-dependent glycosuria was estimated from previous direct measurements. The relation of calorie-to-weight changes was estimated using a mathematical model of human energy metabolism that simulates the time course of weight change for a given change in calorie balance and calculates the corresponding energy intake changes.
   RESULTS
   At week 90, weight loss averaged -3.2 +/- 4.2 kg (corresponding to a median calorie deficit of 51 kcal/day [interquartile range (IQR) 112]). However, the observed calorie loss through glycosuria (206 kcal/day [IQR 90]) was predicted to result in a weight loss of -11.3 +/- 3.1 kg, assuming no compensatory changes in energy intake. Thus, patients lost only 29 +/- 41% of the weight loss predicted by their glycosuria; the model indicated that this difference was accounted for by a 13% (IQR 12) increase in calorie intake (269 kcal/day [IQR 258]) coupled with a 2% (IQR 5) increase in daily energy expenditure (due to diet-induced thermogenesis). This increased calorie intake was inversely related to baseline BMI (partial r = -0.34, P < 0.01) and positively to baseline eGFR (partial r = 0.29, P < 0.01).
   CONCLUSIONS
   Chronic glycosuria elicits an adaptive increase in energy intake. Combining SGLT2 inhibition with caloric restriction is expected to be associated with major weight loss.
C1 [Ferrannini, Giulia] San Lazzaro Hosp, Gen Med, Alba, Italy.
   [Hach, Thomas; Crowe, Susanne] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
   [Sanghvi, Arjun; Hall, Kevin D.] NIDDKD, NIH, Bethesda, MD USA.
   [Ferrannini, Ele] CNR Inst Clin Physiol, Pisa, Italy.
RP Ferrannini, E (reprint author), CNR Inst Clin Physiol, Pisa, Italy.
EM ferranni@ifc.cnr.it
FU Italian Ministry of Education, University and Research [MIUR
   2010329EKE]; National Institutes of Health, National Institute of
   Diabetes and Digestive and Kidney Diseases
FX This work was supported by a grant from the Italian Ministry of
   Education, University and Research (MIUR 2010329EKE). A.S. and K.D.H.
   were supported by the Intramural Research Program of the National
   Institutes of Health, National Institute of Diabetes and Digestive and
   Kidney Diseases.
NR 40
TC 36
Z9 37
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2015
VL 38
IS 9
BP 1730
EP 1735
DI 10.2337/dc15-0355
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CU3HZ
UT WOS:000363416500029
PM 26180105
ER

PT J
AU Zhang, HH
   Takeda, H
   Tsuji, T
   Kamiya, N
   Rajderkar, S
   Louie, K
   Collier, C
   Scott, G
   Ray, M
   Mochida, Y
   Kaartinen, V
   Kunieda, T
   Mishina, Y
AF Zhang, Honghao
   Takeda, Haruko
   Tsuji, Takehito
   Kamiya, Nobuhiro
   Rajderkar, Sudha
   Louie, Ke'Ale
   Collier, Crystal
   Scott, Greg
   Ray, Manas
   Mochida, Yoshiyuki
   Kaartinen, Vesa
   Kunieda, Tetsuo
   Mishina, Yuji
TI Generation of Evc2/Limbin Global and Conditional KO Mice and Its Roles
   during Mineralized Tissue Formation
SO GENESIS
LA English
DT Article
DE Evc2; Limbin; mouse; primary cilium
ID VAN-CREVELD-SYNDROME; WEYERS ACRODENTAL DYSOSTOSIS; HEDGEHOG SIGNAL;
   PRIMARY CILIA; GROWTH-PLATE; EVC; MUTATIONS; COMPLEX; MOUSE; CELLS
AB Ellis-van Creveld (EvC) syndrome (OMIM 225500) is an autosomal recessive disease characterized with chondrodysplastic dwarfism in association with abnormalities in oral cavity. Ciliary proteins EVC and EVC2 have been identified as causative genes and they play an important role on Hedgehog signal transduction. We have also identified a causative gene LIMBIN for bovine chondrodysplastic dwarfism (bcd) that is later identified as the bovine ortholog of EVC2. Here, we report generation of conventional and conditional mutant Evc2/Limbin alleles that mimics mutations found in EvC patients and bcd cattle. Resulted homozygous mice showed no ciliary localization of EVC2 and EVC and displayed reduced Hedgehog signaling activity in association with skeletal and oral defects similar to the EvC patients. Cartilage-specific disruption of Evc2/Limbin resulted in similar but milder skeletal defects, whereas osteoblast-specific disruption did not cause overt changes in skeletal system. Neural crest-specific disruption of Evc2/Limbin resulted in defective incisor growth similar to that seen in conventional knockouts; however, differentiation of amelobolasts was relatively normal in the conditional knockouts. These results showcased functions of EVC2/LIMBIN during formation of mineralized tissues. Availability of the conditional allele for this gene should facilitate further detailed analyses of the role of EVC2/LIMBIN in pathogenesis of EvC syndrome. (C) 2015 Wiley Periodicals, Inc.
C1 [Zhang, Honghao; Kamiya, Nobuhiro; Rajderkar, Sudha; Louie, Ke'Ale; Kaartinen, Vesa; Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
   [Takeda, Haruko; Kamiya, Nobuhiro; Mishina, Yuji] NIEHS, Reprod & Dev Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   [Takeda, Haruko] Univ Liege, GIGA R, Unit Anim Genom, Liege, Belgium.
   [Takeda, Haruko] Univ Liege, Fac Vet Med, Liege, Belgium.
   [Tsuji, Takehito; Kunieda, Tetsuo] Okayama Univ, Grad Sch Environm & Life Sci, Okayama, Japan.
   [Kamiya, Nobuhiro] Tenri Univ, Fac Budo & Sport Studies, Nara, Japan.
   [Collier, Crystal] Univ Michigan, Coll Literature Sci & Arts, Ann Arbor, MI 48109 USA.
   [Scott, Greg; Ray, Manas; Mishina, Yuji] NIEHS, Knock Out Core, NIH, Res Triangle Pk, NC 27709 USA.
   [Mochida, Yoshiyuki] Boston Univ, Henry M Goldman Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02215 USA.
RP Takeda, H (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 N Univ Ave, Ann Arbor, MI 48109 USA.
EM mishina@umich.edu
FU NIH [R01DE020843, ES071003-11, R01DE013085, R01DE019527]; NIH/NCRR
   [S10RR026475]
FX We thank Dr. Kenichi Yamamura for providing P0-Cre mice. We also thank
   Drs. Susan Mackem, Andrew McMahon, Susan Dymecki, Michelle Tallquist,
   Alex Joyner, and Phillipe Soriano for genetically modified mouse lines.
   We would like to express our appreciation to Tony Ward and Xixi Wang for
   technical assistance, Drs. Scott Barolo, Charlotte Mistretta, Noriaki
   Ono for helpful discussions. YMi is supported by NIH (R01DE020843 and
   ES071003-11), VK is supported by NIH (R01DE013085) and YMo is supported
   by NIH (R01DE019527). The mu CT core at the School of Dentistry,
   University of Michigan is funded in part by NIH/NCRR S10RR026475.
NR 32
TC 4
Z9 4
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1526-954X
EI 1526-968X
J9 GENESIS
JI Genesis
PD SEP
PY 2015
VL 53
IS 9
BP 612
EP 626
DI 10.1002/dvg.22879
PG 15
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA CT8HB
UT WOS:000363054600004
ER

PT J
AU Koshiol, J
   Gao, Y
   Fox, JG
   Ljungh
   Rashid, A
   Hildesheim, A
   Hsing, AW
AF Koshiol, J.
   Gao, Y.
   Fox, J. G.
   Ljungh
   Rashid, A.
   Hildesheim, A.
   Hsing, A. W.
TI CHALLENGES IN THE EVALUATION OF HELICOBACTER SPECIES AND BILIARY TRACT
   CANCER
SO HELICOBACTER
LA English
DT Meeting Abstract
CT European-Helicobacter-Study-Group 28th International Workshop on
   Helicobacter and Microbiota in Inflammation and Cancer
CY SEP 24-26, 2015
CL Nicosia, CYPRUS
SP European Helicobacter Study Grp
C1 [Koshiol, J.; Hildesheim, A.; Hsing, A. W.] NCI, Rockville, MD USA.
   [Gao, Y.] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
   [Fox, J. G.] MIT, Dept Biol Engn, Div Comparat Med, Cambridge, MA 02139 USA.
   [Ljungh] Lund Univ, Div Med Microbiol, Lund, Sweden.
   [Rashid, A.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   Canc Prevent Inst Calif, Fremont, CA USA.
   [Hsing, A. W.] Stanford Canc Inst, Palo Alto, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1083-4389
EI 1523-5378
J9 HELICOBACTER
JI Helicobacter
PD SEP
PY 2015
VL 20
SU 1
SI SI
MA W6.6
BP 85
EP 85
PG 1
WC Gastroenterology & Hepatology; Microbiology
SC Gastroenterology & Hepatology; Microbiology
GA CT8KE
UT WOS:000363064400048
ER

PT J
AU Lee, K
   Carter, A
   Jeffers, M
   Cameron, H
   Corbett, D
   Lagace, D
AF Lee, K.
   Carter, A.
   Jeffers, M.
   Cameron, H.
   Corbett, D.
   Lagace, D.
TI Determining the requirement of progenitor cells in stroke recovery
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Meeting Abstract
C1 [Lee, K.; Carter, A.; Jeffers, M.; Corbett, D.; Lagace, D.] Univ Ottawa, Ottawa, ON, Canada.
   [Cameron, H.] NIH, Bethesda, MD 20892 USA.
   [Corbett, D.] Canadian Partnership Stroke Recovery, Ottawa, ON, Canada.
RI Jeffers, Matthew/F-6277-2014
OI Jeffers, Matthew/0000-0002-4148-2638
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD SEP
PY 2015
VL 10
SU 4
SI SI
MA HP1.3
BP 21
EP 21
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CU2DZ
UT WOS:000363334400057
ER

PT J
AU Baker, SG
AF Baker, Stuart G.
TI RE: Leveraging Biospecimen Resources for Discovery or Validation of
   Markers for Early Cancer Detection
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID EARLY INTERVENTION
C1 [Baker, Stuart G.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, 9609 Med Ctr Dr 5E638,MSC 9789, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
NR 6
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 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD SEP
PY 2015
VL 107
IS 9
AR djv215
DI 10.1093/jnci/djv215
PG 1
WC Oncology
SC Oncology
GA CU0KA
UT WOS:000363203800007
ER

PT J
AU Davidoff, AJ
   Hill, SC
   Bernard, D
   Yabroff, KR
AF Davidoff, Amy J.
   Hill, Steven C.
   Bernard, Didem
   Yabroff, K. Robin
TI The Affordable Care Act and Expanded Insurance Eligibility Among
   Nonelderly Adult Cancer Survivors
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HEALTH-CARE; PATIENT PROTECTION; ACCESS; POLICY; INFORMATION;
   DISPARITIES; LEGISLATION; REFORM; IMPACT
AB Background: Cancer survivors may face barriers to accessing health insurance and experience financial hardship because of medical expenditures. We examined potential improvements in access to insurance for cancer survivors through adult Medicaid expansions and premium tax credits in the new insurance marketplaces under the Affordable Care Act (ACA).
   Methods: Eligibility for Medicaid and premium tax credits was simulated for cancer survivors age 18 to 64 years in the 2008 to 2010 Medical Expenditure Panel Survey using a detailed deterministic model. Financial hardship was determined as: 1) delays or unmet need for medical, prescription, or dental care because of cost or insurance issues and/or 2) family out-of-pocket medical spending that was 20% or more of gross income. Descriptive analyses were stratified by whether the state of residence chose to expand Medicaid by January 2015. All statistical tests were two-sided.
   Results: Overall, 14.7% of 9.44 million cancer survivors were uninsured, with 18% reporting financial hardship. Under the ACA, 19% overall, 30% of the uninsured, and 39% of those reporting financial hardship would be Medicaid eligible. An additional 10% would be eligible for premium tax credits, with the remainder able to participate in the Marketplace without tax credits. However, 21% of uninsured cancer survivors in states not expanding Medicaid would be ineligible for assistance with coverage.
   Conclusions: Under the ACA, many of the uninsured and a larger proportion of survivors facing financial hardship will be eligible for Medicaid or premium tax credits in the Marketplaces. ACA implementation will dramatically enhance insurance availability and is likely to reduce financial hardship for vulnerable cancer survivors.
C1 [Davidoff, Amy J.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
   [Hill, Steven C.; Bernard, Didem] Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Rockville, MD USA.
   [Yabroff, K. Robin] Natl Canc Inst, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Bethesda, MD USA.
RP Davidoff, AJ (reprint author), Yale Univ, Sch Publ Hlth, POB 208034,60 Coll St, New Haven, CT 06520 USA.
EM amy.davidoff@yale.edu
NR 36
TC 6
Z9 6
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD SEP
PY 2015
VL 107
IS 9
AR djv181
DI 10.1093/jnci/djv181
PG 8
WC Oncology
SC Oncology
GA CU0KA
UT WOS:000363203800011
ER

PT J
AU Gottesman, MM
   Pastan, IH
AF Gottesman, Michael M.
   Pastan, Ira H.
TI The Role of Multidrug Resistance Efflux Pumps in Cancer: Revisiting a
   JNCI Publication Exploring Expression of the MDR1 (P-glycoprotein) Gene
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID DRUG-RESISTANCE; CELL-LINES; OVARIAN-CANCER; BREAST-CANCER; LUNG-CANCER;
   TRANSPORTER; SENSITIVITY; DOXORUBICIN; CARCINOMAS; RELEVANCE
C1 [Gottesman, Michael M.] NCI, NIH, Ctr Canc Res, Cell Biol Lab, Bethesda, MD 20892 USA.
   [Pastan, Ira H.] NCI, NIH, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, NIH, Ctr Canc Res, Cell Biol Lab, 37 Convent Dr, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
NR 27
TC 2
Z9 2
U1 2
U2 19
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD SEP
PY 2015
VL 107
IS 9
AR djv222
DI 10.1093/jnci/djv222
PG 3
WC Oncology
SC Oncology
GA CU0KA
UT WOS:000363203800015
ER

PT J
AU Rosenberg, PS
   Barker, KA
   Anderson, WF
AF Rosenberg, Philip S.
   Barker, Kimberly A.
   Anderson, William F.
TI Estrogen Receptor Status and the Future Burden of Invasive and In Situ
   Breast Cancers in the United States
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID PERIOD-COHORT ANALYSIS; SCREENING MAMMOGRAPHY; RISK-FACTORS; ASSOCIATION
   CONSORTIUM; INCIDENCE RATES; TUMOR SUBTYPES; TRENDS; WOMEN; MORTALITY;
   MRI
AB Background: No study has predicted the future incidence rate and annual burden (number) of new cases in the United States of invasive and in situ female breast cancers stratified by the estrogen receptor (ER) status.
   Methods: We constructed forecasts for women age 30 to 84 years in 2011 through 2030 using cancer incidence data from the Surveillance, Epidemiology, and End Results Program, novel age-period-cohort forecasting models, and population projections from the US Census Bureau.
   Results: The total number of new tumors (invasive plus in situ) is expected to rise from 283 000 in 2011 to 441 000 in 2030 (plausible range 353 500 to 466 700 cases). The proportion of all new case patients age 70 to 84 years is expected to increase from 24.3% to 34.8%, while the proportion ages 50 to 69 years is expected to decrease from 54.7% to 43.6%. The proportion of ER-positive invasive cancers is expected to remain nearly the same at 62.6%, whereas the proportion of ER-positive in situ cancers is expected to increase from 19.1% to 28.9%. The proportion of ER-negative cancers (invasive and in situ) is expected to decrease from 16.8% to 8.6%.
   Conclusions: Breast cancer overall will rise in the United States through 2030, especially for ER-positive in situ tumors among women age 70 to 84 years. In contrast, ER-negative invasive and in situ tumors will fall, for reasons that are not fully understood. These results highlight a need to optimize case management among older women, characterize the natural history of in situ cancers, and identify those factors responsible for declining ER-negative incidence.
C1 [Rosenberg, Philip S.; Barker, Kimberly A.; Anderson, William F.] NCI, Biostat Branch,Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E-130 MSC 9780, Bethesda, MD 20892 USA.
EM rosenbep@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
   National Cancer Institute (NCI), Division of Cancer Epidemiology and
   Genetics
FX This research was supported entirely by the Intramural Research Program
   of the National Institutes of Health, National Cancer Institute (NCI),
   Division of Cancer Epidemiology and Genetics.
NR 40
TC 4
Z9 4
U1 2
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD SEP
PY 2015
VL 107
IS 9
AR djv159
DI 10.1093/jnci/djv159
PG 7
WC Oncology
SC Oncology
GA CU0KA
UT WOS:000363203800029
ER

PT J
AU Weinfurt, KP
   Lin, L
   Bruner, DW
   Cyranowski, JM
   Dombec, CB
   Hahn, EA
   Jeffery, DD
   Luecht, RM
   Magasi, S
   Porter, LS
   Reese, JB
   Reeve, BB
   Shelby, RA
   Smith, AW
   Willse, JT
   Flynn, KE
AF Weinfurt, Kevin P.
   Lin, Li
   Bruner, Deborah Watkins
   Cyranowski, Jill M.
   Dombec, Carrie B.
   Hahn, Elizabeth A.
   Jeffery, Diana D.
   Luecht, Richard M.
   Magasi, Susan
   Porter, Laura S.
   Reese, Jennifer Barsky
   Reeve, Bryce B.
   Shelby, Rebecca A.
   Smith, Ashley Wilder
   Willse, John T.
   Flynn, Kathryn E.
TI Development and Initial Validation of the PROMIS (R) Sexual Function and
   Satisfaction Measures Version 2.0
SO JOURNAL OF SEXUAL MEDICINE
LA English
DT Article
DE Patient-Reported Outcome Measures; Sexual Function; Quality of Life
ID INFORMATION-SYSTEM PROMIS; ITEM RESPONSE THEORY; CANCER; INDEX
AB Introduction. The Patient-Reported Outcomes Measurement Information System (PROMIS)(R) Sexual Function and Satisfaction measure (SexFS) version 1.0 was developed with cancer populations. There is a need to expand the SexFS and provide evidence of its validity in diverse populations.
   Aim. The aim of this study was to describe the development of the SexFS v2.0 and present preliminary evidence for its validity.
   Methods. Development built on version 1.0, plus additional review of extant items, discussions with 15 clinical experts, 11 patient focus groups (including individuals with diabetes, heart disease, anxiety, depression, and/or are lesbian, gay, bisexual, or aged 65 or older), 48 cognitive interviews, and psychometric evaluation in a random sample of U.S. adults plus an oversample for specific sexual problems (2281 men, 1686 women). We examined differential item functioning (DIF) by gender and sexual activity. We examined convergent and known-groups validity.
   Results. The final set of domains includes 11 scored scales (interest in sexual activity, lubrication, vaginal discomfort, clitoral discomfort, labial discomfort, erectile function, orgasm ability, orgasm pleasure, oral dryness, oral discomfort, satisfaction), and six nonscored item pools (screeners, sexual activities, anal discomfort, therapeutic aids, factors interfering with sexual satisfaction, bother). Domains from version 1.0 were reevaluated and improved. Domains considered applicable across gender and sexual activity status, namely interest, orgasm, and satisfaction, were found to have significant DIF. We identified subsets of items in each domain that provided consistent measurement across these important respondent groups. Convergent and known-groups validity was supported.
   Conclusions. The SexFS version 2.0 has several improvements and enhancements over version 1.0 and other extant measures, including expanded evidence for validity, scores centered around norms for sexually active U.S. adults, new domains, and a final set of items applicable for both men and women and those sexually active with a partner and without. The SexFS is customizable, allowing users to select relevant domains and items for their study.
C1 [Weinfurt, Kevin P.; Lin, Li; Dombec, Carrie B.] Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC 27708 USA.
   [Weinfurt, Kevin P.; Shelby, Rebecca A.] Duke Univ, Dept Psychiat & Behav Sci, Sch Med, Durham, NC USA.
   [Bruner, Deborah Watkins] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA.
   [Cyranowski, Jill M.] Univ Pittsburgh, Dept Psychiat & Psychol, Med Ctr, Pittsburgh, PA USA.
   [Hahn, Elizabeth A.] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Hahn, Elizabeth A.] Northwestern Univ, Ctr Patient Centered Outcomes, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Jeffery, Diana D.; Willse, John T.] TRICARE Management Act, Dept Defense Hlth Affairs, Falls Church, VA USA.
   [Luecht, Richard M.] Univ North Carolina Greensboro, Dept Educ Res Methodol, Sch Educ, Chicago, IL USA.
   [Magasi, Susan] Univ Illinois, Dept Occupat Therapy, Chicago, IL USA.
   [Reese, Jennifer Barsky] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
   [Reeve, Bryce B.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
   [Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Flynn, Kathryn E.] Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, Milwaukee, WI 53226 USA.
RP Weinfurt, KP (reprint author), Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC 27708 USA.
NR 24
TC 5
Z9 5
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-6095
EI 1743-6109
J9 J SEX MED
JI J. Sex. Med.
PD SEP
PY 2015
VL 12
IS 9
BP 1961
EP 1974
DI 10.1111/jsm.12966
PG 14
WC Urology & Nephrology
SC Urology & Nephrology
GA CU3WJ
UT WOS:000363456400015
PM 26346418
ER

PT J
AU Selvaraj, P
   Huang, JSW
   Chen, A
   Skalka, N
   Rosin-Arbesfeld, R
   Loh, YP
AF Selvaraj, Prabhuanand
   Huang, Jane S. W.
   Chen, Alexander
   Skalka, Nir
   Rosin-Arbesfeld, Rina
   Loh, Y. Peng
TI Neurotrophic factor-alpha 1 modulates NGF-induced neurite outgrowth
   through interaction with Wnt-3a and Wnt-5a in PC12 cells and cortical
   neurons
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Carboxypeptidase E; Neurite retraction; PC12 cells; Wnt-3a; Wnt-5a; NGF
ID NERVE GROWTH-FACTOR; ADENOMATOUS POLYPOSIS-COLI; BETA-CATENIN
   DEGRADATION; RHO-ASSOCIATED KINASE; CARBOXYPEPTIDASE-E; SIGNALING
   PATHWAY; AXON GROWTH; SPINAL-CORD; PROTEIN; RECEPTOR
AB Wnt-3a and Wnt-5a signaling activities inhibit and promote neurite outgrowth, respectively, to regulate dendritic and axonal genesis during neurodevelopment. NF-alpha 1, a neurotrophic factor, has been shown to modulate dendritic remodeling and negatively regulate the canonical Wnt-3a pathway. Here, we investigated whether NF-al could modify nerve growth factor (NGF)-induced neurite outgrowth through interaction with Wnt-3a and Wnt-5a in PC12 cells and mouse primary cortical neurons. We showed that NGF-induced neurite outgrowth was inhibited by Wnt-3a, and this inhibition was prevented by NF-alpha 1. Western blot analysis revealed that NF-alpha 1 reduced the expression of both beta-catenin in the canonical Wnt-3a pathway and Rho, a downstream effector of Wnt-3a's non-canonical signaling pathway. Treatment of PC12 cells with a ROCK inhibitor prevented the inhibition of NGF-induced neurite outgrowth by Wnt-3a, suggesting that NF-alpha 1 promotes neurite outgrowth in the presence of Wnt-3a by down-regulating its canonical and non-canonical activities. Interestingly, treatment of PC12 cells with Wnt-5a, which formed a complex with NF-alpha 1, induced neurite outgrowth that was enhanced by treatment with the combination of Wnt-5a, NGF, and NF-alpha 1. These effects of NF-alpha 1 on Wnt 3a's and Wnt 5a's regulation of neurite outgrowth in PC12 cells were also demonstrated in primary cultures of mouse cortical neurons. In addition, we showed in PC12 cells that NF-alpha 1 acts by upregulating adenomatous polyposis coli (APC) accumulation at neurite tips, thereby providing positive and negative Wnt-3a/Wnt-5a mediated cues to modulate neurite outgrowth, a process important during neurodevelopment Published by Elsevier Inc.
C1 [Selvaraj, Prabhuanand; Huang, Jane S. W.; Chen, Alexander; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD USA.
   [Skalka, Nir; Rosin-Arbesfeld, Rina] Tel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, IL-69978 Tel Aviv, Israel.
RP Loh, YP (reprint author), NIH, 49 Convent Dr,Bldg 49,Room 6C10, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
   Institute of Child Health and Human Development (NICHD); National
   Institutes of Health, USA; Israel Science Foundation [829/14]; Israel
   Cancer Research Fund (ICRF) [PG-13-3025]
FX This research was supported by the Intramural Research Program of the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD), National Institutes of Health, USA, and in part by
   the Israel Science Foundation grant 829/14 to RRA and the Israel Cancer
   Research Fund (ICRF) grant PG-13-3025 to RRA and YPL. We would like to
   thank Dr. Niamh Cawley for his critical reading of this manuscript and
   Lynn Holtzclaw and Dr. Vincent Schram (NICHD Microscopy Core Facility)
   for their assistance.
NR 57
TC 2
Z9 2
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1044-7431
EI 1095-9327
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD SEP
PY 2015
VL 68
BP 222
EP 233
DI 10.1016/j.mcn.2015.08.005
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA CU2MO
UT WOS:000363357800021
PM 26276171
ER

PT J
AU Yin, X
   Ren, M
   Jiang, HZ
   Cui, SJ
   Wang, SY
   Jiang, HQ
   Qi, Y
   Wang, J
   Wang, XD
   Dong, GT
   Leeds, P
   Chuang, DM
   Feng, HL
AF Yin, Xiang
   Ren, Ming
   Jiang, Haizhi
   Cui, Shangjin
   Wang, Shuyu
   Jiang, Hongquan
   Qi, Yan
   Wang, Jing
   Wang, Xudong
   Dong, Guangtao
   Leeds, Peter
   Chuang, De-Maw
   Feng, Honglin
TI Downregulated AEG-1 together with inhibited PI3K/Akt pathway is
   associated with reduced viability of motor neurons in an ALS model
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Amyotrophic lateral sclerosis (ALS); Astrocyte elevated gene-1 (AEG-1);
   CREB; PI3K/Akt pathway
ID AMYOTROPHIC-LATERAL-SCLEROSIS; ASTROCYTE-ELEVATED GENE-1;
   GLYCOGEN-SYNTHASE KINASE-3-BETA; CELL LUNG-CANCER; SPINAL-CORD;
   PHOSPHATIDYLINOSITOL 3-KINASE; MOUSE MODEL; PROLONGS SURVIVAL;
   EXPRESSION; GROWTH
AB Astrocyte elevated gene-1 (AEG-1) has been reported to regulate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and is also regulated by it. This study investigated how AEG-1 participates in the survival pathway of motor neurons in amyotrophic lateral sclerosis (ALS). We found reduced levels of AEG-1 in ALS motor neurons, both in vivo and in vitro, compared to wild type controls. Moreover, AEG-1 silencing demonstrated inhibition of the PI3K/Akt pathway and increased cell apoptosis. Additionally, the PI3K/Akt pathway in mSOD1 cells was unresponsive under serum deprivation conditions compared to wtSOD1 cells. These results suggest that AEG-1 deficiency, together with the inhibited PI3K/Akt pathway was associated with decreased viability of ALS motor neurons. However, the mRNA levels of AEG-1 were still lower in mSOD1 cells compared to the control groups, though the signaling pathway was activated by application of a PI3-K activator. This suggests that in ALS motor neurons, some unknown interruption exists in the PI3K/Akt/CREB/AEG-1 feedback loop, thus attenuating the protection by this signaling pathway. Together, these findings support that AEG-1 is a critical factor for cell survival, and the disrupted PI3K/Akt/CREB/AEG-1 cycle is involved in the death of injured motor neurons and pathogenesis of ALS. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Yin, Xiang; Jiang, Haizhi; Wang, Shuyu; Jiang, Hongquan; Qi, Yan; Wang, Jing; Wang, Xudong; Dong, Guangtao; Feng, Honglin] Harbin Med Univ, Dept Neurol, Clin Coll 1, Harbin 150001, Heilongjiang Pr, Peoples R China.
   [Ren, Ming] Waifang Med Univ, Affiliated Hosp, Dept Neurol, Waifang 261000, Shandong, Peoples R China.
   [Cui, Shangjin] Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Div Swine Infect Dis, Harbin 150001, Peoples R China.
   [Leeds, Peter; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Feng, HL (reprint author), Harbin Med Univ, Dept Neurol, Clin Coll 1, Harbin 150001, Heilongjiang Pr, Peoples R China.
EM fenghonglin1120@sina.com
FU Natural Science Foundation of China [81171186]; Major Program of Natural
   Science Foundation of Heilongjiang Province of China [ZD201417]; Health
   Department Project of Heilongjiang Province [2013017]; Intramural
   Research Program of the National Institute of Mental Health National
   Institutes of Health (IRP-NIMH-NIH) of the USA
FX This research was supported in part by the grants from the Natural
   Science Foundation of China (No. 81171186), the Major Program of Natural
   Science Foundation of Heilongjiang Province of China (No. ZD201417), and
   the Health Department Project of Heilongjiang Province (No. 2013017).
   The research was also supported in part by the Intramural Research
   Program of the National Institute of Mental Health National Institutes
   of Health (IRP-NIMH-NIH) of the USA. The authors thank Harbin Veterinary
   Research Institute (CAAS, China) for assistance in the genotyping and
   breeding of the ALS transgenic mice. We also thank Dr. Neil Cashman of
   University of British Columbia, Canada for providing the NSC34 cells. In
   addition, we wish to thank Shengwang Liu of the Division of Avian
   Infectious Diseases, National Key Laboratory of Veterinary
   Biotechnology, Harbin Veterinary Research Institute (CAAS) for
   assistance with our work, and loline Henter of the NIMH-NIH for
   excellent editorial assistance.
NR 49
TC 2
Z9 3
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1044-7431
EI 1095-9327
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD SEP
PY 2015
VL 68
BP 303
EP 313
DI 10.1016/j.mcn.2015.08.009
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CU2MO
UT WOS:000363357800028
PM 26320681
ER

PT J
AU Rouleau, C
   Gianolio, DA
   Smale, R
   Roth, SD
   Krumbholz, R
   Harper, J
   Munroe, KJ
   Green, TL
   Horten, BC
   Schmid, SM
   Teicher, BA
AF Rouleau, Cecile
   Gianolio, Diego A.
   Smale, Robert
   Roth, Stephanie D.
   Krumbholz, Roy
   Harper, Jay
   Munroe, Kenneth J.
   Green, Tessa L.
   Horten, Bruce C.
   Schmid, Steven M.
   Teicher, Beverly A.
TI Anti-Endosialin Antibody-Drug Conjugate: Potential in Sarcoma and Other
   Malignancies
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID MARKER CD248 ENDOSIALIN; MONOCLONAL-ANTIBODIES; CELL MARKER; THERAPEUTIC
   TARGET; ANTICANCER DRUGS; SOLID TUMORS; CANCER; PROTEINS;
   IMMUNOCONJUGATE; TEM1/ENDOSIALIN
AB Endosialin/TEM1/CD248 is a cell surface protein expressed at high levels by the malignant cells of about 50% of sarcomas and neuroblastomas. The antibody-drug conjugate (ADC) anti-endosialin-MC-VC-PABC-MMAE was selectively cytotoxic to endosialin-positive cells in vitro and achieved profound and durable antitumor efficacy in preclinical human tumor xenograft models of endosialin-positive disease. MC-VC-PABC-MMAE was conjugated with anti-endosialin with 3-4 MMAE molecules per ADC. The anti-endosialin-MC-VC-PABC-MMAE conjugate was tested for activity in four human cell lines with varied endosialin levels. The HT-1080 fibrosarcoma cells do not express endosialin, A-673 Ewing sarcoma cells and SK-N-AS neuroblastoma cells are moderate expressers of endosialin, and SJSA-1 osteosarcoma cells express very high levels of endosialin. To determine whether endosialin expression was maintained in vivo, A-673 Ewing sarcoma, SK-N-AS neuroblastoma, and SJSA-1 osteosarcoma cells were grown as xenograft tumors in nude mice. The SK-N-AS neuroblastoma and the A-673 Ewing sarcoma lines were selected for in vivo efficacy testing of the anti-endosialin-MC-VCPABC-MMAE conjugate. The treatment groups included a vehicle control, unconjugated anti-endosialin, an admix control consisting of anti-endosialin and a dose of free MMAE equivalent to the dose administered as the ADC, and the antiendosialin-MC-VC-PABC-MMAE conjugate. The unconjugated anti-endosialin had no antitumor activity and resulted in similar tumor growth as the vehicle control. The admix control produced a modest tumor growth delay. Administration of the anti-endosialin-MC-VC-PABC-MMAE conjugate resulted in a marked prolonged tumor response of both xenograts. These proof-of-concept results break new ground and open a promising drug discovery approach to these rare and neglected tumors. (C) 2015 AACR.
C1 [Rouleau, Cecile; Gianolio, Diego A.; Smale, Robert; Roth, Stephanie D.; Krumbholz, Roy; Harper, Jay; Munroe, Kenneth J.; Green, Tessa L.; Horten, Bruce C.; Schmid, Steven M.; Teicher, Beverly A.] Genzyme Corp, Framingham, MA 01701 USA.
RP Teicher, BA (reprint author), NCI, RM 4-W062,MSC9735,9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM teicherba@mail.nih.gov
NR 46
TC 7
Z9 7
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD SEP
PY 2015
VL 14
IS 9
BP 2081
EP 2089
DI 10.1158/1535-7163.MCT-15-0312
PG 9
WC Oncology
SC Oncology
GA CU3DN
UT WOS:000363404200011
PM 26184481
ER

PT J
AU Lawrenson, K
   Li, Q
   Kar, S
   Seo, JH
   Tyrer, J
   Spindler, TJ
   Lee, J
   Chen, Y
   Karst, A
   Drapkin, R
   Aben, KKH
   Anton-Culver, H
   Antonenkova, N
   Baker, H
   Bandera, EV
   Bean, Y
   Beckmann, MW
   Berchuck, A
   Bisogna, M
   Bjorge, L
   Bogdanova, N
   Brinton, LA
   Brooks-Wilson, A
   Bruinsma, F
   Butzow, R
   Campbell, IG
   Carty, K
   Chang-Claude, J
   Chenevix-Trench, G
   Chen, A
   Chen, Z
   Cook, LS
   Cramer, DW
   Cunningham, JM
   Cybulski, C
   Dansonka-Mieszkowska, A
   Dennis, J
   Dicks, E
   Doherty, JA
   Doerk, T
   Du Bois, A
   Duerst, M
   Eccles, D
   Easton, DT
   Edwards, RP
   Eilber, U
   Ekici, AB
   Fasching, PA
   Fridley, BL
   Gao, YT
   Gentry-Maharaj, A
   Giles, GG
   Glasspool, R
   Goode, EL
   Goodman, MT
   Grownwald, J
   Harrington, P
   Harter, P
   Hasmad, HN
   Hein, A
   Heitz, F
   Hildebrandt, MAT
   Hillemanns, P
   Hogdall, E
   Hogdall, C
   Hosono, S
   Iversen, ES
   Jakubowska, A
   James, P
   Jensen, A
   Ji, BT
   Karlan, BY
   Kjaer, SK
   Kelemen, LE
   Kellar, M
   Kelley, JL
   Kiemeney, LA
   Krakstad, C
   Kupryjanczyk, J
   Lambrechts, D
   Lambrechts, S
   Le, ND
   Lee, AW
   Lele, S
   Leminen, A
   Lester, J
   Levine, DA
   Liang, D
   Lissowska, J
   Lu, K
   Lubinski, J
   Lundvall, L
   Massuger, LFAG
   Matsuo, K
   McGuire, V
   McLaughlin, JR
   Nevanlinna, H
   McNeish, I
   Menon, U
   Modugno, F
   Moysich, KB
   Narod, SA
   Nedergaard, L
   Ness, RB
   Azmi, MAN
   Odunsi, K
   Olson, SH
   Orlow, I
   Orsulic, S
   Weber, RP
   Pearce, CL
   Pejovic, T
   Pelttari, LM
   Permuth-Wey, J
   Phelan, CM
   Pike, MC
   Poole, EM
   Ramus, SJ
   Risch, HA
   Rosen, B
   Rossing, MA
   Rothstein, JH
   Rudolph, A
   Runnebaum, IB
   Rzepecka, IK
   Salvesen, HB
   Schildkraut, JM
   Schwaab, I
   Sellers, TA
   Shu, XO
   Shvetsov, YB
   Siddiqui, N
   Sieh, W
   Song, H
   Southey, MC
   Sucheston, L
   Tangen, IL
   Teo, SH
   Terry, KL
   Thompson, PJ
   Timorek, A
   Tsai, YY
   Tworoger, SS
   Van Altena, AM
   Van Nieuwenhuysen, E
   Vergote, I
   Vierkant, RA
   Wang-Gohrke, S
   Walsh, C
   Wentzensen, N
   Whittemore, AS
   Wicklund, KG
   Wilkens, LR
   Woo, YL
   Wu, X
   Wu, AH
   Yang, H
   Zheng, W
   Ziogas, A
   Monteiro, A
   Pharoah, PD
   Gayther, SA
   Freedman, ML
   Grp, AOCS
   Bowtell, D
   Webb, PM
   Defazio, A
AF Lawrenson, Kate
   Li, Qiyan
   Kar, Siddhartha
   Seo, Ji-Heui
   Tyrer, Jonathan
   Spindler, Tassja J.
   Lee, Janet
   Chen, Yibu
   Karst, Alison
   Drapkin, Ronny
   Aben, Katja K. H.
   Anton-Culver, Hoda
   Antonenkova, Natalia
   Baker, Helen
   Bandera, Elisa V.
   Bean, Yukie
   Beckmann, Matthias W.
   Berchuck, Andrew
   Bisogna, Maria
   Bjorge, Line
   Bogdanova, Natalia
   Brinton, Louise A.
   Brooks-Wilson, Angela
   Bruinsma, Fiona
   Butzow, Ralf
   Campbell, Ian G.
   Carty, Karen
   Chang-Claude, Jenny
   Chenevix-Trench, Georgia
   Chen, Anne
   Chen, Zhihua
   Cook, Linda S.
   Cramer, Daniel W.
   Cunningham, Julie M.
   Cybulski, Cezary
   Dansonka-Mieszkowska, Agnieszka
   Dennis, Joe
   Dicks, Ed
   Doherty, Jennifer A.
   Doerk, Thilo
   Du Bois, Andreas
   Duerst, Matthias
   Eccles, Diana
   Easton, Douglas T.
   Edwards, Robert P.
   Eilber, Ursula
   Ekici, Arif B.
   Fasching, Peter A.
   Fridley, Brooke L.
   Gao, Yu-Tang
   Gentry-Maharaj, Aleksandra
   Giles, Graham G.
   Glasspool, Rosalind
   Goode, Ellen L.
   Goodman, Marc T.
   Grownwald, Jacek
   Harrington, Patricia
   Harter, Philipp
   Hasmad, Hanis Nazihah
   Hein, Alexander
   Heitz, Florian
   Hildebrandt, Michelle A. T.
   Hillemanns, Peter
   Hogdall, Estrid
   Hogdall, Claus
   Hosono, Satoyo
   Iversen, Edwin S.
   Jakubowska, Anna
   James, Paul
   Jensen, Allan
   Ji, Bu-Tian
   Karlan, Beth Y.
   Kjaer, Susanne Kruger
   Kelemen, Linda E.
   Kellar, Melissa
   Kelley, Joseph L.
   Kiemeney, Lambertus A.
   Krakstad, Camilla
   Kupryjanczyk, Jolanta
   Lambrechts, Diether
   Lambrechts, Sandrina
   Le, Nhu D.
   Lee, Alice W.
   Lele, Shashi
   Leminen, Arto
   Lester, Jenny
   Levine, Douglas A.
   Liang, Dong
   Lissowska, Jolanta
   Lu, Karen
   Lubinski, Jan
   Lundvall, Lene
   Massuger, Leon F. A. G.
   Matsuo, Keitaro
   McGuire, Valerie
   McLaughlin, John R.
   Nevanlinna, Heli
   McNeish, Ian
   Menon, Usha
   Modugno, Francesmary
   Moysich, Kirsten B.
   Narod, Steven A.
   Nedergaard, Lotte
   Ness, Roberta B.
   Azmi, Mat Adenan Noor
   Odunsi, Kunle
   Olson, Sara H.
   Orlow, Irene
   Orsulic, Sandra
   Weber, Rachel Palmieri
   Pearce, Celeste L.
   Pejovic, Tanja
   Pelttari, Liisa M.
   Permuth-Wey, Jennifer
   Phelan, Catherine M.
   Pike, Malcolm C.
   Poole, Elizabeth M.
   Ramus, Susan J.
   Risch, Harvey A.
   Rosen, Barry
   Rossing, Mary Anne
   Rothstein, Joseph H.
   Rudolph, Anja
   Runnebaum, Ingo B.
   Rzepecka, Iwona K.
   Salvesen, Helga B.
   Schildkraut, Joellen M.
   Schwaab, Ira
   Sellers, Thomas A.
   Shu, Xiao-Ou
   Shvetsov, Yurii B.
   Siddiqui, Nadeem
   Sieh, Weiva
   Song, Honglin
   Southey, Melissa C.
   Sucheston, Lara
   Tangen, Ingvild L.
   Teo, Soo-Hwang
   Terry, Kathryn L.
   Thompson, Pamela J.
   Timorek, Agnieszka
   Tsai, Ya-Yu
   Tworoger, Shelley S.
   Van Altena, Anne M.
   Van Nieuwenhuysen, Els
   Vergote, Ignace
   Vierkant, Robert A.
   Wang-Gohrke, Shan
   Walsh, Christine
   Wentzensen, Nicolas
   Whittemore, Alice S.
   Wicklund, Kristine G.
   Wilkens, Lynne R.
   Woo, Yin-Ling
   Wu, Xifeng
   Wu, Anna H.
   Yang, Hannah
   Zheng, Wei
   Ziogas, Argyrios
   Monteiro, Alvaro
   Pharoah, Paul D.
   Gayther, Simon A.
   Freedman, Matthew L.
   Grp, Australian Ovarian Canc Study
   Bowtell, David
   Webb, Penelope M.
   Defazio, Anna
CA Australian Ovarian Canc Study Grp
TI Cis-eQTL analysis and functional validation of candidate susceptibility
   genes for high-grade serous ovarian cancer
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; ANALYSES REVEAL;
   FALLOPIAN-TUBE; RISK LOCI; HOX GENES; IDENTIFICATION; EXPRESSION;
   BREAST; VARIANTS
AB Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P <= 10(-5)). For three cis-eQTL associations (P<1.4 x 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P = 6 x 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
C1 [Lawrenson, Kate; Spindler, Tassja J.; Lee, Janet; Lee, Alice W.; Pearce, Celeste L.; Pike, Malcolm C.; Ramus, Susan J.; Wu, Anna H.; Gayther, Simon A.] Univ So Calif, Norris Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA.
   [Li, Qiyan] Xiamen Univ, Coll Med, Xiamen 361102, Peoples R China.
   [Seo, Ji-Heui; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.
   [Kar, Siddhartha; Tyrer, Jonathan; Baker, Helen; Dicks, Ed; Song, Honglin; Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England.
   [Chen, Yibu] Univ So Calif, Bioinformat Serv, Norris Med Lib, Los Angeles, CA 90033 USA.
   [Karst, Alison; Drapkin, Ronny] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02215 USA.
   [Karst, Alison; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Aben, Katja K. H.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6500 HB Nijmegen, Netherlands.
   [Aben, Katja K. H.] Ctr Comprehens Canc, NL-3501 DB Utrecht, Netherlands.
   [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92697 USA.
   [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk 223040, Byelarus.
   [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ USA.
   [Bean, Yukie; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA.
   [Beckmann, Matthias W.; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA.
   [Fasching, Peter A.; Hein, Alexander] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
   [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
   [Bisogna, Maria; Bjorge, Line; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA.
   [Bogdanova, Natalia; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Haukeland Hosp, Dept Gynecol & Obstet, N-5058 Bergen, Norway.
   [Bogdanova, Natalia; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, N-5020 Bergen, Norway.
   [Brinton, Louise A.; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany.
   [Brooks-Wilson, Angela; Ji, Bu-Tian; Wentzensen, Nicolas; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Bruinsma, Fiona] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Bruinsma, Fiona] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
   [Butzow, Ralf; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia.
   [Campbell, Ian G.; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Cent Hosp, SF-00100 Helsinki, Finland.
   [Campbell, Ian G.] Univ Helsinki, Cent Hosp, Dept Pathol, FI-00014 Helsinki, Finland.
   [Carty, Karen] Peter MacCallum Canc Ctr, Canc Genet Lab, Div Res, Melbourne, Vic 3002, Australia.
   [Carty, Karen; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia.
   [Carty, Karen] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia.
   [Chang-Claude, Jenny; Glasspool, Rosalind; James, Paul] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow G12 0YN, Lanark, Scotland.
   [Chenevix-Trench, Georgia; Eilber, Ursula; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
   [Chen, Anne] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4006, Australia.
   [Chen, Zhihua; Cook, Linda S.] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA.
   [Cramer, Daniel W.] Univ New Mexico, Div Epidemiol & Biostat, Dept Internal Med, Albuquerque, NM 87131 USA.
   [Cunningham, Julie M.; Terry, Kathryn L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
   [Cunningham, Julie M.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02215 USA.
   [Cunningham, Julie M.; Terry, Kathryn L.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
   [Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Grownwald, Jacek; Jakubowska, Anna; Kupryjanczyk, Jolanta; Lubinski, Jan; Rzepecka, Iwona K.] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
   [Dennis, Joe; Easton, Douglas T.; Harrington, Patricia] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
   [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Dept Epidemiol, Lebanon, NH 03756 USA.
   [Du Bois, Andreas; Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, D-45136 Essen, Germany.
   [Du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany.
   [Duerst, Matthias; Runnebaum, Ingo B.] Univ Jena, Jena Univ Hosp, Dept Gynecol, D-07737 Jena, Germany.
   [Eccles, Diana] Univ Southampton, Fac Med, Southampton SO16 5YA, Hants, England.
   [Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
   [Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Ovarian Canc Ctr Excellence, Pittsburgh, PA 15213 USA.
   [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-91054 Erlangen, Germany.
   [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA.
   [Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66160 USA.
   [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai 200030, Peoples R China.
   [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Dept Womens Canc, London W1T 7DN, England.
   [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
   [Goode, Ellen L.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
   [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA.
   [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA.
   [Hasmad, Hanis Nazihah; Teo, Soo-Hwang] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya 47500, Malaysia.
   [Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Hillemanns, Peter] Hannover Med Sch, Dept Obstet, D-30625 Hannover, Germany.
   [Hillemanns, Peter] Hannover Med Sch, Dept Gynaecol, D-30625 Hannover, Germany.
   [Hogdall, Estrid] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark.
   [Hogdall, Estrid; Lundvall, Lene] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, DK-1165 Copenhagen, Denmark.
   [Hogdall, Claus] Univ Copenhagen, Gyn Clin, Rigshosp, Copenhagen, Denmark.
   [Hosono, Satoyo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4640021, Japan.
   [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA.
   [Jensen, Allan] Univ Copenhagen, Dept Gynecol, Rigshosp, DK-2100 Copenhagen, Denmark.
   [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
   [Kjaer, Susanne Kruger] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, DK-2100 Copenhagen, Denmark.
   [Kjaer, Susanne Kruger] Univ Copenhagen, Dept Gynaecol, Juliane Marie Ctr, Rigshosp, DK-2100 Copenhagen, Denmark.
   [Kelemen, Linda E.] Med Univ S Carolina, Dept Publ Hlth Sci, Coll Med, Charleston, SC 29435 USA.
   [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Mentre, Radboud Inst Hlth Sci, NL-6500 HB Nijmegen, Netherlands.
   [Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium.
   [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium.
   [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Div Gynecol Oncol, Dept Oncol, B-3000 Leuven, Belgium.
   [Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC V5Z 1L3, Canada.
   [Lele, Shashi; Moysich, Kirsten B.; Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
   [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA.
   [Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
   [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
   [Massuger, Leon F. A. G.; Van Altena, Anne M.] Radboud Univ Nijmegen Med Ctr, Dept Gynaecol, NL-6500 HB Nijmegen, Netherlands.
   [Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 8190395, Japan.
   [McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
   [McLaughlin, John R.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
   [McNeish, Ian] Univ Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Glasgow G61 1QH, Lanark, Scotland.
   [Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA 15213 USA.
   [Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA.
   [Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
   [Narod, Steven A.; Olson, Sara H.; Orlow, Irene] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
   [Nedergaard, Lotte] Univ Copenhagen, Dept Pathol, Rigshosp, DK-2100 Copenhagen, Denmark.
   [Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX 77030 USA.
   [Azmi, Mat Adenan Noor; Woo, Yin-Ling] Univ Malaya, Univ Malaya Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur 50603, Malaysia.
   [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
   [Weber, Rachel Palmieri] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
   [Permuth-Wey, Jennifer; Phelan, Catherine M.; Sellers, Thomas A.; Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
   [Pike, Malcolm C.; Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02215 USA.
   [Pike, Malcolm C.; Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
   [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06510 USA.
   [Rosen, Barry] Univ Toronto, Fac Med, Dept Gynecol Oncol, Princess Margaret Hosp, Toronto, ON M5S 2J7, Canada.
   [Rosen, Barry] Univ Toronto, Fac Med, Dept Obstet & Gynecol, Toronto, ON M5S 2J7, Canada.
   [Rossing, Mary Anne; Wicklund, Kristine G.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC 27710 USA.
   [Schildkraut, Joellen M.; Schwaab, Ira] Inst Humangenet Wiesbaden, D-65187 Wiesbaden, Germany.
   [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Sch Med, Div Epidemiol,Dept Med, Nashville, TN 37232 USA.
   [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
   [Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Canc Epidemiol Program, Ctr Canc, Honolulu, HI 96813 USA.
   [Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland.
   [Teo, Soo-Hwang; Woo, Yin-Ling] Univ Malaya, Canc Res Inst, Fac Med, Med Ctr, Kuala Lumpur 50603, Malaysia.
   [Timorek, Agnieszka] Med Univ Warsaw, Fac Med 2, Dept Obstet Gynecol & Oncol, Warsaw, Poland.
   [Timorek, Agnieszka] Brodnowski Hosp, Warsaw, Poland.
   [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89075 Ulm, Germany.
   [Monteiro, Alvaro] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Canc Epidemiol Program, Tampa, FL 33612 USA.
   [Bowtell, David] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
   [Webb, Penelope M.] QIMR Berghofer, Brisbane, Qld 4006, Australia.
   [Defazio, Anna] Univ Sydney, Westmead Millennium Inst, Westmead Hosp, Westmead, NSW 2145, Australia.
   [Defazio, Anna] Univ Sydney, Westmead Millennium Inst, Ctr Canc Res, Westmead, NSW 2145, Australia.
RP Gayther, SA (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA.
EM simon.gayther@med.usc.edu
RI Dork, Thilo/J-8620-2012; Massuger, Leon/H-8072-2014; Bjorge,
   Line/C-1307-2017; salvesen, Helga/C-1187-2017; Hein,
   Alexander/F-6999-2010; Brooks-Wilson, Angela/E-9399-2012; van Altena,
   Anne/B-9824-2016; U-ID, Kyushu/C-5291-2016; Drapkin, Ronny/E-9944-2016;
   Teo,  Soo-hwang/H-2353-2014; Aben, Katja/G-9686-2016; Bowtell,
   David/H-1007-2016
OI Ramus, Susan/0000-0003-0005-7798; Orlow, Irene/0000-0001-6234-6961;
   Krakstad, Camilla/0000-0002-0174-8139; Giles,
   Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314; Bjorge,
   Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831;
   Glasspool, Rosalind/0000-0002-5000-1680; Hein,
   Alexander/0000-0003-2601-3398; Brooks-Wilson,
   Angela/0000-0003-1009-6408; Drapkin, Ronny/0000-0002-6912-6977; Aben,
   Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525
FU European Commission [223175-HEALTH-F2-2009-223175]; Ovarian Cancer
   Research Fund [PPD/RPCI.07]; US National Cancer Institute (NCI) GAME-ON
   Post-GWAS Initiative [U19-CA148112]; Wellcome Trust [076113]
FX Grant Support-higher level funding: the COGS project is funded through a
   European Commission's Seventh Framework Programme grant (agreement
   number 223175-HEALTH-F2-2009-223175). The Ovarian Cancer Association
   Consortium is supported by a grant from the Ovarian Cancer Research Fund
   thanks to donations by the family and friends of Kathryn Sladek Smith
   (PPD/RPCI.07). The scientific development and funding for this project
   were in part supported by the US National Cancer Institute (NCI) GAME-ON
   Post-GWAS Initiative (U19-CA148112). This study made use of data
   generated by the Wellcome Trust Case Control consortium. Funding for the
   project was provided by the Wellcome Trust under award 076113. The
   results published here are in part based on data generated by The Cancer
   Genome Atlas Project established by the NCI and National Human Genome
   Research Institute.
NR 62
TC 4
Z9 4
U1 3
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD SEP
PY 2015
VL 6
AR 8234
DI 10.1038/ncomms9234
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT7TN
UT WOS:000363017500005
PM 26391404
ER

PT J
AU Wilinski, D
   Qiu, C
   Lapointe, CP
   Nevil, M
   Campbell, ZT
   Hall, TMT
   Wickens, M
AF Wilinski, Daniel
   Qiu, Chen
   Lapointe, Christopher P.
   Nevil, Markus
   Campbell, Zachary T.
   Hall, Traci M. Tanaka
   Wickens, Marvin
TI RNA regulatory networks diversified through curvature of the PUF protein
   scaffold
SO NATURE COMMUNICATIONS
LA English
DT Article
ID BINDING PROTEIN; 3-HYBRID SYSTEM; SACCHAROMYCES-CEREVISIAE;
   CRYSTAL-STRUCTURE; MESSENGER-RNAS; IN-VIVO; YEAST; SPECIFICITY; CLIP;
   LIFE
AB Proteins bind and control mRNAs, directing their localization, translation and stability. Members of the PUF family of RNA-binding proteins control multiple mRNAs in a single cell, and play key roles in development, stem cell maintenance and memory formation. Here we identified the mRNA targets of a S. cerevisiae PUF protein, Puf5p, by ultraviolet-crosslinking-affinity purification and high-throughput sequencing (HITS-CLIP). The binding sites recognized by Puf5p are diverse, with variable spacer lengths between two specific sequences. Each length of site correlates with a distinct biological function. Crystal structures of Puf5p-RNA complexes reveal that the protein scaffold presents an exceptionally flat and extended interaction surface relative to other PUF proteins. In complexes with RNAs of different lengths, the protein is unchanged. A single PUF protein repeat is sufficient to induce broadening of specificity. Changes in protein architecture, such as alterations in curvature, may lead to evolution of mRNA regulatory networks.
C1 [Wilinski, Daniel; Lapointe, Christopher P.; Nevil, Markus; Campbell, Zachary T.; Wickens, Marvin] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
   [Qiu, Chen; Hall, Traci M. Tanaka] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wickens, M (reprint author), Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
EM wickens@biochem.wisc.edu
FU NIH [GM50942]; NIH Postdoctoral Fellowship; Intramural Research Program
   of the National Institutes of Health, National Institute of
   Environmental Health Sciences; US Department of Energy, Office of
   Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
FX We thank Natascha Buter for help with experiments, and colleagues in the
   Wickens lab and NIEHS for comments during the work and discussions of
   the manuscript. We are very grateful to Drs Robert Darnell and Aldo Mele
   for helpful suggestions in troubleshooting HITS-CLIP and Dr Fabio
   Parmeggiani for help analysing the beta-catenin repeats. We thank Dr
   Lars Pedersen and the staff of the Southeast Regional Collaborative
   Access Team beamlines for assistance with X-ray data collection. Work in
   the Wickens lab is supported by NIH (GM50942). Z.T.C was supported by an
   NIH Postdoctoral Fellowship. The work also was supported by the
   Intramural Research Program of the National Institutes of Health,
   National Institute of Environmental Health Sciences (T.M.T.H.). The
   Advanced Photon Source used for this study was supported by the US
   Department of Energy, Office of Science, Office of Basic Energy
   Sciences, under contract no. W-31-109-Eng-38.
NR 49
TC 12
Z9 12
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD SEP
PY 2015
VL 6
AR 8213
DI 10.1038/ncomms9213
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT5MM
UT WOS:000362854500003
PM 26364903
ER

PT J
AU Marzouki, S
   Kammoun-Rebai, W
   Bettaieb, J
   Abdeladhim, M
   Kacem, SH
   Abdelkader, R
   Gritli, S
   Chemkhi, J
   Aslan, H
   Kamhawi, S
   Ben Salah, A
   Louzir, H
   Valenzuela, JG
   Ben Ahmed, M
AF Marzouki, Soumaya
   Kammoun-Rebai, Wafa
   Bettaieb, Jihene
   Abdeladhim, Maha
   Kacem, Saoussen Hadj
   Abdelkader, Rania
   Gritli, Sami
   Chemkhi, Jomaa
   Aslan, Hamide
   Kamhawi, Shaden
   Ben Salah, Afif
   Louzir, Hechmi
   Valenzuela, Jesus G.
   Ben Ahmed, Melika
TI Validation of Recombinant Salivary Protein PpSP32 as a Suitable Marker
   of Human Exposure to Phlebotomus papatasi, the Vector of Leishmania
   major in Tunisia
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID LUTZOMYIA-LONGIPALPIS SALIVA; CANINE ANTIBODY-RESPONSE; SAND FLY SALIVA;
   VISCERAL LEISHMANIASIS; CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSE;
   ENDEMIC AREAS; NORTH-AFRICA; MICE BITTEN; BITES
AB Background
   During a blood meal, female sand flies, vectors of Leishmania parasites, inject saliva into the host skin. Sand fly saliva is composed of a large variety of components that exert different pharmacological activities facilitating the acquisition of blood by the insect. Importantly, proteins present in saliva are able to elicit the production of specific anti-saliva antibodies, which can be used as markers for exposure to vector bites. Serological tests using total sand fly salivary gland extracts are challenging due to the difficulty of obtaining reproducible salivary gland preparations. Previously, we demonstrated that PpSP32 is the immunodominant salivary antigen in humans exposed to Phlebotomus papatasi bites and established that humans exposed to P. perniciosus bites do not recognize it.
   Methodology/Principal Findings
   Herein, we have validated, in a large cohort of 522 individuals, the use of the Phlebotomus papatasi recombinant salivary protein PpSP32 (rPpSP32) as an alternative method for testing exposure to the bite of this sand fly. We also demonstrated that screening for total anti-rPpSP32 IgG antibodies is sufficient, being comparable in efficacy to the screening for IgG2, IgG4 and IgE antibodies against rPpSP32. Additionally, sera obtained from dogs immunized with saliva of P. perniciosus, a sympatric and widely distributed sand fly in Tunisia, did not recognize rPpSP32 demonstrating its suitability as a marker of exposure to P. papatasi saliva.
   Conclusions/Significance
   Our data indicate that rPpSP32 constitutes a useful epidemiological tool to monitor the spatial distribution of P. papatasi in a particular region, to direct control measures against zoonotic cutaneous leishmaniasis, to assess the efficiency of vector control interventions and perhaps to assess the risk of contracting the disease.
C1 [Marzouki, Soumaya; Bettaieb, Jihene; Kacem, Saoussen Hadj; Abdelkader, Rania; Ben Salah, Afif; Louzir, Hechmi; Ben Ahmed, Melika] Inst Pasteur Tunis, Lab Transmiss Control & Immunobiol Infect, Tunis, Tunisia.
   [Kammoun-Rebai, Wafa] Inst Pasteur Tunis, Lab Med Parasitol Biotechnol & Biomol, Tunis, Tunisia.
   [Bettaieb, Jihene; Ben Salah, Afif; Louzir, Hechmi; Ben Ahmed, Melika] Univ Tunis El Manar, Fac Med Tunis, Tunis, Tunisia.
   [Abdeladhim, Maha; Aslan, Hamide; Kamhawi, Shaden] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
   [Gritli, Sami] Charles Nicolle Hosp, Dept Pathol, Tunis, Tunisia.
   [Chemkhi, Jomaa] Inst Pasteur Tunis, Lab Mol Epidemiol & Expt Pathol, Tunis, Tunisia.
RP Marzouki, S (reprint author), Inst Pasteur Tunis, Lab Transmiss Control & Immunobiol Infect, LR11IPT02, Tunis, Tunisia.
EM melika.benahmed@pasteur.rns.tn
FU NIH/NIAID [SP50AI074178]; Intramural Research Program of the NIH,
   National Institute of Allergy and Infectious Diseases
FX The project was supported by the NIH/NIAID Grant Number SP50AI074178 and
   in part by the Intramural Research Program of the NIH, National
   Institute of Allergy and Infectious Diseases (MA, HA, SK, JGV). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 42
TC 2
Z9 2
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD SEP
PY 2015
VL 9
IS 9
AR e0003991
DI 10.1371/journal.pntd.0003991
PG 14
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CT7YI
UT WOS:000363031200013
PM 26368935
ER

PT J
AU Morris, CP
   Bennuru, S
   Kropp, LE
   Zweben, JA
   Meng, ZJ
   Taylor, RT
   Chan, K
   Veenstra, TD
   Nutman, TB
   Mitre, E
AF Morris, C. Paul
   Bennuru, Sasisekhar
   Kropp, Laura E.
   Zweben, Jesse A.
   Meng, Zhaojing
   Taylor, Rebekah T.
   Chan, King
   Veenstra, Timothy D.
   Nutman, Thomas B.
   Mitre, Edward
TI A Proteomic Analysis of the Body Wall, Digestive Tract, and Reproductive
   Tract of Brugia malayi
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID ASPARAGINYL ENDOPEPTIDASE SM32; FILARIAL PARASITE; HAEMONCHUS-CONTORTUS;
   ONCHOCERCA-VOLVULUS; NEUTRALIZING ANTIBODIES; LEUCINE AMINOPEPTIDASE;
   CAENORHABDITIS-ELEGANS; EXPRESSION PATTERNS; SHOTGUN PROTEOMICS;
   HOOKWORM INFECTION
AB Filarial worms are parasitic nematodes that cause devastating diseases such as lymphatic filariasis (LF) and onchocerciasis. Filariae are nematodes with complex anatomy including fully developed digestive tracts and reproductive organs. To better understand the basic biology of filarial parasites and to provide insights into drug targets and vaccine design, we conducted a proteomic analysis of different anatomic fractions of Brugia malayi, a causative agent of LF. Approximately 500 adult female B. malayi worms were dissected, and three anatomical fractions (body wall, digestive tract, and reproductive tract) were obtained. Proteins from each anatomical fraction were extracted, desalted, trypsinized, and analyzed by microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry. In total, we identified 4,785 B. malayi proteins. While 1,894 were identified in all three anatomic fractions, 396 were positively identified only within the digestive tract, 114 only within the body wall, and 1,011 only within the reproductive tract. Gene set enrichment analysis revealed a bias for transporters to be present within the digestive tract, suggesting that the intestine of adult filariae is functional and important for nutrient uptake or waste removal. As expected, the body wall exhibited increased frequencies of cytoskeletal proteins, and the reproductive tract had increased frequencies of proteins involved in nuclear regulation and transcription. In assessing for possible vaccine candidates, we focused on proteins sequestered within the digestive tract, as these could possibly represent "hidden antigens" with low risk of prior allergic sensitization. We identified 106 proteins that are enriched in the digestive tract and are predicted to localize to the surface of cells in the the digestive tract. It is possible that some of these proteins are on the luminal surface and may be accessible by antibodies ingested by the worm. A subset of 27 of these proteins appear especially promising vaccine candidates as they contain significant non-cytoplasmic domains, only 1-2 transmembrane domains, and a high degree of homology to W. bancrofti and/ or O. volvulus.
C1 [Morris, C. Paul; Kropp, Laura E.; Zweben, Jesse A.; Mitre, Edward] Uniformed Serv Univ Hlth Sci, F Edward Herbert Sch Med, Dept Microbiol, Bethesda, MD 20814 USA.
   [Morris, C. Paul; Bennuru, Sasisekhar; Nutman, Thomas B.] NIAID, NIH, Bethesda, MD 20892 USA.
   [Meng, Zhaojing; Chan, King; Veenstra, Timothy D.] Leidos Biomed Res Inc, Frederick Natl Lab, Prot Characterizat Lab, Canc Res Technol Program, Frederick, MD USA.
   [Taylor, Rebekah T.] Frostburg State Univ, Dept Biol, Frostburg, MD 21532 USA.
RP Morris, CP (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Herbert Sch Med, Dept Microbiol, Bethesda, MD 20814 USA.
EM Edward.mitre@usuhs.edu
FU Uniformed Services University of the Health Sciences [R073UE]
FX This project was funded by Uniformed Services University of the Health
   Sciences Grant number R073UE. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 59
TC 2
Z9 2
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD SEP
PY 2015
VL 9
IS 9
AR e0004054
DI 10.1371/journal.pntd.0004054
PG 21
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CT7YI
UT WOS:000363031200037
PM 26367142
ER

PT J
AU Kim, J
   Gravunder, A
   Park, HS
AF Kim, Jonghyun
   Gravunder, Andrew
   Park, Hyung-Soon
TI Commercial Motion Sensor Based Low-Cost and Convenient Interactive
   Treadmill
SO SENSORS
LA English
DT Article
DE motion sensor; interactive treadmill; low-cost; convenience; self-paced
   treadmill; treadmill-on-demand; walking; locomotion
ID SELF-PACED TREADMILL; VIRTUAL ENVIRONMENT; MICROSOFT KINECT;
   CEREBRAL-PALSY; WALKING; SPEED; SYSTEM; FEEDBACK
AB Interactive treadmills were developed to improve the simulation of overground walking when compared to conventional treadmills. However, currently available interactive treadmills are expensive and inconvenient, which limits their use. We propose a low-cost and convenient version of the interactive treadmill that does not require expensive equipment and a complicated setup. As a substitute for high-cost sensors, such as motion capture systems, a low-cost motion sensor was used to recognize the subject's intention for speed changing. Moreover, the sensor enables the subject to make a convenient and safe stop using gesture recognition. For further cost reduction, the novel interactive treadmill was based on an inexpensive treadmill platform and a novel high-level speed control scheme was applied to maximize performance for simulating overground walking. Pilot tests with ten healthy subjects were conducted and results demonstrated that the proposed treadmill achieves similar performance to a typical, costly, interactive treadmill that contains a motion capture system and an instrumented treadmill, while providing a convenient and safe method for stopping.
C1 [Kim, Jonghyun] DGIST, Dept Robot Engn, Daegu 42988, South Korea.
   [Gravunder, Andrew] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
   [Park, Hyung-Soon] Korea Adv Inst Sci & Technol, Dept Mech Engn, Daejeon 34141, South Korea.
RP Park, HS (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, 291 Daehakro, Daejeon 34141, South Korea.
EM jhkim@dgist.ac.kr; andrew.gravunder@nih.gov; hyungspark@kaist.ac.kr
RI Park, Hyung-Soon/B-3334-2010
OI Park, Hyung-Soon/0000-0003-4274-7420
FU Basic Science Research Program through the National Research Foundation
   of Korea (NRF) - Ministry of Education
   [2013R1A1A2063097/2014R1A1A2059068]; Technology Innovation Program -
   Ministry of Trade, Industry and Energy (MI, Korea) [10051147]; KAIST
   End-Run program; DGIST MIREBraiN program; Intramural Research Program of
   the NIH, Clinical Center [90-CC-0168]
FX The authors would like to thank all subjects who volunteered for the
   study. Specifically, the authors would like to thank Christopher J.
   Stanley, and Diane L. Damiano for their support. This work was supported
   in part by Basic Science Research Program through the National Research
   Foundation of Korea (NRF) funded by the Ministry of Education
   (2013R1A1A2063097/2014R1A1A2059068), Technology Innovation Program
   funded by the Ministry of Trade, Industry and Energy (MI, Korea,
   10051147), the KAIST End-Run program, the DGIST MIREBraiN program, and
   by the Intramural Research Program of the NIH, Clinical Center (protocol
   number 90-CC-0168).
NR 27
TC 2
Z9 2
U1 0
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1424-8220
J9 SENSORS-BASEL
JI Sensors
PD SEP
PY 2015
VL 15
IS 9
BP 23667
EP 23683
DI 10.3390/s150923667
PG 17
WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation
SC Chemistry; Electrochemistry; Instruments & Instrumentation
GA CT0UH
UT WOS:000362512200136
PM 26393592
ER

PT J
AU Memedi, M
   Sadikov, A
   Groznik, V
   Zabkar, J
   Mozina, M
   Bergquist, F
   Johansson, A
   Haubenberger, D
   Nyholm, D
AF Memedi, Mevludin
   Sadikov, Aleksander
   Groznik, Vida
   Zabkar, Jure
   Mozina, Martin
   Bergquist, Filip
   Johansson, Anders
   Haubenberger, Dietrich
   Nyholm, Dag
TI Automatic Spiral Analysis for Objective Assessment of Motor Symptoms in
   Parkinson's Disease
SO SENSORS
LA English
DT Article
DE bradykinesia; digital spiral analysis; dyskinesia; machine learning;
   motor fluctuations; objective measures; Parkinson's disease; remote
   monitoring; time series analysis; visualization
ID INDUCED DYSKINESIAS; WEARABLE SENSORS; SYSTEM; TREMOR; BRADYKINESIA;
   PERFORMANCE; SCALE; LIFE
AB A challenge for the clinical management of advanced Parkinson's disease (PD) patients is the emergence of fluctuations in motor performance, which represents a significant source of disability during activities of daily living of the patients. There is a lack of objective measurement of treatment effects for in-clinic and at-home use that can provide an overview of the treatment response. The objective of this paper was to develop a method for objective quantification of advanced PD motor symptoms related to off episodes and peak dose dyskinesia, using spiral data gathered by a touch screen telemetry device. More specifically, the aim was to objectively characterize motor symptoms (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Digitized upper limb movement data of 65 advanced PD patients and 10 healthy (HE) subjects were recorded as they performed spiral drawing tasks on a touch screen device in their home environment settings. Several spatiotemporal features were extracted from the time series and used as inputs to machine learning methods. The methods were validated against ratings on animated spirals scored by four movement disorder specialists who visually assessed a set of kinematic features and the motor symptom. The ability of the method to discriminate between PD patients and HE subjects and the test-retest reliability of the computed scores were also evaluated. Computed scores correlated well with mean visual ratings of individual kinematic features. The best performing classifier (Multilayer Perceptron) classified the motor symptom (bradykinesia or dyskinesia) with an accuracy of 84% and area under the receiver operating characteristics curve of 0.86 in relation to visual classifications of the raters. In addition, the method provided high discriminating power when distinguishing between PD patients and HE subjects as well as had good test-retest reliability. This study demonstrated the potential of using digital spiral analysis for objective quantification of PD-specific and/or treatment-induced motor symptoms.
C1 [Memedi, Mevludin] Dalarna Univ, Sch Technol & Business Studies, Comp Engn, SE-79188 Falun, Sweden.
   [Sadikov, Aleksander; Groznik, Vida; Zabkar, Jure; Mozina, Martin] Univ Ljubljana, Fac Comp & Informat Sci, Artificial Intelligence Lab, Ljubljana 1000, Slovenia.
   [Bergquist, Filip] Univ Gothenburg, Sahlgrenska Acad, Dept Pharmacol, S-40530 Gothenburg, Sweden.
   [Johansson, Anders] Karolinska Inst, Dept Clin Neurosci, Neurol, S-17176 Stockholm, Sweden.
   [Haubenberger, Dietrich] NINDS, Clin Trials Unit, Off Clin Director, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
   [Nyholm, Dag] Uppsala Univ, Dept Neurosci, Neurol, S-75185 Uppsala, Sweden.
RP Memedi, M (reprint author), Dalarna Univ, Sch Technol & Business Studies, Comp Engn, SE-79188 Falun, Sweden.
EM mmi@du.se; aleksander.sadikov@fri.uni-lj.si; vida.groznik@fri.uni-lj.si;
   jure.zabkar@fri.uni-lj.si; martin.mozina@fri.uni-lj.si;
   filip.bergquist@pharm.gu.se; anders.johansson@ki.se;
   haubenbergerd@ninds.nih.gov; dag.nyholm@neuro.uu.se
FU Swedish Knowledge Foundation; Nordforce Technology AB; Animech AB;
   Dalarna University [20130041]; Slovenian Research Agency; Slovenian
   Ministry of Education, Science and Sport; European Regional Development
   Fund (PARKINSCHECK project)
FX The research leading to these results was partly supported by Swedish
   Knowledge Foundation, Nordforce Technology AB, Animech AB, and Dalarna
   University under grant agreement 20130041 (PAULINA project) and partly
   by Slovenian Research Agency (Artificial Intelligence and Intelligent
   Systems research programme), Slovenian Ministry of Education, Science
   and Sport, and European Regional Development Fund (PARKINSCHECK
   project).
NR 37
TC 1
Z9 1
U1 0
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1424-8220
J9 SENSORS-BASEL
JI Sensors
PD SEP
PY 2015
VL 15
IS 9
BP 23727
EP 23744
DI 10.3390/s150923727
PG 18
WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation
SC Chemistry; Electrochemistry; Instruments & Instrumentation
GA CT0UH
UT WOS:000362512200139
PM 26393595
ER

PT J
AU Walton, MK
   Powers, JH
   Hobart, J
   Patrick, D
   Marquis, P
   Vamvakas, S
   Isaac, M
   Molsen, E
   Cano, S
   Burke, LB
AF Walton, Marc K.
   Powers, Johnh. H., III
   Hobart, Jeremy
   Patrick, Donald
   Marquis, Patrick
   Vamvakas, Spiros
   Isaac, Maria
   Molsen, Elizabeth
   Cano, Stefan
   Burke, Laurie B.
TI Clinical Outcome Assessments: Conceptual Foundation-Report of the ISPOR
   Clinical Outcomes Assessment - Emerging Good Practices for Outcomes
   Research Task Force
SO VALUE IN HEALTH
LA English
DT Article
DE clinical outcome assessment; concept of interest; context of use;
   treatment benefit
ID CONTENT VALIDITY; PRO INSTRUMENTS; MULTIPLE-SCLEROSIS; UPPER-EXTREMITY;
   RATING-SCALES; VALIDATION; TRIALS; RECOMMENDATIONS; QUESTIONNAIRE;
   TRANSLATION
AB An outcome assessment, the patient assessment used in an endpoint, is the measuring instrument that provides a radng or score (categofical or continuous) that is intended to represent some aspect of the patient's health status. Outcome assessments are used to define efficacy endpoints when developing a therapy for a disease or condition. Most efficacy endpoints are based on specified clinical assessments of patients. When clinical assessments are used as clinical trial outcomes, they are called clinical outcome assessments (COAs). COAs include any assessment that may be influenced by human choices, judgment, or motivation. COAs must be well-defined and possess adequate measurement properties to demonstrate (directly or indirectly) the benefits of a treatment In contrast, a biomarker assessment is one that is subject to little, if any, patient motivational or rater judgmental influence. This is the first of two reports by the ISPOR Clinical Outcomes Assessment Emerging Good Practices for Outcomes Research Task Force. This report provides foundational definitions important for an understanding of COA measurement principles. The foundation provided in this report includes what it means to demonstrate a beneficial effect, how assessments of patients relate to the objective of showing a treatment's benefit, and how these assessments are used in clinical trial endpoints. In addition, this report describes intrinsic attributes of patient assessments and clinical trial factors that can affect the properties of the measurements. These factors should be considered when developing or refining assessments. These considerations will aid investigators designing trials in their choice of using an existing assessment or developing a new outcome assessment Although the focus of this report is on the development of a new COA to define endpoints in a clinical trial, these principles may be applied more generally. A critical element in appraising or developing a COA is to describe the treatment's intended benefit as an effect on a clearly identified aspect of how a patient feels or functions. l'his aspect must have importance to the patient and be part of the patient's typical life. this meaningful health aspect can be measured directly or measured indirectly when it is impractical to evaluate it directly or when it is difficult to measure. For indirect measurement, a concept of interest (COI) can be identified. The COI must be related to how a patient feels or functions. Procedures are then developed to measure the COI. The relationship of these measurements with how a patient feels or functions in the intended setting and manner of use of the COA (the context of use) could then be defined. A COA has identifiable attributes or characteristics that affect the measurement properties of the COA when used in endpoints. One of these features is whether judgment can influence the measurement, and if so, whose judgment. This attribute defines four categories of COAs: patient reported outcomes, clinician reported outcomes, observer reported outcomes, and performance outcomes. A full description as well as explanation of other important COA features is included in this report. The information in this report should aid in the development, refinement, and standardization of COAs, and, ultimately, improve their measurement propeities.
C1 [Walton, Marc K.] Janssen Res & Dev, Titusville, NJ USA.
   [Powers, Johnh. H., III] NIH, Leidos Biomed Res Support Div Clin Res, Bethesda, MD 20892 USA.
   [Hobart, Jeremy] Univ Plymouth, Peninsula Sch Med & Dent, Plymouth PL4 8AA, Devon, England.
   [Patrick, Donald] Univ Washington, Dept Hlth Serv, Seattle Qual Life Grp, Seattle, WA 98195 USA.
   [Marquis, Patrick] Modus Outcomes, Newton, MA USA.
   [Vamvakas, Spiros; Isaac, Maria] European Med Agcy, London, England.
   [Molsen, Elizabeth] Int Society Pharmacoecon & Outcomes Res, Lawrenceville, NJ USA.
   [Cano, Stefan] Modus Outcomes, Stotfold, England.
   [Burke, Laurie B.] LLC, LORA Grp, Royal Oak, MD USA.
   [Burke, Laurie B.] Univ Maryland, Sch Pharm, Dept Hlth Serv Res, Baltimore, MD 21201 USA.
RP Walton, MK (reprint author), 125 Crystal Spring Dr, Ashton, MD 20861 USA.
EM mwalton9@its.jnj.com
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]
FX There are no financial sponsors of this task force and manuscript. One
   coauthor is required to state the source of funding for his work in
   general (not for this manuscript specifically). Support for J.H. Powers
   has been funded in whole or in part with federal funds from the National
   Cancer Institute, National Institutes of Health (contract no.
   HHSN261200800001E).
NR 38
TC 9
Z9 9
U1 3
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD SEP
PY 2015
VL 18
IS 6
BP 741
EP 752
DI 10.1016/j.jval.2015.08.006
PG 12
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA CU4EN
UT WOS:000363479800002
PM 26409600
ER

PT J
AU Missinato, MA
   Tobita, K
   Romano, N
   Carroll, JA
   Tsang, M
AF Missinato, Maria A.
   Tobita, Kimimasa
   Romano, Nicla
   Carroll, James A.
   Tsang, Michael
TI Extracellular component hyaluronic acid and its receptor Hmmr are
   required for epicardial EMT during heart regeneration
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Zebrafish heart regeneration; Hyaluronic acid; Hmmr; Epicardial cell
   migration; pFAK
ID FOCAL ADHESION KINASE; ZEBRAFISH HEART; GROWTH-FACTOR; MESENCHYMAL
   TRANSITION; VASCULAR DEVELOPMENT; MOUSE HEART; CELLS; MIGRATION;
   INHIBITION; INJURY
AB Aims After injury, the adult zebrafish can regenerate the heart. This requires the activation of the endocardium and epicardium as well as the proliferation of pre-existing cardiomyocytes to replace the lost tissue. However, the molecular mechanisms involved in this process are not completely resolved. In this work, we aim to identify the proteins involved in zebrafish heart regeneration and to explore their function.
   Methods and results Using a proteomic approach, we identified Hyaluronan-mediated motility receptor (Hmmr), a hyaluronic acid (HA) receptor, to be expressed following ventricular resection in zebrafish. Moreover, enzymes that produce HA, hyaluronic acid synthases (has), were also expressed following injury, suggesting that this pathway may serve important functions in the regenerating heart. Indeed, suppression of HA production, as well as depletion of Hmmr, blocked cardiac regeneration. Mechanistically, HA and Hmmr are required for epicardial cell epithelial-mesenchymal transition (EMT) and their subsequent migration into the regenerating ventricle. Furthermore, chemical inhibition of Focal Adhesion Kinase (FAK) or inhibition of Src kinases, downstream effectors of Hmmr, also prevented epicardial cell migration, implicating a HA/Hmmr/FAK/Src pathway in this process. In a rat model of myocardial infarction, both HA and HMMR were upregulated and localized in the infarct area within the first few days following damage, suggesting that this pathway may also play an important role in cardiac repair in mammals.
   Conclusion HA and Hmmr are required for activated epicardial cell EMT and migration involving the FAK/Src pathway for proper heart regeneration.
C1 [Missinato, Maria A.; Tobita, Kimimasa; Tsang, Michael] Univ Pittsburgh, Dept Dev Biol, Pittsburgh, PA 15260 USA.
   [Missinato, Maria A.; Romano, Nicla] Univ Tuscia, Dept Ecol & Biol Sci, Viterbo, Italy.
   [Carroll, James A.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Tsang, M (reprint author), Univ Pittsburgh, Dept Dev Biol, 3501 5th Ave, Pittsburgh, PA 15260 USA.
EM tsang@pitt.edu
RI Tsang, Michael/I-9305-2014; 
OI Tsang, Michael/0000-0001-7123-0063; romano, nicla/0000-0002-0155-8271
FU American Heart Association [14GRNT20480183]; National Institute of
   Health [NHLBI/NIH R01HL088016]; American Recovery and Reinvestment Act
   (ARRA)
FX This work was supported by funding from the American Heart Association
   (14GRNT20480183), the National Institute of Health (NHLBI/NIH
   R01HL088016), and the American Recovery and Reinvestment Act (ARRA)
   supplemental funding.
NR 64
TC 5
Z9 6
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD SEP 1
PY 2015
VL 107
IS 4
BP 487
EP 498
DI 10.1093/cvr/cvv190
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CT5LE
UT WOS:000362850800012
PM 26156497
ER

PT J
AU Mellick, W
   Sharp, C
   Ernst, M
AF Mellick, William
   Sharp, Carla
   Ernst, Monique
TI Neuroeconomics for the Study of Social Cognition in Adolescent
   Depression
SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE
LA English
DT Review
DE adolescent depression; neuroeconomics; social cognition
ID BORDERLINE PERSONALITY-DISORDER; ECONOMIC DECISION-MAKING; MAJOR
   DEPRESSION; PREFRONTAL CORTEX; REWARD ANTICIPATION; MENTAL-DISORDERS;
   IMPAIRED THEORY; ULTIMATUM GAME; SELF-EFFICACY; MIND
AB Traditional social-cognitive approaches for investigating interpersonal problems in adolescent depression are limited. An important functional domain studied in adolescent depression is reward, but experimental paradigms have largely been nonsocial. In this article, we propose the methods and concepts of neuroeconomics may address this gap. We begin by discussing a well-established social reward model for vulnerability to adolescent depression. We then show how neuroeconomics may extend this model by offering the tools to examine the mechanics of social exchanges, in behavioral and neural terms, that maintain (or pose vulnerability to) depression. In doing so, we propose a neuroeconomic model of adolescent depression in which depression is defined as a perturbation of interpersonal motivational/reward exchange. This model serves to guide future research.
C1 [Mellick, William; Sharp, Carla] Univ Houston, Dept Psychol, Houston, TX 77204 USA.
   [Ernst, Monique] NIMH, NIH, New York, NY USA.
RP Sharp, C (reprint author), Univ Houston, Dept Psychol, 126 Heyne Bldg, Houston, TX 77204 USA.
EM csharp2@uh.edu
NR 129
TC 1
Z9 1
U1 11
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0969-5893
EI 1468-2850
J9 CLIN PSYCHOL-SCI PR
JI Clin. Psychol.-Sci. Pract.
PD SEP
PY 2015
VL 22
IS 3
BP 255
EP 276
DI 10.1111/cpsp.12106
PG 22
WC Psychology, Clinical
SC Psychology
GA CT8BQ
UT WOS:000363040400005
ER

PT J
AU Fox-Edmiston, E
   Van de Water, J
AF Fox-Edmiston, Elizabeth
   Van de Water, Judy
TI Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum
   Disorder: Current Knowledge and its Implications for Potential
   Therapeutics
SO CNS DRUGS
LA English
DT Article
ID FETAL-BRAIN; IMMUNOGLOBULIN-G; PROTEASOME INHIBITORS;
   ENVIRONMENTAL-FACTORS; ANTIBRAIN ANTIBODIES; PLASMA-CELLS; CHILDREN;
   MOTHERS; LUPUS; RECEPTOR
AB Several studies have found a correlation between the presence of circulating maternal autoantibodies and neuronal dysfunction in the neonate. Specifically, maternal anti-brain autoantibodies, which may access the fetal compartment during gestation, have been identified as one risk factor for developing autism spectrum disorder (ASD). Studies by our laboratory elucidated seven neurodevelopmental proteins recognized by maternal autoantibodies whose presence is associated with a diagnosis of maternal autoantibody-related (MAR) autism in the child. While the specific process of anti-brain autoantibody generation is unclear and the detailed pathogenic mechanisms are currently unknown, identification of the maternal autoantibody targets increases the therapeutic possibilities. The potential therapies discussed in this review provide a framework for possible future medical interventions.
C1 [Fox-Edmiston, Elizabeth; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA.
   [Fox-Edmiston, Elizabeth; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA.
   [Van de Water, Judy] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA.
RP Van de Water, J (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA.
EM javandewater@ucdavis.edu
FU National Institute of Environmental Health Sciences (NIEHS)
   [5P01ES011269-13]; U.S. Environmental Protection Agency (US EPA) through
   the Science to Achieve Results (STAR) program [R829388]; National
   Institutes of Health (NIH) [U54 HD079125]
FX This work was supported by National Institute of Environmental Health
   Sciences (NIEHS) 5P01ES011269-13, the U.S. Environmental Protection
   Agency (US EPA) through the Science to Achieve Results (STAR) program
   (Grant R829388), and the National Institutes of Health (NIH)-funded
   M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders)
   Institute Intellectual and Developmental Disabilities Research Center
   (U54 HD079125).
NR 50
TC 3
Z9 3
U1 3
U2 5
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1172-7047
EI 1179-1934
J9 CNS DRUGS
JI CNS Drugs
PD SEP
PY 2015
VL 29
IS 9
BP 715
EP 724
DI 10.1007/s40263-015-0279-2
PG 10
WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CT5WO
UT WOS:000362882000001
PM 26369920
ER

PT J
AU Nussinov, R
   Muratcioglu, S
   Tsai, CJ
   Jang, H
   Gursoy, A
   Keskin, O
AF Nussinov, Ruth
   Muratcioglu, Serena
   Tsai, Chung-Jung
   Jang, Hyunbum
   Gursoy, Attila
   Keskin, Ozlem
TI The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas
SO MOLECULAR CANCER RESEARCH
LA English
DT Review
ID PANCREATIC DUCTAL ADENOCARCINOMA; PHOSPHOINOSITIDE 3-KINASE P110-ALPHA;
   PROTEIN-PROTEIN INTERACTIONS; NUCLEOTIDE EXCHANGE FACTOR; RAS-BINDING
   DOMAIN; K-RAS; H-RAS; PHOSPHATIDYLINOSITOL 3-KINASE; INTRAEPITHELIAL
   NEOPLASIA; SIGNALING PATHWAYS
AB KRAS4B is a highly oncogenic splice variant of the KRAS isoform. It is the only isoform associated with initiation of adenocarcinomas. Insight into why and how KRAS4B can mediate ductal adenocarcinomas, particularly of the pancreas, is vastly important for its therapeutics. Here we point out the overlooked critical role of calmodulin (CaM). Calmodulin selectively binds to GTP-bound K-Ras4B; but not to other Ras isoforms. Cell proliferation and growth require the MAPK (Raf/MEK/ERK) and PI3K/Akt pathways. We propose that Ca2+/calmodulin promote PI3K alpha/Akt signaling, and suggest how. The elevated calcium levels clinically observed in adenocarcinomas may explain calmodulin's involvement in recruiting and stimulating PI3K alpha through interaction with its n/cSH2 domains as well as K-Ras4B; importantly, it also explains why K-Ras4B specifically is a key player in ductal carcinomas, such as pancreatic (PDAC), colorectal (CRC), and lung cancers. We hypothesize that calmodulin recruits and helps activate PI3K alpha at the membrane, and that this is the likely reason for Ca2+/calmodulin dependence in adenocarcinomas. Calmodulin can contribute to initiation/progression of ductal cancers via both PI3K alpha/Akt and Raf/MEK/ERK pathways. Blocking the K-Ras4B/MAPK pathway and calmodulin/PI3Ka binding in a K-Ras4B/calmodulin/PI3K alpha trimer could be a promising adenocarcinoma-specific therapeutic strategy. (C) 2015 AACR.
C1 [Nussinov, Ruth; Tsai, Chung-Jung; Jang, Hyunbum] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
   [Muratcioglu, Serena; Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey.
   [Gursoy, Attila] Koc Univ, Dept Comp Engn, Istanbul, Turkey.
RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, NCI Frederick, Bldg 542, Frederick, MD 21702 USA.
EM nussinor@helix.nih.gov
RI Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU TUBITAK [114M196]; Frederick National Laboratory for Cancer Research,
   NIH [HHSN261200800001E]; Intramural Research Program of NIH, Frederick
   National Lab, Center for Cancer Research
FX This work has been supported by TUBITAK Research Grant No. 114M196. This
   project has been funded in whole or in part with federal funds from the
   Frederick National Laboratory for Cancer Research, NIH, under contract
   HHSN261200800001E. This work was supported (in part) by the Intramural
   Research Program of NIH, Frederick National Lab, Center for Cancer
   Research.
NR 131
TC 19
Z9 19
U1 3
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
EI 1557-3125
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD SEP
PY 2015
VL 13
IS 9
BP 1265
EP 1273
DI 10.1158/1541-7786.MCR-15-0165
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CT7KA
UT WOS:000362992400001
PM 26085527
ER

PT J
AU Cameron, E
   Battle, KE
   Bhatt, S
   Weiss, DJ
   Bisanzio, D
   Mappin, B
   Dalrymple, U
   Hay, SI
   Smith, DL
   Griffin, JT
   Wenger, EA
   Eckhoff, PA
   Smith, TA
   Penny, MA
   Gething, PW
AF Cameron, Ewan
   Battle, Katherine E.
   Bhatt, Samir
   Weiss, Daniel J.
   Bisanzio, Donal
   Mappin, Bonnie
   Dalrymple, Ursula
   Hay, Simon I.
   Smith, David L.
   Griffin, Jamie T.
   Wenger, Edward A.
   Eckhoff, Philip A.
   Smith, Thomas A.
   Penny, Melissa A.
   Gething, Peter W.
TI Defining the relationship between infection prevalence and clinical
   incidence of Plasmodium falciparum malaria
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SUB-SAHARAN AFRICA; SEASONAL MALARIA; TRANSMISSION INTENSITY;
   WEST-AFRICA; EPIDEMIOLOGIC MODEL; MATHEMATICAL-MODEL; BURKINA-FASO;
   CHILDREN; MORBIDITY; DISEASE
AB In many countries health system data remain too weak to accurately enumerate Plasmodium falciparum malaria cases. In response, cartographic approaches have been developed that link maps of infection prevalence with mathematical relationships to predict the incidence rate of clinical malaria. Microsimulation (or 'agent-based') models represent a powerful new paradigm for defining such relationships; however, differences in model structure and calibration data mean that no consensus yet exists on the optimal form for use in disease-burden estimation. Here we develop a Bayesian statistical procedure combining functional regression-based model emulation with Markov Chain Monte Carlo sampling to calibrate three selected microsimulation models against a purpose-built data set of age-structured prevalence and incidence counts. This allows the generation of ensemble forecasts of the prevalence-incidence relationship stratified by age, transmission seasonality, treatment level and exposure history, from which we predict accelerating returns on investments in large-scale intervention campaigns as transmission and prevalence are progressively reduced.
C1 [Cameron, Ewan; Battle, Katherine E.; Bhatt, Samir; Weiss, Daniel J.; Bisanzio, Donal; Mappin, Bonnie; Dalrymple, Ursula; Smith, David L.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
   [Hay, Simon I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.
   [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Griffin, Jamie T.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London W2 1PG, England.
   [Wenger, Edward A.; Eckhoff, Philip A.] Inst Dis Modeling, Bellevue, WA 98005 USA.
   [Smith, Thomas A.; Penny, Melissa A.] Univ Basel, Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, CH-4002 Basel, Switzerland.
RP Gething, PW (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg, Oxford OX1 3PS, England.
EM peter.gething@zoo.ox.ac.uk
RI Smith, Thomas/B-5569-2015; Hay, Simon/F-8967-2015; Penny,
   Melissa/N-6838-2015; Smith, David/L-8850-2013; 
OI Smith, Thomas/0000-0002-3650-9381; Hay, Simon/0000-0002-0611-7272;
   Penny, Melissa/0000-0002-4972-593X; Mappin, Bonnie/0000-0002-1205-719X;
   Smith, David/0000-0003-4367-3849; Gething, Peter/0000-0001-6759-5449
FU UK Medical Research Council (MRC) [K00669X]; UK Department for
   International Development (DFID) under the MRC/DFID Concordat agreement
   [K00669X]; Bill and Melinda Gates Foundation [OPP1068048, OPP1106023,
   OPP1119467]; Bill and Melinda Gates Foundation (BMGF) [OPP1032350];
   Wellcome Trust [095066]; RAPIDD program of the Science & Technology
   Directorate, Department of Homeland Security; Fogarty International
   Center, National Institutes of Health; MRC [G1002284]; Global Good Fund
FX P.W.G. is a Career Development Fellow (#K00669X) jointly funded by the
   UK Medical Research Council (MRC) and the UK Department for
   International Development (DFID) under the MRC/DFID Concordat agreement
   and receives support from the Bill and Melinda Gates Foundation
   (#OPP1068048 and #OPP1106023). These grants also support E.C., S.B.,
   B.M., U.D., D.J.W. and D.B. The Swiss TPH component was supported
   through the project #OPP1032350 funded by the Bill and Melinda Gates
   Foundation (BMGF). S.I.H. is funded by a Senior Research Fellowship from
   the Wellcome Trust (#095066), which also supports K.E.B., and a grant
   from the Bill & Melinda Gates Foundation (#OPP1119467). He also
   acknowledges funding support from the RAPIDD program of the Science &
   Technology Directorate, Department of Homeland Security, and the Fogarty
   International Center, National Institutes of Health. J.T.G. is funded by
   an MRC Fellowship (#G1002284). E.A.W. and P.A.E. are funded by the
   Global Good Fund. We also appreciate the support and interactions
   facilitated by the Bill & Melinda Gates Foundation-funded Malaria
   Modeling Consortium (OPP1119467).
NR 76
TC 12
Z9 12
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD SEP
PY 2015
VL 6
AR 8170
DI 10.1038/ncomms9170
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT7TG
UT WOS:000363016800008
PM 26348689
ER

PT J
AU Edwards, DN
   Machwe, A
   Chen, L
   Bohr, VA
   Orren, DK
AF Edwards, Deanna N.
   Machwe, Amrita
   Chen, Li
   Bohr, Vilhelm A.
   Orren, David K.
TI The DNA structure and sequence preferences of WRN underlie its function
   in telomeric recombination events
SO NATURE COMMUNICATIONS
LA English
DT Article
ID WERNER-SYNDROME PROTEIN; G-QUADRUPLEX; MAMMALIAN TELOMERES; HOLLIDAY
   JUNCTIONS; SYNDROME HELICASE; STRAND EXCHANGE; RECQ HELICASES; IN-VITRO;
   D-LOOPS; TRF2
AB Telomeric abnormalities caused by loss of function of the RecQ helicase WRN are linked to the multiple premature ageing phenotypes that characterize Werner syndrome. Here we examine WRN's role in telomeric maintenance, by comparing its action on a variety of DNA structures without or with telomeric sequences. Our results show that WRN clearly prefers to act on strand invasion intermediates in a manner that favours strand invasion and exchange. Moreover, WRN unwinding of these recombination structures is further enhanced when the invading strand contains at least three G-rich single-stranded telomeric repeats. These selectivities are most pronounced at NaCl concentrations within the reported intranuclear monovalent cation concentration range, and are partly conferred by WRN's C-terminal region. Importantly, WRN's specificity for the G-rich telomeric sequence within this precise structural context is particularly relevant to telomere metabolism and strongly suggests a physiological role in telomeric recombination processes, including T-loop dynamics.
C1 [Edwards, Deanna N.; Machwe, Amrita; Orren, David K.] Univ Kentucky, Coll Med, Dept Toxicol & Canc Biol, Lexington, KY 40536 USA.
   [Machwe, Amrita; Chen, Li; Orren, David K.] Univ Kentucky, Coll Med, Markey Canc Ctr, Lexington, KY 40536 USA.
   [Chen, Li] Univ Kentucky, Coll Publ Hlth, Dept Canc Biostat, Lexington, KY 40536 USA.
   [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Machwe, A (reprint author), Univ Kentucky, Coll Med, Dept Toxicol & Canc Biol, Lexington, KY 40536 USA.
EM amach0@uky.edu; dkorre2@uky.edu
OI Edwards, Deanna/0000-0001-5481-5879
FU National Institute of Aging [AG027258]; Intramural Program of the
   National Institute on Aging, National Institutes of Health; National
   Institute of Environmental Health Sciences [T32ES007266]; Biostatistics
   and Bioinformatics Shared Resource of the University of Kentucky Markey
   Cancer Center [P30CA177558]
FX This work was supported by grant AG027258 from the National Institute of
   Aging to D.K.O. and A.M. and also in part by funds from the Intramural
   Program of the National Institute on Aging, National Institutes of
   Health. D.N.E. was supported in part by training grant T32ES007266 from
   the National Institute of Environmental Health Sciences. This research
   was also supported by the Biostatistics and Bioinformatics Shared
   Resource of the University of Kentucky Markey Cancer Center
   (P30CA177558).
NR 64
TC 2
Z9 4
U1 3
U2 13
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 SEP
PY 2015
VL 6
AR 8331
DI 10.1038/ncomms9331
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT7UY
UT WOS:000363021200006
PM 26420422
ER

PT J
AU Ingaramo, M
   York, AG
   Andrade, EJ
   Rainey, K
   Patterson, GH
AF Ingaramo, Maria
   York, Andrew G.
   Andrade, Eric J.
   Rainey, Kristin
   Patterson, George H.
TI Two-photon-like microscopy with orders-of-magnitude lower illumination
   intensity via two-step fluorescence
SO NATURE COMMUNICATIONS
LA English
DT Article
ID RESOLUTION; PROTEINS; SUPERRESOLUTION; NANOSCOPY; LIVE; BREAKING;
   TISSUE; LIMIT
AB We describe two-step fluorescence microscopy, a new approach to non-linear imaging based on positive reversible photoswitchable fluorescent probes. The protein Padron approximates ideal two-step fluorescent behaviour: it equilibrates to an inactive state, converts to an active state under blue light, and blue light also excites this active state to fluoresce. Both activation and excitation are linear processes, but the total fluorescent signal is quadratic, proportional to the square of the illumination dose. Here, we use Padron's quadratic non-linearity to demonstrate the principle of two-step microscopy, similar in principle to two-photon microscopy but with orders-of-magnitude better cross-section. As with two-photon, quadratic non-linearity from two-step fluorescence improves resolution and reduces unwanted out-of-focus excitation, and is compatible with structured illumination microscopy. We also show two-step and two-photon imaging can be combined to give quartic non-linearity, further improving imaging in challenging samples. With further improvements, two-step fluorophores could replace conventional fluorophores for many imaging applications.
C1 [Ingaramo, Maria; York, Andrew G.; Andrade, Eric J.; Rainey, Kristin; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP York, AG (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
EM andrew.g.york+ncomms@gmail.com
FU Intramural Research Program of the National Institutes of Health;
   National Institute of Biomedical Imaging and Bioengineering
FX We thank Hari Shroff (National Institute of Biomedical Imaging and
   Bioengineering, National Institutes of Health, Bethesda, MD) for useful
   discussions, Stefan Jakobs (Max Planck Institute for Biophysical
   Chemistry, Gottingen, Germany) for the pQE31-Padron plasmid, and Clare
   Waterman and Robert Fischer (National Heart, Lung, and Blood Institute,
   National Institutes of Health, Bethesda, MD) for the F-tractin-GFP
   construct. This work was supported by the Intramural Research Program of
   the National Institutes of Health and the National Institute of
   Biomedical Imaging and Bioengineering.
NR 43
TC 2
Z9 2
U1 4
U2 29
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 SEP
PY 2015
VL 6
AR 8184
DI 10.1038/ncomms9184
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT7TJ
UT WOS:000363017100011
PM 26333365
ER

PT J
AU Manna, S
   Kim, JK
   Bauge, C
   Cam, M
   Zhao, YM
   Shetty, J
   Vacchio, MS
   Castro, E
   Tran, B
   Tessarollo, L
   Bosselut, R
AF Manna, Sugata
   Kim, Jong Kyong
   Bauge, Catherine
   Cam, Margaret
   Zhao, Yongmei
   Shetty, Jyoti
   Vacchio, Melanie S.
   Castro, Ehydel
   Tran, Bao
   Tessarollo, Lino
   Bosselut, Remy
TI Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell
   differentiation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; CHIP-SEQ DATA;
   GENE-EXPRESSION; LYMPHOCYTE EGRESS; LINEAGE FATE; POLYCOMB; CHROMATIN;
   RECEPTOR; DOMAINS
AB Although histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4(+) T-cell precursors. Here we show that both enzymes redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Thymocyte expression of S1pr1 was not rescued in Jmjd3- and Utx-deficient male mice, which carry the catalytically inactive Utx homolog Uty, supporting the conclusion that it requires H3K27Me3 demethylase activity. These findings demonstrate that Jmjd3 and Utx are required for T-cell development, and point to a requirement for their H3K27Me3 demethylase activity in cell differentiation.
C1 [Manna, Sugata; Kim, Jong Kyong; Bauge, Catherine; Vacchio, Melanie S.; Castro, Ehydel; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Cam, Margaret] NCI, Collaborat Bioinformat Resource, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Zhao, Yongmei; Shetty, Jyoti; Tran, Bao] Leidos Biomed Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
   [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA.
RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM remy@helix.nih.gov
OI BAUGE, Catherine/0000-0001-5642-998X
FU Intramural Research Program of the National Cancer Institute, Center for
   Cancer Research
FX We thank J. Cyster for the anti-S1pr1 antibody, H. Chi and R. Flavell
   for the S1pr1 transgenic mouse, S. Reid and E. Southon for assistance in
   generating the targeted alleles, B. Taylor, K. Wolcott and S. Banerjee
   for cell sorting, X. Wu for microarray analyses, and J. Ashwell, A.
   Bhandoola, A. Gegonne, P. Love, J. O'Shea and D. Singer for reading the
   manuscript. This work utilized the computational resources of the NIH
   HPC Biowulf cluster and was supported by the Intramural Research Program
   of the National Cancer Institute, Center for Cancer Research.
NR 63
TC 11
Z9 12
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD SEP
PY 2015
VL 6
AR 8152
DI 10.1038/ncomms9152
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT7TB
UT WOS:000363016300001
PM 26328764
ER

PT J
AU McFarland, JM
   Bondy, AG
   Saunders, RC
   Cumming, BG
   Butts, DA
AF McFarland, James M.
   Bondy, Adrian G.
   Saunders, Richard C.
   Cumming, Bruce G.
   Butts, Daniel A.
TI Saccadic modulation of stimulus processing in primary visual cortex
SO NATURE COMMUNICATIONS
LA English
DT Article
ID LATERAL GENICULATE-NUCLEUS; RETINAL GANGLION-CELLS; V1 RECEPTIVE-FIELDS;
   EYE-MOVEMENTS; STRIATE CORTEX; MACAQUE MONKEY; NATURAL SCENES; SUPERIOR
   COLLICULUS; CORTICAL-NEURONS; NEURAL ACTIVITY
AB Saccadic eye movements play a central role in primate vision. Yet, relatively little is known about their effects on the neural processing of visual inputs. Here we examine this question in primary visual cortex (V1) using receptive-field-based models, combined with an experimental design that leaves the retinal stimulus unaffected by saccades. This approach allows us to analyse V1 stimulus processing during saccades with unprecedented detail, revealing robust perisaccadic modulation. In particular, saccades produce biphasic firing rate changes that are composed of divisive gain suppression followed by an additive rate increase. Microsaccades produce similar, though smaller, modulations. We furthermore demonstrate that this modulation is likely inherited from the LGN, and is driven largely by extra-retinal signals. These results establish a foundation for integrating saccades into existing models of visual cortical stimulus processing, and highlight the importance of studying visual neuron function in the context of eye movements.
C1 [McFarland, James M.; Butts, Daniel A.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
   [McFarland, James M.; Butts, Daniel A.] Univ Maryland, Program Neurosci & Cognit Sci, College Pk, MD 20742 USA.
   [Bondy, Adrian G.; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
   [Bondy, Adrian G.] Brown Univ, Brown NIH Neurosci Grad Partnership Program, Providence, RI 02912 USA.
   [Saunders, Richard C.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP McFarland, JM (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
EM jmmcfarl@umd.edu
OI McFarland, James/0000-0001-9978-480X; Butts, Daniel/0000-0002-0158-5317
FU NSF-CRCNS [IIS-0904430/CNS-103331]; NSF [IIS-1350990]; NEI/NIH
   [F32EY023921]; NEI/NIH; NIMH/NIH
FX This work was supported by NSF-CRCNS IIS-0904430/CNS-103331 (J.M.M. and
   D.A.B.), NSF IIS-1350990 (D.A.B.), NEI/NIH F32EY023921 (J.M.M.) and the
   Intramural Research Program of the NEI/NIH (A.G.B. and B.G.C.) and
   NIMH/NIH (R.C.S.). We are grateful to D. Parker and I. Bunea for
   providing excellent animal care, and to Y. Cui for providing code used
   for analysis.
NR 70
TC 7
Z9 7
U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD SEP
PY 2015
VL 6
AR 8110
DI 10.1038/ncomms9110
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT6UV
UT WOS:000362948800001
PM 26370359
ER

PT J
AU Ying, TL
   Prabakaran, P
   Du, LY
   Shi, W
   Feng, Y
   Wang, YP
   Wang, LS
   Li, W
   Jiang, SB
   Dimitrov, DS
   Zhou, TQ
AF Ying, Tianlei
   Prabakaran, Ponraj
   Du, Lanying
   Shi, Wei
   Feng, Yang
   Wang, Yanping
   Wang, Lingshu
   Li, Wei
   Jiang, Shibo
   Dimitrov, Dimiter S.
   Zhou, Tongqing
TI Junctional and allele-specific residues are critical for MERS-CoV
   neutralization by an exceptionally potent germline-like antibody
SO NATURE COMMUNICATIONS
LA English
DT Article
ID RESPIRATORY SYNDROME CORONAVIRUS; HUMAN MONOCLONAL-ANTIBODIES;
   MATURATION PATHWAY; IMMUNOGEN DESIGN; STRUCTURAL BASIS; BAT CORONAVIRUS;
   SAUDI-ARABIA; RECEPTOR; HIV-1; VIRUSES
AB The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (similar to 36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.
C1 [Ying, Tianlei; Li, Wei; Jiang, Shibo] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Minist Educ, Shanghai 200032, Peoples R China.
   [Ying, Tianlei; Li, Wei; Jiang, Shibo] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Minist Hlth, Shanghai 200032, Peoples R China.
   [Prabakaran, Ponraj; Feng, Yang; Wang, Yanping; Li, Wei; Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
   [Du, Lanying; Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10065 USA.
   [Shi, Wei; Wang, Lingshu; Zhou, Tongqing] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Ying, TL (reprint author), Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Minist Educ, Shanghai 200032, Peoples R China.
EM tlying@fudan.edu.cn; tzhou@nih.gov
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU Intramural Research Programs of the Vaccine Research Center, National
   Institute of Allergy and Infectious Diseases; Center for Cancer
   Research, National Cancer Institute, National Institutes of Health;
   National Science and Technology Major Project of China [2012ZX10002002];
   US Department of Energy, Basic Energy Sciences, Office of Science
   [W-31-109-Eng-38]
FX We thank members of the Structural Biology Section, Structural
   Bioinformatics Core Section, Vaccine Research Center, National Institute
   of Allergy and Infectious Diseases, National Institutes for Health, for
   comments and suggestions on the manuscript. We thank Peter Kwong and
   Barney Graham for advices on the structural study. Support for this work
   was provided by the Intramural Research Programs of the Vaccine Research
   Center, National Institute of Allergy and Infectious Diseases and the
   Center for Cancer Research, National Cancer Institute, National
   Institutes of Health, as well as by the National Science and Technology
   Major Project of China (2012ZX10002002). Use of sector 22 (Southeast
   Region Collaborative Access Team) at the Advanced Photon Source was
   supported by the US Department of Energy, Basic Energy Sciences, Office
   of Science, under contract number W-31-109-Eng-38.
NR 50
TC 9
Z9 10
U1 0
U2 11
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 SEP
PY 2015
VL 6
AR 8223
DI 10.1038/ncomms9223
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT7TK
UT WOS:000363017200003
PM 26370782
ER

PT J
AU Zanvit, P
   Konkel, JE
   Jiao, X
   Kasagi, S
   Zhang, DF
   Wu, RQ
   Chia, C
   Ajami, NJ
   Smith, DP
   Petrosino, JF
   Abbatiello, B
   Nakatsukasa, H
   Chen, QM
   Belkaid, Y
   Chen, ZJ
   Chen, WJ
AF Zanvit, Peter
   Konkel, Joanne E.
   Jiao, Xue
   Kasagi, Shimpei
   Zhang, Dunfang
   Wu, Ruiqing
   Chia, Cheryl
   Ajami, Nadim J.
   Smith, Daniel P.
   Petrosino, Joseph F.
   Abbatiello, Brittany
   Nakatsukasa, Hiroko
   Chen, Qianming
   Belkaid, Yasmine
   Chen, Zi-Jiang
   Chen, WanJun
TI Antibiotics in neonatal life increase murine susceptibility to
   experimental psoriasis
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DELTA T-CELLS; INTESTINAL MICROBIOTA; GUT MICROBIOTA; SKIN INFLAMMATION;
   MICE; IMIQUIMOD; DISEASE; HEALTH; LYMPHOCYTES; MECHANISMS
AB Psoriasis is an inflammatory skin disease affecting similar to 2% of the world's population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing gamma delta(+) T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis.
C1 [Zanvit, Peter; Konkel, Joanne E.; Jiao, Xue; Kasagi, Shimpei; Zhang, Dunfang; Wu, Ruiqing; Chia, Cheryl; Abbatiello, Brittany; Nakatsukasa, Hiroko; Chen, WanJun] NIDCR, Mucosal Immunol Sect, OPCB, NIH, Bethesda, MD 20892 USA.
   [Konkel, Joanne E.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
   [Jiao, Xue; Chen, Zi-Jiang] Shandong Univ, Shandong Prov Hosp, Ctr Reprod Med, Jinan 250001, Peoples R China.
   [Zhang, Dunfang; Wu, Ruiqing; Chen, Qianming] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China.
   [Ajami, Nadim J.; Smith, Daniel P.; Petrosino, Joseph F.] Baylor Coll Med, Dept Mol Virol & Microbiol, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 USA.
   [Belkaid, Yasmine] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, WJ (reprint author), NIDCR, Mucosal Immunol Sect, OPCB, NIH, Bethesda, MD 20892 USA.
EM wchen@mail.nih.gov
OI Smith, Daniel/0000-0002-2479-2044
FU NIH, NIDCR
FX We thank Nathan Goldberg at MIU, NIDCR for critical reading of the
   manuscript. We thank Ginger A. Metcalf, Donna M. Muzny, and Richard A.
   Gibbs at the Human Genome Sequencing Center at Baylor College of
   Medicine for their support in sequencing. The Intramural Research
   Program of the NIH, NIDCR, supported this research.
NR 34
TC 7
Z9 8
U1 1
U2 8
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 SEP
PY 2015
VL 6
AR 8424
DI 10.1038/ncomms9424
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT9MC
UT WOS:000363140200002
PM 26416167
ER

PT J
AU Zhang, YY
   Li, F
   Wang, Y
   Pitre, A
   Fang, ZZ
   Frank, MW
   Calabrese, C
   Krausz, KW
   Neale, G
   Frase, S
   Vogel, P
   Rock, CO
   Gonzalez, FJ
   Schuetz, JD
AF Zhang, Yuanyuan
   Li, Fei
   Wang, Yao
   Pitre, Aaron
   Fang, Zhong-ze
   Frank, Matthew W.
   Calabrese, Christopher
   Krausz, Kristopher W.
   Neale, Geoffrey
   Frase, Sharon
   Vogel, Peter
   Rock, Charles O.
   Gonzalez, Frank J.
   Schuetz, John D.
TI Maternal bile acid transporter deficiency promotes neonatal demise
SO NATURE COMMUNICATIONS
LA English
DT Article
ID RESPIRATORY-DISTRESS-SYNDROME; INTRAHEPATIC CHOLESTASIS; PREGNANCY;
   EXPRESSION; SURFACTANT; SERUM; MICE; PROFILES; FETAL; METABOLISM
AB Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to atelectasis-producing pulmonary hypoxia, which recapitulates the neonatal respiratory distress of human ICP. Neonates of Abcb11-deficient mothers have elevated pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile acid concentrations and increases neonatal survival. We identify pulmonary bile acids as a key factor in the disruption of the structure of pulmonary surfactant in neonates of ICP. These findings have important implications for neonatal respiratory failure, especially when maternal bile acids are elevated during pregnancy, and highlight potential pathways and targets amenable to therapeutic intervention to ameliorate this condition.
C1 [Zhang, Yuanyuan; Wang, Yao; Pitre, Aaron; Schuetz, John D.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
   [Li, Fei; Fang, Zhong-ze; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
   [Frank, Matthew W.; Rock, Charles O.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
   [Calabrese, Christopher] St Jude Childrens Res Hosp, Small Anim Imaging Core, Memphis, TN 38105 USA.
   [Neale, Geoffrey] St Jude Childrens Res Hosp, Hartwell Ctr, Memphis, TN 38105 USA.
   [Frase, Sharon] St Jude Childrens Res Hosp, Cellular Imaging Shared Resource, Memphis, TN 38105 USA.
   [Vogel, Peter] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
RP Schuetz, JD (reprint author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM john.schuetz@stjude.org
RI Pitre, Aaron/C-3423-2016; 
OI Pitre, Aaron/0000-0002-3017-2140; Frank, Matthew/0000-0002-4914-1440
FU NIH [HL114066 GM60904]; COR [GM034496]; ALSAC; Cancer Center [P30
   CA021765]
FX We thank Melissa Johnson (Small Animal Imaging Core) for high resolution
   ultrasound imaging and timed pregnancy assessments. We thank Dr Paul
   Dawson's laboratory (Emory University) for the Asbt, Ost alpha and Ost
   beta antibodies and expert advice on the everted gut sac method. This
   research was supported in part by grants from the NIH (JDS (HL114066
   GM60904)), COR (GM034496), ALSAC and Cancer Center support grant P30
   CA021765. We thank Drs William E. Evans (St Jude Children's Research
   Hospital) and Laura Bull (University of San Francisco) for insightful
   comments and suggestions.
NR 40
TC 3
Z9 3
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD SEP
PY 2015
VL 6
AR 8186
DI 10.1038/ncomms9186
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CT7TJ
UT WOS:000363017100013
PM 26416771
ER

PT J
AU Smith, LM
   Diaz, S
   LaGasse, LL
   Wouldes, T
   Derauf, C
   Newman, E
   Arria, A
   Huestis, MA
   Haning, W
   Strauss, A
   Della Grotta, S
   Dansereau, LM
   Neal, C
   Lester, BM
AF Smith, Lynne M.
   Diaz, Sabrina
   LaGasse, Linda L.
   Wouldes, Trecia
   Derauf, Chris
   Newman, Elana
   Arria, Amelia
   Huestis, Marilyn A.
   Haning, William
   Strauss, Arthur
   Della Grotta, Sheri
   Dansereau, Lynne M.
   Neal, Charles
   Lester, Barry M.
TI Developmental and behavioral consequences of prenatal methamphetamine
   exposure: A review of the Infant Development, Environment, and Lifestyle
   (IDEAL) study
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Review
DE Longitudinal; Methamphetamine; Neurodevelopment; Prenatal exposure
ID SUBSTANCE USE; POSTNATAL-DEVELOPMENT; INTRAUTERINE GROWTH; MATERNAL
   DEPRESSION; PREWEANING PERIODS; RAT PUPS; PREGNANCY; CHILDREN; AGE;
   OUTCOMES
AB This study reviews the findings from the Infant Development, Environment, and Lifestyle (IDEAL) study, a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children. No neonatal abstinence syndrome requiring pharmacologic intervention was observed but heavy drug exposure was associated with increased stress responses in the neonatal period. Poorer inhibitory control was also observed in heavy methamphetamine exposed children placing them at high risk for impaired executive function. Independent of methamphetamine exposure, children with more responsive home environments to developmental and emotional needs demonstrated lower risks for internalizing and externalizing behavior. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Smith, Lynne M.; Diaz, Sabrina] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Dept Pediat, Los Angeles, CA USA.
   [Smith, Lynne M.; Diaz, Sabrina] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [LaGasse, Linda L.; Della Grotta, Sheri; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Pediat Div,Ctr Study Children Risk, Providence, RI USA.
   [LaGasse, Linda L.; Neal, Charles] Univ Auckland, Dept Psychol Med, Auckland 1, New Zealand.
   [Derauf, Chris; Haning, William] Univ Hawaii, John A Burns Sch Med, Dept Pediat, Honolulu, HI 96822 USA.
   [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
   [Arria, Amelia] Univ Maryland, Sch Publ Hlth, Family Sci Dept, Ctr Young Adult Hlth & Dev, College Pk, MD 20742 USA.
   [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
   [Strauss, Arthur] MCHLB, Long Beach, CA USA.
RP Smith, LM (reprint author), Dept Pediat, Div Neonatol, 1124 West Carson St,RB 1,Box 446, Torrance, CA 90502 USA.
EM smith@labiomed.org
OI Arria, Amelia/0000-0002-6360-9265; Wouldes, Trecia/0000-0002-6609-8464
FU NCATS NIH HHS [1UL1-TR000124, UL1 TR000124]; NCRR NIH HHS [5P20 RR11091,
   P20 RR011091]; NIDA NIH HHS [R01 DA014948, 1R01DA014948]
NR 69
TC 6
Z9 6
U1 12
U2 22
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
EI 1872-9738
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD SEP-OCT
PY 2015
VL 51
BP 35
EP 44
DI 10.1016/j.ntt.2015.07.006
PG 10
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA CT6LQ
UT WOS:000362924900005
PM 26212684
ER

PT J
AU Kadri, SS
   Remy, KE
   Strich, JR
   Gea-Banacloche, J
   Leitman, SF
AF Kadri, Sameer S.
   Remy, Kenneth E.
   Strich, Jeffrey R.
   Gea-Banacloche, Juan
   Leitman, Susan F.
TI Role of granulocyte transfusions in invasive fusariosis: systematic
   review and single-center experience
SO TRANSFUSION
LA English
DT Review
ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC-CELL TRANSPLANTATION; SEVERE
   APLASTIC-ANEMIA; AMPHOTERICIN-B; IMMUNOCOMPROMISED PATIENTS; HEMATOLOGIC
   MALIGNANCIES; MARROW-TRANSPLANTATION; DISSEMINATED INFECTION;
   ACUTE-LEUKEMIA; MANAGEMENT
AB BACKGROUND: Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia.
   STUDY DESIGN AND METHODS: We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single-center case series detailing our experience (1996-2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone-and granulocyte-colony-stimulating factor-stimulated donors.
   RESULTS: Twenty-three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor-stimulated GTs generated mean "same-day" neutrophil increments of 3.35 x 10(9) +/- 1.24 x 10(9)/L and mean overall posttransfusion neutrophil increments of 2.46 x 10(9) +/- 0.85 x 10(9)/L. Progressive decrements in neutrophil response to GTs in two cases were attributed to GT-related HLA alloimmunization.
   CONCLUSION: In patients with IF, donor-stimulated GTs may contribute to high response rates by effectively bridging periods of neutropenia or marrow suppression. However, their utility in the absence of neutrophil recovery remains questionable.
C1 [Kadri, Sameer S.; Remy, Kenneth E.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
   [Strich, Jeffrey R.] MedStar Georgetown Univ Hosp, Dept Internal Med, Washington, DC USA.
   [Gea-Banacloche, Juan] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Leitman, Susan F.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Kadri, SS (reprint author), NIH, Ctr Clin, Dept Crit Care Med, 10 Ctr Dr,Bldg 10 2C-145, Bethesda, MD 20892 USA.
EM sameer.kadri@nih.gov
OI Remy, Kenneth/0000-0001-5222-9884
FU intramural National Institutes of Health funds; US government
FX This work was supported by intramural National Institutes of Health
   funds. The work by the authors was done as part of US government-funded
   research; however, the opinions expressed are not necessarily those of
   the National Institutes of Health.
NR 39
TC 5
Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
IS 9
BP 2076
EP 2085
DI 10.1111/trf.13099
PG 10
WC Hematology
SC Hematology
GA CT6HO
UT WOS:000362914300007
PM 25857209
ER

PT J
AU Spitalnik, SL
   Triulzi, D
   Devine, DV
   Dzik, WH
   Eder, AF
   Gernsheimer, T
   Josephson, CD
   Kor, DJ
   Luban, NLC
   Roubinian, NH
   Mondoro, T
   Welniak, LA
   Zou, SM
   Glynn, S
AF Spitalnik, Steven L.
   Triulzi, Darrell
   Devine, Dana V.
   Dzik, Walter H.
   Eder, Anne F.
   Gernsheimer, Terry
   Josephson, Cassandra D.
   Kor, Daryl J.
   Luban, Naomi L. C.
   Roubinian, Nareg H.
   Mondoro, Traci
   Welniak, Lisbeth A.
   Zou, Shimian
   Glynn, Simone
CA State Sci Transfusion Med Working
TI 2015 proceedings of the National Heart, Lung, and Blood Institute's
   State of the Science in Transfusion Medicine symposium
SO TRANSFUSION
LA English
DT Article; Proceedings Paper
CT Meeting on the State of the Science in Transfusion Medicine
CY MAR 25-26, 2015
CL Natl Inst Hlth, Bethesda, MD
SP Natl Heart Lung & Blood Inst
HO Natl Inst Hlth
ID SICKLE-CELL-DISEASE; TRAUMA-ASSOCIATED COAGULOPATHY;
   RANDOMIZED-CLINICAL-TRIAL; CARDIAC-SURGERY; PLATELET TRANSFUSIONS;
   NONIDENTICAL PLASMA; DRIED PLASMA; STEM-CELLS; MORTALITY;
   ALLOIMMUNIZATION
AB On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three "classical" transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Before the meeting, four working groups, one for each area, prepared five major questions for discussion along with a list of five to 10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in keynote lectures, small-group breakout sessions, and large-group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross-cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine.
C1 [Spitalnik, Steven L.] Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York Presbyterian Hosp, New York, NY 10032 USA.
   [Triulzi, Darrell] Univ Pittsburgh, Inst Transfus Med, Pittsburgh, PA USA.
   [Triulzi, Darrell] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
   [Devine, Dana V.] Univ British Columbia, Canadian Blood Serv, Vancouver, BC V5Z 1M9, Canada.
   [Devine, Dana V.] Univ British Columbia, Ctr Blood Res, Vancouver, BC V5Z 1M9, Canada.
   [Dzik, Walter H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Dzik, Walter H.] Harvard Univ, Sch Med, Boston, MA USA.
   [Eder, Anne F.] Amer Red Cross, Natl Headquarters, Rockville, MD USA.
   [Gernsheimer, Terry] Univ Washington, Dept Med, Seattle, WA USA.
   [Josephson, Cassandra D.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
   [Kor, Daryl J.] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN USA.
   [Luban, Naomi L. C.] George Washington Univ, Sch Med, Div Lab Med, Ctr Canc & Blood Dis,Childrens Natl Hlth Syst, Washington, DC USA.
   [Luban, Naomi L. C.] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA.
   [Roubinian, Nareg H.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA.
   [Roubinian, Nareg H.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
   [Mondoro, Traci; Welniak, Lisbeth A.; Zou, Shimian; Glynn, Simone] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
RP Spitalnik, SL (reprint author), Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York Presbyterian Hosp, 630 West 168th St,Room P&S 14-434, New York, NY 10032 USA.
EM ss2479@cumc.columbia.edu
RI Karam, Oliver/N-6216-2014; Dumont, Larry/B-3994-2011; Li,
   Renhao/B-1257-2012; 
OI Karam, Oliver/0000-0001-6606-1736; Dumont, Larry/0000-0002-1715-0748;
   Li, Renhao/0000-0002-5806-5080; Spitalnik, Steven/0000-0002-8528-4561
FU NHLBI NIH HHS [P01 HL107146, R01 HL089224, R01 HL115557, R01 HL121232]
NR 56
TC 20
Z9 20
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2015
VL 55
IS 9
BP 2282
EP 2290
DI 10.1111/trf.13250
PG 9
WC Hematology
SC Hematology
GA CT6HO
UT WOS:000362914300028
PM 26260861
ER

PT J
AU Levine, ME
   Hosgood, HD
   Chen, B
   Absher, D
   Assimes, T
   Horvath, S
AF Levine, Morgan E.
   Hosgood, H. Dean
   Chen, Brian
   Absher, Devin
   Assimes, Themistocles
   Horvath, Steve
TI DNA methylation age of blood predicts future onset of lung cancer in the
   women's health initiative
SO AGING-US
LA English
DT Article
DE epigenetic clock; biological age; lung cancer
ID T-CELLS; SUSCEPTIBILITY LOCUS; 15Q25; RISK; IMMUNOSENESCENCE;
   CENTENARIANS; MORTALITY; VARIANTS
AB Lung cancer is considered an age-associated disease, whose progression is in part due to accumulation of genomic instability as well as age-related decline in system integrity and function. Thus even among individuals exposed to high levels of genotoxic carcinogens, such as those found in cigarette smoke, lung cancer susceptibility may vary as a function of individual differences in the rate of biological aging. We recently developed a highly accurate candidate biomarker of aging based on DNA methylation (DNAm) levels, which may prove useful in assessing risk of aging-related diseases, such as lung cancer. Using data on 2,029 females from the Women's Health Initiative, we examined whether baseline measures of "intrinsic epigenetic age acceleration" (IEAA) predicted subsequent lung cancer incidence. We observed 43 lung cancer cases over the nearly twenty years of follow-up. Results showed that standardized measures of IEAA were significantly associated with lung cancer incidence (HR: 1.50, P= 3.4x10(-3)). Furthermore, stratified Cox proportional hazard models suggested that the association may be even stronger among older individuals (70 years or above) or those who are current smokers. Overall, our results suggest that IEAA may be a useful biomarker for evaluating lung cancer susceptibility from a biological aging perspective.
C1 [Levine, Morgan E.; Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA.
   [Levine, Morgan E.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA.
   [Hosgood, H. Dean] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
   [Chen, Brian] NIA, Longitudinal Study Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
   [Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Assimes, Themistocles] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Assimes, Themistocles] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA.
RP Horvath, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA.
EM shorvath@mednet.ucla.edu
FU NIH/NHLBI [60442456 BAA23]; National Institutes of Health NIH/NIA
   [5R01AG042511-02]; NIH/NINDS [T32NS048004]; National Heart, Lung, and
   Blood Institute, National Institutes of Health, U.S. Department of
   Health and Human Services [HHSN268201100046C, HHSN268201100001C,
   HHSN268201100002C, HHSN268201100003C, HHSN268201100004C,
   HHSN271201100004C]
FX This study was supported by NIH/NHLBI 60442456 BAA23 (Assimes, Absher,
   Horvath); National Institutes of Health NIH/NIA 5R01AG042511-02 (Horvath
   and Levine); and NIH/NINDS T32NS048004 (Levine). The WHI program is
   funded by the National Heart, Lung, and Blood Institute, National
   Institutes of Health, U.S. Department of Health and Human Services
   through contracts HHSN268201100046C, HHSN268201100001C,
   HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and
   HHSN271201100004C.
NR 38
TC 16
Z9 16
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD SEP
PY 2015
VL 7
IS 9
BP 690
EP 700
PG 11
WC Cell Biology
SC Cell Biology
GA CS7KA
UT WOS:000362261300013
PM 26411804
ER

PT J
AU Moore, CG
   Spillane, S
   Simon, G
   Maxwell, B
   Rahbari-Oskoui, FF
   Braun, WE
   Chapman, AB
   Schrier, RW
   Torres, VE
   Perrone, RD
   Steinman, TI
   Brosnahan, G
   Czarnecki, PG
   Harris, PC
   Miskulin, DC
   Flessner, MF
   Bae, KT
   Abebe, KZ
   Hogan, MC
AF Moore, Charity G.
   Spillane, Susan
   Simon, Gertrude
   Maxwell, Barbara
   Rahbari-Oskoui, Frederic F.
   Braun, William E.
   Chapman, Arlene B.
   Schrier, Robert W.
   Torres, Vicente E.
   Perrone, Ronald D.
   Steinman, Theodore I.
   Brosnahan, Godela
   Czarnecki, Peter G.
   Harris, Peter C.
   Miskulin, Dana C.
   Flessner, Michael F.
   Bae, K. Ty
   Abebe, Kaleab Z.
   Hogan, Marie C.
TI Closeout of the HALT-PKD trials
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Closeout; Unblinding; Regulatory; Data coordination; Patient safety
ID POLYCYSTIC KIDNEY-DISEASE; HEART-ATTACK TRIAL; CLINICAL-TRIALS;
   FOLLOW-UP; CLINICALTRIALS.GOV; PARTICIPANTS
AB Background: The HALT Polycystic Kidney Disease Trials Network consisted of two randomized, double blind, placebo-controlled trials among patients with autosomal dominant polycystic kidney disease. The trials involved 5-8 years of participant follow-up with interventions in blood pressure and antihypertensive therapy. We provide a framework for designing and implementing closeout near the end of a trial while ensuring patient safety and maintaining scientific rigor and study morale.
   Methods: We discuss issues and resolutions for determining the last visit, tapering medications, and unblinding of participants to study allocation and results. We also discuss closure of clinical sites and Data Coordinating Center responsibilities to ensure timely release of study results and meeting the requirements of regulatory and funding authorities.
   Results: Just over 90%. of full participants had a 6-month study visit prior to their last visit preparing them for trial closeout. Nearly all patients wanted notification of study results (99%) and treatment allocation (99%). All participants were safely tapered off study and open label blood pressure medications. Within 6 months, the trials were closed, primary papers published, and 805 letters distributed to participants with results and allocation. DCC obligations for data repository and clinicaltrials.gov reporting were completed within 12 months of the last study visit.
   Conclusions: Closeout of our trials involved years of planning and significant human and financial resources. We provide questions for investigators to consider when planning closeout of their trials with focus on (1) patient safety, (2) dissemination of study results and (3) compliance with regulatory and funding responsibilities. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Moore, Charity G.] Carolinas HealthCare Syst, Charlotte, NC 28237 USA.
   [Spillane, Susan; Bae, K. Ty; Abebe, Kaleab Z.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Simon, Gertrude; Perrone, Ronald D.; Miskulin, Dana C.] Tufts Med Ctr, Boston, MA USA.
   [Maxwell, Barbara; Steinman, Theodore I.; Czarnecki, Peter G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Rahbari-Oskoui, Frederic F.] Emory Univ, Atlanta, GA 30322 USA.
   [Braun, William E.] Cleveland Clin, Cleveland, OH 44106 USA.
   [Chapman, Arlene B.] Univ Chicago, Chicago, IL 60637 USA.
   [Schrier, Robert W.; Brosnahan, Godela] Univ Colorado, Denver, CO 80202 USA.
   [Torres, Vicente E.; Harris, Peter C.; Hogan, Marie C.] Mayo Clin, Coll Med, Rochester, MN USA.
   [Flessner, Michael F.] NIH, Bethesda, MD 20892 USA.
RP Moore, CG (reprint author), Carolinas HealthCare Syst, Dickson Adv Analyt, 1540 Garden Terrace Dr,Res Off Bldg,Suite 410, Charlotte, NC 28237 USA.
EM charity.patterson@carolinashealthcare.org
OI Abebe, Kaleab/0000-0002-3644-8419
FU National Center for Research Resources General Clinical Research Centers
   [RR000039, RR000585, RR000054, RR000051, RR023940, RR001032]; Clinical
   and Translational Science Awards at the participating institutions
   [RR025008, UL1TR000454, RR024150, UL1TR00135, RR025752, UL1TR001064,
   RR025780, UL1TR001082, RR025758, UL1TR001102, RR033179, UL1TR000001,
   RR024989, UL1TR000439]; PKD Foundation; National Institute of Diabetes
   and Digestive and Kidney Diseases, National Institutes of Health; 
   [U01DK62408];  [U01DK62401];  [U01DK62410];  [U01DK62402]; 
   [U01DK62411];  [U01DK082230]
FX This study was supported by cooperative agreements (grants U01DK62408
   Emory University, U01DK62401 Washington University in St. Louis,
   U01DK62410 Mayo Clinic, U01DK62402 University of Colorado, U01DK62411
   Tufts Medical Center, and U01DK082230 University of Pittsburgh) with the
   National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health, the National Center for Research
   Resources General Clinical Research Centers (RR000039 Emory University,
   RR000585 Mayo Clinic, RR000054 Tufts Medical Center, RR000051 University
   of Colorado, RR023940 University of Kansas Medical Center, and RR001032
   Beth Israel Deaconess Medical Center), and the Clinical and
   Translational Science Awards at the participating institutions (RR025008
   and UL1TR000454 Emory University, RR024150 and UL1TR00135 Mayo Clinic,
   RR025752 and UL1TR001064 Tufts University, RR025780 and UL1TR001082
   University of Colorado, RR025758 and UL1TR001102 Beth Israel Deaconess
   Medical Center, RR033179 and UL1TR000001 University of Kansas Medical
   Center and RR024989 and UL1TR000439 Cleveland Clinic). Support for study
   coordinators and grants to the Publications and Communications
   Committees were provided by the PKD Foundation. Study drugs were donated
   by Boehringer Ingelheim Pharmaceuticals Inc (telmisartan and matched
   placebo) and Merck & Co Inc (lisinopril).
NR 22
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD SEP
PY 2015
VL 44
BP 48
EP 55
DI 10.1016/j.cct.2015.07.017
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA CT2FB
UT WOS:000362616300008
PM 26231556
ER

PT J
AU Ledgerwood, JE
   Hu, Z
   Costner, P
   Yamshchikov, G
   Enama, ME
   Plummer, S
   Hendel, CS
   Holman, L
   Larkin, B
   Gordon, I
   Bailer, RT
   Poretz, DM
   Sarwar, U
   Kabadi, A
   Koup, R
   Mascola, JR
   Graham, BS
AF Ledgerwood, Julie E.
   Hu, Zonghui
   Costner, Pamela
   Yamshchikov, Galina
   Enama, Mary E.
   Plummer, Sarah
   Hendel, Cynthia S.
   Holman, Lasonji
   Larkin, Brenda
   Gordon, Ingelise
   Bailer, Robert T.
   Poretz, Donald M.
   Sarwar, Uzma
   Kabadi, Alisha
   Koup, Richard
   Mascola, John R.
   Graham, Barney S.
CA VRC 307 Study Team
   VRC 309 Study Team
TI Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA
   vaccine prime followed by trivalent influenza inactivated vaccine (IIV3)
   boost
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE DNA vaccine; Seasonal influenza; Immune response
ID T-CELL RESPONSES; HEALTHY-ADULTS; NEUTRALIZING ANTIBODY; VIRUS; TRIAL;
   IMMUNOGENICITY; IMMUNIZATION; EFFICACY; INTERVAL; SAFETY
AB Annual influenza vaccination reduces the risks of influenza when the vaccines are well matched to circulating strains, but development of an approach that induces broader and more durable immune responses would be beneficial. We conducted two companion Phase 1 studies, VRC 307 and VRC 309, over sequential seasons (2008-2009 and 2009-2010) in which only the influenza B strain component of the vaccines differed. Objectives were safety and immunogenicity of prime-boost vaccination schedules. A schedule of DNA vaccine encoding for seasonal influenza hemagglutinins (HA) prime followed by seasonal trivalent influenza inactivated vaccine (IIV3) boost (HA DNA-IIV3) was compared to placebo (PBS)-IIV3 or IIV3-IIV3. Cumulatively, 111 adults were randomized to HA DNA-IIV3 (n = 66), PBS-IIV3 (n = 25) or IIV3-IIV3 (n = 20). Safety was assessed by clinical observations, laboratory parameters and 7-day solicited reactogenicity. The seasonal HA DNA prime-IIV3 boost regimen was evaluated as safe and well tolerated. There were no serious adverse events. The local and systemic reactogenicity for HA DNA, IIV and placebo were reported predominantly as none or mild within the first 5 days post-vaccination. There was no significant difference in immunogenicity detected between the treatment groups as evaluated by hemagglutination inhibition (HAI) assay. The studies demonstrated the safety and immunogenicity of seasonal HA DNA-IIV3 regimen, but the 3-4 week prime-boost interval was suboptimal for improving influenza-specific immune responses. This is consistent with observations in avian H5 DNA vaccine prime-boost studies in which a long interval, but not a short interval, was associated with improved immunogenicity. Published by Elsevier Inc.
C1 [Ledgerwood, Julie E.; Costner, Pamela; Yamshchikov, Galina; Enama, Mary E.; Plummer, Sarah; Hendel, Cynthia S.; Holman, Lasonji; Larkin, Brenda; Gordon, Ingelise; Bailer, Robert T.; Sarwar, Uzma; Kabadi, Alisha; Koup, Richard; Mascola, John R.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Hu, Zonghui] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
   [Poretz, Donald M.] CARE ID, Annandale, VA 22003 USA.
RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Ledgerwood@mail.nih.gov; yamshchikovgv@mail.nih.gov
FU NIAID Intramural program
FX The authors thank the vaccine trial volunteers for their contribution
   and commitment to vaccine research. We acknowledge the contributions of
   our NIH Clinical Center and NIAID colleagues, the EMMES Corporation,
   colleagues at the NIAID Vaccine Research Center, especially Gary Nabel
   and Abraham Mittelman, colleagues at the NIAID Division of Clinical
   Research, especially H. Clifford Lane, Jerome Pierson and John Tierney,
   and assistance from Rick Stout at Bioject (Tualatin, Oregon). We also
   thank the NIAID Intramural IRB and NIAID Intramural Data and Safety
   Monitoring Board. These clinical trials were funded by the NIAID
   Intramural program. The findings and conclusions in this report are
   those of the authors and do not necessarily reflect the views of the
   funding agency or collaborators.
NR 30
TC 2
Z9 2
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD SEP
PY 2015
VL 44
BP 112
EP 118
DI 10.1016/j.cct.2015.08.006
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA CT2FB
UT WOS:000362616300016
ER

PT J
AU Jelovsek, JE
   Markland, AD
   Whitehead, WE
   Barber, MD
   Newman, DK
   Rogers, RG
   Dyer, K
   Visco, A
   Sung, VW
   Sutkin, G
   Meikle, SF
   Gantz, MG
AF Jelovsek, J. Eric
   Markland, Alayne D.
   Whitehead, William E.
   Barber, Matthew D.
   Newman, Diane K.
   Rogers, Rebecca G.
   Dyer, Keisha
   Visco, Anthony
   Sung, Vivian W.
   Sutkin, Gary
   Meikle, Susan F.
   Gantz, Marie G.
CA Pelvic Floor Disorders Network
TI Controlling anal incontinence in women by performing anal exercises with
   biofeedback or loperamide (CAPABLe) trial: Design and methods
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Fecal incontinence; Randomized placebo controlled trial; Loperamide;
   Manometry-assisted biofeedback; Anal sphincter exercises; Factorial
   design
ID QUALITY-OF-LIFE; FECAL INCONTINENCE; ANORECTAL FUNCTION; SPHINCTER
   FUNCTION; FUNCTIONAL BOWEL; CHRONIC DIARRHEA; TRANSIT-TIME; BODY-IMAGE;
   QUESTIONNAIRE; DISORDERS
AB The goals of this trial are to determine the efficacy and safety of two treatments for women experiencing fecal incontinence. First, we aim to compare the use of loperamide to placebo and second, to compare the use of anal sphincter exercises with biofeedback to usual care. The primary outcome is the change from baseline in the St. Mark's (Vaizey) Score 24 weeks after treatment initiation. As a Pelvic Floor Disorders Network (PFDN) trial, subjects are enrolling from eight PFDN clinical centers across the United States. A centralized data coordinating center supervises data collection and analysis. These two first-line treatments for fecal incontinence are being investigated simultaneously using a two-by-two randomized factorial design: a medication intervention (loperamide versus placebo) and a pelvic floor strength and sensory training intervention (anal sphincter exercises with manometry-assisted biofeedback versus usual care using an educational pamphlet). Interventionists providing the anal sphincter exercise training with biofeedback have received standardized training and assessment. Symptom severity, diary, standardized anorectal manometry and health-related quality of life out-comes are assessed using validated instruments administered by researchers masked to randomized interventions. Cost effectiveness analyses will be performed using prospectively collected data on care costs and resource utilization. This article describes the rationale and design of this randomized trial, focusing on specific research concepts of interest to researchers in the field of female pelvic floor disorders and all other providers who care for patients with fecal incontinence. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Jelovsek, J. Eric; Barber, Matthew D.] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44195 USA.
   [Markland, Alayne D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
   [Whitehead, William E.] Univ N Carolina, Dept Gastroenterol, Chapel Hill, NC USA.
   [Newman, Diane K.] Univ Penn, Dept Surg, Div Urol, Philadelphia, PA 19104 USA.
   [Rogers, Rebecca G.] Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
   [Rogers, Rebecca G.] Univ New Mexico, Hlth Sci Ctr, Dept Surg, Albuquerque, NM 87131 USA.
   [Dyer, Keisha] Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA.
   [Visco, Anthony] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
   [Sung, Vivian W.] Brown Univ, Dept Obstet & Gynecol, Alpert Med Sch, Providence, RI 02912 USA.
   [Sutkin, Gary] Univ Pittsburgh, Med Ctr, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
   [Meikle, Susan F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
   [Gantz, Marie G.] RTI Int, Res Triangle Pk, NC USA.
RP Jelovsek, JE (reprint author), Cleveland Clin, 9500 Euclid Ave A81, Cleveland, OH 44195 USA.
EM jelovsj@ccf.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [U10 HD054215, U10 HD041261, U10 HD054214, U10 HD041267, U10
   HD069025, U10 HD069010, U10 HD069006, U01 HD069031]; National Institutes
   of Health Office of Research on Women's Health
FX Supported by grants from the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (U10 HD054215, U10 HD041261, U10
   HD041261, U10 HD054214, U10 HD041267, U10 HD069025, U10 HD069010, U10
   HD069006, U01 HD069031) and the National Institutes of Health Office of
   Research on Women's Health.
NR 38
TC 2
Z9 2
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD SEP
PY 2015
VL 44
BP 164
EP 174
DI 10.1016/j.cct2015.08.009
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA CT2FB
UT WOS:000362616300023
ER

PT J
AU Koutros, S
   Langseth, H
   Grimsrud, TK
   Barr, DB
   Vermeulen, R
   Portengen, L
   Wacholder, S
   Freeman, LEB
   Blair, A
   Hayes, RB
   Rothman, N
   Engel, LS
AF Koutros, Stella
   langseth, HilDe
   Grimsrud, Tom K.
   Barr, Dana Boyd
   Vermeulen, Roel
   Portengen, Luetzen
   Wacholder, Sholom
   Freeman, Laura E. Beane
   Blair, Aaron
   Hayes, Richard B.
   Rothman, Nathaniel
   Engel, Lawrence S.
TI Prediagnostic Serum Organochlorine Concentrations and Metastatic
   Prostate Cancer: A Nested Case-Control Study in the Norwegian Janus
   Serum Bank Cohort
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID POLYCHLORINATED-BIPHENYLS; AGRICULTURAL HEALTH; RISK; EXPOSURE; PCBS;
   MORTALITY
AB Background: Organochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, anti-estrogenic, or anti-androgenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern.
   Objectives: We conducted a nested case-control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway.
   Methods: Sera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression.
   Results: Metastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but non-significant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log-transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02).
   Conclusions: Our study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer.
C1 [Koutros, Stella; Wacholder, Sholom; Freeman, Laura E. Beane; Blair, Aaron; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
   [langseth, HilDe; Grimsrud, Tom K.] Canc Registry Norway, Dept Res, Inst Populat Based Canc Res, Oslo, Norway.
   [Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA.
   [Vermeulen, Roel; Portengen, Luetzen] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands.
   [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA.
   [Engel, Lawrence S.] UNC, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6-E124,MSC 9771, Bethesda, MD 20892 USA.
EM koutross@mail.nih.gov
RI Vermeulen, Roel/F-8037-2011; 
OI Vermeulen, Roel/0000-0003-4082-8163; Hayes, Richard/0000-0002-0918-661X;
   Engel, Lawrence/0000-0001-9268-4830
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
   National Institutes of Health; Norwegian Cancer Society
FX This work was supported by the Intramural Research Program of the
   Division of Cancer Epidemiology and Genetics, National Cancer Institute,
   National Institutes of Health. The Norwegian Cancer Society provided
   funding for the Janus Serum Bank from the start in 1972 until 2004.
NR 32
TC 3
Z9 3
U1 1
U2 8
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD SEP
PY 2015
VL 123
IS 9
BP 867
EP 872
DI 10.1289/ehp.1408245
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA CT3CA
UT WOS:000362682700009
PM 25734605
ER

PT J
AU Resnik, DB
   Miller, AK
   Kwok, RK
   Engel, LS
   Sandler, DP
AF Resnik, David B.
   Miller, Aubrey K.
   Kwok, Richard K.
   Engel, Lawrence S.
   Sandler, Dale P.
TI Ethical Issues in Environmental Health Research Related to Public Health
   Emergencies: Reflections on the GuLF STUDY
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID HURRICANE-KATRINA; NIEHS RESPONDS
AB Health research in the context of an environmental disaster with implications for public health raises challenging ethical issues. This article explores ethical issues that arose in the Gulf Long-term Follow-up Study (GuLF STUDY) and provides guidance for future research. Ethical issues encountered by GuLF STUDY investigators included a) minimizing risks and promoting benefits to participants, b) obtaining valid informed consent, c) providing financial compensation to participants, d) working with vulnerable participants, e) protecting participant confidentiality, f) addressing conflicts of interest, g) dealing with legal implications of research, and h) obtaining expeditious review from the institutional review board (IRB), community groups, and other committees. To ensure that ethical issues are handled properly, it is important for investigators to work closely with IRBs during the development and implementation of research and to consult with groups representing the community. Researchers should consider developing protocols, consent forms, survey instruments, and other documents prior to the advent of a public health emergency to allow for adequate and timely review by constituents. When an emergency arises, these materials can be quickly modified to take into account unique circumstances and implementation details.
C1 [Resnik, David B.] NIEHS, Bioeth Program, NIH, Res Triangle Pk, NC 27709 USA.
   [Miller, Aubrey K.] NIEHS, Off Director, NIH, Res Triangle Pk, NC 27709 USA.
   [Kwok, Richard K.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
   [Engel, Lawrence S.] Univ N Carolina, Dept Epidemiol, Gillings Sch Publ Hlth, Chapel Hill, NC USA.
RP Resnik, DB (reprint author), NIEHS, Bioeth Program, NIH, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
RI Kwok, Richard/B-6907-2017; 
OI Kwok, Richard/0000-0002-6794-8360; Sandler, Dale/0000-0002-6776-0018;
   Engel, Lawrence/0000-0001-9268-4830
FU NIH, NIEHS [Z01-ES-102945]; NIH Common Fund
FX The authors declare they have no actual or potential competing financial
   interests. D.P.S., R.K.K., L.S.E., and A.K.M. are investigators on the
   GuLF STUDY. D.B.R. is the NIEHS IRB Chair. This research is supported by
   the Intramural Program of the NIH, NIEHS (Z01-ES-102945) and by the NIH
   Common Fund. It does not represent the views of the NIEHS, NIH, or the
   U.S. government.
NR 19
TC 1
Z9 1
U1 2
U2 5
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD SEP
PY 2015
VL 123
IS 9
BP A227
EP A231
DI 10.1289/ehp.1509889
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA CT3CA
UT WOS:000362682700003
PM 26325057
ER

PT J
AU Apolo, AB
   Infante, JR
   Hamid, O
   Patel, M
   Wang, D
   Kelly, K
   Mega, A
   Britten, CD
   Mita, A
   Ravaud, A
   Cuillerot, JM
   Von Heydebreck, A
   Gulley, JL
AF Apolo, A. B.
   Infante, J. R.
   Hamid, O.
   Patel, M.
   Wang, D.
   Kelly, K.
   Mega, A.
   Britten, C. D.
   Mita, A.
   Ravaud, A.
   Cuillerot, J. M.
   Von Heydebreck, A.
   Gulley, J. L.
TI Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally
   advanced or metastatic urothelial carcinoma: A phase Ib trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Apolo, A. B.] NCI, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
   [Infante, J. R.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, North Nashville, TN USA.
   [Hamid, O.] Angeles Clin & Res Inst, Translat Res & Immunotherapy, Los Angeles, CA USA.
   [Patel, M.] Florida Canc Specialists, Sarah Cannon Res Inst, Hematol Oncol, Sarasota, FL USA.
   [Wang, D.] Henry Ford Hosp, Hematol Oncol, Detroit, MI 48202 USA.
   [Kelly, K.] Univ Calif Davis, Ctr Comprehens Canc, Internal Med, Sacramento, CA USA.
   [Mega, A.] Brown Univ, Warren Alpert Med Sch, Hematol Oncol, Providence, RI 02912 USA.
   [Britten, C. D.] Med Univ S Carolina, Hematol Oncol, Charleston, SC 29425 USA.
   [Mita, A.] Cedars Sinai Med Ctr, Expt Therapeut Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
   [Ravaud, A.] CHU Bordeaux, Hop St Andre, Bordeaux, France.
   [Cuillerot, J. M.] EMD Serono Inc, Immunooncol, Billerica, MA USA.
   [Von Heydebreck, A.] Merck KGaA, R&D Global Biostat, Darmstadt, Germany.
   [Gulley, J. L.] NCI, Genitourinary Malignancy Branch, NIH, Lab Tumor Immunol & Biol,Ctr Canc Res, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 2630
BP S522
EP S522
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887402332
ER

PT J
AU Atun, R
   Jaffray, D
   Barton, M
   Baumann, M
   Vikram, B
   Bray, F
   Hanna, T
   Knaul, F
   Lievens, Y
   O'Sullivan, B
   Rodin, D
   Van Dyke, J
   Rosenblatt, E
   Yap, M
   Zubizarreta, E
   Gospodarowicz, M
AF Atun, R.
   Jaffray, D.
   Barton, M.
   Baumann, M.
   Vikram, B.
   Bray, F.
   Hanna, T.
   Knaul, F.
   Lievens, Y.
   O'Sullivan, B.
   Rodin, D.
   Van Dyke, J.
   Rosenblatt, E.
   Yap, M.
   Zubizarreta, E.
   Gospodarowicz, M.
TI Responding to the cancer crisis: Expanding global access to radiotherapy
   - a Lancet Oncology Commission
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Atun, R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Jaffray, D.] Univ Toronto, Dept Med Phys, Toronto, ON, Canada.
   [Barton, M.] Univ New S Wales, Ingham Inst Appl Med Res, Sydney, NSW, Australia.
   [Baumann, M.] Tech Univ Dresden, Univ Krankenhaus, D-01062 Dresden, Germany.
   [Baumann, M.] Tech Univ Dresden, Fak Med, D-01062 Dresden, Germany.
   [Vikram, B.] NCI, NIH, Bethesda, MD 20892 USA.
   [Bray, F.] Int Agcy Res Canc, Epidemiol, F-69372 Lyon, France.
   [Hanna, T.] Queens Univ, Div Canc Care & Epidemiol, Canc Res Inst, Kingston, ON, Canada.
   [Knaul, F.] Univ Miami, Miami Inst Amer, Miami, FL USA.
   [Lievens, Y.] Univ Ghent, Univ Hosp Ghent, Ghent, Netherlands.
   [O'Sullivan, B.] Univ Toronto, Univ Hosp Network, Toronto, ON, Canada.
   [Rodin, D.; Gospodarowicz, M.] Univ Toronto, Dept Radiat Oncol, Univ Hosp Network, Toronto, ON, Canada.
   [Van Dyke, J.] Univ Western Ontario, Med Phys, London, ON N6A 3K7, Canada.
   [Rosenblatt, E.] IAEA, Dept Nucl Sci & Applicat, A-1400 Vienna, Austria.
   [Yap, M.] Univ New S Wales, Ingham Hlth Res Inst, Sydney, NSW, Australia.
RI Barton, Michael/M-7183-2015
OI Barton, Michael/0000-0003-0112-0680
NR 0
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 2LBA
BP S707
EP S708
PG 2
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887403248
ER

PT J
AU Decosterd, S
   Bavaud, S
   Brennan, C
   Eicher, M
AF Decosterd, S.
   Bavaud, S.
   Brennan, C.
   Eicher, M.
TI Translation and validation of an instrument to measure oncology
   inpatient acuity: The Oncology Acuity Tool - French (for Switzerland)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Decosterd, S.; Bavaud, S.; Eicher, M.] Univ Lausanne, Inst Univ Format & Rech Soins, Fac Biol & Med, Lausanne, Switzerland.
   [Decosterd, S.] Hop Cantonal Univ Geneva, Oncol Ctr, Geneva, Switzerland.
   [Brennan, C.] NIH, Res & Practice Dev Sect, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA.
   [Eicher, M.] Univ Appl Arts & Sci Western Switzerland, Sch Hlth Fribourg, Fribourg, Switzerland.
RI Eicher, Manuela/A-8349-2015
NR 0
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 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 1702
BP S249
EP S249
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887401126
ER

PT J
AU Disis, ML
   Patel, M
   Pant, S
   Hamilton, EP
   Lockhart, AC
   Kelly, K
   Thaddeus-Beck, J
   Gordon, M
   Weiss, GJ
   Ejadi, S
   Taylor, MH
   Chin, K
   Cuillerot, JM
   Von Heydebreck, A
   Gulley, JL
AF Disis, M. L.
   Patel, M.
   Pant, S.
   Hamilton, E. P.
   Lockhart, A. C.
   Kelly, K.
   Thaddeus-Beck, J.
   Gordon, M.
   Weiss, G. J.
   Ejadi, S.
   Taylor, M. H.
   Chin, K.
   Cuillerot, J. M.
   Von Heydebreck, A.
   Gulley, J. L.
TI Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with
   recurrent or refractory ovarian cancer: A phase Ib trial reporting
   safety and clinical activity
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Disis, M. L.] Univ Washington, Sch Med, Pathol & Obstet & Gynecol, Seattle, WA USA.
   [Patel, M.] Sarah Cannon Res Inst, Florida Canc Specialists, Sarasota, FL USA.
   [Pant, S.] Peggy & Charles Stephenson Oklahoma Canc Ctr, Oklahoma City, OK USA.
   [Hamilton, E. P.] Tennessee Oncol LLC, Sarah Cannon Res Inst, North Nashville, TN USA.
   [Lockhart, A. C.] Washington Univ, Sch Med, Hematol Oncol, St Louis, MO USA.
   [Kelly, K.] UC Davis Comprehens Canc Ctr, Hematol Oncol, Sacramento, CA USA.
   [Thaddeus-Beck, J.] Highlands Oncol Grp, Hematol Oncol, Fayetteville, AR USA.
   [Gordon, M.] Pinnacle Oncol Hematol, Hematol Oncol, Scottsdale, AZ USA.
   [Weiss, G. J.] Western Reg Med Ctr, Cancer Treatment Ctr Amer, Goodyear, AZ USA.
   [Ejadi, S.] Scottsdale Heatlhcare Res Inst, Hematol Oncol, Scottsdale, AZ USA.
   [Taylor, M. H.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
   [Chin, K.] EMD Serono Inc, Oncol Clin Res, Billerica, MA USA.
   [Cuillerot, J. M.] EMD Serono Inc, Immunooncol, Billerica, MA USA.
   [Von Heydebreck, A.] Merck KGaA, R&D Global Biostat, Darmstadt, Germany.
   [Gulley, J. L.] NCI, Genitourinary Malignancy Branch, NIH, Lab Tumor Immunol & Biol,Ctr Canc Res, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 2
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 2749
BP S546
EP S547
PG 2
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887402402
ER

PT J
AU Gharwan, H
   Thomas, A
   Berman, A
   Yang, Z
   Rajan, A
AF Gharwan, H.
   Thomas, A.
   Berman, A.
   Yang, Z.
   Rajan, A.
TI Brain Metastases in thymic epithelial tumors
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Gharwan, H.; Thomas, A.; Berman, A.; Rajan, A.] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
   [Yang, Z.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
NR 0
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 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 1626
BP S247
EP S247
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887401120
ER

PT J
AU Greten, T
   Duffy, A
   Rusher, O
   Kerkar, S
   Kleiner, D
   Figg, W
   Steinberg, S
   Abi-Jaoudeh, N
   Wood, B
AF Greten, T.
   Duffy, A.
   Rusher, O.
   Kerkar, S.
   Kleiner, D.
   Figg, W.
   Steinberg, S.
   Abi-Jaoudeh, N.
   Wood, B.
TI Tremelimumab - A monoclonal antibody against CTLA-4-in combination with
   local tumor ablation (TACE or RFA) in patients with hepatocellular
   carcinoma (HCC)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Greten, T.; Duffy, A.; Rusher, O.] NCI, GI Malignancy Branch, Bethesda, MD 20892 USA.
   [Kerkar, S.; Kleiner, D.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
   [Figg, W.] NCI, Clin Pharmacol Core, Bethesda, MD 20892 USA.
   [Steinberg, S.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
   [Abi-Jaoudeh, N.; Wood, B.] NCI, Intervent Radiol Sect, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 2259
BP S419
EP S419
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887402056
ER

PT J
AU Gulley, JL
   Rajan, A
   Spigel, DR
   Iannotti, N
   Chandler, J
   Wong, DJL
   Leach, JL
   Edenfield, WJ
   Wang, D
   Bajars, M
   Von Heydebreck, A
   Kelly, K
AF Gulley, J. L.
   Rajan, A.
   Spigel, D. R.
   Iannotti, N.
   Chandler, J.
   Wong, D. J. L.
   Leach, J. L.
   Edenfield, W. J.
   Wang, D.
   Bajars, M.
   Von Heydebreck, A.
   Kelly, K.
TI Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with
   metastatic or recurrent non-small-cell lung cancer progressing after
   platinum-based chemotherapy: A phase Ib trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Gulley, J. L.] NCI, Genitourinary Malignancy Branch, NIH, Lab Tumor Immunol & Biol,Ctr Canc Res, Bethesda, MD 20892 USA.
   [Rajan, A.] NCI, Ctr Canc Res, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
   [Spigel, D. R.] Tennessee Oncol LLC, Sarah Cannon Res Inst, North Nashville, TN USA.
   [Iannotti, N.] Hematol Oncol Associates Treasure Coast, Hematol Oncol, Port St Lucie, FL USA.
   [Chandler, J.] West Clin PC, Hematol Oncol, Memphis, TN USA.
   [Wong, D. J. L.] Univ Calif Los Angeles, Med Ctr, Div Hematol Oncol, Los Angeles, CA 90024 USA.
   [Leach, J. L.] Virginia Piper Canc Inst, Dept Hematol Oncol, Minneapolis, MN USA.
   [Edenfield, W. J.] Inst Translat Oncol Res, Hematol Oncol, Greenville, SC USA.
   [Wang, D.] Henry Ford Hosp, Hematol Oncol, Detroit, MI 48202 USA.
   [Bajars, M.] EMD Serono, ImmunoOncol, Billerica, MA USA.
   [Von Heydebreck, A.] Merck Serono, R&D Global Biostat, Darmstadt, Germany.
   [Kelly, K.] UC Davis Comprehens Canc Ctr, Hematol Oncol, Sacramento, CA USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 3
Z9 3
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 3090
BP S629
EP S629
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887403048
ER

PT J
AU Hassan, R
   Thomas, A
   Patel, M
   Nemunaitis, J
   Bennouna, J
   Powderly, J
   Taylor, M
   Cuillerot, JM
   Von Heydebreck, A
   Gulley, JL
AF Hassan, R.
   Thomas, A.
   Patel, M.
   Nemunaitis, J.
   Bennouna, J.
   Powderly, J.
   Taylor, M.
   Cuillerot, J. M.
   Von Heydebreck, A.
   Gulley, J. L.
TI Safety and clinical activity of avelumab (MSB0010718C), an anti-PD-L1
   antibody, in patients with advanced, unresectable mesothelioma: A phase
   IB trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Hassan, R.] NCI, NIH, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
   [Thomas, A.] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Patel, M.] Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA.
   [Nemunaitis, J.] Mary Crowley Canc Res Ctr, Oncol, Dallas, TX USA.
   [Bennouna, J.] ICO Site ReneGauducheau, St Herblain, Loire Atlantiqu, France.
   [Powderly, J.] Carolina BioOncol Inst LLC, Hematol Oncol, Huntersville, NC USA.
   [Taylor, M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
   [Cuillerot, J. M.] EMD Serono, Immunooncol, Billerica, MA USA.
   [Von Heydebreck, A.] Merck Serono, R&D Global Biostat, Darmstadt, Germany.
   [Gulley, J. L.] NCI, Genitourinary Malignancy Branch, NIH, Lab Tumor Immunol & Biol,Ctr Canc Res, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 3110
BP S639
EP S639
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887403068
ER

PT J
AU Hassan, R
   Antonia, SJ
   Alley, EW
   Kindler, HL
   Jahan, T
   Grous, JJ
   Honarmand, S
   McDougall, K
   Whiting, CC
   Nair, N
   Lemmens, E
   Tsujikawa, T
   Kumar, S
   Coussens, L
   Murphy, AL
   Thomas, A
   Brockstedt, DG
AF Hassan, R.
   Antonia, S. J.
   Alley, E. W.
   Kindler, H. L.
   Jahan, T.
   Grous, J. J.
   Honarmand, S.
   McDougall, K.
   Whiting, C. C.
   Nair, N.
   Lemmens, E.
   Tsujikawa, T.
   Kumar, S.
   Coussens, L.
   Murphy, A. L.
   Thomas, A.
   Brockstedt, D. G.
TI CRS-207, a mesothelin-targeted immunotherapy, in combination with
   standard of care chemotherapy as treatment for malignant pleural
   mesothelioma (MPM)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Hassan, R.] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Antonia, S. J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
   [Alley, E. W.] Univ Penn, Philadelphia, PA 19104 USA.
   [Kindler, H. L.] Univ Chicago, Chicago, IL 60637 USA.
   [Jahan, T.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Grous, J. J.; Honarmand, S.; McDougall, K.; Whiting, C. C.; Nair, N.; Lemmens, E.; Murphy, A. L.; Brockstedt, D. G.] Aduro Biotech, Berkeley, CA USA.
   [Tsujikawa, T.; Kumar, S.; Coussens, L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
   [Thomas, A.] NCI, Bethesda, MD 20892 USA.
NR 0
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 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 515
BP S108
EP S108
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887400325
ER

PT J
AU Kawachi, A
   Yonemori, K
   Hirakawa, A
   Kinoshita, F
   Tamura, K
   Fujiwara, Y
   Takebe, N
AF Kawachi, A.
   Yonemori, K.
   Hirakawa, A.
   Kinoshita, F.
   Tamura, K.
   Fujiwara, Y.
   Takebe, N.
TI Incidence and risk factors of interstitial lung disease in phase 1
   trials
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Kawachi, A.; Yonemori, K.; Tamura, K.; Fujiwara, Y.] Natl Canc Ctr, Breast & Med Oncol, Tokyo, Japan.
   [Hirakawa, A.; Kinoshita, F.] Nagoya Univ, Biostat & Bioinformat Sect, Ctr Adv Med & Clin Res, Grad Sch Med, Nagoya, Aichi 4648601, Japan.
   [Takebe, N.] NIH, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD USA.
RI Kinoshita, Fumie/A-3506-2016
NR 0
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 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 360
BP S74
EP S74
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887400229
ER

PT J
AU Nghiem, P
   Bhatia, S
   Daud, A
   Friedlander, P
   Kluger, H
   Kohrt, H
   Kudchadkar, R
   Lipson, E
   Lundgren, L
   Margolin, K
   Reddy, S
   Shantha, E
   Sharfman, W
   Sharon, E
   Thompson, J
   Topalian, S
   Cheever, M
AF Nghiem, P.
   Bhatia, S.
   Daud, A.
   Friedlander, P.
   Kluger, H.
   Kohrt, H.
   Kudchadkar, R.
   Lipson, E.
   Lundgren, L.
   Margolin, K.
   Reddy, S.
   Shantha, E.
   Sharfman, W.
   Sharon, E.
   Thompson, J.
   Topalian, S.
   Cheever, M.
TI Activity of PD-1 blockade with pembrolizumab as first systemic therapy
   in patients with advanced Merkel cell carcinoma
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Nghiem, P.] Univ Washington, Fred Hutchinson, Dermatol Med, Seattle, WA 98195 USA.
   [Bhatia, S.; Thompson, J.] Univ Washington, Fred Hutchinson, Med Oncol, Seattle, WA 98195 USA.
   [Daud, A.] Univ Calif San Francisco, Med Oncol, San Francisco, CA 94143 USA.
   [Friedlander, P.] Mt Sinai Med Ctr, Med Oncol, New York, NY 10029 USA.
   [Kluger, H.] Yale Univ, Med Oncol, New Haven, CT USA.
   [Kohrt, H.; Margolin, K.; Reddy, S.] Stanford Univ, Med Oncol, Stanford, CA 94305 USA.
   [Kudchadkar, R.] Emory Univ, Med Oncol, Atlanta, GA 30322 USA.
   [Lipson, E.; Sharfman, W.] Johns Hopkins Kimmel Canc Ctr, Med Oncol, Baltimore, MD USA.
   [Lundgren, L.] Fred Hutchinson Canc Ctr, Canc Immunotherapy Trials Network, Seattle, WA USA.
   [Shantha, E.] Univ Washington, Dermatol Med, Seattle, WA 98195 USA.
   [Sharon, E.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   [Topalian, S.] Johns Hopkins Kimmel Canc Ctr, Surg Surg Oncol, Baltimore, MD USA.
   [Cheever, M.] Fred Hutchinson Canc Res Ctr, Canc Immunotherapy Trials Network, Seattle, WA 98104 USA.
RI Nghiem, Paul/A-9210-2011
OI Nghiem, Paul/0000-0003-2784-963X
NR 0
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 22LBA
BP S720
EP S721
PG 3
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887403273
ER

PT J
AU Sparano, J
   Gray, R
   Zujewski, JA
   Makower, D
   Pritchard, K
   Albain, K
   Hayes, D
   Geyer, C
   Dees, C
   Perez, E
   Keane, M
   Vallejos, C
   Goggins, T
   Mayer, I
   Brufsky, A
   Toppmeyer, D
   Kaklamani, V
   Atkins, J
   Olson, J
   Sledge, G
AF Sparano, J.
   Gray, R.
   Zujewski, J. A.
   Makower, D.
   Pritchard, K.
   Albain, K.
   Hayes, D.
   Geyer, C.
   Dees, C.
   Perez, E.
   Keane, M.
   Vallejos, C.
   Goggins, T.
   Mayer, I.
   Brufsky, A.
   Toppmeyer, D.
   Kaklamani, V.
   Atkins, J.
   Olson, J.
   Sledge, G.
TI Prospective trial of endocrine therapy alone in patients with
   estrogen-receptor positive, HER2-negative, node-negative breast cancer:
   Results of the TAILORx low risk registry
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Sparano, J.; Makower, D.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Oncol, New York, NY USA.
   [Gray, R.] Dana Farber Canc Inst, Biostat, Boston, MA 02115 USA.
   [Zujewski, J. A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   [Pritchard, K.] Sunnybrook Odette Canc Ctr, Oncol, Toronto, ON, Canada.
   [Albain, K.] Loyola Univ, Chicago Stritch Sch Med, Oncol, Maywood, IL USA.
   [Hayes, D.] Univ Michigan, Oncol, Ann Arbor, MI 48109 USA.
   [Geyer, C.] Virginia Commonwealth Univ, Massey Canc Ctr, Oncol, Richmond, VA USA.
   [Dees, C.] Univ N Carolina, Oncol, Chapel Hill, NC USA.
   [Perez, E.] Mayo Clin, Oncol, Jacksonville, FL 32224 USA.
   [Keane, M.] West Ireland Canc Ctr, Oncol, Galway, Ireland.
   [Vallejos, C.] Inst Nacl Enfermedades Neoplas, Oncol, Lim, Peru.
   [Goggins, T.] Fox Valley Hematol Oncol, Oncol, Appleton, WI USA.
   [Mayer, I.] Vanderbilt Ingram Canc Ctr, Oncol, Nashville, TN USA.
   [Brufsky, A.] Magee Womens Hosp, Oncol, Pittsburgh, PA USA.
   [Toppmeyer, D.] Canc Inst New Jersey, New Brunswick, NJ USA.
   [Kaklamani, V.] Northwestern Univ, Oncol, Chicago, IL 60611 USA.
   [Atkins, J.] Southeastern Med Ctr, Oncol, Goldsboro, NC USA.
   [Olson, J.] Univ Maryland, Baltimore, MD 21201 USA.
   [Sledge, G.] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA.
NR 0
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 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 5BA
BP S714
EP S714
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887403260
ER

PT J
AU Tubin, S
   Mansoor, AM
   Gupta, S
AF Tubin, S.
   Mansoor, A. M.
   Gupta, S.
TI Radiation-induced abscopal effect in normoxic and hypoxic conditions and
   hypoxia-induced abscopal effect in human lung cancer cells
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Cancer Congress
CY 2015
CL Vienna, AUSTRIA
C1 [Tubin, S.] Osped St Andrea La Sapienza, Radiotherapy, Rome, Italy.
   [Mansoor, A. M.] NCI, Radiotherapy Dev Branch, Radiat Res Program, NIH,Div Canc Treatment & Diag, Rockville, MD 20850 USA.
   [Gupta, S.] Albert Einstein Coll Med, Dept Radiat Oncol, Bronx, NY 10461 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2015
VL 51
SU 3
MA 112
BP S4
EP S4
PG 1
WC Oncology
SC Oncology
GA CS2GP
UT WOS:000361887400013
ER

PT J
AU Rodriguez, V
   Mancuso, ME
   Warad, D
   Hay, CRM
   Dimichele, DM
   Valentino, L
   Kenet, G
   Kulkarni, R
AF Rodriguez, V.
   Mancuso, M. E.
   Warad, D.
   Hay, C. R. M.
   Dimichele, D. M.
   Valentino, L.
   Kenet, G.
   Kulkarni, R.
TI Central venous access device (CVAD) complications in Haemophilia with
   inhibitors undergoing immune tolerance induction: Lessons from the
   international immune tolerance study
SO HAEMOPHILIA
LA English
DT Article
DE central venous access; complications; immune tolerance; inhibitors
ID FACTOR-IX INHIBITORS; CONSENSUS RECOMMENDATIONS; BLEEDING DISORDERS;
   FACTOR-VIII; CHILDREN; THERAPY; CATHETERS; FEASIBILITY; PROPHYLAXIS;
   PREVALENCE
AB Introduction: Central venous access devices (CVADs) are frequently required as stable long-lasting venous access in children with haemophilia, especially those requiring immune tolerance induction (ITI) for inhibitors. CVAD infection is one of the most frequently reported catheter-related complications in this patient population. Aim: Detailed review of CVAD complications from the International ITI (I-ITI) study and analysis of potential risk factors for such complications. Methods: Retrospective analysis of prospectively obtained data from the I-ITI study primarily focused on CVAD-related complications. Results: A total of 115 children were recruited and 183 CVADs were placed in 99 subjects resulting in 121,206 CVAD-days observed on-study. A total of 124 CVAD infections were reported in 41 of 99 (41%) subjects with an overall infection rate of 0.94 per 1000 CVAD-days (interquartile ranges 0-1.7). A similar number of infections were observed in the two treatment arms (median: 2 and 3 in high dose and low dose respectively). Infections occurred more frequently in the presence of external catheters than with fully implanted catheters (P = 0.026). Infected patients were significantly younger at the time of CVAD insertion (median age: 22 vs. 25 months, P = 0.020). Patients with Gram-positive infections were also significantly younger than those with Gram-negative infections (median age: 17 vs. 25 months, P < 0.0001). Conclusion: CVAD infection was the most common complication observed in children with severe haemophilia and inhibitors in the frame of the I-ITI study. Younger age at CVAD insertion and external CVAD were associated with higher risk for infection. ITI outcome was unaffected by CVAD infections.
C1 [Rodriguez, V.; Warad, D.] Mayo Clin, Comprehens Hemophilia Ctr, Rochester, MN 55905 USA.
   [Mancuso, M. E.] Fdn IRCCS Ca Granda, Osped Maggiore Policlin, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy.
   [Hay, C. R. M.] Univ Manchester, Manchester Royal Infirm, Dept Haematol, Manchester M13 9WL, Lancs, England.
   [Dimichele, D. M.] Weill Cornell Med Coll, New York, NY USA.
   [Valentino, L.] Rush Univ, Med Ctr, Rush Hemophilia & Thrombophilia Ctr, Chicago, IL 60612 USA.
   [Kenet, G.] Tel Aviv Univ, Sheba Med Ctr, Natl Hemophilia Ctr, Tel Hashomer, Israel.
   [Kenet, G.] Tel Aviv Univ, Sackler Sch Med, Tel Hashomer, Israel.
   [Kulkarni, R.] Michigan State Univ, MSU Ctr Bleeding & Clotting Disorders, E Lansing, MI 48824 USA.
   [Dimichele, D. M.] NHLBI, Div Blood Dis & Resources, Deefield, IL USA.
RP Rodriguez, V (reprint author), Mayo Clin, Mayo Comprehens Hemophilia Ctr, 200 First St SW, Rochester, MN 55905 USA.
EM rodriguez.vilmarie@mayo.edu
FU Novo Nordisk; CSL Behring; Bayer Healthcare; Pfizer; Baxter Healthcare;
   Baxter Bioscience; Biogen; GTC Biotherapeutics; Inspiration Bioscience;
   rEVO Biologics
FX MEM has acted as a paid consultant to Novo Nordisk, CSL Behring, Bayer
   Healthcare, Pfizer and Baxter Healthcare. Rush University Medical Center
   (RUMC) has received grant support on behalf of Leonard A. Valentino
   (LAV) from Baxter Bioscience, Bayer Healthcare, Biogen, CSL Behring, GTC
   Biotherapeutics, Inspiration Bioscience, Novo Nordisk and Pfizer; and
   RUMC has also received payments on behalf of LAV for his participation
   in Advisory Boards and as a consultant for Baxter Bioscience, Bayer
   Healthcare, Biogen, CSL Behring, GTC Biotherapeutics, rEVO Biologics,
   Inspiration Bioscience, Novo Nordisk and Pfizer. Since the preparation
   of this work, LAV became an employee of Baxter Bioscience but continues
   in an academic capacity as a faculty member of RUMC.
NR 32
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
EI 1365-2516
J9 HAEMOPHILIA
JI Haemophilia
PD SEP
PY 2015
VL 21
IS 5
BP E369
EP E374
DI 10.1111/hae.12740
PG 6
WC Hematology
SC Hematology
GA CS9XK
UT WOS:000362446700004
PM 26178581
ER

PT J
AU Fry, TJ
   Aplan, PD
AF Fry, Terry J.
   Aplan, Peter D.
TI A robust in vivo model for B cell precursor acute lymphoblastic leukemia
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID CHILDHOOD; PROGNOSIS; CHILDREN; CANCER; CLASSIFICATION; RISK
AB B cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common malignancy in children. While treatments have improved remarkably over the past four decades, resistant disease and late effects that result from cytotoxic chemotherapy remain serious problems for individuals with BCP ALL. Improved genetic tools have led to the discovery of numerous somatic mutations associated with BCP ALL, leading to a framework for the genetic classification of BCP ALL. In this issue of the JCI, Duque-Afonso et al. develop an accurate in vivo model for BCP ALL that recapitulates the key features of human disease, including acquired mutations in genes encoding PAX5 and components of the JAK/STAT pathway. The authors further show, as proof of principle, that this model can be used to evaluate the efficacy of drugs designed to target specific acquired mutations in patients with BCP ALL.
C1 [Fry, Terry J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Aplan, PD (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bldg 37,Room 6002,37 Convent Dr, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
RI Aplan, Peter/K-9064-2016
FU Intramural NIH HHS; NCI NIH HHS [ZIA BC010982, ZIA BC011295, ZIA
   BC011565, ZIA SC010378]
NR 28
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2015
VL 125
IS 9
BP 3427
EP 3429
DI 10.1172/JCI83799
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CS7YT
UT WOS:000362303600019
PM 26301807
ER

PT J
AU Zhu, LC
   Olsen, RJ
   Nasser, W
   Beres, SB
   Vuopio, J
   Kristinsson, KG
   Gottfredsson, M
   Porter, AR
   DeLeo, FR
   Musser, JM
AF Zhu, Luchang
   Olsen, Randall J.
   Nasser, Waleed
   Beres, Stephen B.
   Vuopio, Jaana
   Kristinsson, Karl G.
   Gottfredsson, Magnus
   Porter, Adeline R.
   DeLeo, Frank R.
   Musser, James M.
TI A molecular trigger for intercontinental epidemics of group A
   Streptococcus
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID NAD-GLYCOHYDROLASE; STAPHYLOCOCCUS-AUREUS; PYOGENES DISEASE;
   GENE-EXPRESSION; VIRULENCE; ORIGIN; TRANSMISSION; PHAGOCYTOSIS;
   INHIBITOR; EMERGENCE
AB The identification of the molecular events responsible for strain emergence, enhanced virulence, and epidemicity has been a long-pursued goal in infectious diseases research. A recent analysis of 3,615 genomes of serotype M1 group A Streptococcus strains (the so-called "flesh-eating" bacterium) identified a recombination event that coincides with the global M1 pandemic beginning in the early 1980s. Here, we have shown that the allelic variation that results from this recombination event, which replaces the chromosomal region encoding secreted NADase and streptolysin 0, is the key driver of increased toxin production and enhanced infection severity of the M1 pandemic strains. Using isoallelic mutant strains, we found that 3 polymorphisms in this toxin gene region increase resistance to killing by human polymorphonuclear leukocytes, increase bacterial proliferation, and increase virulence in animal models of pharyngitis and necrotizing fasciitis. Genome sequencing of an additional 1,125 streptococcal strains and virulence studies revealed that a highly similar recombinational replacement event underlies an ongoing intercontinental epidemic of serotype M89 group A Streptococcus infections. By identifying the molecular changes that enhance upper respiratory tract fitness, increased resistance to innate immunity, and increased tissue destruction, we describe a mechanism that underpins epidemic streptococcal infections, which have affected many millions of people.
C1 [Zhu, Luchang; Olsen, Randall J.; Nasser, Waleed; Beres, Stephen B.; Musser, James M.] Houston Methodist Res Inst, Dept Pathol & Genom Med, Ctr Mol & Translat Human Infect Dis Res, Houston, TX USA.
   [Zhu, Luchang; Olsen, Randall J.; Nasser, Waleed; Beres, Stephen B.; Musser, James M.] Houston Methodist Hosp, Houston, TX 77030 USA.
   [Olsen, Randall J.; Musser, James M.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA.
   [Vuopio, Jaana] Natl Inst Hlth & Welf, Bacterial Infect Unit, Turku, Finland.
   [Vuopio, Jaana] Univ Turku, Fac Med, Dept Med Microbiol & Immunol, Turku, Finland.
   [Kristinsson, Karl G.; Gottfredsson, Magnus] Landspitali Univ Hosp, Dept Clin Microbiol, Reykjavik, Iceland.
   [Kristinsson, Karl G.; Gottfredsson, Magnus] Landspitali Univ Hosp, Dept Infect Dis, Reykjavik, Iceland.
   [Kristinsson, Karl G.; Gottfredsson, Magnus] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
   [Porter, Adeline R.; DeLeo, Frank R.] NIAID, Bacteriol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Musser, JM (reprint author), Houston Methodist Hosp, 6565 Fannin,Suite B490, Houston, TX 77030 USA.
EM jmmusser@houstonmethodist.org
RI Zhu, Luchang/C-9784-2017; 
OI Zhu, Luchang/0000-0002-4064-5781; DeLeo, Frank/0000-0003-3150-2516;
   Gottfredsson, Magnus/0000-0003-2465-0422
FU Fondren Foundation; Houston Methodist Hospital and Research Institute;
   Academy of Finland [255636]; National Institute of Allergy and
   Infectious Diseases, NIH
FX This study was supported in part by the Fondren Foundation, Houston
   Methodist Hospital and Research Institute, the Academy of Finland (grant
   255636), and the Intramural Research Program of the National Institute
   of Allergy and Infectious Diseases, NIH. We thank Neal Copeland, David
   Ginsburg, Nancy Jenkins, David Huston, Vivek Kapur, David Morens, and
   James Versalovic for critical comments and suggestions for improving the
   manuscript; Kathryn Stockbauer for critical comments and editorial
   assistance; Concepcion Cantu, Helga Erlendsdottir, Yu Joe, Jesus Paez
   Mayorga, and Audrey Ponce De Leon for technical assistance; Leslie
   Jenkins and Annessa Raiford for veterinary assistance; Laura Lindholm,
   Jan Jalava, and the Finnish Study Group for Antimicrobial Resistance
   (FiRe); and Chris Van Beneden, Bernard Beall, and the Active Bacterial
   Core Surveillance of the CDC's Emerging Infections Programs network.
NR 45
TC 14
Z9 14
U1 0
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2015
VL 125
IS 9
BP 3545
EP 3559
DI 10.1172/JCI82478
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CS7YT
UT WOS:000362303600029
PM 26258415
ER

PT J
AU Radin, RG
   Mumford, SL
   Silver, RM
   Lesher, LL
   Galai, N
   Faraggi, D
   Wactawski-Wende, J
   Townsend, JM
   Lynch, AM
   Simhan, HN
   Sjaarda, LA
   Perkins, NJ
   Zarek, SM
   Schliep, KC
   Schisterman, EF
AF Radin, Rose G.
   Mumford, Sunni L.
   Silver, Robert M.
   Lesher, Laurie L.
   Galai, Noya
   Faraggi, David
   Wactawski-Wende, Jean
   Townsend, Janet M.
   Lynch, Anne M.
   Simhan, Hyagriv N.
   Sjaarda, Lindsey A.
   Perkins, Neil J.
   Zarek, Shvetha M.
   Schliep, Karen C.
   Schisterman, Enrique F.
TI Sex ratio following preconception low-dose aspirin in women with prior
   pregnancy loss
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID INTRACYTOPLASMIC SPERM INJECTION; IN-VITRO FERTILIZATION;
   PREIMPLANTATION EMBRYO; OVARIAN RESPONSIVENESS; RECURRENT MISCARRIAGE;
   SPONTANEOUS-ABORTION; RANDOMIZED-TRIAL; NEWBORN-INFANTS; BIRTH;
   IMPLANTATION
AB BACKGROUND. Several lines of evidence suggest that male embryos may have greater vulnerability than female embryos to disordered inflammation; therefore, antiinflammatory drugs, such as low-dose aspirin (LDA), may alter the sex ratio. Here, weassessed the effect of LDA on male live birth and male offspring, incorporating pregnancy losses (n = 56) via genetic assessment, as part of a parallel-design, block-randomized, placebo-controlled trial of preconception LDA.
   METHODS. Participants (615 treated with LDA, 613 treated with placebo) ranged in age from 18 to 40 years of age, with1 to 2 prior pregnancy losses. We estimated the intention-to-treat (ITT) risk ratio (RR) and 95% Cl and assessed interaction with baseline high-sensitivity C-reactive protein (hsCRP) serum concentration a marker of systemic inflammation.
   RESULTS. Among the 1,078 women who completed follow-up (535 treated with LDA, 543 treated with placebo), the male live birth ITT RR equaled 1.31 (95% Cl: 1.07-1.59). With increasing tertile of hsCRP, the proportion of males at birth decreased in the placebo group, and the effect of LDA on male live birth increased (first tertile: 48% male in LDA vs. 52% in placebo, ITT RR = 0.97, 95% CI: 0.70-1.35; second tertile: 57% male in LOA vs. 43% in placebo, ITT RR = 1.36, 95% Cl: 0.98-1.90; third tertile: 53% male in LDA vs. 35% in placebo, ITT RR = 1.70, 95% Cl: 1.13-2.57; P interaction = 0.03). Analysis of pregnancy with male offspringyielded similar results.
   CONCLUSION. Initiation of LDA prior to conception restored numbers of male live births and pregnancy with male offspring among women with1 to 2 prior pregnancy losses. Moreover, our data suggest that LDA modulates inflammation that would otherwise reduce the conception or survival of male embryos.
C1 [Radin, Rose G.; Mumford, Sunni L.; Sjaarda, Lindsey A.; Perkins, Neil J.; Zarek, Shvetha M.; Schliep, Karen C.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD 20854 USA.
   [Silver, Robert M.; Lesher, Laurie L.] Univ Utah, Hlth Sci Ctr, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT USA.
   [Galai, Noya; Faraggi, David] Univ Haifa, Dept Stat, IL-31999 Haifa, Israel.
   [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
   [Townsend, Janet M.] Commonwealth Med Coll, Dept Family Community & Rural Hlth, Scranton, PA USA.
   [Lynch, Anne M.] Univ Colorado Denver, Dept Obstet & Gynecol, Aurora, CO USA.
   [Simhan, Hyagriv N.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd, Rockville, MD 20854 USA.
EM schistee@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Sjaarda, Lindsey/0000-0003-0539-8110;
   Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, NIH, Bethesda, Maryland [HHSN267200603423,
   HHSN267200603424, HHSN267200603426]
FX This research was supported by the Intramural Research Program of the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, NIH, Bethesda, Maryland (contract nos. HHSN267200603423,
   HHSN267200603424, and HHSN267200603426). The study funder had no role in
   study design, data collection, data analysis, data interpretation, or
   writing of the report. The content of this article is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the Eunice Kennedy Shriver National Institute of Child
   Health and Human Development or the NIH. The authors thank Emily
   Mitchell for advice on data analysis and Allen Wilcox and anonymous
   reviewers for valuable comments on the paper.
NR 35
TC 2
Z9 2
U1 2
U2 5
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2015
VL 125
IS 9
BP 3619
EP 3626
DI 10.1172/JCI82357
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CS7YT
UT WOS:000362303600035
PM 26280577
ER

PT J
AU Simons-Morton, BG
   Klauer, SG
   Ouimet, MC
   Guo, F
   Albert, PS
   Lee, SE
   Ehsani, JP
   Pradhan, AK
   Dingus, TA
AF Simons-Morton, Bruce G.
   Klauer, Sheila G.
   Ouimet, Marie Claude
   Guo, Feng
   Albert, Paul S.
   Lee, Suzanne E.
   Ehsani, Johnathon P.
   Pradhan, Anuj K.
   Dingus, Thomas A.
TI Naturalistic teenage driving study: Findings and lessons learned
SO JOURNAL OF SAFETY RESEARCH
LA English
DT Article
DE Adolescence; Risk taking; Accidents; Speeding; Kinematic; Expertise
ID NOVICE DRIVERS; ADOLESCENT DRIVERS; RISK-TAKING; CRASH; PASSENGERS;
   PERSPECTIVE; EVENTS; RATES
AB Introduction: This paper summarizes the findings on novice teenage driving outcomes (e.g., crashes and risky driving behaviors) from the Naturalistic Teenage Driving Study. Method: Survey and driving data from a data acquisition system (global positioning system, accelerometers, cameras) were collected from 42 newly licensed teenage drivers and their parents during the first 18 months of teenage licensure; stress responsivity was also measured in teenagers. Result Overall teenage crash and near-crash (CNC) rates declined over time, but were >4 times higher among teenagers than adults. Contributing factors to teenage CNC rates included secondary task engagement (e.g., distraction), kinematic risky driving, low stress responsivity, and risky social norms. Conclusions: The data support the contention that the high novice teenage CNC risk is due both to inexperience and risky driving behavior, particularly kinematic risky driving and secondary task engagement Practical Applications: Graduated driver licensing policy and other prevention efforts should focus on kinematic risky driving, secondary task engagement, and risky social norms. (C) 2015 National Safety Council and Elsevier Ltd. All rights reserved.
C1 [Simons-Morton, Bruce G.; Ouimet, Marie Claude; Albert, Paul S.; Ehsani, Johnathon P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
   [Klauer, Sheila G.; Guo, Feng; Lee, Suzanne E.; Dingus, Thomas A.] Virginia Tech, Transportat Inst, Blacksburg, VA 24061 USA.
   [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Psychol, Longueuil, PQ, Canada.
   [Guo, Feng] Virginia Tech, Dept Stat, Blacksburg, VA 24061 USA.
   [Pradhan, Anuj K.] Univ Michigan, Transportat Res Inst, Ann Arbor, MI 48109 USA.
RP Simons-Morton, BG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 7B13M, Bethesda, MD 20892 USA.
EM mortonb@mail.nih.gov
OI Pradhan, Anuj/0000-0002-7612-4208; Simons-Morton,
   Bruce/0000-0003-1099-6617
FU Intramural Research Program of Eunice Kennedy Shriver National Institute
   of Child Health and Human Development [N01-HD-5-3405]
FX This research was supported by the Intramural Research Program of Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development, Contract #N01-HD-5-3405.
NR 37
TC 1
Z9 1
U1 2
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-4375
EI 1879-1247
J9 J SAFETY RES
JI J. Saf. Res.
PD SEP
PY 2015
VL 54
BP 41
EP 48
DI 10.1016/j.jsr.2015.06.010
PG 8
WC Ergonomics; Public, Environmental & Occupational Health; Social
   Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
   Sciences - Other Topics; Transportation
GA CT2AN
UT WOS:000362604500008
PM 26403899
ER

PT J
AU Ehsani, JP
   Li, KG
   Simons-Morton, BG
   Tree-McGrath, CF
   Perlus, JG
   O'Brien, F
   Klauer, SG
AF Ehsani, Johnathon P.
   Li, Kaigang
   Simons-Morton, Bruce G.
   Tree-McGrath, Cheyenne Fox
   Perlus, Jessamyn G.
   O'Brien, Fearghal
   Klauer, Sheila G.
TI Conscientious personality and young drivers' crash risk
SO JOURNAL OF SAFETY RESEARCH
LA English
DT Article
DE Crashes; Teenage drivers; Personality
ID SENSATION SEEKING; DRIVING BEHAVIOR; INVOLVEMENT; NOVICE; AGE
AB Introduction: Personality characteristics are associated with many risk behaviors. However, the relationship between personality traits, risky driving behavior, and crash risk is poorly understood. The purpose of this study was to examine the association between personality, risky driving behavior, and crashes and near-crashes, using naturalistic driving research methods. Method: Participants' driving exposure, kinematic risky driving (KRD), high-risk secondary task engagement, and the frequency of crashes and near-crashes (CNC) were assessed over the first 18 months of licensure using naturalistic driving methods. A personality survey (NEO-Five Factor Inventory) was administered at baseline. The association between personality characteristics, KRD rate, secondary task engagement rate, and CNC rate was estimated using a linear regression model. Mediation analysis was conducted to examine if participants' KRD rate or secondary task engagement rate mediated the relationship between personality and CNC. Data were collected as part of the Naturalistic Teen Driving Study. Results: Conscientiousness was marginally negatively associated with CNC (path c = -0.034, p = .09) and both potential mediators KRD (path a = 0.040, p = .09) and secondary task engagement while driving (path a = 0.053, p = .03). KRD, but not secondary task engagement, was found to mediate (path b = 0376, p = .02) the relationship between conscientiousness and CNC (path c' = 0.025, p = .20). Conclusions: Using objective measures of driving behavior and a widely used personality construct, these findings present a causal pathway through which personality and risky driving are associated with CNC Specifically, more conscientious teenage drivers engaged in fewer risky driving maneuvers, and suffered fewer CNC Practical Applications: Part of the variability in crash risk observed among newly licensed teenage drivers can be explained by personality. Parents and driving instructors may take teenage drivers' personality into account when providing guidance, and establishing norms and expectations about driving. (C) 2015 National Safety Council and Elsevier Ltd. All rights reserved.
C1 [Ehsani, Johnathon P.; Li, Kaigang; Simons-Morton, Bruce G.; Tree-McGrath, Cheyenne Fox; Perlus, Jessamyn G.; O'Brien, Fearghal] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
   [Klauer, Sheila G.] Virginia Tech Transportat Inst, Blacksburg, VA USA.
RP Ehsani, JP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
EM johnathon.ehsani@nih.gov
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU Intramural Research Program of the NICHD [N01-HD-5-3405]
FX This research was supported by the Intramural Research Program of the
   NICHD, contract no. N01-HD-5-3405. A complex project such as this cannot
   succeed without help from people from a variety of backgrounds and
   capabilities. The authors would like to thank Jennifer Mullen for
   project management and data collection.
NR 27
TC 3
Z9 3
U1 3
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-4375
EI 1879-1247
J9 J SAFETY RES
JI J. Saf. Res.
PD SEP
PY 2015
VL 54
BP 83
EP 87
DI 10.1016/j.jsr.2015.06.015
PG 5
WC Ergonomics; Public, Environmental & Occupational Health; Social
   Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
   Sciences - Other Topics; Transportation
GA CT2AN
UT WOS:000362604500014
PM 26403906
ER

PT J
AU Oakley, RH
   Cidlowski, JA
AF Oakley, Robert H.
   Cidlowski, John A.
TI Glucocorticoid signaling in the heart: A cardiomyocyte perspective
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
DE Glucocorticoids; Glucocorticoid receptor; Mineralocorticoid receptor;
   Cardiomyocytes; Transgenic mice
ID SARCOPLASMIC-RETICULUM FUNCTION; CARDIOVASCULAR-DISEASE;
   MINERALOCORTICOID RECEPTOR; GENE-REGULATION; MESSENGER-RNA; CA2+
   CURRENT; CELL-DEATH; RAT HEART; DEXAMETHASONE; CORTICOSTEROIDS
AB Heart failure is one of the leading causes of death in the Western world. Glucocorticoids are primary stress hormones that regulate a vast array of biological processes, and synthetic derivatives of these steroids have been mainstays in the clinic for the last half century. Abnormal levels of glucocorticoids are known to negatively impact the cardiovascular system; however, surprisingly little is known about the direct role of glucocorticoid signaling in the heart. The actions of glucocorticoids are mediated classically by the glucocorticoid receptor (GR). In certain cells, such as cardiomyocytes, glucocorticoid occupancy and activation of the mineralocorticoid receptor (MR) may also contribute to the observed response. Recently, there has been a surge of reports investigating the in vivo function of glucocorticoid signaling in the heart using transgenic mice that specifically target GR or MR in cardiomyocytes. Results from these studies suggest that GR signaling in cardiomyocytes is critical for the normal development and function of the heart. In contrast, MR signaling in cardiomyocytes participates in the development and progression of cardiac disease. In the following review, we discuss these genetic mouse models and the new insights they are providing into the direct role cardiomyocyte glucocorticoid signaling plays in heart physiology and pathophysiology. This article is part of a Special Issue entitled 'Steroid Perspectives'. Published by Elsevier Ltd.
C1 [Oakley, Robert H.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Oakley, RH (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233,MD F3-07, Res Triangle Pk, NC 27709 USA.
EM oakleyr2@niehs.nih.gov; cidlows1@niehs.nih.gov
FU Intramural Research Program of the NIH, NIEHS
FX This research was supported by the Intramural Research Program of the
   NIH, NIEHS.
NR 87
TC 12
Z9 12
U1 0
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD SEP
PY 2015
VL 153
SI SI
BP 27
EP 34
DI 10.1016/j.jsbmb.2015.03.009
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CS9AY
UT WOS:000362382700003
PM 25804222
ER

PT J
AU Galeone, C
   Turati, F
   Zhang, ZF
   Guercio, V
   Tavani, A
   Serraino, D
   Brennan, P
   Fabianova, E
   Lissowska, J
   Mates, D
   Rudnai, P
   Shangina, O
   Szeszenia-Dabrowska, N
   Vaughan, TL
   Kelsey, K
   McClean, M
   Levi, F
   Hayes, RB
   Purdue, MP
   Bosetti, C
   Brenner, H
   Pelucchi, C
   Lee, YCA
   Hashibe, M
   Boffetta, P
   La Vecchia, C
AF Galeone, Carlotta
   Turati, Federica
   Zhang, Zuo-Feng
   Guercio, Valentina
   Tavani, Alessandra
   Serraino, Diego
   Brennan, Paul
   Fabianova, Eleonora
   Lissowska, Jola
   Mates, Dana
   Rudnai, Peter
   Shangina, Oxana
   Szeszenia-Dabrowska, Neonila
   Vaughan, Thomas L.
   Kelsey, Karl
   McClean, Michael
   Levi, Fabio
   Hayes, Richard B.
   Purdue, Mark P.
   Bosetti, Cristina
   Brenner, Hermann
   Pelucchi, Claudio
   Lee, Yuan-Chin Amy
   Hashibe, Mia
   Boffetta, Paolo
   La Vecchia, Carlo
TI Relation of allium vegetables intake with head and neck cancers:
   Evidence from the INHANCE consortium
SO MOLECULAR NUTRITION & FOOD RESEARCH
LA English
DT Article
DE Allium vegetables; Diet; Garlic; Head and Neck Neoplasms; Onion
ID UPPER AERODIGESTIVE TRACT; BUCCAL POUCH CARCINOGENESIS; EPIDEMIOLOGY
   CONSORTIUM; INTERNATIONAL HEAD; POOLED ANALYSIS; PHARYNGEAL CANCER;
   ALCOHOL-DRINKING; LARYNGEAL-CANCER; GASTRIC-CANCER; RISK-FACTORS
AB Scope: Only a few studies analyzed the role of allium vegetables with reference to head and neck cancers (HNC), with mixed results. We investigated the potential favorable role of garlic and onion within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.
   Methods and results: We analyzed pooled individual-level data from eight case-control studies, including 4590 cases and 7082 controls. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between garlic and onion intakes and HNC risk. Compared with no or low garlic use, the ORs of HNC were 0.95 (95% CI 0.71-1.27) for intermediate and 0.74 (95% CI 0.55-0.99) for high garlic use (p for trend = 0.02). The ORs of HNC for increasing categories of onion intake were 0.91 (95% CI 0.68-1.21) for > 1 to <= 3 portions per week, and 0.83 (95% CI 0.60-1.13) for > 3 portions per week (p for trend = 0.02), as compared to <1 portion per week. We found an inverse association between high onion intake and laryngeal cancer risk (OR = 0.69; 95% CI 0.54-0.88), but no significant association for other subsites.
   Conclusion: The results of this pooled-analysis support a possible moderate inverse association between garlic and onion intake and HNC risk.
C1 [Galeone, Carlotta; Turati, Federica; Tavani, Alessandra; Bosetti, Cristina; Pelucchi, Claudio] IRCCS, Ist Ric Farmacol Mario Negri, Dept Epidemiol, Milan, Italy.
   [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
   [Guercio, Valentina; La Vecchia, Carlo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
   [Serraino, Diego] CRO Aviano Natl Canc Inst, Epidemiol & Biostat Unit, Aviano, Italy.
   [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
   [Fabianova, Eleonora] Reg Author Publ Hlth BanskaBystr, Banska Bystrica, Slovakia.
   [Lissowska, Jola] M Skasodowska Curie Mem Canc Ctr, Warsaw, Poland.
   [Lissowska, Jola] Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
   [Mates, Dana] Natl Inst Publ Hlth, Bucharest, Romania.
   [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
   [Shangina, Oxana] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia.
   [Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Lodz, Poland.
   [Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Kelsey, Karl] Brown Univ, Providence, RI 02912 USA.
   [McClean, Michael] Boston Univ, Boston, MA 02215 USA.
   [Levi, Fabio] CHU Vaudois, Canc Epidemiol Unit, Inst Univ Med Sociale & Prevent, CH-1011 Lausanne, Switzerland.
   [Levi, Fabio] Univ Lausanne, Lausanne, Switzerland.
   [Hayes, Richard B.] NYU, Sch Med, Dept Populat Heath, Div Epidemiol, New York, NY USA.
   [Purdue, Mark P.] NCI, Bethesda, MD 20892 USA.
   [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
   [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany.
   [Lee, Yuan-Chin Amy; Hashibe, Mia] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA.
   [Hashibe, Mia] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
   [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
   [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
RP Galeone, C (reprint author), IRCCS, Ist Ric Farmacol Mario Negri, Dept Epidemiol, Milan, Italy.
EM galeone@marionegri.it
RI Brenner, Hermann/B-4627-2017; Szeszenia-Dabrowska, Neonila/F-7190-2010;
   Purdue, Mark/C-9228-2016; Turati, Federica/K-3841-2016
OI Brenner, Hermann/0000-0002-6129-1572; Serraino,
   Diego/0000-0003-0565-8920; La Vecchia, Carlo/0000-0003-1441-897X; Hayes,
   Richard/0000-0002-0918-661X; Purdue, Mark/0000-0003-1177-3108; Turati,
   Federica/0000-0002-5841-5773
FU NIH [NCI R03CA113157, NIDCR R03DE016611]; Italy Multicenter study:
   Italian Ministry of Health, General Directorate of European and
   International Relations; Swiss study: Swiss study: Swiss League against
   Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700,
   OCS-1633]; Central Europe study: Central Europe study: World Cancer
   Research Fund and the European Commission INCO-COPERNICUS Program [IC15-
   CT98-0332]; German - Saaland study: Ministry of Science, Research and
   Arts Baden-Wurttemberg; Milan study: Italian Association for Research on
   Cancer (AIRC); Seattle-LEO study: NIH [R01CA030022]; Boston study: NIH
   [R01CA078609, R01CA100679]; Puerto Rico study: National Institutes of
   Health (NCI) US and NIDCR intramural programs; Fondazione Veronesi;
   Italian Foundation of Cancer Research (FIRC)
FX The authors would like to thank I. Garimoldi for her editorial
   assistance and all of the participants who took part in this research
   for providing us very insightful and constructive comments, which helped
   to improve this manuscript. The INHANCE core data pooling was supported
   by NIH grants (NCI R03CA113157 & NIDCR R03DE016611). The individual
   studies were supported by the following grants: Italy Multicenter study:
   Italian Ministry of Health, General Directorate of European and
   International Relations; Swiss study: Swiss study: Swiss League against
   Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700,
   OCS-1633]; Central Europe study: Central Europe study: World Cancer
   Research Fund and the European Commission INCO-COPERNICUS Program
   [Contract No. IC15- CT98-0332]; German - Saaland study: Ministry of
   Science, Research and Arts Baden-Wurttemberg; Milan study: Italian
   Association for Research on Cancer (AIRC); Seattle-LEO study:
   NIH[R01CA030022]; Boston study: NIH [R01CA078609, R01CA100679]; Puerto
   Rico study: jointly funded by National Institutes of Health (NCI) US and
   NIDCR intramural programs. The work of CG was supported by Fondazione
   Veronesi. FT was supported by a fellowship from the Italian Foundation
   of Cancer Research (FIRC).
NR 60
TC 3
Z9 3
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1613-4125
EI 1613-4133
J9 MOL NUTR FOOD RES
JI Mol. Nutr. Food Res.
PD SEP
PY 2015
VL 59
IS 9
BP 1641
EP 1650
DI 10.1002/mnfr.201500042
PG 10
WC Food Science & Technology
SC Food Science & Technology
GA CT1IG
UT WOS:000362551400001
PM 26018663
ER

PT J
AU Maunder, K
   Walton, K
   Williams, P
   Ferguson, M
   Beck, E
   Ayres, E
   Hoggle, L
AF Maunder, Kirsty
   Walton, Karen
   Williams, Peter
   Ferguson, Maree
   Beck, Eleanor
   Ayres, Elaine
   Hoggle, Lindsey
TI Uptake of nutrition informatics in Australia compared with the USA
SO NUTRITION & DIETETICS
LA English
DT Article
DE dietetics; electronic health record; health information technology;
   information management; nutrition care; nutrition informatics
ID MEMBER SURVEY; TECHNOLOGY
AB AimTo determine the method and extent of health information technology (HIT) utilisation, roles in relation to HIT in the workplace and perceived barriers and benefits of HIT by dietitians in Australia and provide a comparison with dietitians in the USA.
   MethodsA survey adapted from the 2011 Academy of Nutrition and Dietetics (Academy) was utilised and circulated electronically to Dietitians Association of Australia members and advertised through a professional nutrition website in 2013. The survey encompassed 25 questions on computer access and use, data sources, experience using HIT, organisational involvement and perceived barriers and benefits to HIT. Descriptive statistics, independent t-tests, chi-square tests and z-tests were computed to investigate and compare responses from the 2013 Australian and 2011 Academy surveys.
   ResultsThe survey completion rate represented 14.5% of Dietitians Association of Australia members (747) and 5% of Academy members (3342). The Australian and Academy respondents reported similar high levels of comfort using technology, awareness of workplace HIT benefits (such as enhanced time management and improved ability to access data) and low levels of organisational involvement. However, there were a significantly greater number of Academy organisations utilising electronic health records (P < 0.05), and significantly more Academy respondents (55%) reported no barriers' to using HIT compared with Australians (37%) (P < 0.05).
   ConclusionsEducational programmes will be central to ensuring dietitians are equipped with technology and information management skills required to be involved in and make informed decisions about dietetic-related HIT projects as these will soon be fundamental to dietetic practice.
C1 [Maunder, Kirsty; Walton, Karen; Beck, Eleanor] Univ Wollongong, Sch Med, Wollongong, NSW 2522, Australia.
   [Williams, Peter] Univ Canberra, Fac Hlth, Canberra, ACT 2601, Australia.
   [Ferguson, Maree] Princess Alexandra Hosp, Nutr & Dietet, Woolloongabba, Qld 4102, Australia.
   [Ferguson, Maree] Univ Queensland, Sch Human Movement Studies, St Lucia, Qld, Australia.
   [Ayres, Elaine] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD USA.
   [Hoggle, Lindsey] Acad Nutr & Dietet, Nutr Informat, Washington, DE USA.
RP Maunder, K (reprint author), Univ Wollongong, Sch Med, Wollongong, NSW 2522, Australia.
EM km932@uowmail.edu.au
OI Williams, Peter/0000-0003-2311-5559
NR 16
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1446-6368
EI 1747-0080
J9 NUTR DIET
JI Nutr. Diet.
PD SEP
PY 2015
VL 72
IS 3
BP 291
EP 298
DI 10.1111/1747-0080.12207
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CT1VL
UT WOS:000362590300014
ER

PT J
AU Clausen, R
   Ma, BY
   Nussinov, R
   Shehu, A
AF Clausen, Rudy
   Ma, Buyong
   Nussinov, Ruth
   Shehu, Amarda
TI Mapping the Conformation Space of Wildtype and Mutant H-Ras with a
   Memetic, Cellular, and Multiscale Evolutionary Algorithm
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID MOLECULAR-DYNAMICS; EQUILIBRIUM FLUCTUATIONS; GEOMETRIC SIMULATION;
   SIGNAL-TRANSDUCTION; PROTEIN FUNCTION; FOLDING FUNNELS; REACTION PATHS;
   BINDING; SWITCH; GDP
AB An important goal in molecular biology is to understand functional changes upon single-point mutations in proteins. Doing so through a detailed characterization of structure spaces and underlying energy landscapes is desirable but continues to challenge methods based on Molecular Dynamics. In this paper we propose a novel algorithm, SIfTER, which is based instead on stochastic optimization to circumvent the computational challenge of exploring the breadth of a protein's structure space. SIfTER is a data-driven evolutionary algorithm, leveraging experimentally-available structures of wildtype and variant sequences of a protein to define a reduced search space from where to efficiently draw samples corresponding to novel structures not directly observed in the wet laboratory. The main advantage of SIfTER is its ability to rapidly generate conformational ensembles, thus allowing mapping and juxtaposing landscapes of variant sequences and relating observed differences to functional changes. We apply SIfTER to variant sequences of the H-Ras catalytic domain, due to the prominent role of the Ras protein in signaling pathways that control cell proliferation, its well-studied conformational switching, and abundance of documented mutations in several human tumors. Many Ras mutations are oncogenic, but detailed energy landscapes have not been reported until now. Analysis of SIfTER-computed energy landscapes for the wildtype and two oncogenic variants, G12V and Q61L, suggests that these mutations cause constitutive activation through two different mechanisms. G12V directly affects binding specificity while leaving the energy landscape largely unchanged, whereas Q61L has pronounced, starker effects on the landscape. An implementation of SIfTER is made available at http://www.cs.gmu.edu/similar to ashehu/?q=OurTools. We believe SIfTER is useful to the community to answer the question of how sequence mutations affect the function of a protein, when there is an abundance of experimental structures that can be exploited to reconstruct an energy landscape that would be computationally impractical to do via Molecular Dynamics.
C1 [Clausen, Rudy; Shehu, Amarda] George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA.
   [Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21701 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
   [Shehu, Amarda] George Mason Univ, Dept Bioengn, Fairfax, VA 22030 USA.
   [Shehu, Amarda] George Mason Univ, Sch Syst Biol, Manassas, VA USA.
RP Clausen, R (reprint author), George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA.
EM nussinor@helix.nih.gov; amarda@gmu.edu
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU National Science Foundation [1421001, 1144106]; Thomas F. and Kate
   Miller Jeffress Memorial Trust Award; NCI; NIH [HHSN261200800001E];
   Intramural Research Program of NIH; NCI, Center for Cancer Research
FX Funding for this work is provided in part by the National Science
   Foundation (Grant No. 1421001 and CAREER Award No. 1144106 to AS) and
   the Thomas F. and Kate Miller Jeffress Memorial Trust Award to AS. This
   project has also been funded in whole or in part with Federal funds from
   the NCI, NIH, under contract number HHSN261200800001E. The content of
   this publication does not necessarily reflect the views or policies of
   the Department of Health and Human Services, nor does mention of trade
   names, commercial products, or organizations imply endorsement by the
   U.S. Government. This study was supported (in part) by the Intramural
   Research Program of the NIH, NCI, Center for Cancer Research. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 55
TC 12
Z9 12
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD SEP
PY 2015
VL 11
IS 9
AR e1004470
DI 10.1371/journal.pcbi.1004470
PG 26
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CS7LZ
UT WOS:000362266400032
PM 26325505
ER

PT J
AU Haass-Koffler, CL
   Aoun, EG
   Swift, RM
   de la Monte, SM
   Kenna, GA
   Leggio, L
AF Haass-Koffler, C. L.
   Aoun, E. G.
   Swift, R. M.
   de la Monte, S. M.
   Kenna, G. A.
   Leggio, L.
TI LEPTIN LEVELS ARE REDUCED BY INTRAVENOUS GHRELIN ADMINISTRATION AND
   CORRELATED WITH CUE INDUCED-ALCOHOL CRAVING
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Haass-Koffler, C. L.; Leggio, L.] Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Providence, RI 02912 USA.
   [Aoun, E. G.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
   [Swift, R. M.; Kenna, G. A.] Brown Univ, Dept Psychiat & Human Behav, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
   [Swift, R. M.] Vet Affairs Med Ctr, Providence, RI USA.
   [de la Monte, S. M.] Brown Univ, Rhode Isl Hosp, Dept Pathol, Providence, RI 02903 USA.
   [de la Monte, S. M.] Brown Univ, Rhode Isl Hosp, Dept Neurol, Providence, RI 02903 USA.
   [de la Monte, S. M.] Brown Univ, Rhode Isl Hosp, Dept Neurosurg, Providence, RI 02903 USA.
   [de la Monte, S. M.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
   [Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD USA.
   [de la Monte, S. M.] NIDA, NIH, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
EI 1464-3502
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2015
VL 50
SU 1
MA P-44
PG 1
WC Substance Abuse
SC Substance Abuse
GA CR7JN
UT WOS:000361525900215
ER

PT J
AU Pfarr, S
   Meinhardt, MW
   Klee, ML
   Hansson, AC
   Vengeliene, V
   Schonig, K
   Bartsch, D
   Hope, BT
   Spanagel, R
   Sommer, WH
AF Pfarr, S.
   Meinhardt, M. W.
   Klee, M. L.
   Hansson, A. C.
   Vengeliene, V.
   Schoenig, K.
   Bartsch, D.
   Hope, B. T.
   Spanagel, R.
   Sommer, W. H.
TI LOSING CONTROL: EXCESSIVE ALCOHOL SEEKING AFTER SELECTIVE INACTIVATION
   OF CUE-RESPONSIVE NEURONS IN THE INFRALIMBIC CORTEX
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Pfarr, S.; Meinhardt, M. W.; Klee, M. L.; Hansson, A. C.; Vengeliene, V.; Spanagel, R.; Sommer, W. H.] NIDA, Inst Psychopharmacol, IRP, NIH, Baltimore, MD USA.
   [Schoenig, K.; Bartsch, D.] NIDA, Dept Mol Biol, IRP, NIH, Baltimore, MD USA.
   [Hope, B. T.] NIDA, IRP, NIH, Behav Neurosci Branch, Baltimore, MD USA.
   [Sommer, W. H.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Addict Med, D-68159 Heidelberg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
EI 1464-3502
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2015
VL 50
SU 1
MA P-67
PG 1
WC Substance Abuse
SC Substance Abuse
GA CR7JN
UT WOS:000361525900238
ER

PT J
AU Claus, ED
   Hendershot, CS
   Ramchandani, VA
AF Claus, E. D.
   Hendershot, C. S.
   Ramchandani, V. A.
TI VASCULAR REACTIVITY AS A SIGNIFICANT CONFOUND IN BOLD STUDIES OF ALCOHOL
   USE DISORDERS AND ALCOHOL ADMINISTRATION
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Claus, E. D.] Mind Res Network, Albuquerque, NM USA.
   [Hendershot, C. S.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M5S 1A1, Canada.
   [Hendershot, C. S.] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada.
   [Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
EI 1464-3502
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2015
VL 50
SU 1
MA FOC1-6
PG 1
WC Substance Abuse
SC Substance Abuse
GA CR7JN
UT WOS:000361525900142
ER

PT J
AU Suchankova, P
   Yan, J
   Schwandt, ML
   Stangl, BL
   Caparelli, EC
   Momenan, R
   Hodgkinson, CA
   Goldman, D
   Heilig, M
   Ramchandani, VA
   Nilsson, S
   von der Pahlen, B
   Santtila, P
   Sandnabba, K
   Johansson, A
   Jern, P
   Leggio, L
   Engel, JA
   Jerlhag, E
AF Suchankova, P.
   Yan, J.
   Schwandt, M. L.
   Stangl, B. L.
   Caparelli, E. C.
   Momenan, R.
   Hodgkinson, C. A.
   Goldman, D.
   Heilig, M.
   Ramchandani, V. A.
   Nilsson, S.
   von der Pahlen, B.
   Santtila, P.
   Sandnabba, K.
   Johansson, A.
   Jern, P.
   Leggio, L.
   Engel, J. A.
   Jerlhag, E.
TI THE ROLE OF THE GUT-BRAIN-AXIS IN SUBSTANCE USE DISORDERS: EVIDENCE FROM
   HUMAN GENETIC STUDIES
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Suchankova, P.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychopha, LCTS, NIH, Bethesda, MD USA.
   [Suchankova, P.; Johansson, A.; Engel, J. A.; Jerlhag, E.] Univ Gothenburg, Sahlgrenska Acad, Dept Pharmacol, Gothenburg, Sweden.
   [Yan, J.; Stangl, B. L.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, LCTS, NIH, Bethesda, MD USA.
   [Yan, J.] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
   [Schwandt, M. L.; Heilig, M.] NIAAA, LCTS, NIH, Bethesda, MD USA.
   [Caparelli, E. C.; Leggio, L.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
   [Momenan, R.] NIAAA, Sect Brain Elect & Imaging, LCTS, NIH, Bethesda, MD USA.
   [Hodgkinson, C. A.; Goldman, D.] NIAAA, Lab Neurogenet, NIH, Bethesda, MD USA.
   [Nilsson, S.] Chalmers, Inst Math Sci, Dept Math Stat, S-41296 Gothenburg, Sweden.
   [von der Pahlen, B.; Santtila, P.; Sandnabba, K.; Johansson, A.; Jern, P.] Abo Akad Univ, Dept Psychol & Logoped, Turku, Finland.
   [Jern, P.] Univ Turku, Dept Behav Sci & Philosophy, Turku, Finland.
   [Leggio, L.] Brown Univ, Dept Behav & Social Sci, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
EI 1464-3502
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2015
VL 50
SU 1
MA SY15-3
PG 1
WC Substance Abuse
SC Substance Abuse
GA CR7JN
UT WOS:000361525900071
ER

PT J
AU Song, JB
   Yang, XY
   Jacobson, O
   Lin, LS
   Huang, P
   Niu, G
   Ma, QJ
   Chen, XY
AF Song, Jibin
   Yang, Xiangyu
   Jacobson, Orit
   Lin, Lisen
   Huang, Peng
   Niu, Gang
   Ma, Qingjie
   Chen, Xiaoyuan
TI Sequential Drug Release and Enhanced Photothermal and Photoacoustic
   Effect of Hybrid Reduced Graphene Oxide-Loaded Ultrasmall Gold Nanorod
   Vesicles for Cancer Therapy
SO ACS NANO
LA English
DT Article
DE hybrid nanovesicle; sequential release; photothermal effect;
   photoacoustic imaging; PET imaging
ID PLASMONIC VESICLES; DELIVERY; NANOPARTICLES; NANOMATERIALS;
   NANOCRYSTALS; LIGHT; BLUE
AB We report a hybrid reduced graphene oxide (rGO)-loaded ultrasmall plasmonic gold nanorod vesicle (rGO-AuNRVe) (similar to 65 nm in size) with remarkably amplified photoacoustic (PA) performance and photothermal effects. The hybrid vesicle also exhibits a high loading capacity of doxorubicin (DOX), as both the cavity of the vesicle and the large surface area of the encapsulated rGO can be used for loading DOX, making it an excellent drug carrier. The loaded DOX is released sequentially: near-infrared photothermal heating induces DOX release from the vesicular cavity, and an intracellular acidic environment induces DOX release from the rGO surface. Positron emission tomography imaging showed high passive U87MG tumor accumulation of Cu-64-labeled rGO-AuNRVes (similar to 9.7% ID/g at 24 h postinjection) and strong PA signal in the tumor region. Single intravenous injection of rGO-AuNRVe-DOX followed by low-power-density 808 nm laser In Veto Sequential Drug Release irradiation (0.25 W/cm(2)) revealed effective inhibition of tumor growth due to the combination of chemo- and photothermal therapies. The rGO-AuNRVe-DOX capable of sequential DOX release by laser light and acid environment may have the potential for clinical translation to treat cancer patients with tumors accessible by light.
C1 [Song, Jibin; Ma, Qingjie] Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China.
   [Song, Jibin; Yang, Xiangyu; Jacobson, Orit; Lin, Lisen; Huang, Peng; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Ma, QJ (reprint author), Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China.
EM maqingjiejlu@163.com; shawn.chen@nih.gov
RI Huang, Peng/R-2480-2016
OI Huang, Peng/0000-0003-3651-7813
FU China-Japan Union Hospital of Jilin University; National Institute of
   Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
   Health (NIH)
FX This work was supported by a research program of China-Japan Union
   Hospital of Jilin University and intramural research program of the
   National Institute of Biomedical Imaging and Bioengineering (NIBIB),
   National Institutes of Health (NIH).
NR 38
TC 31
Z9 31
U1 45
U2 181
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
EI 1936-086X
J9 ACS NANO
JI ACS Nano
PD SEP
PY 2015
VL 9
IS 9
BP 9199
EP 9209
DI 10.1021/acsnano.5b03804
PG 11
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
   Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA CS2XR
UT WOS:000361935800058
PM 26308265
ER

PT J
AU El Haj, M
   Antoine, P
   Nandrino, JL
   Kapogiannis, D
AF El Haj, Mohamad
   Antoine, Pascal
   Nandrino, Jean Louis
   Kapogiannis, Dimitrios
TI Autobiographical memory decline in Alzheimer's disease, a theoretical
   and clinical overview
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Alzheimer' s disease; Autobiographical memory; Rehabilitation; Executive
   function; Hippocampus; Personal identity; Sense of self
ID MILD COGNITIVE IMPAIRMENT; DEFAULT MODE NETWORK; EPISODIC MEMORY;
   AUTONOETIC CONSCIOUSNESS; HIPPOCAMPAL COMPLEX; RETROGRADE-AMNESIA;
   SEMANTIC DEMENTIA; SELF-RECOGNITION; RETRIEVAL; FUTURE
AB Autobiographical memory, or memory for personal experiences, allows individuals to define themselves and construct a meaningful life story. Decline of this ability, as observed in Alzheimer's disease (AD), results in an impaired sense of self and identity. In our model (AMAD: Autobiographical Memory in Alzheimer's Disease), we present a critical review of theories and findings regarding cognitive and neuroanatomical underpinnings of autobiographical memory and its decline in AD and highlight studies on its clinical rehabilitation. We propose that autobiographical recall in AD is mainly characterized by loss of associated episodic information, which leads to de-contextualization of autobiographical memories and a shift from reliving past events to a general sense of familiarity. This decline refers to retrograde, but also anterograde amnesia that affects newly acquired memories besides remote ones. One consequence of autobiographical memory decline in AD is decreased access to memories that shape self-consciousness, self-knowledge, and self-images, leading to a diminished sense of self and identity. The link between autobiographical decline and compromised sense of self in AD can also manifest itself as low correspondence and coherence between past memories and current goals and beliefs. By linking cognitive, neuroanatomical, and clinical aspects of autobiographical decline in AD, our review provides a theoretical foundation, which may lead to better rehabilitation strategies. (C) 2015 Elsevier B.V. All rights reserved.
C1 [El Haj, Mohamad; Antoine, Pascal; Nandrino, Jean Louis] Univ Lille, Lab SCALab UMR CNRS 9193, F-59653 Villeneuve Dascq, France.
   [Kapogiannis, Dimitrios] NIA, Lab Neurosci, Baltimore, MD 21224 USA.
RP El Haj, M (reprint author), Univ Lille, Lab SCALab UMR CNRS 9193, Domaine Pont de Bois, F-59653 Villeneuve Dascq, France.
EM mohamad.elhaj@univ-lille3.fr
OI el haj, mohamad/0000-0001-7635-7557
FU LABEX (excellence laboratory, program investment for the future) DISTALZ
   (Development of Innovative Strategies for a Transdisciplinary approach
   to Alzheimer disease); Intramural Research Program of the National
   Institute on Aging, National Institutes of Health (NIA/NIH)
FX Drs. El Haj and Dr. Antoine were supported by the LABEX (excellence
   laboratory, program investment for the future) DISTALZ (Development of
   Innovative Strategies for a Transdisciplinary approach to Alzheimer
   disease). Dr. Kapogiannis was supported by the Intramural Research
   Program of the National Institute on Aging, National Institutes of
   Health (NIA/NIH).
NR 111
TC 12
Z9 12
U1 4
U2 26
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD SEP
PY 2015
VL 23
BP 183
EP 192
DI 10.1016/j.arr.2015.07.001
PN B
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA CS1ZW
UT WOS:000361868600005
PM 26169474
ER

PT J
AU Hendler, RW
   Meuse, CW
   Gallagher, T
   Labahn, J
   Kubicek, J
   Smith, PD
   Kakareka, JW
AF Hendler, Richard W.
   Meuse, Curtis W.
   Gallagher, Travis
   Labahn, Joerg
   Kubicek, Jan
   Smith, Paul D.
   Kakareka, John W.
TI Stray Light Correction in the Optical Spectroscopy of Crystals
SO APPLIED SPECTROSCOPY
LA English
DT Article
DE Absorption flattening; Kinetic analysis; Membrane crystals; Stray light
ID ARTIFACTS; SPECTRA
AB It has long been known in spectroscopy that light not passing through a sample, but reaching the detector (i.e., stray light), results in a distortion of the spectrum known as absorption flattening. In spectroscopy with crystals, one must either include such stray light or take steps to exclude it. In the former case, the derived spectra are not accurate. In the latter case, a significant amount of the crystal must be masked off and excluded. In this paper, we describe a method that allows use of the entire crystal by correcting the distorted spectrum.
C1 [Hendler, Richard W.] NHLBI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA.
   [Hendler, Richard W.; Meuse, Curtis W.; Gallagher, Travis] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
   [Hendler, Richard W.; Meuse, Curtis W.; Gallagher, Travis] NIST, Rockville, MD 20850 USA.
   [Labahn, Joerg] Cube Biotech GmbH, Monheim, Germany.
   [Labahn, Joerg; Kubicek, Jan] DESY, Ctr Struct Syst Biol, Hamburg, Germany.
   [Kubicek, Jan] Forschungszentrum Julich, Inst Complex Syst, ICS Struct Biochem 6, D-52425 Julich, Germany.
   [Smith, Paul D.] NHLBI, NIH, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA.
   [Kakareka, John W.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Hendler, RW (reprint author), NHLBI, NIH, Cell Biol Lab, Bldg 10, Bethesda, MD 20892 USA.
EM hendlerr@helix.nih.gov
OI Kakareka, John/0000-0003-0072-0035
FU National Institutes of Health; National Heart, Lung, and Blood
   Institute; National Institute of Biomedical Imaging and Bioengineering;
   Center for Information Technology; National Institute for Standards and
   Technology
FX This research was supported in part by the Intramural Research Program
   of the National Institutes of Health, National Heart, Lung, and Blood
   Institute, National Institute of Biomedical Imaging and Bioengineering,
   the Center for Information Technology, and the National Institute for
   Standards and Technology. Certain commercial equipment, instruments, or
   materials are identified in this paper to foster understanding. Such
   identification does not imply recommendation or endorsement by the
   National Institutes of Health or the National Institutes of Standards
   and Technology or that the materials and equipment are necessarily the
   best available for the purpose.
NR 11
TC 0
Z9 0
U1 0
U2 2
PU SOC APPLIED SPECTROSCOPY
PI FREDERICK
PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA
SN 0003-7028
EI 1943-3530
J9 APPL SPECTROSC
JI Appl. Spectrosc.
PD SEP
PY 2015
VL 69
IS 9
BP 1106
EP 1111
DI 10.1366/14-07716
PG 6
WC Instruments & Instrumentation; Spectroscopy
SC Instruments & Instrumentation; Spectroscopy
GA CS2VE
UT WOS:000361929300014
PM 26688880
ER

PT J
AU Patel, S
   Kilburn, B
   Imudia, A
   Armant, DR
   Skafar, DF
AF Patel, Shivali
   Kilburn, Brian
   Imudia, Anthony
   Armant, D. Randall
   Skafar, Debra F.
TI Estradiol Elicits Proapoptotic and Antiproliferative Effects in Human
   Trophoblast Cells
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE apoptosis; developmental biology; estradiol; first-trimester placenta;
   steroid hormone receptors; steroid hormones
ID 1ST TRIMESTER; UTERINE RECEPTIVITY; EXTRAVILLOUS TROPHOBLASTS; PLACENTAL
   APOPTOSIS; EMBRYO IMPLANTATION; OXIDATIVE STRESS; BABOON PREGNANCY;
   SPIRAL ARTERIES; GROWTH-FACTOR; ESTROGEN
AB During the first trimester of pregnancy, appropriate regulation of estradiol (E2) is essential for normal placental development. Previous studies demonstrate that premature elevation in E2 concentrations can lead to abnormal placentation, but have not fully elaborated the mechanism of this effect in the first-trimester trophoblast. Our aim was to determine whether E2 elicits trophoblast cell death or inhibits proliferation. The first-trimester human cytotrophoblast cell line HTR-8/SVneo was cultured in phenol red-free medium containing charcoal-stripped serum and treated with 17beta-E2 at concentrations between 0 and 100 nM. TUNEL and invasion assays indicated that E2 significantly increased cell death and reduced cell invasion at 10 nM, and nuclear Ki67 expression revealed that it decreased cell proliferation at 1 nM. A similar effect on cell death was observed in first-trimester placental explants. The E2 antagonist fulvestrant blocked all effects of E2. Immunohistochemistry showed that protein expression of proapoptotic caspases 3, 8, and 9 increased at E2 concentrations of 25 nM and greater, whereas expression of antiapoptotic BCL2-alpha decreased at E2 concentrations of 10 nM and greater. Additionally, treatments with estrogen receptor (ER) alpha-specific and ERbeta-specific agonists at concentrations between 0 and 1000 nM indicated that only ERalpha mediates E2's effects, although immunohistochemistry and Western immunoblotting showed that HTR-8/SVneo cells and placental explants express both ERalpha and ERbeta. Taken together, these findings reveal the interplay between elevated serum E2 and apoptosis in the first trimester of pregnancy. These factors could be associated with pregnancy complications including infertility and uteroplacental insufficiency.
C1 [Patel, Shivali; Skafar, Debra F.] Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 USA.
   [Kilburn, Brian; Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
   [Imudia, Anthony] Univ S Florida, Dept Obstet & Gynecol, Tampa, FL 33620 USA.
   [Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Skafar, DF (reprint author), Wayne State Univ, Sch Med, Dept Physiol, 540 E Canfield, Detroit, MI 48201 USA.
EM dskafar@med.wayne.edu
OI Armant, D. Randall/0000-0001-5904-9325
FU Intramural Research Program of the National Institutes of Health, Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development, NIH [HD045966, HD071408]; Office of the Vice President for
   Research of Wayne State University
FX Supported in part by the Intramural Research Program of the National
   Institutes of Health, Eunice Kennedy Shriver National Institute of Child
   Health and Human Development, NIH grants HD045966 and HD071408, and the
   Office of the Vice President for Research of Wayne State University.
   Presented in part at the 96th Annual Meeting of the Endocrine Society,
   21-24 June 2014, Chicago, Illinois.
NR 65
TC 2
Z9 2
U1 0
U2 5
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD SEP 1
PY 2015
VL 93
IS 3
AR 74
DI 10.1095/biolreprod.115.129114
PG 10
WC Reproductive Biology
SC Reproductive Biology
GA CS5OZ
UT WOS:000362128900016
PM 26246219
ER

PT J
AU Rawal, S
   Hoffman, HJ
   Honda, M
   Huedo-Medina, TB
   Duffy, VB
AF Rawal, Shristi
   Hoffman, Howard J.
   Honda, Mallory
   Huedo-Medina, Tania B.
   Duffy, Valerie B.
TI The Taste and Smell Protocol in the 2011-2014 US National Health and
   Nutrition Examination Survey (NHANES): Test-Retest Reliability and
   Validity Testing
SO CHEMOSENSORY PERCEPTION
LA English
DT Article
DE Taste perception; Smell perception; NHANES; Psychophysics; Bitter;
   Health status
ID ORAL SENSORY PHENOTYPE; OLFACTORY IMPAIRMENT; IDENTIFICATION TEST;
   ADULT-POPULATION; NIH TOOLBOX; INTENSITY; ASSOCIATION; PREVALENCE;
   SENSITIVITY; PERCEPTION
AB The US NHANES 2011-2014 protocol includes a taste and smell questionnaire (CSQ) in home-based interviews and brief assessments in mobile exam centers. We report the short- and longer-term test-retest reliability and validity of this protocol against broader chemosensory measures.
   A convenience sample of 73 adults (age = 39.5 +/- 20.8 years) underwent the NHANES protocol at baseline, 2 weeks and 6 months. For taste, participants rated intensities of two tastants (1 M NaCl, 1 mM quinine) applied to the tongue tip and three tastants (1 M NaCl, 1 mM quinine, 0.32 M NaCl) sampled with the whole mouth. Smell function was assessed with a Pocket Smell Test (TM) (PST; eight-item odor identification test). The CSQ asked about chemosensory problems, distortions, and age-related changes. Broader baseline measurements were a 40-item olfactometer-generated identification task and additional whole-mouth taste intensities (1 M sucrose, 32 mM citric acid, 3.2 mM propylthiouracil).
   Intraclass correlations (ICCs) for NHANES taste measures showed moderate-to-good agreement after 2 weeks and 6 months (ICCs 0.42-0.71). Whole-mouth quinine intensity was significantly correlated with other taste intensities, supporting its utility as a marker for overall taste functioning. Olfactory classification from PSTs agreed for 98.5 % of participants across 2 weeks (kappa = 0.85; 95 % CI 0.71-0.99) and had good correspondence with the olfactometer task. CSQ items showed good-to-excellent agreement over 6 months (ICCs 0.66-0.90).
   These findings further support that the NHANES chemosensory protocol has moderate-to-good test-retest reliability when administered to healthy, educated adults. Despite being a brief procedure with limited measures, the NHANES taste and smell assessments provided good information when compared to broader measures of taste and smell function.
C1 [Rawal, Shristi; Honda, Mallory; Huedo-Medina, Tania B.; Duffy, Valerie B.] Univ Connecticut, Dept Allied Hlth Sci, Storrs, CT 06269 USA.
   [Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
RP Duffy, VB (reprint author), Univ Connecticut, Dept Allied Hlth Sci, 358 Mansfield Rd,Unit 1101, Storrs, CT 06269 USA.
EM valerie.duffy@uconn.edu
FU National Institute on Deafness and Other Communication Disorders
   (NIDCD); National Institutes of Health (NIH); National Center for Health
   Statistics (NCHS); Centers for Disease Control and Prevention (CDC)
FX This research is supported by an Interagency Agreement (Y1-DC-0013)
   between the National Institute on Deafness and Other Communication
   Disorders (NIDCD), National Institutes of Health (NIH), and the National
   Center for Health Statistics (NCHS), Centers for Disease Control and
   Prevention (CDC).
NR 41
TC 6
Z9 6
U1 4
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1936-5802
EI 1936-5810
J9 CHEMOSENS PERCEPT
JI Chemosens. Percept.
PD SEP
PY 2015
VL 8
IS 3
SI SI
BP 138
EP 148
DI 10.1007/s12078-015-9194-7
PG 11
WC Food Science & Technology; Neurosciences
SC Food Science & Technology; Neurosciences & Neurology
GA CS7UO
UT WOS:000362292400006
PM 27833669
ER

PT J
AU Reinhold, WC
   Sunshine, M
   Varma, S
   Doroshow, JH
   Pommier, Y
AF Reinhold, William C.
   Sunshine, Margot
   Varma, Sudhir
   Doroshow, James H.
   Pommier, Yves
TI Using CellMiner 1.6 for Systems Pharmacology and Genomic Analysis of the
   NCI-60
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID MELANOMA-CELL INVASIVENESS; CANCER-CELLS; MESSENGER-RNA;
   DRUG-SENSITIVITY; LINE SET; GENES; PANEL; IDENTIFICATION; EXPRESSION;
   INHIBITOR
AB The NCI-60 cancer cell line panel provides a premier model for data integration, and systems pharmacology being the largest publicly available database of anticancer drug activity, genomic, molecular, and phenotypic data. It comprises gene expression (25,722 transcripts), microRNAs (360 miRNAs), whole-genome DNA copy number (23,413 genes), whole-exome sequencing (variants for 16,568 genes), protein levels (94 genes), and cytotoxic activity (20,861 compounds). Included are 158 FDA-approved drugs and 79 that are in clinical trials. To improve data accessibility to bioinformaticists and non-bioinformaticists alike, we have developed the CellMiner web-based tools. Here, we describe the newest CellMiner version, including integration of novel databases and tools associated with whole-exome sequencing and protein expression, and review the tools. Included are (i) "Cell line signature" for DNA, RNA, protein, and drugs; (ii) "Cross correlations" for up to 150 input genes, microRNAs, and compounds in a single query; (iii) "Pattern comparison" to identify connections among drugs, gene expression, genomic variants, microRNA, and protein expressions; (iv) "Genetic variation versus drug visualization" to identify potential new drug: gene DNA variant relationships; and (v) "Genetic variant summation" designed to provide a synopsis of mutational burden on any pathway or gene group for up to 150 genes. Together, these tools allow users to flexibly query the NCI-60 data for potential relationships between genomic, molecular, and pharmacologic parameters in a manner specific to the user's area of expertise. Examples for both gain-(RAS) and loss-of-function (PTEN) alterations are provided. (C)2015 AACR.
C1 [Reinhold, William C.; Sunshine, Margot; Varma, Sudhir; Doroshow, James H.; Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
   [Reinhold, William C.; Sunshine, Margot; Varma, Sudhir; Doroshow, James H.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Sunshine, Margot; Varma, Sudhir] Syst Res & Applicat Corp, Fairfax, VA USA.
   [Varma, Sudhir] HiThru Analyt LLC, Laurel, MD USA.
   [Doroshow, James H.] NCI, Dev Therapeut Program, DCTD, NIH, Bethesda, MD 20892 USA.
RP Reinhold, WC (reprint author), NIH, 9000 Rockville Pike,Bldg 37,Room 5041, Bethesda, MD 20892 USA.
EM wcr@mail.nih.gov; pommier@nih.gov
FU Intramural NIH HHS [ZIC BC011475-02]
NR 41
TC 8
Z9 8
U1 2
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 1
PY 2015
VL 21
IS 17
BP 3841
EP 3852
DI 10.1158/1078-0432.CCR-15-0335
PG 12
WC Oncology
SC Oncology
GA CS2OF
UT WOS:000361910000007
PM 26048278
ER

PT J
AU Janssen, I
   Blanchet, EM
   Adams, K
   Chen, CC
   Millo, CM
   Herscovitch, P
   Taieb, D
   Kebebew, E
   Lehnert, H
   Fojo, AT
   Pacak, K
AF Janssen, Ingo
   Blanchet, Elise M.
   Adams, Karen
   Chen, Clara C.
   Millo, Corina M.
   Herscovitch, Peter
   Taieb, David
   Kebebew, Electron
   Lehnert, Hendrik
   Fojo, Antonio T.
   Pacak, Karel
TI Superiority of [Ga-68]-DOTATATE PET/CT to Other Functional Imaging
   Modalities in the Localization of SDHB-Associated Metastatic
   Pheochromocytoma and Paraganglioma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; RADIOLABELED SOMATOSTATIN ANALOG;
   NEUROENDOCRINE TUMORS; MALIGNANT PHEOCHROMOCYTOMAS; GA-68-DOTATATE
   PET/CT; GERMLINE MUTATIONS; I-123-MIBG SPECT; HIGH-FREQUENCY; FOLLOW-UP;
   THERAPY
AB Purpose: Patients with succinate dehydrogenase subunit B (SDHB) mutation-related pheochromocytoma/paraganglioma (PHEO/PGL) are at a higher risk for metastatic disease than other hereditary PHEOs/PGLs. Current therapeutic approaches are limited, but the best outcomes are based on the early and proper detection of as many lesions as possible. Because PHEOs/PGLs overexpress somatostatin receptor 2 (SSTR2), the goal of our study was to assess the clinical utility of [Ga-68]-DOTA(0)-Tyr(3)-octreotate ([Ga-68]-DOTATATE) positron emission tomography/computed tomography (PET/CT) and to evaluate its diagnostic utility in comparison with the currently recommended functional imaging modalities [F-18]-fluorodopamine ([F-18]-FDA), [F-18]-fluorodihydroxyphenylalanine ([F-18]-FDOPA), [F-18]-fluoro-2-deoxy-D-glucose ([F-18]FDG) PET/CT as well as CT/MRI.
   Experimental Design: [Ga-68]-DOTATATE PET/CT was prospectively performed in 17 patients with SDHB-related metastatic PHEOs/PGLs. All patients also underwent [F-18]-FDG PET/CT and CT/MRI, with 16 of the 17 patients also receiving [F-18]-FDOPA and [F-18]-FDA PET/CT scans. Detection rates of metastatic lesions were compared between all these functional imaging studies. A composite synthesis of all used functional and anatomical imaging studies served as the imaging comparator.
   Results: [Ga-68]-DOTATATE PET/CT demonstrated a lesion-based detection rate of 98.6% [95% confidence interval (CI), 96.5%-99.5%], [F-18]-FDG, [F-18]-FDOPA, [F-18]-FDA PET/CT, and CT/MRI showed detection rates of 85.8% (CI, 81.3%-89.4%; P < 0.01), 61.4% (CI, 55.6%-66.9%; P < 0.01), 51.9% (CI, 46.1%57.7%; P < 0.01), and 84.8% (CI, 80.0%-88.5%; P < 0.01), respectively.
   Conclusions: [Ga-68]-DOTATATE PET/CT showed a significantly superior detection rate to all other functional and anatomical imaging modalities and may represent the preferred future imaging modality in the evaluation of SDHB-related metastatic PHEO/ PGL. (C)2015 AACR.
C1 [Janssen, Ingo; Adams, Karen; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD USA.
   [Janssen, Ingo] Univ Hosp Schleswig Holstein, Dept Radiol & Nucl Med, Nucl Med Sect, Lubeck, Germany.
   [Blanchet, Elise M.] Hop Xavier Bichat, Dept Nucl Med, Paris, France.
   [Chen, Clara C.] NIH, Nucl Med Div, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
   [Millo, Corina M.; Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, NIH Clin Ctr, Bethesda, MD 20892 USA.
   [Taieb, David] Aix Marseille Univ, Dept Nucl Med, La Timone Univ Hosp, CERIMED, Marseille, France.
   [Kebebew, Electron] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
   [Lehnert, Hendrik] Univ Hosp Schleswig Holstein, Dept Internal Med 1, Lubeck, Germany.
   [Fojo, Antonio T.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), NIH, 10 Ctr Dr MSC 1109,Bldg 10,Room 1E-3140, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Intramural Research Program of the NIH, Eunice Kennedy Shriver National
   Institute of Child Health and Human Development
FX This work was supported, in part, by the Intramural Research Program of
   the NIH, Eunice Kennedy Shriver National Institute of Child Health and
   Human Development.
NR 40
TC 28
Z9 28
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 1
PY 2015
VL 21
IS 17
BP 3888
EP 3895
DI 10.1158/1078-0432.CCR-14-2751
PG 8
WC Oncology
SC Oncology
GA CS2OF
UT WOS:000361910000012
PM 25873086
ER

PT J
AU Mohan, S
   Vander Broek, R
   Shah, S
   Eytan, DF
   Pierce, ML
   Carlson, SG
   Coupar, JF
   Zhang, JL
   Cheng, H
   Chen, Z
   Van Waes, C
AF Mohan, Suresh
   Vander Broek, Robert
   Shah, Sujay
   Eytan, Danielle F.
   Pierce, Matthew L.
   Carlson, Sophie G.
   Coupar, Jamie F.
   Zhang, Jialing
   Cheng, Hui
   Chen, Zhong
   Van Waes, Carter
TI MEK Inhibitor PD-0325901 Overcomes Resistance to PI3K/mTOR Inhibitor
   PF-5212384 and Potentiates Antitumor Effects in Human Head and Neck
   Squamous Cell Carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NF-KAPPA-B; GROWTH-FACTOR-RECEPTOR; SIGNAL PATHWAYS; PROANGIOGENIC
   FACTORS; PI3K PATHWAY; HUMAN TUMORS; AKT; ACTIVATION; CANCER;
   SENSITIVITY
AB Purpose: Head and neck squamous cell carcinomas exhibit variable sensitivity to inhibitors of the PI3K/mTOR pathway, an important target of genomic alterations in this cancer type. The mitogen-activated protein kinase kinase (MEK)/ERK/activator protein 1 (AP-1) and nuclear factor-kB (NF-kB) pathways are also frequently co-activated, but their roles in resistance mechanisms to PI3K/mTOR inhibitors and as therapeutic targets in head and neck squamous cell carcinoma (HNSCC) are not well defined.
   Experimental Design: We determined the IC(50)s of dual PI3K/mTOR inhibitor PF-05212384 (PF-384) by XTT assays in 14 HNSCC lines with PI3K/Akt/mTOR cascade alterations. In two resistant models, we further characterized the molecular, cellular, and in vivo attributes and effects of combining PF-384 with MEK inhibitor PD-0325901 (PD-901).
   Results: PF-384 IC50s varied between 0.75 and 133 nmol/L in 14 HNSCC lines with overexpression or mutations of PIK3CA, and sensitivity correlated with increased phospho-AKT(T308/S473). In resistant UMSCC-1 and -46 models, PF-384 increased G(0)-/G(1)-phase accumulation but weakly induced sub-G(0) cell death. PF-384 inhibited direct targets of PI3K/mTOR, but incompletely attenuated co-activated ERK and UMSCC-1 xenograft growth in vivo. PD-901 strongly inhibited MEK/ERK targets, and the combination of PF-384 and PD-901 inhibited downstream NF-kB and AP-1 transactivation, and IL8 and VEGF production in vitro. PD-901 potently inhibited tumor growth alone and with PF384, enhanced antiproliferative, apoptotic, and anti-angiogenesis activity in vivo.
   Conclusions: PI3K/mTOR inhibitor PF-384 exhibits variable activity in a panel of HNSCC cell lines with differing PIK3CA expression and mutation status. MEK inhibitor PD-901 overcomes resistance and enhances antitumor effects observed with PF-384 in vivo. (C) 2015 AACR.
C1 [Mohan, Suresh; Vander Broek, Robert; Shah, Sujay; Eytan, Danielle F.; Pierce, Matthew L.; Carlson, Sophie G.; Coupar, Jamie F.; Zhang, Jialing; Cheng, Hui; Chen, Zhong; Van Waes, Carter] NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
   [Mohan, Suresh; Vander Broek, Robert; Eytan, Danielle F.] NIH, Med Res Scholars Program, Bethesda, MD 20892 USA.
   [Pierce, Matthew L.] Georgetown Univ Hosp, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA.
RP Van Waes, C (reprint author), NIDCD, NIH, Bldg 10 CRC,4-2732,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chenz@nidcd.nih.gov; vanwaesc@nidcd.nih.gov
OI Eytan, Danielle/0000-0003-1032-2276
FU National Institutes of Health (NIH) Medical Research Scholars Program;
   NIH; National Institute on Deafness and other Communication Disorders
   projects [ZIA-DC-000016, 73, 74]
FX S. Mohan, R. Vander Broek, and D.F. Eytan were supported by the National
   Institutes of Health (NIH) Medical Research Scholars Program, a
   public-private partnership supported jointly by the NIH and generous
   contributions to the Foundation for the NIH from Pfizer Inc., The Doris
   Duke Charitable Foundation, Alexandria Real Estate Equities, Inc. and
   Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as
   well as other private donors. C. Van Waes and Z. Chen were supported by
   the National Institute on Deafness and other Communication Disorders
   projects ZIA-DC-000016, 73, and 74.
NR 49
TC 5
Z9 5
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 1
PY 2015
VL 21
IS 17
BP 3946
EP 3956
DI 10.1158/1078-0432.CCR-14-3377
PG 11
WC Oncology
SC Oncology
GA CS2OF
UT WOS:000361910000018
PM 25977343
ER

PT J
AU Hannan, FM
   Walls, GV
   Babinsky, VN
   Nesbit, MA
   Kallay, E
   Hough, TA
   Fraser, WD
   Cox, RD
   Hu, JX
   Spiegel, AM
   Thakker, RV
AF Hannan, Fadil M.
   Walls, Gerard V.
   Babinsky, Valerie N.
   Nesbit, M. Andrew
   Kallay, Enikoe
   Hough, Tertius A.
   Fraser, William D.
   Cox, Roger D.
   Hu, Jianxin
   Spiegel, Allen M.
   Thakker, Rajesh V.
TI The Calcilytic Agent NPS 2143 Rectifies Hypocalcemia in a Mouse Model
   With an Activating Calcium-Sensing Receptor (CaSR) Mutation: Relevance
   to Autosomal Dominant Hypocalcemia Type 1 (ADH1)
SO ENDOCRINOLOGY
LA English
DT Article
ID NEGATIVE ALLOSTERIC MODULATORS; PARATHYROID-HORMONE;
   FUNCTIONAL-CHARACTERIZATION; 7-TRANSMEMBRANE DOMAIN; TRANSMEMBRANE
   DOMAIN; BONE-FORMATION; BINDING-SITES; HUMAN CA2+; DISORDERS; MICE
AB Autosomal dominant hypocalcemia type 1 (ADH1) is caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR) and may lead to symptomatic hypocalcemia, inappropriately low serum PTH concentrations and hypercalciuria. Negative allosteric CaSR modulators, known as calcilytics, have been shown to normalize the gain-of-function associated with ADH-causing CaSR mutations in vitro and represent a potential targeted therapy for ADH1. However, the effectiveness of calcilytic drugs for the treatment of ADH1-associated hypocalcemia remains to be established. We have investigated NPS 2143, a calcilytic compound, for the treatment of ADH1 by in vitro and in vivo studies involving a mouse model, known as Nuf, which harbors a gain-of-function CaSR mutation, Leu723Gln. Wild-type (Leu723) and Nuf mutant (Gln723) CaSRs were expressed in HEK293 cells, and the effect of NPS 2143 on their intracellular calcium responses was determined by flow cytometry. NPS 2143 was also administered as a single ip bolus to wild-type and Nuf mice and plasma concentrations of calcium and PTH, and urinary calcium excretion measured. In vitro administration of NPS 2143 decreased the intracellular calcium responses of HEK293 cells expressing the mutant Gln723 CaSR in a dose-dependent manner, thereby rectifying the gain-of-function associated with the Nuf mouse CaSR mutation. Intraperitoneal injection of NPS 2143 in Nuf mice led to significant increases in plasma calcium and PTH without elevating urinary calcium excretion. These studies of a mouse model with an activating CaSR mutation demonstrate NPS 2143 to normalize the gain-of-function causing ADH1 and improve the hypocalcemia associated with this disorder.
C1 [Hannan, Fadil M.; Walls, Gerard V.; Babinsky, Valerie N.; Nesbit, M. Andrew; Kallay, Enikoe; Thakker, Rajesh V.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Acad Endocrine Unit, Oxford OX3 7LJ, England.
   [Hough, Tertius A.; Cox, Roger D.] MRC, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England.
   [Hough, Tertius A.; Cox, Roger D.] MRC Harwell, Mary Lyon Ctr, Didcot OX11 0RD, Oxon, England.
   [Fraser, William D.] Univ E Anglia, Dept Med, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England.
   [Hu, Jianxin] NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
   [Spiegel, Allen M.] Albert Einstein Coll Med, Bronx, NY 10461 USA.
RP Thakker, RV (reprint author), Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Acad Endocrine Unit, Oxford OX3 7LJ, England.
EM rajesh.thakker@ndm.ox.ac.uk
OI Thakker, Rajesh/0000-0002-1438-3220; Kallay, Eniko/0000-0002-4996-0104
FU United Kingdom Medical Research Council [G9825289, G1000467]; National
   Institute for Health Research Oxford Biomedical Research Centre
   Programme
FX This work was supported by the United Kingdom Medical Research Council
   Program Grants G9825289 and G1000467 (to M.A.N., F.M.H., and R.V.T.) and
   by the National Institute for Health Research Oxford Biomedical Research
   Centre Programme (M.A.N. and R.V.T.).
NR 34
TC 13
Z9 13
U1 0
U2 6
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD SEP
PY 2015
VL 156
IS 9
BP 3114
EP 3121
DI 10.1210/en.2015-1269
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS6ZV
UT WOS:000362234100009
PM 26052899
ER

PT J
AU Deng, Q
   Riquelme, D
   Trinh, L
   Low, MJ
   Tomic, M
   Stojilkovic, S
   Aguilera, G
AF Deng, Qiong
   Riquelme, Denise
   Trinh, Loc
   Low, Malcolm J.
   Tomic, Melanija
   Stojilkovic, Stanko
   Aguilera, Greti
TI Rapid Glucocorticoid Feedback Inhibition of ACTH Secretion Involves
   Ligand-Dependent Membrane Association of Glucocorticoid Receptors
SO ENDOCRINOLOGY
LA English
DT Article
ID CORTICOTROPIN-RELEASING HORMONE; ANTERIOR-PITUITARY GLAND; INTRACELLULAR
   CALCIUM TRANSIENTS; ADRENOCORTICOTROPIN RELEASE; STEROID-HORMONES;
   PLASMA-MEMBRANE; NONGENOMIC MECHANISM; CELL-PROLIFERATION; TYROSINE
   KINASES; PROTEIN-KINASE
AB The hypothesis that rapid glucocorticoid inhibition of pituitary ACTH secretion mediates a feed-forward/feedback mechanism responsible for the hourly glucocorticoid pulsatility was tested in cultured pituitary cells. Perifusion with 30 pM CRH caused sustained the elevation of ACTH secretion. Superimposed corticosterone pulses inhibited CRH-stimulated ACTH release, depending on prior glucocorticoid clearance. When CRH perifusion started after 2 hours of glucocorticoid-free medium, corticosterone levels in the stress range (1 mu M) caused a delayed (25 min) and prolonged inhibition of CRH-stimulated ACTH secretion, up to 60 minutes after corticosterone withdrawal. In contrast, after 6 hours of glucocorticoid-free medium, basal corticosterone levels inhibited CRH-stimulated ACTH within 5 minutes, after rapid recovery 5 minutes after corticosterone withdrawal. The latter effect was insensitive to actinomycin D but was prevented by the glucocorticoid receptor antagonist, RU486, suggesting nongenomic effects of the classical glucocorticoid receptor. In hypothalamic-derived 4B cells, 10 nM corticosterone increased immunoreactive glucocorticoid receptor content in membrane fractions, with association and clearance rates paralleling the effects on ACTH secretion from corticotrophs. Corticosterone did not affect CRH-stimulated calcium influx, but in AtT-20 cells, it had biphasic effects on CRH-stimulated Src phosphorylation, with early inhibition and late stimulation, suggesting a role for Src phosphorylation on the rapid glucocorticoid feedback. The data suggest that the nongenomic/membrane effects of classical GR mediate rapid and reversible glucocorticoid feedback inhibition at the pituitary corticotrophs downstream of calcium influx. The sensitivity and kinetics of these effects is consistent with the hypothesis that pituitary glucocorticoid feedback is part of the mechanism for adrenocortical ultradian pulse generation.
C1 [Deng, Qiong; Riquelme, Denise; Trinh, Loc; Aguilera, Greti] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA.
   [Tomic, Melanija; Stojilkovic, Stanko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA.
   [Deng, Qiong] Jilin Univ, Coll Anim Sci, Changchun 130021, Peoples R China.
   [Low, Malcolm J.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
RP Aguilera, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 10 CRC,Room 1E-3330, Bethesda, MD 20892 USA.
EM greti_aguilera@nih.gov
RI Tomic, Melanija/C-3371-2016
FU Intramural Research Program of the Eunice Kennedy Shiver National
   Institute of Child Health and Human Development, National Institutes of
   Health; National Institutes of Health [DK066604]; China Scholarship
   Council, China
FX This work was supported by the Intramural Research Program of the Eunice
   Kennedy Shiver National Institute of Child Health and Human Development,
   National Institutes of Health (to G.A. and S.S.), National Institutes of
   Health Grant DK066604 (to M.J.L.), and China Scholarship Council, China
   (to Q.D.).
NR 61
TC 6
Z9 6
U1 1
U2 3
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD SEP
PY 2015
VL 156
IS 9
BP 3215
EP 3227
DI 10.1210/EN.2015-1265
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS6ZV
UT WOS:000362234100018
PM 26121342
ER

PT J
AU Li, R
   Diao, HL
   Zhao, F
   Xiao, S
   El Zowalaty, AE
   Dudley, EA
   Mattson, MP
   Ye, XQ
AF Li, Rong
   Diao, Honglu
   Zhao, Fei
   Xiao, Shuo
   El Zowalaty, Ahmed E.
   Dudley, Elizabeth A.
   Mattson, Mark P.
   Ye, Xiaoqin
TI Olfactomedin 1 Deficiency Leads to Defective Olfaction and Impaired
   Female Fertility
SO ENDOCRINOLOGY
LA English
DT Article
ID HORMONE-RELEASING HORMONE; SUPRACHIASMATIC NUCLEUS; EMBRYO IMPLANTATION;
   HYPOGONADOTROPIC HYPOGONADISM; RECEPTOR COMPLEX; FOS EXPRESSION; MICE;
   MOUSE; PROTEIN; REPRODUCTION
AB Olfactomedin 1 (OLFM1) is a glycoprotein highly expressed in the brain. Olfm1(-/-) female mice were previously reported to have reduced fertility. Previous microarray analysis revealed Olfm1 among the most highly upregulated genes in the uterine luminal epithelium upon embryo implantation, which was confirmed by in situ hybridization. We hypothesized that Olfm1 deficiency led to defective embryo implantation and thus impaired fertility. Indeed, Olfm1(-/-) females had defective embryo implantation. However, Olfm1(-/-) females rarely mated and those that mated rarely became pregnant. Ovarian histology indicated the absence of corpora lutea in Olfm1(-/-) females, indicating defective ovulation. Superovulation using equine chorionic gonadotropin-human chorionic gonadotropin rescued mating, ovulation, and pregnancy, and equine chorionic gonadotropin alone rescued ovulation in Olfm1(-/-) females. Olfm1(-/-) females had a 13% reduction of hypothalamic GnRH neurons but comparable basal serum LH levels and GnRH-induced LH levels compared with wild-type controls. These results indicated no obvious local defects in the female reproductive system and a functional hypothalamic-pituitary-gonadal axis. Olfm1(-/-) females were unresponsive to the effects of male bedding stimulation on pubertal development and estrous cycle. There were 41% fewer cFos-positive cells in the mitral cell layer of accessory olfactory bulb upon male urine stimulation for 90 minutes. OLFM1 was expressed in the main and accessory olfactory systems including main olfactory epithelium, vomeronasal organ, main olfactory bulb, and accessory olfactory bulb, with the highest expression detected in the axon bundles of olfactory sensory neurons. These data demonstrate that defective fertility in Olfm1(-/-) females is most likely a secondary effect of defective olfaction.
C1 [Li, Rong; Diao, Honglu; Zhao, Fei; Xiao, Shuo; El Zowalaty, Ahmed E.; Dudley, Elizabeth A.; Ye, Xiaoqin] Univ Georgia, Dept Physiol & Pharmacol, Coll Vet Med, Athens, GA 30602 USA.
   [Li, Rong; Zhao, Fei; Xiao, Shuo; El Zowalaty, Ahmed E.; Dudley, Elizabeth A.; Ye, Xiaoqin] Univ Georgia, Interdisciplinary Toxicol Program, Athens, GA 30602 USA.
   [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Ye, XQ (reprint author), Univ Georgia, Dept Physiol & Pharmacol, Coll Vet Med, Interdisciplinary Toxicol Program, 501 DW Brooks Dr, Athens, GA 30602 USA.
EM ye@uga.edu
FU Office of the Vice President for Research, Interdisciplinary Toxicology
   Program; Department of Physiology and Pharmacology (University of
   Georgia), the National Institutes of Health; National Institutes of
   Health [R15HD066301, R01HD065939]; Office of Research on Women's Health;
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; Intramural Research Program of the National Institute on
   Aging
FX We thank the Department of Pathology in the College of Veterinary
   Medicine, University of Georgia, for access to the imaging system; Dr
   Simonetta Camandola (National Institutes on Aging) for preparing the
   founder mice; Dr Jesse Schank (University of Georgia) for providing the
   anti-cFos antibody; and the Office of the Vice President for Research,
   Interdisciplinary Toxicology Program, and Department of Physiology and
   Pharmacology (University of Georgia), the National Institutes of Health
   for financial support.; This work was supported by National Institutes
   of Health Grants R15HD066301 and R01HD065939 (cosupported by the Office
   of Research on Women's Health and the Eunice Kennedy Shriver National
   Institute of Child Health and Human Development) (to X.Y.). This work
   was also supported, in part, by the Intramural Research Program of the
   National Institute on Aging.
NR 75
TC 2
Z9 3
U1 0
U2 5
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD SEP
PY 2015
VL 156
IS 9
BP 3344
EP 3357
DI 10.1210/en.2015-1389
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS6ZV
UT WOS:000362234100028
PM 26107991
ER

PT J
AU Okada, M
   Miller, TC
   Fu, LZ
   Shi, YB
AF Okada, Morihiro
   Miller, Thomas C.
   Fu, Liezhen
   Shi, Yun-Bo
TI Direct Activation of Amidohydrolase Domain-Containing 1 Gene by Thyroid
   Hormone Implicates a Role in the Formation of Adult Intestinal Stem
   Cells During Xenopus Metamorphosis
SO ENDOCRINOLOGY
LA English
DT Article
ID RETINOIC ACID RECEPTORS; AMPHIBIAN METAMORPHOSIS; TRANSCRIPTIONAL
   ACTIVATION; POSTEMBRYONIC DEVELOPMENT; CHROMATIN DISRUPTION; LAEVIS
   METAMORPHOSIS; MAMMALIAN METABOLISM; ANURAN METAMORPHOSIS; FROG
   METAMORPHOSIS; CONNECTIVE-TISSUE
AB The T-3-dependent anuran metamorphosis resembles postembryonic development in mammals, the period around birth when plasma T-3 levels peak. In particular, the remodeling of the intestine during metamorphosis mimics neonatal intestinal maturation in mammals when the adult intestinal epithelial self-renewing system is established. We have been using intestinal metamorphosis to investigate how the organ-specific adult stem cells are formed during vertebrate development. Early studies in Xenopus laevis have shown that this process involves complete degeneration of the larval epithelium and de novo formation of adult stem cells. A tissue-specific microarray analysis of intestinal gene expression during Xenopus laevis metamorphosis has identified a number of candidate stem cell genes. Here we have carried out detailed analyses of one such gene, amidohydrolase domain containing 1 (AMDHD1) gene, which encodes an enzyme in the histidine catabolic pathway. We show that AMDHD1 is exclusively expressed in the proliferating adult epithelial stem cells during metamorphosis with little expression in other intestinal tissues. We further provide evidence that T-3 activates AMDHD1 gene expression directly at the transcription level through T-3 receptor binding to the AMDHD1 gene in the intestine. In addition, we have reported earlier that histidine ammonia-lyase gene, another gene in histidine catabolic pathway, is similarly regulated by T-3 in the intestine. These results together suggest that histidine catabolism plays a critical role in the formation and/or proliferation of adult intestinal stem cells during metamorphosis.
C1 [Okada, Morihiro; Miller, Thomas C.; Fu, Liezhen; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 18T Room 106,18 Lib Dr,MSC 5431, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
FU Intramural Research Program of National Institute of Child Health and
   Human Development, National Institutes of Health; Japan Society for the
   Promotion of Science Research Fellowship
FX This work was supported by the Intramural Research Program of National
   Institute of Child Health and Human Development, National Institutes of
   Health. M.O. was supported in part by a Japan Society for the Promotion
   of Science Research Fellowship for Japanese Biomedical and Behavioral
   Researchers at the National Institutes of Health.
NR 91
TC 2
Z9 2
U1 0
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD SEP
PY 2015
VL 156
IS 9
BP 3381
EP 3393
DI 10.1210/en.2015-1190
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS6ZV
UT WOS:000362234100031
PM 26086244
ER

PT J
AU Callier, SL
   Bonham, VL
AF Callier, Shawneequa L.
   Bonham, Vence L.
TI Taking a Stand: The Genetics Community's Responsibility for Intelligence
   Research
SO HASTINGS CENTER REPORT
LA English
DT Article
ID SCIENCE
AB There is a longstanding debate about genetics research into intelligence. Some scholars question the value of focusing on genetic contributions to intelligence in a society where social and environmental determinants powerfully influence cognitive ability and educational outcomes. Others warn that censoring certain research questions, such as inquiries about genetic differences in intellectual potential, compromises academic freedom. Still others view interest in this subject as a corollary to a long and troublesome history of eugenics research. The dawn of a new era in genome sequencing as a commodity will sustain scientific interest in the genetics of intelligence for the foreseeable future, but deep-rooted challenges threaten the scientific merit of the research. The use of imprecise definitions of study populations, the difficult nature of studying the environment, and the potential of researcher bias are inextricably linked with concerns about the trustworthiness and utility of research in this area. Leadership by the genetics community is essential to ensure the value and trustworthiness of these studies.
C1 [Callier, Shawneequa L.] George Washington Univ, Sch Med & Hlth Sci, Dept Clin Res, Bioeth & Hlth Care Law & Regulat, Washington, DC 20052 USA.
   [Callier, Shawneequa L.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA.
   [Bonham, Vence L.] NHGRI, Div Intramural Res, NIH, Bethesda, MD USA.
   [Bonham, Vence L.] Social & Behav Res Branch, Hlth Dispar Res Unit, Bethesda, MD USA.
RP Callier, SL (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Clin Res, Bioeth & Hlth Care Law & Regulat, Washington, DC 20052 USA.
NR 22
TC 0
Z9 0
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0093-0334
EI 1552-146X
J9 HASTINGS CENT REP
JI Hastings Cent. Rep.
PD SEP-OCT
PY 2015
VL 45
SU 1
SI SI
BP S54
EP S58
DI 10.1002/hast.500
PG 5
WC Ethics; Health Care Sciences & Services; Medical Ethics; Social
   Sciences, Biomedical
SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical
   Ethics; Biomedical Social Sciences
GA CS5ME
UT WOS:000362121500010
PM 26413950
ER

PT J
AU Fuchs, A
   Kuhl, JT
   Chen, MY
   Helquist, S
   Razeto, M
   Arakita, K
   Steveson, C
   Arai, AE
   Kofoed, KF
AF Fuchs, Andreas
   Kuhl, J. Tobias
   Chen, Marcus Y.
   Helquist, Steffen
   Razeto, Marco
   Arakita, Kazumasa
   Steveson, Chloe
   Arai, Andrew E.
   Kofoed, Klaus F.
TI Feasibility of coronary calcium and stent image subtraction using
   320-detector row CT angiography
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Article
DE Coronary; Subtraction; CT; CCTA; Angiography
ID COMPUTED-TOMOGRAPHY
AB Background: The reader confidence and diagnostic accuracy of coronary CT angiography (CCTA) can be compromised by the presence of calcified plaques and stents causing blooming artifacts. Compared to conventional invasive coronary angiography (ICA), this may cause an overestimation of stenosis severity leading to false-positive results. In a pilot study, we tested the feasibility of a new coronary calcium image subtraction algorithm in relation to reader confidence and diagnostic accuracy.
   Methods: Forty-three patients underwent clinically indicated ICA and CCTA using a 320-detector row CT. Median Agatston score was 510. Two data sets were reconstructed: a conventional CCTA (CCTA(conv)) and a subtracted CCTA (CCTA(sub)), where calcifications detected on noncontrast images were subtracted from the CCTA. Reader confidence and concordance with ICA for identification of >50% stenosis were recorded. We defined target segments on CCTA(conv), as motion-free coronary segments with calcification or stent and low reader confidence. The effect of CCTA(sub) was assessed. No approval from the ethics committee was required according to Danish law.
   Results: A total of 76 target segments were identified. The use of coronary calcium image subtraction improved the reader confidence in 66% of these segments. In target segments, specificity (86% vs 65%; P < .01) and positive predictive value (71% vs 51%, P = .03) were improved using CCTA(sub) compared to CCTA(conv), without loss in negative predictive value.
   Conclusions: Our initial experience with coronary calcium image subtraction suggests that it is feasible and could lead to an improvement in reader confidence and diagnostic accuracy for identification of significant coronary artery disease. (C) 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
C1 [Fuchs, Andreas; Kuhl, J. Tobias; Helquist, Steffen; Kofoed, Klaus F.] Univ Copenhagen, Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark.
   [Chen, Marcus Y.; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Razeto, Marco] Toshiba Med Visualizat Syst Europe, Edinburgh, Midlothian, Scotland.
   [Arakita, Kazumasa; Steveson, Chloe] Toshiba Med Syst Corp, Otawara, Japan.
   [Kofoed, Klaus F.] Univ Copenhagen, Rigshosp, Dept Radiol, DK-2100 Copenhagen, Denmark.
RP Fuchs, A (reprint author), Univ Copenhagen, Rigshosp, Dept Cardiol, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
EM mck601@alumni.ku.dk
FU Interreg IVA
FX This work was supported in part internally by Interreg IVA.
NR 13
TC 10
Z9 10
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD SEP-OCT
PY 2015
VL 9
IS 5
BP 393
EP 398
DI 10.1016/j.jcct.2015.03.016
PG 6
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
   Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
   Medical Imaging
GA CS2VS
UT WOS:000361930700003
PM 26091841
ER

PT J
AU Andriamaharavo, NR
   Garraffo, HM
   Spande, TF
   Giddings, LA
   Vieites, DR
   Vences, M
   Saporito, RA
AF Andriamaharavo, Nirina R.
   Garraffo, H. Martin
   Spande, Thomas F.
   Giddings, Lesley-Ann
   Vieites, David R.
   Vences, Miguel
   Saporito, Ralph A.
TI Individual and Geographic Variation of Skin Alkaloids in Three
   Swamp-Forest Species of Madagascan Poison Frogs (Mantella)
SO JOURNAL OF CHEMICAL ECOLOGY
LA English
DT Article
DE Arthropods; Chemical defense; Mantella aurantiaca; Mantella
   milotympanum; Mantella crocea; Mantellidae; Myrmicine ants; Oribatid
   mites; Sequestration; Single-skin analyses; Endangered species
ID BUFONID TOADS MELANOPHRYNISCUS; PUMILIOTOXINS; DECAHYDROQUINOLINES;
   QUINOLIZIDINES; PYRROLIZIDINES; SEQUESTRATION; INDOLIZIDINES; EVOLUTION;
   PATTERNS; PANAMA
AB Seventy skins of three mantellid frog species from Madagascan swamp-forest habitats, Mantella aurantiaca, M. crocea, and M. milotympanum, were individually examined for skin alkaloids using GC/MS. These poison frogs were found to differ significantly in their alkaloid composition from species of Mantella originating from non-flooded rainforest in eastern Madagascar, which were examined in earlier work. Only 16 of the previously detected 106 alkaloids were represented among the 60 alkaloids from the swamp-forest frogs of the present study. We hypothesize this difference is related mainly to habitat but cannot exclude a phylogenetic component as the three swamp-forest species are a closely related monophyletic group. The paucity of alkaloids with unbranched-carbon skeletons (ant-derived) and the commonness of alkaloids with branched-carbon skeletons (mite-derived) indicate that oribatid mites are a major source of alkaloids in these species of mantellids. Furthermore, most of the alkaloids have an oxygen atom in their formulae. Differences in alkaloids were observed among species, populations of the same species, and habitats. In M. aurantiaca, small geographic distances among populations were associated with differences in alkaloid profiles, with a remote third site illustrating even greater differences. The present study and an earlier study of three other mantellid species suggest that oribatid mites, and not ants, are the major source of alkaloids in the species of mantellids examined thus far.
C1 [Andriamaharavo, Nirina R.; Garraffo, H. Martin; Spande, Thomas F.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA.
   [Giddings, Lesley-Ann] Middlebury Coll, Dept Chem & Biochem, Middlebury, VT 05753 USA.
   [Vieites, David R.] CSIC, Museo Nacl Ciencias Nat, E-28006 Madrid, Spain.
   [Vences, Miguel] Tech Univ Carolo Wilhelmina Braunschweig, Inst Zool, Div Evolutionary Biol, D-38106 Braunschweig, Germany.
   [Saporito, Ralph A.] John Carroll Univ, Dept Biol, University Hts, OH 44118 USA.
RP Saporito, RA (reprint author), John Carroll Univ, Dept Biol, University Hts, OH 44118 USA.
EM ralph.saporito@gmail.com
OI Vieites, David/0000-0001-5551-7419; Vences, Miguel/0000-0003-0747-0817
FU NIDDK
FX Research in Madagascar was made possible by collaboration with the
   Departement de Biologie Animale, Universite d'Antananarivo, and research
   and export permits (CITES export permits # 1100-EAL/MG01/CWO from 19
   December 2001 and 070C to 074C-EA02/MG05 from 18 Feb 2005) kindly issued
   by the Malagasy authorities. The Volkswagen Foundation, Biopat, and the
   Deutsche Forschungsgemeinschaft supported fieldwork of M.V. and D.R.V.
   The work at NIH was supported by intramural funds of NIDDK.
NR 40
TC 0
Z9 0
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0098-0331
EI 1573-1561
J9 J CHEM ECOL
JI J. Chem. Ecol.
PD SEP
PY 2015
VL 41
IS 9
BP 837
EP 847
DI 10.1007/s10886-015-0616-4
PG 11
WC Biochemistry & Molecular Biology; Ecology
SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology
GA CS8JL
UT WOS:000362333400007
PM 26329921
ER

PT J
AU Freeman, ZT
   Krall, C
   Rice, KA
   Adams, RJ
   Pate, KAM
   Hutchinson, EK
AF Freeman, Zachary T.
   Krall, Caroline
   Rice, Kelly A.
   Adams, Robert J.
   Pate, Kelly A. Metcalf
   Hutchinson, Eric K.
TI Severity and Distribution of Wounds in Rhesus Macaques (Macaca mulatta)
   Correlate with Observed Self-Injurious Behavior
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Article
ID RETROSPECTIVE ANALYSIS; MONKEYS; ENVIRONMENT
AB Self-injurious behavior (SIB) occurs within laboratory-housed NHP at low frequency but can have a devastating effect on animal research and wellbeing. One barrier to the study and clinical management of these cases is the cost of equipment and personnel time to quantify the behavior according to the current standard of observation and to score remotely obtained video recordings. In studies of human SIB, in which direct observation is difficult or prohibited, researchers have demonstrated that quantifying the tissue damage resulting from SIB can be a useful proxy to represent the underlying behavior. We hypothesized that the nature of wounds resulting from SIB in NHP could be used in a similar manner to measure the abnormal behavior. Using a cohort of rhesus macaques with high-incidence SIB, we examined severity, distribution, and number of wounds and compared them with observed incidences of SIB during a 12-wk experiment. We found that the number, severity, and distribution of physical wounds were associated with the incidences of biting behavior observed during the 2 wk prior to measurement. We also found that an increased number of wounds was associated with increased severity Animals with wounds of moderate severity were more likely to also have severe wounds than were macaques with wounds that were lower than moderate in severity. This work is the first representative study in NHP to find that behavioral SIB correlates with physical wounding and that increases in the frequency and number of the body regions affected correlates with the severity of wounding.
C1 [Freeman, Zachary T.; Krall, Caroline; Rice, Kelly A.; Adams, Robert J.; Pate, Kelly A. Metcalf] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA.
   [Rice, Kelly A.; Hutchinson, Eric K.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
RP Hutchinson, EK (reprint author), NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA.
EM EricHutchinsonDVM@gmail.com
FU NIH ORIP [T32 OD011089, K01 OD018244, P40 OD013117, P40 RR019995]; Johns
   Hopkins University School of Medicine Research Animal Resources
FX We acknowledge the following funding sources: NIH ORIP T32 OD011089, NIH
   ORIP K01 OD018244, NIH ORIP P40 OD013117, P40 RR019995, and Johns
   Hopkins University School of Medicine Research Animal Resources. In
   addition, we thank the following people for their assistance in the
   experiments described: Melanie Albano, Nicole Azene, Tori Baxter,
   Caroline Garrett, Tracey Graham, Kristy Koenig, and Theresa Meade.
NR 22
TC 0
Z9 0
U1 5
U2 5
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2015
VL 54
IS 5
BP 516
EP 520
PG 5
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA CS4OS
UT WOS:000362056000008
PM 26424249
ER

PT J
AU Anderlini, P
   Wu, J
   Gersten, I
   Ewell, M
   Tolar, J
   Antin, JH
   Adams, R
   Arai, S
   Eames, G
   Horwitz, ME
   McCarty, J
   Nakamura, R
   Pulsipher, MA
   Rowley, S
   Leifer, E
   Carter, SL
   DiFronzo, NL
   Horowitz, MM
   Confer, D
   Deeg, HJ
   Eapen, M
AF Anderlini, Paolo
   Wu, Juan
   Gersten, Iris
   Ewell, Marian
   Tolar, Jakob
   Antin, Joseph H.
   Adams, Roberta
   Arai, Sally
   Eames, Gretchen
   Horwitz, Mitchell E.
   McCarty, John
   Nakamura, Ryotaro
   Pulsipher, Michael A.
   Rowley, Scott
   Leifer, Eric
   Carter, Shelly L.
   DiFronzo, Nancy L.
   Horowitz, Mary M.
   Confer, Dennis
   Deeg, H. Joachim
   Eapen, Mary
TI Cyclophosphamide conditioning in patients with severe aplastic anaemia
   given unrelated marrow transplantation: a phase 1-2 dose de-escalation
   study
SO LANCET HAEMATOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; ALTERNATIVE DONOR TRANSPLANTS; TOTAL-BODY
   IRRADIATION; SAA WORKING PARTY; BONE-MARROW; ANTITHYMOCYTE GLOBULIN;
   FLUDARABINE; TOXICITY; FAILURE; REGIMEN
AB Background The optimum preparative regimen for unrelated donor marrow transplantation in patients with severe aplastic anaemia remains to be established. We investigated whether the combination of fludarabine, anti-thymocyte globulin, and total body irradiation (TBI) would enable reduction of the cyclophosphamide dose to less than 200 mg/kg while maintaining engraftment and having a survival similar to or better than that with standard regimens using a cyclophosphamide dose of 200 mg/kg (known to be associated with significant organ toxicity) for unrelated donor transplantation for severe aplastic anaemia. We have previously shown that cyclophosphamide at 150 mg/kg resulted in excess toxicity and its omission (0 mg/kg) resulted in unacceptable graft failure (three of three patients had secondary graft failure). Here we report results for the 50 mg/kg and 100 mg/kg cohorts.
   Methods In a multicentre phase 1-2 study, patients (aged <= 65 years) with severe aplastic anaemia, adequate organ function, and an unrelated adult marrow donor HLA matched at the allele level for HLA A, B, C, and DRB1 or mismatched at a single HLA locus received bone marrow grafts from unrelated donors. All patients received anti-thymocyte globulin (rabbit derived 3 mg/kg per day, intravenously, on days -4 to -2, or equine derived 30 mg/kg per day, intravenously, on days -4 to -2), fludarabine (30 mg/m.per day, intravenously, on days -5 to -2), and TBI (2 Gy). Cyclophosphamide dosing started at 150 mg/kg and was de-escalated in steps of 50 mg/kg (to 100 mg/kg, 50 mg/kg, and 0 mg/kg). The primary endpoint was the selection of the optimum cyclophosphamide dose based on assessments of graft failure (primary or secondary), toxicity, and early death during 100 days of follow-up after the transplant; this is the planned final analysis for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT00326417.
   Findings 96 patients had bone marrow transplant. At day 100, 35 (92%) of 38 patients were engrafted and alive in the cyclophosphamide 50 mg/kg cohort and 35 (85%) of 41 in the 100 mg/kg cohort. Cyclophosphamide 50 mg/kg and 100 mg/kg resulted in posterior means for fatality without graft failure of 0.7% (credible interval 0-3.3) and 1.4% (0-4.9), respectively. Three patients (8%) had graft failure with cyclophosphamide 50 mg/kg and six (15%) with cyclophosphamide 100 mg/kg. Four (11%) patients had major regimen-related toxicity with cyclophosphamide 50 mg/kg and nine (22%) with cyclophosphamide 100 mg/kg. The most common organ toxicity was pulmonary (grade 3 or 4 dyspnoea or hypoxia including mechanical ventilation), and occurred in three (8%) and four (10%) patients given cyclophosphamide 50 mg/kg and 100 mg/kg, respectively.
   Interpretation Cyclophosphamide at 50 mg/kg and 100 mg/kg with TBI 2 Gy, fludarabine, and anti-thymocyte globulin results in effective conditioning and few early deaths after unrelated donor transplantation for severe aplastic anaemia. These doses of cyclophosphamide provide a framework for further regimen optimisation strategies.
C1 [Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Wu, Juan; Gersten, Iris; Ewell, Marian; Carter, Shelly L.] Emmes Corp, Rockville, MD USA.
   [Tolar, Jakob] Univ Minnesota, Minneapolis, MN USA.
   [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Adams, Roberta] Phoenix Childrens Hosp, Phoenix, AZ USA.
   [Arai, Sally] Stanford Hosp & Clin, Stanford, CA USA.
   [Eames, Gretchen] Cooks Childrens Hosp, Ft Worth, TX USA.
   [Horwitz, Mitchell E.] Duke Univ, Durham, NC USA.
   [McCarty, John] Virginia Commonwealth Univ, Richmond, VA USA.
   [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
   [Pulsipher, Michael A.] Univ Utah, Salt Lake City, UT USA.
   [Rowley, Scott] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
   [Leifer, Eric; DiFronzo, Nancy L.] NHLBI, Bethesda, MD 20892 USA.
   [Horowitz, Mary M.; Eapen, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
   [Confer, Dennis] Natl Marrow Donor Program, Minneapolis, MN USA.
   [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Anderlini, P (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Room FC5-3062,1515 Holcombe Blvd,Unit 0423, Houston, TX 77030 USA.
EM panderli@mdanderson.org
FU US National, Heart, Lung and Blood Institute [U10HL069294]; National
   Cancer Institute
FX This trial was fully supported by grant number U10HL069294 from the US
   National, Heart, Lung and Blood Institute and the National Cancer
   Institute. EL and NLD are US Government employees (National Heart, Lung,
   and Blood Institute). We thank the clinical investigators who entered
   this study and managed patients; and Ellen Parker (Emmes Corporation,
   Rockville, MD, USA) for her assistance in the preparation of the
   manuscript. The findings reported in this paper are those of the
   authors.
NR 31
TC 11
Z9 11
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2352-3026
J9 LANCET HAEMATOL
JI Lancet Haematol.
PD SEP
PY 2015
VL 2
IS 9
BP E367
EP E375
PG 9
WC Hematology
SC Hematology
GA CS4VV
UT WOS:000362075100007
PM 26685770
ER

PT J
AU Gotts, SJ
   Milleville, SC
   Martin, A
AF Gotts, Stephen J.
   Milleville, Shawn C.
   Martin, Alex
TI Object identification leads to a conceptual broadening of object
   representations in lateral prefrontal cortex
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Sharpening; Priming; Repetition suppression; Synchrony; Semantic memory;
   Tuning curve
ID INFERIOR TEMPORAL CORTEX; PICTURE-WORD INTERFERENCE; MONKEY
   INFEROTEMPORAL CORTEX; REPETITION SUPPRESSION; SEMANTIC INTERFERENCE;
   NEURAL MECHANISMS; VISUAL EXPERIENCE; COGNITIVE CONTROL; SPEECH
   PRODUCTION; FRONTAL-CORTEX
AB Recent experience identifying objects leads to later improvements in both speed and accuracy ("repetition priming"), along with simultaneous reductions of neural activity ("repetition suppression"). A popular interpretation of these joint behavioral and neural phenomena is that object representations become perceptually "sharper" with stimulus repetition, eliminating cells that are poorly stimulus-selective and responsive and reducing support for competing representations downstream. Here, we test this hypothesis in an fMRI-adaptation experiment using pictures of objects. Prior to fMRI, participants repeatedly named a set of object pictures. During fMRI, participants viewed adaptation sequences composed of rapidly repeated objects (3-6 repetitions over several seconds) that were either named previously or that were new for the fMRI session, followed by single "deviant" object pictures used to measure recovery from adaptation and that shared a relationship to the adapted picture (a different exemplar of the same object, a conceptual associate, or an unrelated picture). Effects of adaptation and recovery were found throughout visually responsive brain regions. Occipitotemporal cortical regions displayed repetition suppression to previously named relative to new adapters but failed to exhibit pronounced changes in neural tuning. In contrast, changes in the slope of the recovery curves were found in the left lateral prefrontal cortex: Greater residual adaptation was observed to exemplar stimuli and conceptual associates following previously named adapting stimuli, consistent with greater rather than reduced neural overlap among representations of conceptually related objects. Furthermore, this change in neural tuning was directly related to the proportion of conceptual errors made by participants in the naming sessions pre- and post-fMRI, establishing that the experience-dependent conceptual broadening of object representations seen in fMRI is also manifest in behavior. In a follow-up behavioral experiment, we further show that recent naming experience leads to greater semantic priming when using the previously named pictures as briefly presented primes. Taken together, our results fail to support perceptual sharpening as the primary mediator between repetition suppression and behavioral priming at durations typically used to study priming and instead highlight an experience-dependent broadening of conceptual representations. We suggest that alternative mechanisms, such as increases in neural synchronization, are more promising in explaining priming in the face of repetition suppression. Published by Elsevier Ltd.
C1 [Gotts, Stephen J.; Milleville, Shawn C.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Gotts, SJ (reprint author), NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bldg 10,Rm 4C-104, Bethesda, MD 20892 USA.
EM gottss@mail.nih.gov
FU National Institute of Mental Health (NIH), Division of Intramural
   Research [93-M-0170]
FX The authors would like to thank Sharon Thompson-Schill and an anonymous
   reviewer for many helpful comments on the manuscript and Pat Bellgowan,
   Chris Baker, Nico Kriegeskorte, Avniel Ghuman, Kathleen Hansen, John
   Dylan Haynes, Kyle Simmons, and Dale Stevens for helpful discussions.
   This study was supported by the National Institute of Mental Health
   (NIH), Division of Intramural Research, and it was conducted under NIH
   Clinical Study Protocol 93-M-0170 (ClinicalTrials.gov ID: NCT00001360).
NR 113
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U1 5
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
EI 1873-3514
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD SEP
PY 2015
VL 76
SI SI
BP 62
EP 78
DI 10.1016/j.neuropsychologia.2014.10.041
PG 17
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA CS5QX
UT WOS:000362134200007
PM 25445775
ER

PT J
AU Bilanchone, V
   Clemens, K
   Kaake, R
   Dawson, AR
   Matheos, D
   Nagashima, K
   Sitlani, P
   Patterson, K
   Chang, I
   Huang, L
   Sandmeyer, S
AF Bilanchone, Virginia
   Clemens, Kristina
   Kaake, Robyn
   Dawson, Anthony R.
   Matheos, Dina
   Nagashima, Kunio
   Sitlani, Parth
   Patterson, Kurt
   Chang, Ivan
   Huang, Lan
   Sandmeyer, Suzanne
TI Ty3 Retrotransposon Hijacks Mating Yeast RNA Processing Bodies to Infect
   New Genomes
SO PLOS GENETICS
LA English
DT Article
ID PROTEIN-INTERACTION NETWORKS; P-BODY COMPONENTS; CELL-CYCLE ARREST;
   SACCHAROMYCES-CEREVISIAE; STRESS GRANULES; FUNCTIONAL DOMAINS; BUDDING
   YEAST; TRANSPOSITION; TRANSLATION; ELEMENT
AB Retrotransposition of the budding yeast long terminal repeat retrotransposon Ty3 is activated during mating. In this study, proteins that associate with Ty3 Gag3 capsid protein during virus-like particle (VLP) assembly were identified by mass spectrometry and screened for roles in mating-stimulated retrotransposition. Components of RNA processing bodies including DEAD box helicases Dhh1/DDX6 and Ded1/DDX3, Sm-like protein Lsm1, decapping protein Dcp2, and 5' to 3' exonuclease Xrn1 were among the proteins identified. These proteins associated with Ty3 proteins and RNA, and were required for formation of Ty3 VLP retrosome assembly factories and for retrotransposition. Specifically, Dhh1/DDX6 was required for normal levels of Ty3 genomic RNA, and Lsm1 and Xrn1 were required for association of Ty3 protein and RNA into retrosomes. This role for components of RNA processing bodies in promoting VLP assembly and retrotransposition during mating in a yeast that lacks RNA interference, contrasts with roles proposed for orthologous components in animal germ cell ribonucleoprotein granules in turnover and epigenetic suppression of retrotransposon RNAs.
C1 [Bilanchone, Virginia; Clemens, Kristina; Dawson, Anthony R.; Matheos, Dina; Sitlani, Parth; Patterson, Kurt; Chang, Ivan; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA.
   [Clemens, Kristina; Kaake, Robyn; Huang, Lan] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA.
   [Nagashima, Kunio] SAIC Frederick Inc, Electron Microscopy Lab, NCI Frederick, Frederick Natl Lab Canc Res, Frederick, MD USA.
   [Sandmeyer, Suzanne] Univ Calif Irvine, Inst Genom & Bioinformat, Irvine, CA 92717 USA.
RP Bilanchone, V (reprint author), Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA.
EM sbsandme@uci.edu
FU Public Health Services grant [GM33281, GM074830]; National Cancer
   Institute Grant [P30CA062203]; National Institute for Allergy and
   Infectious Diseases NIAID [T32 AI-07319]; Grace Beekhuis Bell Endowed
   Chair
FX This work was funded by: Public Health Services grant GM33281 to SS;
   Public Health Services grant GM074830 to LH; National Cancer Institute
   Grant to Cancer Center P30CA062203; and National Institute for Allergy
   and Infectious Diseases NIAID T32 AI-07319 to KP. Funds from the Grace
   Beekhuis Bell Endowed Chair paid for publication. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
NR 115
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U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2015
VL 11
IS 9
AR e1005528
DI 10.1371/journal.pgen.1005528
PG 29
WC Genetics & Heredity
SC Genetics & Heredity
GA CS7MZ
UT WOS:000362269000042
PM 26421679
ER

PT J
AU Chertow, JH
   Alkaitis, MS
   Nardone, G
   Ikeda, AK
   Cunnington, AJ
   Okebe, J
   Ebonyi, AO
   Njie, M
   Correa, S
   Jayasooriya, S
   Casals-Pascual, C
   Billker, O
   Conway, DJ
   Walther, M
   Ackerman, H
AF Chertow, Jessica H.
   Alkaitis, Matthew S.
   Nardone, Glenn
   Ikeda, Allison K.
   Cunnington, Aubrey J.
   Okebe, Joseph
   Ebonyi, Augustine O.
   Njie, Madi
   Correa, Simon
   Jayasooriya, Shamanthi
   Casals-Pascual, Climent
   Billker, Oliver
   Conway, David J.
   Walther, Michael
   Ackerman, Hans
TI Plasmodium Infection Is Associated with Impaired Hepatic
   Dimethylarginine Dimethylaminohydrolase Activity and Disruption of
   Nitric Oxide Synthase Inhibitor/Substrate Homeostasis
SO PLOS PATHOGENS
LA English
DT Article
ID SEVERE FALCIPARUM-MALARIA; ASYMMETRIC DIMETHYLARGININE; CEREBRAL
   MALARIA; ENDOGENOUS INHIBITOR; PARASITE SEQUESTRATION;
   CLINICAL-FEATURES; MALAWIAN CHILDREN; DEPENDENT PATHWAY; AFRICAN
   CHILDREN; ARGININE
AB Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesis.
C1 [Chertow, Jessica H.; Alkaitis, Matthew S.; Ikeda, Allison K.; Ackerman, Hans] NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Rockville, MD 20852 USA.
   [Alkaitis, Matthew S.] Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Headington Oxford, England.
   [Nardone, Glenn] NIAID, Res Technol Branch, Div Intramural Res, NIH, Rockville, MD USA.
   [Cunnington, Aubrey J.] Univ London Imperial Coll Sci Technol & Med, Paediat Sect, London, England.
   [Okebe, Joseph; Ebonyi, Augustine O.; Njie, Madi; Correa, Simon; Jayasooriya, Shamanthi; Conway, David J.; Walther, Michael] MRC Unit, Fajara, Gambia.
   [Casals-Pascual, Climent] Wellcome Trust Ctr Human Genet, Oxford, England.
   [Billker, Oliver] Wellcome Trust Sanger Inst, Hinxton Cambridge, England.
   [Conway, David J.] London Sch Hyg & Trop Med, London WC1, England.
RP Chertow, JH (reprint author), NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Rockville, MD 20852 USA.
EM hans.ackerman@nih.gov
OI Conway, David/0000-0002-8711-3037; Cunnington,
   Aubrey/0000-0002-1305-3529; Billker, Oliver/0000-0003-1716-168X
FU NIAID Division of Intramural Research; Wellcome Trust [WT098051]
FX Funding to support patient enrollment and sample collection was provided
   by the MRC Unit, The Gambia. Biochemical analyses of clinical samples
   and animal model experiments were funded by the NIAID Division of
   Intramural Research and the Wellcome Trust (grant WT098051). The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 80
TC 6
Z9 6
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2015
VL 11
IS 9
AR e1005119
DI 10.1371/journal.ppat.1005119
PG 20
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CS7NH
UT WOS:000362269800009
PM 26407009
ER

PT J
AU Guo, S
   Yang, CY
   Diao, B
   Huang, XY
   Jin, MH
   Chen, LL
   Yan, WM
   Ning, Q
   Zheng, LX
   Wu, YZ
   Chen, YW
AF Guo, Sheng
   Yang, Chengying
   Diao, Bo
   Huang, Xiaoyong
   Jin, Meihua
   Chen, Lili
   Yan, Weiming
   Ning, Qin
   Zheng, Lixin
   Wu, Yuzhang
   Chen, Yongwen
TI The NLRP3 Inflammasome and IL-1 beta Accelerate Immunologically Mediated
   Pathology in Experimental Viral Fulminant Hepatitis
SO PLOS PATHOGENS
LA English
DT Article
ID INFLUENZA-VIRUS INFECTION; IL-1 RECEPTOR ANTAGONIST;
   NECROSIS-FACTOR-ALPHA; TNF-ALPHA; NALP3 INFLAMMASOME; LIVER-INJURY;
   ACTIVATION; MACROPHAGE; ROS; CONTRIBUTES
AB Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wildtype mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1 beta expression in the serum and liver. Whereas, the viral infection in IL-1 beta receptor-I deficient (IL-1R1(-/-)) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45(+) Gr-1(high) neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47(phox), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1 beta secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1 beta induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1 beta axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases.
C1 [Guo, Sheng; Yang, Chengying; Diao, Bo; Huang, Xiaoyong; Wu, Yuzhang; Chen, Yongwen] Third Mil Med Univ, PLA, Inst Immunol, Chongqing, Peoples R China.
   [Jin, Meihua] Yanbian Univ, Dept Pharmacol, Yanji, Jilin Province, Peoples R China.
   [Chen, Lili] Yanbian Univ, Dept Basic Med, Yanji, Jilin Province, Peoples R China.
   [Yan, Weiming; Ning, Qin] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept & Inst Infect Dis, Wuhan 430074, Peoples R China.
   [Zheng, Lixin] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Guo, S (reprint author), Third Mil Med Univ, PLA, Inst Immunol, Chongqing, Peoples R China.
EM wuyuzhang@tmmu.edu.cn; yongwench@163.com
FU Intramural Research Program of US National Institutes of Health
FX We wish to thank Dr. Dayan Cao, Huan Xu and Xi Chen for their helpful
   comments and constructive suggestions. LXZ is supported by the
   Intramural Research Program of the US National Institutes of Health.
NR 49
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Z9 2
U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2015
VL 11
IS 9
AR e1005155
DI 10.1371/journal.ppat.1005155
PG 21
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CS7NH
UT WOS:000362269800030
PM 26367131
ER

PT J
AU Kenna, G
   Haass-Koffler, C
   Swift, R
   Zywiak, W
   Brickley, M
   Edwards, S
   Leggio, L
AF Kenna, G.
   Haass-Koffler, C.
   Swift, R.
   Zywiak, W.
   Brickley, M.
   Edwards, S.
   Leggio, L.
TI A PILOT DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL USING DOXAZOSIN FOR
   ALCOHOL DEPENDENCE
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Kenna, G.; Haass-Koffler, C.; Swift, R.; Zywiak, W.; Brickley, M.] Brown Univ, Providence, RI 02912 USA.
   [Edwards, S.] Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA.
   [Leggio, L.] NIAAA, NIDA, NIH, Bethesda, MD USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
EI 1464-3502
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2015
VL 50
SU 1
MA P86
PG 1
WC Substance Abuse
SC Substance Abuse
GA CR7JN
UT WOS:000361525900257
ER

PT J
AU Aronis, KN
   Wang, N
   Phillips, CL
   Benjamin, EJ
   Marcus, GM
   Newman, AB
   Rodondi, N
   Satterfield, S
   Harris, TB
   Magnani, JW
AF Aronis, Konstantinos N.
   Wang, Na
   Phillips, Caroline L.
   Benjamin, Emelia J.
   Marcus, Gregory M.
   Newman, Anne B.
   Rodondi, Nicolas
   Satterfield, Suzanne
   Harris, Tamara B.
   Magnani, Jared W.
TI Associations of obesity and body fat distribution with incident atrial
   fibrillation in the biracial health aging and body composition cohort of
   older adults
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID P-WAVE INDEXES; ATHEROSCLEROSIS RISK; CARDIOVASCULAR-DISEASE; EPICARDIAL
   FAT; METABOLIC SYNDROME; AFRICAN-AMERICANS; FUTURE-DIRECTIONS; MUSCLE
   STRENGTH; WOMENS HEALTH; UNITED-STATES
AB Introduction Obesity is a well-recognized risk factor for atrial fibrillation (AF), yet adiposity measures other than body mass index (BMI) have had limited assessment in relation to AF risk. We examined the associations of adiposity measures with AF in a biracial cohort of older adults. Given established racial differences in obesity and AF, we assessed for differences by black and white race in relating adiposity and AF.
   Methods We analyzed data from 2,717 participants of the Health, Aging, and Body Composition Study. Adiposity measures were BMI, abdominal circumference, subcutaneous and visceral fat area, and total and percent fat mass. We determined the associations between the adiposity measures and 10-year incidence of AF using Cox proportional hazards models and assessed for their racial differences in these estimates.
   Results In multivariable-adjusted models, 1-SD increases in BMI, abdominal circumference, and total fat mass were associated with a 13% to 16% increased AF risk (hazard ratio [HR] 1.14, 95% CI 1.02-1.28; HR 1.16, 95% CI 1.04-1.28; and HR 1.13, 95% CI 1.002-1.27). Subcutaneous and visceral fat areas were not significantly associated with incident AF. We did not identify racial differences in the associations between the adiposity measures and AF.
   Conclusion Body mass index, abdominal circumference, and total fat mass are associated with risk of AF for 10 years among white and black older adults. Obesity is one of a limited number of modifiable risk factors for AF; future studies are essential to evaluate how obesity reduction can modify the incidence of AF.
C1 [Aronis, Konstantinos N.] Boston Univ, Boston Med Ctr, Dept Med, Boston, MA 02118 USA.
   [Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA.
   [Phillips, Caroline L.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
   [Benjamin, Emelia J.; Magnani, Jared W.] Boston Univ, Sch Med, Evans Dept Med, Cardiol Sect,Whitaker Cardiovas Inst, Boston, MA 02215 USA.
   [Benjamin, Emelia J.; Magnani, Jared W.] NHLBI, Framingham, MA USA.
   [Benjamin, Emelia J.; Magnani, Jared W.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
   [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
   [Marcus, Gregory M.] Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, San Francisco, CA 94143 USA.
   [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
   [Rodondi, Nicolas] Univ Hosp Bern, Inselspital, Dept Gen Internal Med, Bern, Switzerland.
   [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
RP Magnani, JW (reprint author), Boston Univ, Div Cardiol, 88 E Newton St,Suite D-7, Boston, MA 02118 USA.
EM jmagnani@bu.edu
RI Aronis, Konstantinos/F-3586-2012; Newman, Anne B./C-6408-2013; 
OI Aronis, Konstantinos/0000-0001-7189-8434; Newman, Anne
   B./0000-0002-0106-1150; Benjamin, Emelia/0000-0003-4076-2336
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
   N01-AG-6-2106]; Intramural Research Program of the NIH/NIA; NIH
   [R01-AG028050, 5R03-AG045075, R01-NR012459, 2R01HL092577]; NINR
   [R01-NR012459]; Boston University School of Medicine Department of
   Medicine Career Investment Award
FX This research was supported by National Institute on Aging (NIA)
   Contracts N01-AG-6-2101, N01-AG-6-2103 and N01-AG-6-2106 and the
   Intramural Research Program of the NIH/NIA; NIH grants R01-AG028050,
   5R03-AG045075, R01-NR012459, and 2R01HL092577. NINR grant R01-NR012459.
   Dr. Magnani is further supported by a Boston University School of
   Medicine Department of Medicine Career Investment Award.
NR 51
TC 4
Z9 5
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD SEP
PY 2015
VL 170
IS 3
BP 498
EP +
DI 10.1016/j.ahj.2015.06.007
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BC
UT WOS:000361575100010
PM 26385033
ER

PT J
AU Lewis, JD
   Krueger, F
   Raymont, V
   Solomon, J
   Knutson, KM
   Barbey, AK
   Poore, JC
   Wassermann, EM
   Grafman, J
AF Lewis, Jeffrey D.
   Krueger, Frank
   Raymont, Vanessa
   Solomon, Jeffrey
   Knutson, Kristine M.
   Barbey, Aron K.
   Poore, Joshua C.
   Wassermann, Eric M.
   Grafman, Jordan
TI Anhedonia in combat veterans with penetrating head injury
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Anhedonia; Traumatic brain injury; Reward; Motivational anhedonia;
   Depression; Ventrolateral prefrontal cortex
ID BECK DEPRESSION INVENTORY; TRAUMATIC BRAIN-INJURY; DISORDER;
   SCHIZOPHRENIA; PTSD
AB Anhedonia is a common symptom following traumatic brain injury. The neural basis of anhedonia is poorly understood, but believed to involve disturbed reward processing, rather than the loss of sense of pleasure. This analysis was undertaken to determine if injury to specific regions of prefrontal cortex (PFC) result in anhedonia. A CT-based lesion analysis was undertaken in 192 participants of the Vietnam Head Injury Study, most with penetrating head injury. Participants were divided into left and right ventrolateral prefrontal, bilateral ventromedial prefrontal, and other injury locations. Anhedonia was measured by self-report in each group using the four-item anhedonia subscale score of the Beck Depression Inventory-II. Individuals with right ventrolateral injury reported greater severity of anhedonia compared to those with injury in the left ventrolateral region. These findings support an association between injury in the right ventrolateral PFC and anhedonia.
C1 [Lewis, Jeffrey D.; Krueger, Frank; Raymont, Vanessa; Knutson, Kristine M.; Wassermann, Eric M.; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20824 USA.
   [Raymont, Vanessa] West London Mental Hlth Trust, London, England.
   [Raymont, Vanessa] Univ London Imperial Coll Sci Technol & Med, London, England.
   [Solomon, Jeffrey] Expert Image Anal, Potomac, MD USA.
   [Barbey, Aron K.] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL USA.
   [Poore, Joshua C.] Draper Labs, Cambridge, MA USA.
   [Grafman, Jordan] Rehabil Inst Chicago, Chicago, IL 60611 USA.
   [Grafman, Jordan] Northwestern Univ, Chicago, IL 60611 USA.
RP Wassermann, EM (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20824 USA.
EM WassermannE@ninds.nih.gov
OI Barbey, Aron/0000-0002-6092-0912
NR 23
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
EI 1931-7565
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD SEP
PY 2015
VL 9
IS 3
BP 456
EP 460
DI 10.1007/s11682-015-9414-4
PG 5
WC Neuroimaging
SC Neurosciences & Neurology
GA CR8LQ
UT WOS:000361604300007
PM 26049926
ER

PT J
AU Johnson, B
   Zhang, K
   Hallett, M
   Slobounov, S
AF Johnson, Brian
   Zhang, Kai
   Hallett, Mark
   Slobounov, Semyon
TI Functional neuroimaging of acute oculomotor deficits in concussed
   athletes
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Concussion; Oculomotor; Mild traumatic brain injury; Eye-Tracking
ID TRAUMATIC BRAIN-INJURY; CLOSED-HEAD INJURY; MEMORY-GUIDED SACCADES;
   EVENT-RELATED FMRI; SMOOTH-PURSUIT; EYE-MOVEMENT; VOLITIONAL SACCADES;
   PREFRONTAL CORTEX; NEUROPHYSIOLOGY; ABNORMALITIES
AB In the pursuit to better understand the neural underpinnings of oculomotor deficits following concussion we performed a battery of oculomotor tests while performing simultaneous functional magnetic resonance imaging (fMRI). Based on the increasing evidence that concussion can disrupt multiple brain functional networks, including the oculomotor control networks, a series of classic saccadic and smooth pursuit tasks were implemented. Nine concussed athletes were tested within seven days of injury along with nine age and sex matched healthy normal volunteers. Both behavioral and fMRI data revealed differential results between the concussed and normal volunteer groups. Concussed subjects displayed longer latency time in the saccadic tasks, worse position errors, and fewer numbers of self-paced saccades compared to normal volunteer subjects. Furthermore, the concussed group showed recruitment of additional brain regions and larger activation sites as evidenced by fMRI. As a potential diagnostic and management tool for concussion, oculomotor testing shows promise, and here we try to understand the reasons for this disrupted performance with the aide of advanced neuroimaging tools.
C1 [Johnson, Brian; Zhang, Kai; Slobounov, Semyon] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA.
   [Slobounov, Semyon] Penn State Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
   [Hallett, Mark; Slobounov, Semyon] NINDS, NIH, Bethesda, MD 20892 USA.
RP Slobounov, S (reprint author), Penn State Univ, Dept Kinesiol, Penn 276 Recreat Bldg, University Pk, PA 16802 USA.
EM sms18@psu.edu
NR 44
TC 4
Z9 4
U1 4
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
EI 1931-7565
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD SEP
PY 2015
VL 9
IS 3
BP 564
EP 573
DI 10.1007/s11682-014-9316-x
PG 10
WC Neuroimaging
SC Neurosciences & Neurology
GA CR8LQ
UT WOS:000361604300016
PM 25179246
ER

PT J
AU Bodogai, M
   Moritoh, K
   Lee-Chang, C
   Hollander, CM
   Sherman-Baust, CA
   Wersto, RP
   Araki, Y
   Miyoshi, I
   Yang, L
   Trinchieri, G
   Biragyn, A
AF Bodogai, Monica
   Moritoh, Kanako
   Lee-Chang, Catalina
   Hollander, Christine M.
   Sherman-Baust, Cheryl A.
   Wersto, Robert P.
   Araki, Yoshihiko
   Miyoshi, Ichiro
   Yang, Li
   Trinchieri, Giorgio
   Biragyn, Arya
TI Immunosuppressive and Prometastatic Functions of Myeloid-Derived
   Suppressive Cells Rely upon Education from Tumor-Associated B Cells
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER METASTASIS; T-CELLS; TGF-BETA; CHRONIC INFLAMMATION;
   IMMUNE-RESPONSES; NITRIC-OXIDE; BEARING MICE; EXPRESSION; CARCINOMA;
   PHENOTYPE
AB Myeloid-derived suppressive cells (MDSC) have been reported to promote metastasis, but the loss of cancer-induced B cells/B regulatory cells (tBreg) can block metastasis despite MDSC expansion in cancer. Here, using multiple murine tumor models and human MDSC, we show that MDSC populations that expand in cancer have only partially primed regulatory function and limited prometastatic activity unless they are fully educated by tBregs. Cancer-induced tBregs directly activate the regulatory function of both the monocyte and granulocyte subpopulations of MDSC, relying, in part, on TgfbR1/TgfbR2 signaling. MDSC fully educated in this manner exhibit an increased production of reactive oxygen species and NO and more efficiently suppress CD4(+) and CD8(+) T cells, thereby promoting tumor growth and metastasis. Thus, loss of tBregs or TgfbR deficiency in MDSC is sufficient to disable their suppressive function and to block metastasis. Overall, our data indicate that cancer-induced B cells/B regulatory cells are important regulators of the immunosuppressive and prometastatic functions of MDSC. (C)2015 AACR.
C1 [Bodogai, Monica; Moritoh, Kanako; Lee-Chang, Catalina; Sherman-Baust, Cheryl A.; Biragyn, Arya] NIA, Lab Mol Biol & Immunol, Immune Regulat Sect, Baltimore, MD 21224 USA.
   [Hollander, Christine M.; Yang, Li] NCI, Tumor Microenvironm Sect, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
   [Wersto, Robert P.] NIA, Flow Cytometry Unit, Baltimore, MD 21224 USA.
   [Araki, Yoshihiko] Juntendo Univ, Grad Sch Med, Chiba, Japan.
   [Miyoshi, Ichiro] Nagoya City Univ, Grad Sch Med, Ctr Expt Anim Sci, Nagoya, Aichi, Japan.
   [Trinchieri, Giorgio] NCI, Canc Immunobiol Sect, Expt Immunol Lab, Frederick, MD 21701 USA.
RP Biragyn, A (reprint author), NIA, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM biragyna@mail.nih.gov
RI Lee-Chang, Catalina/A-5580-2015
OI Lee-Chang, Catalina/0000-0002-7675-2124
FU Intramural Research Program of the National Institute on Aging, NIH;
   CRADA; Janssen Research Development program
FX This research was supported by the Intramural Research Program of the
   National Institute on Aging, NIH, and CRADA with Janssen Research
   Development program.
NR 40
TC 7
Z9 8
U1 1
U2 8
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 SEP 1
PY 2015
VL 75
IS 17
BP 3456
EP 3465
DI 10.1158/0008-5472.CAN-14-3077
PG 10
WC Oncology
SC Oncology
GA CS2QV
UT WOS:000361917100005
PM 26183924
ER

PT J
AU Glennon, SG
   Rawal, S
   Hoffman, HJ
   Duffy, VB
AF Glennon, S. Grace
   Rawal, Shristi
   Hoffman, Howard J.
   Duffy, Valerie B.
TI Chronic Cigarette Exposure Associates with Self-reported Smell
   Alterations: Findings from the US National Health and Nutrition
   Examination Survey (NHANES) 2011-2012
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 37th Annual Meeting of the Association-for-Chemoreception-Sciences
   (AChemS)
CY APR 22-25, 2015
CL Bonita Springs, FL
SP Assoc Chemorecept Sci
C1 [Glennon, S. Grace; Rawal, Shristi; Duffy, Valerie B.] Univ Connecticut Allied Hlth Sci, Storrs, CT USA.
   [Hoffman, Howard J.] NIDCD, NIH, Epidemiol & Stat Program, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD SEP
PY 2015
VL 40
IS 7
MA 172
BP 624
EP 625
PG 2
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
   Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
   Neurology; Physiology
GA CR7KM
UT WOS:000361528400251
ER

PT J
AU Pallotto, M
   Briggman, KL
AF Pallotto, Marta
   Briggman, Kevin L.
TI Perinatal and Adult-Born Granule Cell Connectivity in the Mouse
   Olfactory Bulb
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 37th Annual Meeting of the Association-for-Chemoreception-Sciences
   (AChemS)
CY APR 22-25, 2015
CL Bonita Springs, FL
SP Assoc Chemorecept Sci
C1 [Pallotto, Marta; Briggman, Kevin L.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD SEP
PY 2015
VL 40
IS 7
MA 242
BP 652
EP 653
PG 2
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
   Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
   Neurology; Physiology
GA CR7KM
UT WOS:000361528400321
ER

PT J
AU Rawal, S
   Hoffman, HJ
   Duffy, VB
AF Rawal, Shristi
   Hoffman, Howard J.
   Duffy, Valerie B.
TI Pathways of Associations between Taste-related Risk Factors, Regional
   Taste Function and Adiposity in Adult Women
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 37th Annual Meeting of the Association-for-Chemoreception-Sciences
   (AChemS)
CY APR 22-25, 2015
CL Bonita Springs, FL
SP Assoc Chemorecept Sci
C1 [Rawal, Shristi; Duffy, Valerie B.] Univ Connecticut, Allied Hlth Sci, Storrs, CT USA.
   [Hoffman, Howard J.] NIDCD, NIH, Epidemiol & Stat Program, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD SEP
PY 2015
VL 40
IS 7
MA 268
BP 663
EP 663
PG 1
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
   Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
   Neurology; Physiology
GA CR7KM
UT WOS:000361528400347
ER

PT J
AU Bartoshuk, LM
   Hubbard, BM
   Stamps, JJ
   Duffy, VB
   Hoffmann, HJ
   Odabasi, AZ
   Sims, CA
AF Bartoshuk, Linda M.
   Hubbard, Brittany M.
   Stamps, Jennifer J.
   Duffy, Valerie B.
   Hoffmann, Howard J.
   Odabasi, Asli Z.
   Sims, Charles A.
TI Otitis media, food preferences and weight gain in college students
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 37th Annual Meeting of the Association-for-Chemoreception-Sciences
   (AChemS)
CY APR 22-25, 2015
CL Bonita Springs, FL
SP Assoc Chemorecept Sci
C1 [Bartoshuk, Linda M.; Hubbard, Brittany M.; Stamps, Jennifer J.; Odabasi, Asli Z.; Sims, Charles A.] Univ Florida, Food Sci & Human Nutr, Gainesville, FL USA.
   [Duffy, Valerie B.] Univ Florida, Dept Allied Hlth Sci, Gainesville, FL USA.
   [Hoffmann, Howard J.] NIDCD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD SEP
PY 2015
VL 40
IS 7
MA 271
BP 664
EP 664
PG 1
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
   Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
   Neurology; Physiology
GA CR7KM
UT WOS:000361528400350
ER

PT J
AU Chang, KE
   Pratt, D
   Mishra, BB
   Edwards, N
   Hallett, M
   Ray-Chaudhury, A
AF Chang, Ki-Eun
   Pratt, Drew
   Mishra, Bibhuti B.
   Edwards, Nancy
   Hallett, Mark
   Ray-Chaudhury, Abhik
TI Type II (adult onset) Alexander disease in a paraplegic male with a rare
   D128N mutation in the GFAP gene
SO CLINICAL NEUROPATHOLOGY
LA English
DT Letter
C1 [Chang, Ki-Eun] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Pratt, Drew] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   [Mishra, Bibhuti B.] Inova Fairfax Hosp, Dept Neurosci, Neurol Sect, Falls Church, VA USA.
   [Edwards, Nancy; Ray-Chaudhury, Abhik] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA.
   [Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA.
RP Ray-Chaudhury, A (reprint author), 10 Ctr Dr Room 3D20, Bethesda, MD 20892 USA.
EM Abhik.ray-chaudhury@nih.gov
NR 12
TC 0
Z9 1
U1 0
U2 2
PU DUSTRI-VERLAG DR KARL FEISTLE
PI DEISENHOFEN-MUENCHEN
PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY
SN 0722-5091
J9 CLIN NEUROPATHOL
JI Clin. Neuropathol.
PD SEP-OCT
PY 2015
VL 34
IS 5
BP 298
EP 301
DI 10.5414/NP300863
PG 4
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA CS1VC
UT WOS:000361855600009
PM 25997626
ER

PT J
AU Rowe, S
   Siegel, D
   Benjamin, DK
AF Rowe, Stevie
   Siegel, David
   Benjamin, Daniel K., Jr.
CA Best Pharmaceuticals Children Act
TI Gaps in Drug Dosing for Obese Children: A Systematic Review of Commonly
   Prescribed Emergency Care Medications
SO CLINICAL THERAPEUTICS
LA English
DT Review
DE obesity; children; pharmacokinetics; emergency care
ID LEAN BODY-MASS; US CHILDREN; PHARMACOKINETICS; ADOLESCENTS; PREVALENCE;
   OVERWEIGHT; CHILDHOOD; THERAPY; HUMANS; TRENDS
AB Purpose: Approximately 1 of 6 children in the United States is obese. This has important implications for drug dosing and safety because pharmacokinetic (PK) changes are known to occur in obesity due to altered body composition and physiologic mechanisms. Inappropriate drug dosing in an emergency setting can limit therapeutic efficacy and increase drug-related toxic effects for obese children. Few systematic reviews examining PK properties and drug dosing in obese children have been performed.
   Methods: We identified 25 emergency care drugs from the Strategic National Stockpile and Acute Care Supportive Drugs List and performed a systematic review for each drug in 3 study populations: obese children (2-18 years of age), normal weight children, and obese adults (aged >18 years). For each study population, we first reviewed a drug's Food and Drug Administration label and then performed a systematic literature review. From the literature, we extracted drug PK data, biochemical properties, and dosing information. We then reviewed data in 3 age subpopulations (2-7 years, 8-12 years, and 13-18 years) for obese and normal weight children and by route of drug administration (intramuscular, intravenous, oral, and inhaled). If sufficient PK data were not available by age and route of administration, a data gap was identified.
   Findings: Only 2 of 25 emergency care drugs (8%) contained dosing information on the Food and Drug Administration label for obese children and adults compared with 22 of 25 (88%) for normal weight children. We found no sufficient PK data in the literature for any of the emergency care drugs in obese children. Sufficient PK data were found for 7 of 25 emergency care drugs (28%) in normal weight children and 3 of 25 (12%) in obese adults. (C) 2015 Elsevier HS Journals, Inc. All rights reserved.
C1 [Rowe, Stevie; Benjamin, Daniel K., Jr.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
   [Siegel, David] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Benjamin, Daniel K., Jr.] Duke Clin Res Inst, Durham, NC 27710 USA.
RP Benjamin, DK (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27710 USA.
EM Danny.Benjamin@dm.duke.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development for the Pediatric Trials Network [HHSN 2752010000031];
   National Center for Advancing Translational Sciences of the National
   Institutes of Health [UL1TR001117]
FX This work was funded under contract HHSN 2752010000031 from the Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   for the Pediatric Trials Network. Research reported in this publication
   was also supported by award UL1TR001117 from the National Center for
   Advancing Translational Sciences of the National Institutes of Health.
   The content is solely the responsibility of the authors and does not
   necessarily represent the official views of the National Institutes of
   Health.
NR 40
TC 3
Z9 3
U1 1
U2 3
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 0149-2918
EI 1879-114X
J9 CLIN THER
JI Clin. Ther.
PD SEP
PY 2015
VL 37
IS 9
BP 1924
EP 1932
DI 10.1016/j.clinthera.2015.08.006
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CS0VL
UT WOS:000361780200005
PM 26323523
ER

PT J
AU Hall, JE
AF Hall, Janet E.
TI Endocrinology of the Menopause
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Article
DE Ovary; Hypothalamus; Pituitary; Menopause; Estradiol;
   Follicle-stimulating hormone
ID GONADOTROPIN-RELEASING-HORMONE; ANTI-MULLERIAN HORMONE;
   FOLLICLE-STIMULATING-HORMONE; STRENGTH-DURATION CHARACTERISTICS;
   REPRODUCTIVE-AGE WOMEN; POSTMENOPAUSAL WOMEN; INHIBIN-B; NATURAL
   MENOPAUSE; OVARIAN-FUNCTION; LUTEINIZING-HORMONE
AB In women, age-related changes in ovarian function begin in the mid-30s with decreased fertility and compensatory hormonal changes in the hypothalamus-pituitary-gonadal axis that maintain follicle development and estrogen secretion in the face of a waning pool of ovarian follicles. The menopause transition is characterized by marked variability in follicle development, ovulation, bleeding patterns, and symptoms of hyper- and hypoestrogenism. The menopause, which is clinically defined by the final menstrual period, is followed by the consistent absence of ovarian secretion of estradiol.
C1 [Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02460 USA.
   [Hall, Janet E.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Hall, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02460 USA.
EM hall.janet@mgh.harvard.edu
OI Hall, Janet/0000-0003-4644-3061
NR 78
TC 2
Z9 2
U1 4
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8529
EI 1558-4410
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD SEP
PY 2015
VL 44
IS 3
BP 485
EP +
DI 10.1016/j.ecl.2015.05.010
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS0UF
UT WOS:000361777000004
PM 26316238
ER

PT J
AU Furman, CA
   Roof, RA
   Moritz, AE
   Miller, BN
   Doyle, TB
   Free, RB
   Banala, AK
   Paul, NM
   Kumar, V
   Sibley, CD
   Newman, AH
   Sibley, DR
AF Furman, Cheryse A.
   Roof, Rebecca A.
   Moritz, Amy E.
   Miller, Brittney N.
   Doyle, Trevor B.
   Free, R. Benjamin
   Banala, Ashwini K.
   Paul, Noel M.
   Kumar, Vivek
   Sibley, Christopher D.
   Newman, Amy Hauck
   Sibley, David R.
TI Investigation of the binding and functional properties of extended
   length D3 dopamine receptor-selective antagonists
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Dopamine receptor; D-3 receptor; Bivalent; Bitopic; Allosteric; Dopamine
   antagonists
ID PROTEIN-COUPLED RECEPTORS; INVOLUNTARY MOVEMENTS; ALLOSTERIC MODULATION;
   THERAPEUTIC AGENTS; BITOPIC LIGANDS; LINKING CHAINS; HIGH-AFFINITY; D-3;
   AGONIST; DISORDERS
AB The D-3 dopamine receptor represents an important target in drug addiction in that reducing receptor activity may attenuate the self-administration of drugs and/or disrupt drug or cueinduced relapse. Medicinal chemistry efforts have led to the development of D-3 preferring antagonists and partial agonists that are >100-fold selective vs. the closely related D-2 receptor, as best exemplified by extended-length 4-phenylpiperazine derivatives. Based on the D-3 receptor crystal structure, these molecules are known to dock to two sites on the receptor where the 4-phenylpiperazine moiety binds to the orthosteric site and an extended aryl amide moiety docks to a secondary binding pocket. The bivalent nature of the receptor binding of these compounds is believed to contribute to their D-3 selectivity. In this study, we examined if such compounds might also be "bitopic" such that their aryl amide moieties act as allosteric modulators to further enhance the affinities of the full-length molecules for the receptor. First, we deconstructed several extended-length D-3-selective ligands into fragments, termed "synthons", representing either orthosteric or secondary aryl amide pharmacophores and investigated their effects on D-3 receptor binding and function. The orthosteric synthons were found to inhibit radioligand binding and to antagonize dopamine activation of the D-3 receptor, albeit with lower affinities than the full-length compounds. Notably, the aryl amide-based synthons had no effect on the affinities or potencies of the orthosteric synthons, nor did they have any effect on receptor activation by dopamine. Additionally, pharmacological investigation of the full-length D-3-selective antagonists revealed that these compounds interacted with the D-3 receptor in a purely competitive manner. Our data further support that the 4-phenylpiperazine D-3-selective antagonists are bivalent and that their enhanced affinity for the D-3 receptor is due to binding at both the orthosteric site as well as a secondary binding pocket. Importantly, however, their interactions at the secondary site do not allosterically modulate their binding to the orthosteric site. Published by Elsevier B.V.
C1 [Furman, Cheryse A.; Roof, Rebecca A.; Moritz, Amy E.; Miller, Brittney N.; Doyle, Trevor B.; Free, R. Benjamin; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA.
   [Banala, Ashwini K.; Paul, Noel M.; Kumar, Vivek; Sibley, Christopher D.; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, NIH, Baltimore, MD 21224 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, NIH, 333 Cassell Dr,Room 3444, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov; sibleyd@helix.nih.gov
RI Kumar, Vivek/F-6183-2016; 
OI Paul, Noel/0000-0002-4980-9383
FU Intramural NIH HHS [ZIA DA000424-16]
NR 39
TC 4
Z9 4
U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2015
VL 25
IS 9
SI SI
BP 1448
EP 1461
DI 10.1016/j.euroneuro.2014.11.013
PG 14
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CS1XP
UT WOS:000361862500007
PM 25583363
ER

PT J
AU Melters, DP
   Nye, J
   Zhao, HQ
   Dalal, Y
AF Melters, Daniel P.
   Nye, Jonathan
   Zhao, Haiqing
   Dalal, Yamini
TI Chromatin Dynamics in Vivo: A Game of Musical Chairs
SO GENES
LA English
DT Review
DE histones; chromatin; CENP-A; H3; 3; H2A; Z; macroH2A; chaperones
ID HISTONE VARIANT H2A.Z; CENP-A NUCLEOSOMES; INACTIVE X-CHROMOSOME;
   RNA-POLYMERASE-II; CENTROMERIC CHROMATIN; CELL-CYCLE; GENE-EXPRESSION;
   CRYSTAL-STRUCTURE; POSTTRANSLATIONAL MODIFICATION;
   SACCHAROMYCES-CEREVISIAE
AB Histones are a major component of chromatin, the nucleoprotein complex fundamental to regulating transcription, facilitating cell division, and maintaining genome integrity in almost all eukaryotes. In addition to canonical, replication-dependent histones, replication-independent histone variants exist in most eukaryotes. In recent years, steady progress has been made in understanding how histone variants assemble, their involvement in development, mitosis, transcription, and genome repair. In this review, we will focus on the localization of the major histone variants H3.3, CENP-A, H2A.Z, and macroH2A, as well as how these variants have evolved, their structural differences, and their functional significance in vivo.
C1 [Melters, Daniel P.; Nye, Jonathan; Zhao, Haiqing; Dalal, Yamini] NCI, Chromatin Struct & Epigenet Mech Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Zhao, Haiqing] Univ Maryland, Biophys Grad Program, College Pk, MD 20742 USA.
RP Dalal, Y (reprint author), NCI, Chromatin Struct & Epigenet Mech Unit, Ctr Canc Res, NIH, 41 Lib Dr, Bethesda, MD 20892 USA.
EM daniel.melters@nih.gov; jon.nye@nih.gov; haiqing.zhao@nih.gov;
   dalaly@mail.nih.gov
FU CCR/NCI Intramural Research Program; UMD-NCI Partnership for Cancer
   Technology fellowship
FX Daniel P. Melters, Jonathan Nye and Yamini Dalal are supported by the
   CCR/NCI Intramural Research Program. Haiqing Zhao is supported by
   UMD-NCI Partnership for Cancer Technology fellowship.
NR 180
TC 8
Z9 8
U1 11
U2 24
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2073-4425
J9 GENES-BASEL
JI Genes
PD SEP
PY 2015
VL 6
IS 3
BP 751
EP 776
DI 10.3390/genes6030751
PG 26
WC Genetics & Heredity
SC Genetics & Heredity
GA CS0OS
UT WOS:000361761900019
PM 26262644
ER

PT J
AU Khurana, S
   Oberdoerffer, P
AF Khurana, Simran
   Oberdoerffer, Philipp
TI Replication Stress: A Lifetime of Epigenetic Change
SO GENES
LA English
DT Review
DE replication stress; DNA repair; chromatin; histones; senescence
ID ONCOGENE-INDUCED SENESCENCE; CHROMATIN REMODELING COMPLEX; DNA-DAMAGE
   RESPONSE; CELL-CYCLE PROGRESSION; FRAGILE SITE STABILITY; GENOME
   STABILITY; HISTONE H3; HOMOLOGOUS RECOMBINATION; S-PHASE;
   HETEROCHROMATIN FORMATION
AB DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs) and has been linked to both genome instability and irreversible cell cycle arrest (senescence). Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function.
C1 [Khurana, Simran; Oberdoerffer, Philipp] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Khurana, S (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, 41 Lib Dr, Bethesda, MD 20892 USA.
EM Simran.Khurana@nih.gov; Philipp.Oberdoerffer@nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
   NCI, Center for Cancer Research
FX We apologize to those whose publications we were unable to cite owing to
   space limitations. This work was supported by the Intramural Research
   Program of the National Institutes of Health (NIH), NCI, Center for
   Cancer Research. The authors declare no competing financial interests.
NR 116
TC 5
Z9 5
U1 0
U2 12
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2073-4425
J9 GENES-BASEL
JI Genes
PD SEP
PY 2015
VL 6
IS 3
BP 858
EP 877
DI 10.3390/genes6030858
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA CS0OS
UT WOS:000361761900024
PM 26378584
ER

PT J
AU Parsons, HM
   Harlan, LC
   Schmidt, S
   Keegan, THM
   Lynch, CF
   Kent, EE
   Wu, XC
   Schwartz, SM
   Chu, RL
   Keel, G
   Smith, AW
AF Parsons, Helen M.
   Harlan, Linda C.
   Schmidt, Susanne
   Keegan, Theresa H. M.
   Lynch, Charles F.
   Kent, Erin E.
   Wu, Xiao-Cheng
   Schwartz, Stephen M.
   Chu, Roland L.
   Keel, Gretchen
   Smith, Ashley Wilder
CA AYA HOPE Collaborative Grp
TI Who Treats Adolescents and Young Adults with Cancer? A Report from the
   AYA HOPE Study
SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY
LA English
DT Article
DE treatment; physicians; place of care; AYA HOPE Study
ID HEALTH-CARE; AGE; DIAGNOSIS; SURVIVAL; ONCOLOGY; OUTCOMES; QUALITY
AB Purpose: Physicians play a critical role in delivering effective treatment and enabling successful transition to survivorship among adolescent and young adult (AYA) cancer patients. However, with no AYA cancer medical specialty, information on where and by whom AYAs with cancer are treated is limited.
   Methods: Using the National Cancer Institute's population-based AYA HOPE Study, 464 AYAs aged 15-39 at diagnosis treated by 903 physicians were identified. Differences in physician and hospital characteristics were examined by age at diagnosis and cancer type (germ cell cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, acute lymphocytic leukemia [ALL], and sarcoma) using chi-square tests.
   Results: Treating physicians were predominately 51-64 years old, male, United States-trained in non-pediatric specialties, and in group practices within large metropolitan areas. Older patients were less often treated by pediatric physicians (p < 0.01) and more likely to be treated by United States-trained physicians without research/teaching responsibilities and in hospitals without residency programs (p < 0.05). The majority of the few pediatricians (n = 44) treated ALL patients. Physicians with research/teaching responsibilities and those based in medical schools were more likely to treat patients with ALL and sarcoma compared with other cancer types (p < 0.01). Of HL patients, 73% were treated at a cancer center compared with 56% of patients with germ cell cancer (p < 0.01), while ALL (85%) and sarcoma (87%) patients were more likely to be treated in hospitals with residency programs (p < 0.01).
   Conclusions: Most AYAs with cancer were treated by non-pediatric physicians in community settings, although physician characteristics varied significantly by patient cancer type and age at diagnosis.
C1 [Parsons, Helen M.; Schmidt, Susanne] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
   [Harlan, Linda C.; Kent, Erin E.; Smith, Ashley Wilder] NCI, Appl Res Program, Bethesda, MD 20892 USA.
   [Keegan, Theresa H. M.] Canc Prevent Inst Calif, Fremont, CA USA.
   [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
   [Wu, Xiao-Cheng] Louisiana State Univ, Hlth Sci Ctr, Louisiana Tumor Registry, New Orleans, LA USA.
   [Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA.
   [Chu, Roland L.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
   [Keel, Gretchen] Informat Management Serv Inc, Calverton, MD USA.
RP Parsons, HM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, 7703 Floyd Curl Dr,Mail Code 7933, San Antonio, TX 78229 USA.
EM parsonsh@uthscsa.edu
FU National Cancer Institute of the National Institutes of Health
   [N01PC-2010-00032, N01PC-35136, N01PC-2010-00034, N01PC-2010-00035,
   N01PC-2010-00029, N01PC-2010-00028, N01PC-2010-00030, N01PC-35143]; 
   [K07CA175063]
FX Research reported in this publication was supported by the National
   Cancer Institute of the National Institutes of Health under contract
   numbers N01PC-2010-00032, N01PC-35136, N01PC-2010-00034,
   N01PC-2010-00035, N01PC-2010-00029, N01PC-2010-00028, N01PC-2010-00030,
   and N01PC-35143. Dr. Parsons is supported by K07CA175063.
NR 37
TC 1
Z9 1
U1 1
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2156-5333
EI 2156-535X
J9 J ADOLESC YOUNG ADUL
JI J. Adolesc. Young Adult Oncol.
PD SEP
PY 2015
VL 4
IS 3
BP 141
EP 150
DI 10.1089/jayao.2014.0041
PG 10
WC Oncology
SC Oncology
GA CR8VA
UT WOS:000361631000009
PM 26421222
ER

PT J
AU Torres-Salazar, D
   Jiang, J
   Divito, CB
   Garcia-Olivares, J
   Amara, SG
AF Torres-Salazar, Delany
   Jiang, Jie
   Divito, Christopher B.
   Garcia-Olivares, Jennie
   Amara, Susan G.
TI A Mutation in Transmembrane Domain 7 (TM7) of Excitatory Amino Acid
   Transporters Disrupts the Substrate-dependent Gating of the Intrinsic
   Anion Conductance and Drives the Channel into a Constitutively Open
   State
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NEURONAL GLUTAMATE TRANSPORTER; CHLORIDE CHANNEL; FUNCTIONAL-PROPERTIES;
   VOLTAGE-DEPENDENCE; EXTRACELLULAR GATE; NOISE-ANALYSIS; ION-CHANNEL;
   BINDING; HOMOLOG; TRANSLOCATION
AB In the mammalian central nervous system, excitatory amino acid transporters (EAATs) are responsible for the clearance of glutamate after synaptic release. This energetically demanding activity is crucial for precise neuronal communication and for maintaining extracellular glutamate concentrations below neurotoxic levels. In addition to their ability to recapture glutamate from the extracellular space, EAATs exhibit a sodium-and glutamate-gated anion conductance. Here we show that substitution of a conserved positively charged residue (Arg-388, hEAAT1) in transmembrane domain 7 with a negatively charged amino acid eliminates the ability of glutamate to further activate the anion conductance. When expressed in oocytes, R388D or R388E mutants show large anion currents that display no further increase in amplitude after application of saturating concentrations of Na+ and glutamate. They also show a substantially reduced transport activity. The mutant transporters appear to exist preferentially in a sodium-and glutamate-independent constitutive open channel state that rarely transitions to complete the transport cycle. In addition, the accessibility of cytoplasmic residues to membrane-permeant modifying reagents supports the idea that this substrate-independent open state correlates with an intermediate outward facing conformation of the transporter. Our data provide additional insights into the mechanism by which substrates gate the anion conductance in EAATs and suggest that in EAAT1, Arg-388 is a critical element for the structural coupling between the substrate translocation and the gating mechanisms of the EAAT-associated anion channel.
C1 [Torres-Salazar, Delany; Garcia-Olivares, Jennie; Amara, Susan G.] NIMH, Bethesda, MD 20892 USA.
   [Jiang, Jie; Divito, Christopher B.; Amara, Susan G.] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15213 USA.
RP Torres-Salazar, D (reprint author), NIMH, Lab Mol & Cellular Neurobiol, NIH, 35 Convent Dr,Rm 3A-207, Bethesda, MD 20892 USA.
EM delany.torressalazar@nih.gov; susan.amara@nih.gov
RI Regan, Clinton/E-6250-2012; 
OI Torres-Salazar, Delany/0000-0002-6789-9810
FU National Institutes of Health [MH080726]; National Institute of Mental
   Health [MH002946]; American Heart Association [09POST2010115]
FX This work was supported, in whole or in part, by National Institutes of
   Health Grant MH080726 (to S. G. A.) and National Institute of Mental
   Health intramural research program Grant MH002946. This work was also
   supported by American Heart Association postdoctoral fellowship
   09POST2010115 (to D. T. S.). The authors declare that they have no
   conflicts of interest with the contents of this article.
NR 57
TC 6
Z9 6
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP
PY 2015
VL 290
IS 38
BP 22977
EP 22990
DI 10.1074/jbc.M115.660860
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CR9OE
UT WOS:000361685500011
PM 26203187
ER

PT J
AU Yao, PL
   Chen, LP
   Hess, RA
   Muller, R
   Gonzalez, FJ
   Peters, JM
AF Yao, Pei-Li
   Chen, LiPing
   Hess, Rex A.
   Mueller, Rolf
   Gonzalez, Frank J.
   Peters, Jeffrey M.
TI Peroxisome Proliferator-activated Receptor-D (PPARD) Coordinates Mouse
   Spermatogenesis by Modulating Extracellular Signal-regulated Kinase
   (ERK)-dependent Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RAT SERTOLI-CELLS; SEMINIFEROUS EPITHELIUM; IN-VITRO;
   MONO-(2-ETHYLHEXYL) PHTHALATE; ABNORMAL SPERMATOGENESIS; LIGAND
   ACTIVATION; SPERMATID HEAD; MUTANT MICE; TESTIS; BETA/DELTA
AB Ppard(-/-) mice exhibit smaller litter size compared with Ppard(+/+) mice. To determine whether peroxisome proliferator- activated receptor-D (PPARD) could possibly influence this phenotype, the role of PPARD in testicular biology was examined. Atrophic testes and testicular degeneration were observed in Ppard(-/-) mice compared with Ppard(+/+) mice, indicating that PPARD modulates spermatogenesis. Higher expression of p27 and decreased expression of proliferating cellular nuclear antigen in Sertoli cells were observed in Ppard(+/+) mice as compared with Ppard(-/-) mice, and these were associated with decreased Sertoli cell number in Ppard(+/+) mice. Cyclin D1 and cyclin D2 expression was lower in Ppard(+/+) as compared with Ppard(-/-) mice. Ligand activation of PPARD inhibited proliferation of a mouse Sertoli cell line, TM4, and an inverse agonist of PPARD (DG172) rescued this effect. Temporal inhibition of extracellular signal-regulated kinase (ERK) activation by PPARD in the testis was observed in Ppard(+/+) mice and was associated with decreased serum follicle-stimulating hormone and higher claudin-11 expression along the blood-testis barrier. PPARD-dependent ERK activation also altered expression of claudin-11, p27, cyclin D1, and cyclin D2 in TM4 cells, causing inhibition of cell proliferation, maturation, and formation of tight junctions in Sertoli cells, thus confirming a requirement for PPARD in accurate Sertoli cell function. Combined, these results reveal for the first time that PPARD regulates spermatogenesis by modulating the function of Sertoli cells during early testis development.
C1 [Yao, Pei-Li; Chen, LiPing; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
   [Yao, Pei-Li; Chen, LiPing; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
   [Hess, Rex A.] Univ Illinois, Coll Vet Med, Dept Comparat Biosci, Reprod Biol & Toxicol, Urbana, IL 61802 USA.
   [Mueller, Rolf] Univ Marburg, Inst Mol Biol & Tumor Res, Ctr Tumor & Immunobiol, D-35043 Marburg, Germany.
   [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA.
EM pxy11@psu.edu; jmp21@psu.edu
RI Regan, Clinton/E-6250-2012; Muller, Rolf/L-4997-2016
OI Muller, Rolf/0000-0003-3339-4248
FU National Institutes of Health [CA124533, CA141029]; NCI Intramural
   Research Program [ZIABC005561, ZIABC005562, ZIABC005708]
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants CA124533 and CA141029 (to J. M. P.) and ZIABC005561,
   ZIABC005562, and ZIABC005708 from the NCI Intramural Research Program
   (to F. J. G.). The authors declare that they have no conflicts of
   interest with the contents of this article.
NR 60
TC 5
Z9 5
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP
PY 2015
VL 290
IS 38
BP 23416
EP 23431
DI 10.1074/jbc.M115.664508
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CR9OE
UT WOS:000361685500046
PM 26242735
ER

PT J
AU Marassi, FM
   Ding, Y
   Schwieters, CD
   Tian, Y
   Yao, Y
AF Marassi, Francesca M.
   Ding, Yi
   Schwieters, Charles D.
   Tian, Ye
   Yao, Yong
TI Backbone structure of Yersinia pestis Ail determined in micelles by
   NMR-restrained simulated annealing with implicit membrane solvation
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Ail; Yersinia pestis; Membrane protein; Structure; NMR; Implicit
   solvation
ID MOLECULAR-STRUCTURE DETERMINATION; EFFECTIVE ENERGY FUNCTION;
   SOLID-STATE NMR; STRUCTURE VALIDATION; LIPID-BILAYERS; YOP DELIVERY;
   PROTEIN AIL; XPLOR-NIH; PLAGUE; WATER
AB The outer membrane protein Ail (attachment invasion locus) is a virulence factor of Yersinia pestis that mediates cell invasion, cell attachment and complement resistance. Here we describe its three-dimensional backbone structure determined in decyl-phosphocholine (DePC) micelles by NMR spectroscopy. The NMR structure was calculated using the membrane function of the implicit solvation potential, eefxPot, which we have developed to facilitate NMR structure calculations in a physically realistic environment. We show that the eefxPot force field guides the protein towards its native fold. The resulting structures provide information about the membrane-embedded global position of Ail, and have higher accuracy, higher precision and improved conformational properties, compared to the structures calculated with the standard repulsive potential.
C1 [Marassi, Francesca M.; Ding, Yi; Tian, Ye; Yao, Yong] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Marassi, FM (reprint author), Sanford Burnham Med Res Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM fmarassi@sbmri.org
FU National Institutes of Health [NIH: R01GM110658, R01GM100265,
   P41EB002031, P30CA030199]; NIH Intramural Research Program of The Center
   for Information Technology
FX This research was supported by grants from the National Institutes of
   Health (NIH: R01GM110658, R01GM100265, P41EB002031, P30CA030199). CDS
   was supported by funds from the NIH Intramural Research Program of The
   Center for Information Technology.
NR 48
TC 4
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U1 1
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
EI 1573-5001
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD SEP
PY 2015
VL 63
IS 1
BP 59
EP 65
DI 10.1007/s10858-015-9963-2
PG 7
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA CR8OD
UT WOS:000361612700006
PM 26143069
ER

PT J
AU Mantsyzov, AB
   Shen, Y
   Lee, JH
   Hummer, G
   Bax, A
AF Mantsyzov, Alexey B.
   Shen, Yang
   Lee, Jung Ho
   Hummer, Gerhard
   Bax, Ad
TI MERA: a webserver for evaluating backbone torsion angle distributions in
   dynamic and disordered proteins from NMR data
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Coil library; IDP; Karplus curve; Random coil; Short-range NOE;
   alpha-Synuclein
ID CHEMICAL-SHIFTS; COUPLING-CONSTANTS; UNFOLDED PROTEINS; ALPHA-SYNUCLEIN;
   STRUCTURAL-CHARACTERIZATION; KARPLUS EQUATIONS; RESIDUAL DIPOLAR; RANDOM
   COIL; PEPTIDES; ENSEMBLES
AB MERA (Maximum Entropy Ramachandran map Analysis from NMR data) is a new webserver that generates residue-by-residue Ramachandran map distributions for disordered proteins or disordered regions in proteins on the basis of experimental NMR parameters. As input data, the program currently utilizes up to 12 different parameters. These include three different types of short-range NOEs, three types of backbone chemical shifts (N-15, C-13(alpha), and C-13'), six types of J couplings ((3)J(HNH alpha), (3)J(C'C'), (3)J(C'H alpha), (1)J(H alpha C alpha), (2)J(C alpha N) and (1)J(C alpha N)), as well as the N-15-relaxation derived J(0) spectral density. The Ramachandran map distributions are reported in terms of populations of their 15A degrees A xA 15A degrees voxels, and an adjustable maximum entropy weight factor is available to ensure that the obtained distributions will not deviate more from a newly derived coil library distribution than required to account for the experimental data. MERA output includes the agreement between each input parameter and its distribution-derived value. As an application, we demonstrate performance of the program for several residues in the intrinsically disordered protein alpha-synuclein, as well as for several static and dynamic residues in the folded protein GB3.
C1 [Mantsyzov, Alexey B.] Moscow MV Lomonosov State Univ, Fac Fundamental Med, Moscow 119991, Russia.
   [Shen, Yang; Lee, Jung Ho; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Hummer, Gerhard] Max Planck Inst Biophys, D-60438 Frankfurt, Germany.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Shen, Yang/C-3064-2008; Hummer, Gerhard/A-2546-2013
OI Shen, Yang/0000-0003-1408-8034; Hummer, Gerhard/0000-0001-7768-746X
FU Russian Science Foundation [14-14-00598]; National Institute of Diabetes
   and Digestive and Kidney Diseases; Office of the Director, NIH; Max
   Planck Society; KVSTA fellowship
FX This work was supported by the Russian Science Foundation (Grant
   14-14-00598) and by the Intramural Research Program of the National
   Institute of Diabetes and Digestive and Kidney Diseases and the
   Intramural Antiviral Target Program of the Office of the Director, NIH,
   and by the Max Planck Society. JHL is the recipient of a KVSTA
   fellowship.
NR 50
TC 5
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U1 4
U2 22
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
EI 1573-5001
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD SEP
PY 2015
VL 63
IS 1
BP 85
EP 95
DI 10.1007/s10858-015-9971-2
PG 11
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA CR8OD
UT WOS:000361612700009
PM 26219516
ER

PT J
AU Denlinger, DS
   Lozano-Fuentes, S
   Lawyer, PG
   Black, WC
   Bernhardt, SA
AF Denlinger, David S.
   Lozano-Fuentes, Saul
   Lawyer, Phillip G.
   Black, William C.
   Bernhardt, Scott A.
TI Assessing Insecticide Susceptibility of Laboratory Lutzomyia longipalpis
   and Phlebotomus papatasi Sand Flies (Diptera: Psychodidae:
   Phlebotominae)
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE Phlebotomus papatasi; Lutzomyia longipalpis; insecticide resistance; CDC
   bottle bioassay; WHO
ID CUTANEOUS LEISHMANIASIS; VISCERAL LEISHMANIASIS; VECTOR CONTROL;
   AEDES-AEGYPTI; CULEX-QUINQUEFASCIATUS; MOLECULAR-BIOLOGY; PUBLIC-HEALTH;
   RESISTANCE; DISEASE; DDT
AB Chemical insecticides are effective for controlling Lutzomyia and Phlebotomus sand fly (Diptera: Psychodidae) vectors of Leishmania parasites. However, repeated use of certain insecticides has led to tolerance and resistance. The objective of this study was to determine lethal concentrations (LCs) and lethal exposure times (LTs) to assess levels of susceptibility of laboratory Lutzomyia longipalpis (Lutz and Nieva) and Phlebotomus papatasi (Scopoli) to 10 insecticides using a modified version of the World Health Organization (WHO) exposure kit assay and Centers for Disease Control and Prevention (CDC) bottle bioassay. Sand flies were exposed to insecticides coated on the interior of 0.5-gallon and 1,000-ml glass bottles. Following exposure, the flies were allowed to recover for 24 h, after which mortality was recorded. From dose-response survival curves for L. longipalpis and P. papatasi generated with the QCal software, LCs causing 50, 90, and 95% mortality were determined for each insecticide. The LCs and LTs from this study will be useful as baseline reference points for future studies using the CDC bottle bioassays to assess insecticide susceptibility of sand fly populations in the field. There is a need for a larger repository of sand fly insecticide susceptibility data from the CDC bottle bioassays, including a range of LCs and LTs for more sand fly species with more insecticides. Such a repository would be a valuable tool for vector management.
C1 [Denlinger, David S.; Bernhardt, Scott A.] Utah State Univ, Dept Biol, Logan, UT 84322 USA.
   [Lozano-Fuentes, Saul; Black, William C.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
   [Lawyer, Phillip G.] NIAID, Parasit Dis Lab, Intracellular Parasite Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Bernhardt, SA (reprint author), Utah State Univ, Dept Biol, Logan, UT 84322 USA.
EM scott.bernhardt@usu.edu
FU Utah State University's Office of Research and Graduate Studies
FX We are grateful to J.C. McAllister and W.G. Brogdon (CDC) for their
   careful review and constructive critique of the manuscript. We thank the
   many undergraduate research students in the Bernhardt laboratory for
   their assistance with maintaining and rearing the sand fly colonies. The
   maintenance of SKH1 hairless mice (Charles River, Wilmington MA) and the
   experimental animal-use protocol was approved by Utah State University's
   Institutional Animal-Care and Use Committee. This work was supported by
   Utah State University's Office of Research and Graduate Studies.
NR 52
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U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-2585
EI 1938-2928
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD SEP
PY 2015
VL 52
IS 5
BP 1003
EP 1012
DI 10.1093/jme/tjv091
PG 10
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA CS0PS
UT WOS:000361764900031
PM 26336231
ER

PT J
AU Danforth, ME
   Reisen, WK
   Barker, CM
AF Danforth, Mary E.
   Reisen, William K.
   Barker, Christopher M.
TI Extrinsic Incubation Rate is Not Accelerated in Recent California
   Strains of West Nile Virus in Culex tarsalis (Diptera: Culicidae)
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE Culex tarsalis; West Nile virus; transmission; temperature; incubation
   period
ID LOUIS ENCEPHALITIS-VIRUS; VECTOR COMPETENCE; UNITED-STATES; MOSQUITOS
   DIPTERA; NORTH-AMERICA; NEW-YORK; TRANSMISSION; GENOTYPE; TEMPERATURE;
   EPIDEMIC
AB The efficiency of West Nile virus (WNV) transmission by competent mosquito vectors is driven by temperature and defined, in part, by the extrinsic incubation period, which is the time from a mosquito's consumption of an infected bloodmeal until it becomes capable of transmitting the virus to the next vertebrate host. The extrinsic incubation period can be altered by a variety of factors involved in vector-pathogen interactions, and in North America, the WN02 strain of WNV emerged and displaced the founding NY99 strain reportedly because the duration of the extrinsic incubation period in Culex mosquitoes was shortened by a single positively selected mutation. However, recent work has suggested that this change is not universal and may depend on vector species or strain. In the current study, we estimated the extrinsic incubation periods at 22 and 30A degrees C in Culex tarsalis Coquillett. We found that the time to transmission of the original North American WNV strain, NY99, was not different from two more recent California isolates of the WN02 genotype: one of the earliest California isolates from the southeastern deserts, and a more recent 2011 isolate from a hyperendemic region in the Central Valley. We conclude with a model-based assessment of the epidemiological effects of temperature on the duration of mosquitoes' infectious life, which estimated that most mosquitoes have an infectious life of only a few days, but its duration expands markedly at warmer temperatures.
C1 [Danforth, Mary E.; Reisen, William K.; Barker, Christopher M.] Univ Calif Davis, Sch Vet Med, Ctr Vectorborne Dis, Davis, CA 95616 USA.
   [Danforth, Mary E.; Reisen, William K.; Barker, Christopher M.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
   [Barker, Christopher M.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Barker, CM (reprint author), Univ Calif Davis, Sch Vet Med, Ctr Vectorborne Dis, Davis, CA 95616 USA.
EM cmbarker@ucdavis.edu
FU Mosquito Research Foundation [2013-17]; Research and Policy for
   Infectious Disease Dynamics (RAPIDD) program of the Science and
   Technology Directorate, Department of Homeland Security and Fogarty
   International Center, National Institutes of Health
FX We thank Ying Fang, Sandra Garcia, Sarah Wheeler, and Veronica Armijos
   (Center for Vectorborne Diseases, Department of Pathology, Microbiology,
   and Immunology, School of Veterinary Medicine, University of California,
   Davis) for technical support and Dr. Philip Kass (Department of
   Population Health and Reproduction, School of Veterinary Medicine,
   University of California, Davis) for statistical advice and editing.
   This research was funded by Grant 2013-17 from the Mosquito Research
   Foundation. CMB acknowledges additional support from the Research and
   Policy for Infectious Disease Dynamics (RAPIDD) program of the Science
   and Technology Directorate, Department of Homeland Security and Fogarty
   International Center, National Institutes of Health.
NR 39
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U1 0
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-2585
EI 1938-2928
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD SEP
PY 2015
VL 52
IS 5
BP 1083
EP 1089
DI 10.1093/jme/tjv082
PG 7
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA CS0PS
UT WOS:000361764900041
PM 26336222
ER

PT J
AU Jaffray, DA
   Knaul, FM
   Atun, R
   Adams, C
   Barton, MB
   Baumann, M
   Lievens, Y
   Lui, TYM
   Rodin, DL
   Rosenblatt, E
   Torode, J
   Van Dyk, J
   Vikram, B
   Gospodarowicz, M
AF Jaffray, David A.
   Knaul, Felicia M.
   Atun, Rifat
   Adams, Cary
   Barton, Michael B.
   Baumann, Michael
   Lievens, Yolande
   Lui, Tracey Y. M.
   Rodin, Danielle L.
   Rosenblatt, Eduardo
   Torode, Julie
   Van Dyk, Jacob
   Vikram, Bhadrasain
   Gospodarowicz, Mary
TI Global Task Force on Radiotherapy for Cancer Control
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID COUNTRIES; FUND
C1 [Jaffray, David A.; Gospodarowicz, Mary] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
   [Jaffray, David A.; Rodin, Danielle L.; Gospodarowicz, Mary] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada.
   [Jaffray, David A.; Lui, Tracey Y. M.] Univ Hlth Network, TECHNA Inst, Toronto, ON, Canada.
   [Knaul, Felicia M.] Harvard Univ, Harvard Global Equ Initiat, Cambridge, MA 02138 USA.
   [Knaul, Felicia M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
   [Atun, Rifat] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Cambridge, MA 02138 USA.
   [Adams, Cary; Torode, Julie] Union Int Canc Control, Geneva, Switzerland.
   [Barton, Michael B.] Univ New S Wales, Ingham Inst Appl Med Res, Liverpool, NSW, Australia.
   [Baumann, Michael] Tech Univ Dresden, Dept Radiat Oncol, Fac Med, D-01062 Dresden, Germany.
   [Baumann, Michael] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, D-01062 Dresden, Germany.
   [Lievens, Yolande] Ghent Univ Hosp, Ghent, Belgium.
   [Lievens, Yolande] Univ Ghent, B-9000 Ghent, Belgium.
   [Rosenblatt, Eduardo] IAEA, A-1400 Vienna, Austria.
   [Van Dyk, Jacob] Univ Western Ontario, Dept Med Biophys, London, ON, Canada.
   [Vikram, Bhadrasain] NCI, US NIH, Bethesda, MD 20892 USA.
RP Jaffray, DA (reprint author), Princess Margaret Canc Ctr, 610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM Mary.Gospodarowicz@rmp.uhn.on.ca
RI Barton, Michael/M-7183-2015
OI Barton, Michael/0000-0003-0112-0680
NR 14
TC 2
Z9 2
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 10
BP 1144
EP 1146
PG 3
WC Oncology
SC Oncology
GA CS2CE
UT WOS:000361874600002
PM 26419349
ER

PT J
AU Coleman, CN
   Minsky, BD
AF Coleman, C. Norman
   Minsky, Bruce D.
TI The verdict is in: the time for effective solutions to the global cancer
   burden is now
SO LANCET ONCOLOGY
LA English
DT Editorial Material
C1 [Coleman, C. Norman] NCI, Radiat Res Program, NIH, Bethesda, MD 20892 USA.
   [Coleman, C. Norman] Int Canc Expert Corps, New York, NY USA.
   [Minsky, Bruce D.] Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA.
RP Coleman, CN (reprint author), NCI, Radiat Res Program, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM ccoleman@mail.nih.gov
NR 10
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 10
BP 1146
EP 1147
PG 3
WC Oncology
SC Oncology
GA CS2CE
UT WOS:000361874600003
PM 26419350
ER

PT J
AU Atun, R
   Jaffray, DA
   Barton, MB
   Bray, F
   Baumann, M
   Vikram, B
   Hanna, TP
   Knaul, FM
   Lievens, Y
   Lui, TYM
   Milosevic, M
   O'Sullivan, B
   Rodin, DL
   Rosenblatt, E
   Van Dyk, J
   Yap, ML
   Zubizarreta, E
   Gospodarowicz, M
AF Atun, Rifat
   Jaffray, David A.
   Barton, Michael B.
   Bray, Freddie
   Baumann, Michael
   Vikram, Bhadrasain
   Hanna, Timothy P.
   Knaul, Felicia M.
   Lievens, Yolande
   Lui, Tracey Y. M.
   Milosevic, Michael
   O'Sullivan, Brian
   Rodin, Danielle L.
   Rosenblatt, Eduardo
   Van Dyk, Jacob
   Yap, Mei Ling
   Zubizarreta, Eduardo
   Gospodarowicz, Mary
TI Expanding global access to radiotherapy
SO LANCET ONCOLOGY
LA English
DT Review
ID MIDDLE-INCOME COUNTRIES; ESTRO-HERO SURVEY; BRINGING CANCER CARE;
   SUB-SAHARAN AFRICA; RADIATION-THERAPY; CERVICAL-CANCER; BREAST-CANCER;
   EUROPEAN COUNTRIES; HUMAN-PAPILLOMAVIRUS; PALLIATIVE RADIOTHERAPY
AB Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$ 26.6 billion in low-income countries, $62.6 billion in lower-middle-income countries, and $94.8 billion in upper-middle-income countries, which amounts to $184.0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14.1 billion in low-income, $33.3 billion in lower-middle-income, and $49.4 billion in upper-middle-income countries-a total of $96.8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26.9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278.1 billion in 2015-35 ($265.2 million in low-income countries, $38.5 billion in lower-middle-income countries, and $239.3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365.4 billion ($12.8 billion in low-income countries, $67.7 billion in lower-middle-income countries, and $284.7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16.9 billion in 2015-35 (-$14.9 billion in low-income countries; -$18.7 billion in lower-middle-income countries, and $50.5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104.2 billion (-$2.4 billion in low-income countries, $10.7 billion in lower-middle-income countries, and $95.9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not
C1 [Atun, Rifat] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Cambridge, MA 02138 USA.
   [Knaul, Felicia M.] Harvard Univ, Harvard Global Equ Initiat, Cambridge, MA 02138 USA.
   [Knaul, Felicia M.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02138 USA.
   [Jaffray, David A.; Milosevic, Michael; O'Sullivan, Brian; Gospodarowicz, Mary] Princess Margaret Canc Ctr, Toronto, ON, Canada.
   [Jaffray, David A.; Lui, Tracey Y. M.] Univ Hlth Network, TECHNA Inst, Toronto, ON, Canada.
   [Jaffray, David A.; O'Sullivan, Brian; Rodin, Danielle L.; Gospodarowicz, Mary] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada.
   [Barton, Michael B.; Hanna, Timothy P.; Yap, Mei Ling] Univ New S Wales, Ingham Inst Appl Med Res, Liverpool, NSW, Australia.
   [Bray, Freddie] Int Agcy Res Canc, F-69372 Lyon, France.
   [Baumann, Michael] Tech Univ Dresden, Dept Radiat Oncol, Fac Med, D-01062 Dresden, Germany.
   [Baumann, Michael] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, D-01062 Dresden, Germany.
   [Vikram, Bhadrasain] NCI, US NIH, Bethesda, MD 20892 USA.
   [Hanna, Timothy P.] Queens Univ, Div Canc Care & Epidemiol, Canc Res Inst, Kingston, ON, Canada.
   [Lievens, Yolande] Ghent Univ Hosp, Ghent, Belgium.
   [Lievens, Yolande] Univ Ghent, B-9000 Ghent, Belgium.
   [Rosenblatt, Eduardo] IAEA, A-1400 Vienna, Austria.
   [Van Dyk, Jacob] Univ Western Ontario, Dept Med Biophys, London, ON, Canada.
   [Zubizarreta, Eduardo] Global Task Force Radiotherapy Canc Control, Toronto, ON, Canada.
RP Atun, R (reprint author), Harvard Univ, Harvard TH Chan Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM ratun@hsph.harvard.edu
RI Barton, Michael/M-7183-2015; 
OI Barton, Michael/0000-0003-0112-0680; Hanna, Timothy/0000-0003-3228-6042
FU Raysearch Laboratories; Philips Medical Systmes; Eletka; Varian Medical
   Systems; Siemens Medical; IMRIS; American Society for Radiation
   Oncology; GlaxoSmithKline; Pfizer; NADRO; Chinoin; Sanofi SA; Roche;
   Susan G Komen for the Cure; Fogarty International Center; Pan-American
   Health Organization; WHO; International Development Research Center;
   National Institute of Public Health Mexico; Centro de Investigacion y
   Docencias Economicas Mexico; PISA; Celgene; Grunenthal; Union for
   International Cancer Control
FX DAJ reports grants or sponsored research agreements from Raysearch
   Laboratories, Philips Medical Systmes, Eletka, Varian Medical Systems,
   Siemens Medical, and IMRIS; presenter fees from the American Society for
   Radiation Oncology; and royalties from Modus Medical and Precision X-ray
   related to non-patentable inventions, outside the submitted work.
   Additionally he has pending patents (US 2013/026137 A1, US61/178 319,
   US61/157738, and US2013/0113802 A1), issued patents (7399977,
   US11/867998, and PCT/US2007/067847), issued patents licensed to Elekta
   (8 039 790 [with royalties received], 20040234115, 20040096038,
   20040218719, 7472765 [with royalties received], and 7 147 373 [with
   royalties received]), and issued patents licensed to iRT (US60/806842,
   PCT/CA2007/001209, and EP20070763872). TPH received non-financial
   support from the Canadian Association of Radiation Oncology during this
   work. FMK has received grants from GlaxoSmithKline, Pfizer, NADRO,
   Chinoin, Sanofi SA, Roche, Susan G Komen for the Cure, Fogarty
   International Center, the Pan-American Health Organization, WHO, and the
   International Development Research Center; and support from the National
   Institute of Public Health Mexico, Centro de Investigacion y Docencias
   Economicas Mexico, PISA, Celgene, and Grunenthal. She is director of the
   Secretariat of the Global Task Force on Expanded Access to Cancer Care
   and Control, a board member of the Union for International Cancer
   Control, and the founding President of Tomatelo a Pecho. YL is
   president-elect of the European Society for Radiotherapy and Oncology,
   an unpaid position. TYML's institution received funds from the Union for
   International Cancer Control to support her salary for time spent
   working on this Commission. JVD received travel support from the
   Canadian Organization of Medical Physicists to attend meetings related
   to the Commission. MG is a member of the board of directors of IBA,
   which manufactures proton therapy equipment. RA, MBB, FB, MB, BV, MM,
   BOS, DLR, ER, MLY, and EZ declare no competing interests.
NR 175
TC 57
Z9 58
U1 3
U2 23
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 10
BP 1153
EP 1186
PG 34
WC Oncology
SC Oncology
GA CS2CE
UT WOS:000361874600007
PM 26419354
ER

PT J
AU Rubin, G
   Berendsen, A
   Crawford, SM
   Dommett, R
   Earle, C
   Emery, J
   Fahey, T
   Grassi, L
   Grunfeld, E
   Gupta, S
   Hamilton, W
   Hiom, S
   Hunter, D
   Lyratzopoulos, G
   Macleod, U
   Mason, R
   Mitchell, G
   Neal, RD
   Peake, M
   Roland, M
   Seifert, B
   Sisler, J
   Sussman, J
   Taplin, S
   Vedsted, P
   Voruganti, T
   Walter, F
   Wardle, J
   Watson, E
   Weller, D
   Wender, R
   Whelan, J
   Whitlock, J
   Wilkinson, C
   de Wit, N
   Zimmermann, C
AF Rubin, Greg
   Berendsen, Annette
   Crawford, S. Michael
   Dommett, Rachel
   Earle, Craig
   Emery, Jon
   Fahey, Tom
   Grassi, Luigi
   Grunfeld, Eva
   Gupta, Sumit
   Hamilton, Willie
   Hiom, Sara
   Hunter, David
   Lyratzopoulos, Georgios
   Macleod, Una
   Mason, Robert
   Mitchell, Geoffrey
   Neal, Richard D.
   Peake, Michael
   Roland, Martin
   Seifert, Bohumil
   Sisler, Jeff
   Sussman, Jonathan
   Taplin, Stephen
   Vedsted, Peter
   Voruganti, Teja
   Walter, Fiona
   Wardle, Jane
   Watson, Eila
   Weller, David
   Wender, Richard
   Whelan, Jeremy
   Whitlock, James
   Wilkinson, Clare
   de Wit, Niek
   Zimmermann, Camilla
TI The expanding role of primary care in cancer control
SO LANCET ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY PALLIATIVE CARE; BRIEF ALCOHOL
   INTERVENTIONS; PRACTICE RESEARCH DATABASE; DECISION-SUPPORT-SYSTEMS;
   ACUTE ONCOLOGY SERVICE; PRIMARY-HEALTH-CARE; EARLY BREAST-CANCER;
   GENERAL-PRACTITIONERS; COLORECTAL-CANCER
AB The nature of cancer control is changing, with an increasing emphasis, fuelled by public and political demand, on prevention, early diagnosis, and patient experience during and after treatment. At the same time, primary care is increasingly promoted, by governments and health funders worldwide, as the preferred setting for most health care for reasons of increasing need, to stabilise health-care costs, and to accommodate patient preference for care close to home. It is timely, then, to consider how this expanding role for primary care can work for cancer control, which has long been dominated by highly technical interventions centred on treatment, and in which the contribution of primary care has been largely perceived as marginal. In this Commission, expert opinion from primary care and public health professionals with academic and clinical cancer expertise-from epidemiologists, psychologists, policy makers, and cancer specialists-has contributed to a detailed consideration of the evidence for cancer control provided in primary care and community care settings. Ranging from primary prevention to end-of-life care, the scope for new models of care is explored, and the actions needed to effect change are outlined. The strengths of primary care-its continuous, coordinated, and comprehensive care for individuals and families-are particularly evident in prevention and diagnosis, in shared follow-up and survivorship care, and in end-of-life care. A strong theme of integration of care runs throughout, and its elements (clinical, vertical, and functional) and the tools needed for integrated working are described in detail. All of this change, as it evolves, will need to be underpinned by new research and by continuing and shared multiprofessional development.
C1 [Rubin, Greg; Hunter, David] Univ Durham, Sch Med Pharm & Hlth, Stockton On Tees TS17 6BH, England.
   [Berendsen, Annette] Univ Groningen, Univ Med Ctr Groningen, Dept Gen Practice, Groningen, Netherlands.
   [Crawford, S. Michael] Airedale Natl Hlth Serv Fdn Trust, Keighley, England.
   [Dommett, Rachel] Univ Bristol, Sch Clin Sci, Bristol, Avon, England.
   [Earle, Craig; Grunfeld, Eva] Ontario Inst Canc Res, Toronto, ON, Canada.
   [Emery, Jon] Univ Melbourne, Dept Gen Practice, Melbourne, Vic, Australia.
   [Fahey, Tom] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
   [Grassi, Luigi] Univ Ferrara, Dept Biomed & Specialty Surg Sci, I-44100 Ferrara, Italy.
   [Gupta, Sumit] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
   [Voruganti, Teja] Univ Toronto, Fac Med, Toronto, ON, Canada.
   [Whitlock, James] Univ Toronto, Dept Paediat, Toronto, ON M5S 1A1, Canada.
   [Zimmermann, Camilla] Univ Toronto, Dept Med, Div Med Oncol & Haematol, Toronto, ON, Canada.
   [Hamilton, Willie] Univ Exeter, Sch Med, Exeter, Devon, England.
   [Hiom, Sara] Canc Res UK, London, England.
   [Lyratzopoulos, Georgios; Wardle, Jane] UCL, Dept Epidemiol & Publ Hlth, London, England.
   [Whelan, Jeremy] UCL, Res Dept Oncol, London, England.
   [Macleod, Una] Univ Hull, Hull York Med Sch, Kingston Upon Hull HU6 7RX, N Humberside, England.
   [Mason, Robert] Kings Coll London, Fac Life Sci & Med, London, England.
   [Mitchell, Geoffrey] Univ Queensland, Fac Med & Biomed Sci, Brisbane, Qld, Australia.
   [Neal, Richard D.; Wilkinson, Clare] Bangor Univ, North Wales Ctr Primary Care Res, Bangor, Wales.
   [Peake, Michael] Glenfield Hosp, Leicester, Leics, England.
   [Roland, Martin; Walter, Fiona] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Seifert, Bohumil] Charles Univ Prague, Dept Gen Practice, Prague, Czech Republic.
   [Sisler, Jeff] Univ Manitoba, Dept Family Med, Winnipeg, MB, Canada.
   [Sussman, Jonathan] Juravinski Canc Ctr, Hamilton, ON, Canada.
   [Taplin, Stephen] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Vedsted, Peter] Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.
   [Watson, Eila] Oxford Brookes Univ, Dept Clin Hlth Care, Oxford OX3 0BP, England.
   [Weller, David] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
   [Wender, Richard] Amer Canc Soc, Atlanta, GA 30329 USA.
   [de Wit, Niek] Univ Med Ctr Utrecht, Dept Gen Practice, Utrecht, Netherlands.
RP Rubin, G (reprint author), Univ Durham, Sch Med Pharm & Hlth, Stockton On Tees TS17 6BH, England.
EM g.p.rubin@durham.ac.uk
RI Vedsted, Peter/C-2583-2008; Fahey, Tom/C-9367-2012
OI Vedsted, Peter/0000-0003-2113-5599; Fahey, Tom/0000-0002-5896-5783
FU Cancer Research UK [A18180]; Public Health Wales; Betsi Cadwaladr
   University Health Board
FX GL is supported by a Cancer Research UK Clinician Scientist Fellowship
   (A18180). RDN receives funding from Public Health Wales and Betsi
   Cadwaladr University Health Board. We thank Christina Dobson for
   managing the references.
NR 346
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U1 2
U2 29
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2015
VL 16
IS 12
BP 1231
EP 1272
PG 42
WC Oncology
SC Oncology
GA CS2CS
UT WOS:000361876000006
PM 26431866
ER

PT J
AU Rysavy, MA
   Li, L
   Bell, EF
   Das, A
   Hintz, SR
   Stoll, BJ
   Vohr, BR
   Carlo, WA
   Shankaran, S
   Walsh, MC
   Tyson, JE
   Cotten, CM
   Smith, PB
   Murray, JC
   Colaizy, TT
   Brumbaugh, JE
   Higgins, RD
AF Rysavy, Matthew A.
   Li, Lei
   Bell, Edward F.
   Das, Abhik
   Hintz, Susan R.
   Stoll, Barbara J.
   Vohr, Betty R.
   Carlo, Waldemar A.
   Shankaran, Seetha
   Walsh, Michele C.
   Tyson, Jon E.
   Cotten, C. Michael
   Smith, P. Brian
   Murray, Jeffrey C.
   Colaizy, Tarah T.
   Brumbaugh, Jane E.
   Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst C
TI Between-Hospital Variation in Treatment and Outcomes in Extremely
   Preterm Infants
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB When an infant is born near the limit of viability, clinicians face difficulties in determining whether active treatment is in the patient's best interest. The outcomes for extremely preterm birth vary widely. The aim of this study was to investigate whether that variation may reflect differences between hospitals in the decision to actively treat neonates versus provide comfort care. Data were collected from 24 hospitals in the United States between April 1, 2006, and March 31, 2011, for infants born before 27 weeks' gestation. Active treatment was defined by a number of treatments but did not include obstetrical treatment or consider later decisions to withdraw treatment, as this study focused on the decision to initiate active treatment. Outcomes included survival, survival without severe impairment, and survival without moderate or severe impairment. At 18 to 22 months corrected age, data on neurodevelopmental impairment and survival were collected. Multivariable multilevel logistic regression models were used for statistical analysis. Of the 4987 infants included in the study, 4329 (86.8%) received active treatment. Of infants born at 22 weeks' gestation, 22.1% received active treatment (95% confidence interval [CI], 18.1%-26.8%). At 23 weeks, 71.8% received treatment (95% CI, 68.5%-74.9%); 97.1% (95% CI, 96.0%-98.0%) received treatment at 24 weeks, 99.6% (95% CI, 99.1%-99.8%) born at 25 weeks; and 99.8% (95% CI, 99.4%-100.0%) born at 26 weeks. Of those who received treatment with known outcomes (n = 4046), 65% survived, 56.1% survived without severe neurodevelopmental impairment, and 40.8% survived without moderate or severe neurodevelopmental impairment. Hospital rates of active treatment varied widely in infants born at 22 to 24 weeks. At 23 weeks' gestation, interquartile range for active treatment rates in hospitals ranged from 52.5% to 96.5%. The initiation of active treatment clustered at the hospital level, according to multilevel models. Hospital rates of active treatment did not account for any variation in outcomes among infants born at 25 or 26 weeks' gestation, but did account for 78% and 75% of the variation in survival and survival without severe impairment in children born at 22 or 23 weeks' gestation, and also accounted for 22% and 16% for infants born at 24 weeks. Some of the between-hospital variation in survival and impairment rates among infants can be explained by between-hospital differences in the practice of initiating active treatment in infants born between 22 and 24 weeks.
C1 [Rysavy, Matthew A.; Bell, Edward F.; Murray, Jeffrey C.; Colaizy, Tarah T.; Brumbaugh, Jane E.] Univ Iowa, Stead Family Dept Pediat, Iowa City, IA 52242 USA.
   [Rysavy, Matthew A.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
   [Li, Lei] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA.
   [Das, Abhik] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA.
   [Hintz, Susan R.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
   [Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
   [Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
   [Vohr, Betty R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02912 USA.
   [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
   [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
   [Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
   [Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
   [Cotten, C. Michael; Smith, P. Brian] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Rysavy, MA (reprint author), Univ Iowa, Stead Family Dept Pediat, Iowa City, IA 52242 USA.
NR 0
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 0029-7828
EI 1533-9866
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD SEP
PY 2015
VL 70
IS 9
BP 549
EP 551
DI 10.1097/01.ogx.0000471596.46762.bf
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CS0LE
UT WOS:000361749900003
ER

PT J
AU Goldstein, DS
   Holmes, C
   Sullivan, P
   Mash, DC
   Sidransky, E
   Stefani, A
   Kopin, IJ
   Sharabi, Y
AF Goldstein, David S.
   Holmes, Courtney
   Sullivan, Patti
   Mash, Deborah C.
   Sidransky, Ellen
   Stefani, Alessandro
   Kopin, Irwin J.
   Sharabi, Yehonatan
TI Deficient vesicular storage: A common theme in catecholaminergic
   neurodegeneration
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Catecholamine; Dopamine; Norepinephrine; Parkinson's disease;
   Neurodegeneration
ID MULTIPLE SYSTEM ATROPHY; CARDIAC SYMPATHETIC DENERVATION; TOXIC DOPAMINE
   METABOLITE; PURE AUTONOMIC FAILURE; DISTINGUISH PARKINSON DISEASE; GLIAL
   CYTOPLASMIC INCLUSIONS; POSITRON-EMISSION-TOMOGRAPHY; LEWY BODY DISEASE;
   ALPHA-SYNUCLEIN; IN-VIVO
AB Several neurodegenerative diseases involve loss of catecholamine neurons-Parkinson's disease (PD) is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are lost has been mysterious. Accumulating evidence supports the concept of "autotoxicity" inherent cytotoxicity caused by catecholamine metabolites. Since vesicular sequestration limits the buildup of toxic products of enzymatic and spontaneous oxidation of catecholamines, a vesicular storage defect could play a pathogenic role in the death of catecholaminergic neurons in a variety of neurodegenerative diseases. In putamen, deficient vesicular storage is revealed in vivo by accelerated loss of F-18-DOPA-derived radioactivity and post-mortem by decreased tissue dopamine (DA):DOPA ratios; in myocardium in vivo by accelerated loss of F-18-dopamine-derived radioactivity and post-mortem by increased 3,4-dihydroxyphenylglycohnorepinephrine (DHPG:NE) ratios; and in sympathetic noradrenergic nerves overall in vivo by increased plasma F-dihydroxyphenylacetic acid (F-DOPAC):DHPG ratios. We retrospectively analyzed data from 20 conditions with decreased or intact catecholaminergic innervation, involving different etiologies, pathogenetic mechanisms, and lesion locations. All conditions involving parkinsonism had accelerated loss of putamen F-18-DOPA-derived radioactivity; in those with postmortem data there were also decreased putamen DA:DOPA ratios. All conditions involving cardiac sympathetic denervation had accelerated loss of myocardial F-18-dopamine-derived radioactivity; in those with post-mortem data there were increased myocardial DHPG:NE ratios. All conditions involving localized loss of catecholaminergic innervation had evidence of decreased vesicular storage specifically in the denervated regions. Thus, across neurodegenerative diseases, loss of catecholaminergic neurons seems to be associated with decreased vesicular storage in the residual neurons. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Goldstein, David S.; Holmes, Courtney; Sullivan, Patti; Kopin, Irwin J.] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA.
   [Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
   [Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Stefani, Alessandro] Univ Tor Vergata, Movement Disorder Ctr, Rome, Italy.
   [Sharabi, Yehonatan] Chaim Sheba Med Ctr, Dept Internal Med, IL-52621 Tel Hashomer, Israel.
   [Sharabi, Yehonatan] Tel Aviv Univ, Sch Med, Sackler Fac Med, Tel Avid, Israel.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, 9000 Rockville Pike,Bldg 10,Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
OI STEFANI, ALESSANDRO/0000-0002-1806-8922; Kopin,
   Irwin/0000-0002-8234-870X
FU Division of Intramural Research, NINDS, NIH
FX Division of Intramural Research, NINDS, NIH.
NR 58
TC 2
Z9 2
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
EI 1873-5126
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD SEP
PY 2015
VL 21
IS 9
BP 1013
EP 1022
DI 10.1016/j.parkreldis.2015.07.009
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA CR8BR
UT WOS:000361576600002
PM 26255205
ER

PT J
AU Maurer, CW
   LaFaver, K
   Ameli, R
   Toledo, R
   Hallett, M
AF Maurer, Carine W.
   LaFaver, Kathrin
   Ameli, Rezvan
   Toledo, Ryan
   Hallett, Mark
TI A biological measure of stress levels in patients with functional
   movement disorders
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Functional movement disorders; Psychogenic movement disorders;
   Conversion disorder; Stress; Hypothalamic-pituitary adrenal axis;
   Cortisol
ID CONVERSION DISORDER; SALIVARY CORTISOL; LIFE-EVENTS; DEPRESSION; TRAUMA
AB Introduction: While the presence of co-existing psychological stressors has historically been used as a supportive factor in the diagnosis of functional neurological disorders, many patients with functional neurological disorders deny the presence of these stressors. The stress response circuitry in these patients remains largely unexplored.
   Methods: We performed an observational study examining biological stress levels in patients with functional movement disorders as compared with matched healthy controls. Specifically, we compared levels of circulating cortisol, the end-product of the hypothalamic-pituitary-adrenal axis. Salivary cortisol samples were collected from patients with "clinically definite" functional movement disorders (n = 33) and their age- and sex-matched controls (n = 33). Collections were performed at five standardized time points, reflecting participants' diurnal cortisol cycles. To rule out confounders, participants also underwent extensive psychological assessment including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Hamilton Anxiety Rating Scale, and Hamilton Rating Scale for Depression.
   Results: Patients with functional movement disorders did not differ from matched controls with respect to levels of circulating cortisol.
   Conclusion: We demonstrate that current stress levels are not altered in patients with functional movement disorders. Our results warrant careful review of current management of patients with functional neurological symptoms, and suggest that the insistence on heightened stress levels in these patients is unjustified. Published by Elsevier Ltd.
C1 [Maurer, Carine W.; LaFaver, Kathrin; Toledo, Ryan; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
   [LaFaver, Kathrin] Univ Louisville, Dept Neurol, Louisville, KY 40292 USA.
   [Ameli, Rezvan] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Maurer, CW (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 7D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM carine.maurer@nih.gov; kathrin.lafaver@gmail.com; amelir@mail.nih.gov;
   ryan.toledo21@gmail.com; hallettm@ninds.nih.gov
FU US World Meds; Neurotoxin Institute; NIH Intramural Program; Kinetics
   Foundation; NIH from Brainsway
FX Dr. LaFaver reports consulting fees from US World Meds.; Dr. Hallett
   serves as Chair of the Medical Advisory Board for and receives honoraria
   and funding for travel from the Neurotoxin Institute. He may accrue
   revenue on US Patent #6,780,413 B2 (Issued: August 24, 2004):
   Immunotoxin (MAB-Ricin) for the treatment of focal movement disorders,
   and US Patent #7,407,478 (Issued: August 5, 2008): Coil for Magnetic
   Stimulation and methods for using the same (H-coil); in relation to the
   latter, he has received license fee payments from the NIH (from
   Brainsway) for licensing of this patent. He is on the Editorial Board of
   20 journals, and received royalties and/or honoraria from publishing
   from Cambridge University Press, Oxford University Press, John Wiley &
   Sons, Wolters Kluwer, Springer, and Elsevier. He has received honoraria
   for lecturing from Columbia University. Dr. Hallett's research at the
   NIH is largely supported by the NIH Intramural Program. Supplemental
   research funds have been granted by the Kinetics Foundation for studies
   of instrumental methods to monitor Parkinson's disease, BCN Peptides,
   S.A. for treatment studies of blepharospasm, Medtronics, Inc., for
   studies of deep brain stimulation, Parkinson Alliance for studies of eye
   movements in Parkinson's disease, Merz for treatment studies of focal
   hand dystonia, and Allergan for studies of methods to inject botulinum
   toxins.
NR 20
TC 5
Z9 5
U1 1
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
EI 1873-5126
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD SEP
PY 2015
VL 21
IS 9
BP 1072
EP 1075
DI 10.1016/j.parkreldis.2015.06.017
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA CR8BR
UT WOS:000361576600010
PM 26117436
ER

PT J
AU Inta, D
   Cameron, HA
   Gass, P
AF Inta, Dragos
   Cameron, Heather A.
   Gass, Peter
TI New neurons in the adult striatum: from rodents to humans
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
DE adult neurogenesis; striatum; GABAergic interneurons; subventricular
   zone; humans
ID INTERNEURONS EXPRESSING CALRETININ; POSTNATAL SUBVENTRICULAR ZONE;
   NEURAL STEM-CELLS; HIPPOCAMPAL NEUROGENESIS; OLFACTORY-BULB; GABAERGIC
   INTERNEURONS; GRANULE CELLS; NEOCORTICAL INTERNEURONS; SUBCORTICAL
   FOREBRAIN; HUNTINGTONS-DISEASE
AB Most neurons are generated during development and are not replaced during adulthood, even if they are lost to injury or disease. However, it is firmly established that new neurons are generated in the dentate gyrus of the hippocampus of almost all adult mammals, including humans. Nevertheless, many questions remain regarding adult neurogenesis in other brain regions and particularly in humans, where standard birth-dating methods are not generally feasible. Exciting recent evidence indicates that calretinin-expressing interneurons are added to the adult human striatum at a substantial rate. The role of new neurons is unknown, but studies in rodents will be able to further elucidate their identity and origin and then we may begin to understand their regulation and function.
C1 [Inta, Dragos; Gass, Peter] Heidelberg Univ, Dept Psychiat & Psychotherapy, RG Anim Models Psychiat, Cent Inst Mental Hlth,Med Fac Mannheim, Heidelberg, Germany.
   [Cameron, Heather A.] NIMH, Sect Neuroplast, NIH, Bethesda, MD 20892 USA.
RP Inta, D (reprint author), Heidelberg Univ, Dept Psychiat & Psychotherapy, RG Anim Models Psychiat, Cent Inst Mental Hlth,Med Fac Mannheim, Heidelberg, Germany.
EM Dragos.Inta@zi-mamtheim.de
RI Cameron, Heather/E-6221-2011
OI Cameron, Heather/0000-0002-3245-5777
FU Intramural NIH HHS [ZIA MH002784-08]; NIMH NIH HHS [ZIA MH002784]; PHS
   HHS [1ZIAMH002784]
NR 78
TC 12
Z9 13
U1 2
U2 17
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD SEP
PY 2015
VL 38
IS 9
BP 517
EP 523
DI 10.1016/j.tins.2015.07.005
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA CS0VA
UT WOS:000361779100001
PM 26298770
ER

PT J
AU Song, JB
   Huang, P
   Duan, HW
   Chen, XY
AF Song, Jibin
   Huang, Peng
   Duan, Hongwei
   Chen, Xiaoyuan
TI Plasmonic Vesicles of Amphiphilic Nanocrystals: Optically Active
   Multifunctional Platform for Cancer Diagnosis and Therapy
SO ACCOUNTS OF CHEMICAL RESEARCH
LA English
DT Review
ID ENHANCED RAMAN-SCATTERING; HUMAN BREAST-CANCER; GOLD NANOPARTICLES;
   PHOTOTHERMAL THERAPY; DRUG-DELIVERY; SERS; NANOSTRUCTURES; ASSEMBLIES;
   NANORODS; DRIVEN
AB CONSPECTUS: Vesicular structures with compartmentalized, water-filled cavities, such as liposomes of natural and synthetic amphiphiles, have tremendous potential applications in nanomedicine. When block copolymers self-assemble, the result is polymersomes with tailored structural properties and built-in releasing mechanisms, controlled by stimuli-responsive polymer building blocks. More recently, chemists are becoming interested in multifunctional hybrid vesicles containing inorganic nanocrystals with unique optical, electronic, and magnetic properties. In this Account, We review our recent progress in assembling amphiphilic plasmonic nanostructures to create a new class of multifunctional hybrid vesicles and applying them towards cancer diagnosis and therapy.
   Localized surface plasmon resonance (LSPR) gives plasmonic nanomaterials a unique set of optical properties that are potentially useful for both biosensing and nanomedicine. For instance, the strong light scattering at their LSPR wavelength opens up the applications of plasmonic nanostructures in single particle plasmonic imaging. Their superior photothermal conversion properties, on the other hand, make them excellent transducers for photothermal ablation and contrast agents for photoacoustic imaging. Of particular note for ultrasensitive detection is that the confined electromagnetic field resulting from excitation of LSPR can give rise to highly efficient surface enhanced Raman scattering (SERS) for molecules in close proximity. We have explored several ways to combine well-defined plasmonic nanocrystals with amphiphilic polymer brushes of diverse chemical functionalities. In multiple systems, we have shown that the polymer grafts impart amphiphilicity-driven self-assembly to the hybrid nanoparticles. This has allowed us to synthesize well-defined vesicles in which we have embedded plasmonic nanocrystals in the shell of collapsed hydrophobic polymers. The hydrophilic brushes extend into external and interior aqueous environment to stabilize the vesicular structure. More importantly, we have demonstrated that strong interparticle coupling greatly enhances the optical properties (scattering, photothermal conversion, and SERS) in plasmonic vesicles. In combination with the loading capacity of the vesicles, this technology can provide unique opportunities for integrated diagnosis and therapy, multimodality combination therapy, and imaging-guided therapy. One key property differentiating the plasmonic vesicles from other vesicular structures containing nanocrystals is that we can tailor the interparticle coupling and disintegration of the plasmonic vesicles by altering structural parameters and conformational changes of the covalently bound polymer-brushes. This gives us tremendous flexibility to engineer plasmonic vesicles for ultrasensitive detection and targeted therapy. Through bringing together advances in nanochemistry, polymer chemistry, self-assembly, and nanophotonics, we expect to further expand our capability of tailoring optical and structural characteristics of plasmonic vesicles to address challenges in medical settings.
C1 [Song, Jibin; Huang, Peng; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
   [Song, Jibin; Duan, Hongwei] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore 637457, Singapore.
RP Duan, HW (reprint author), Nanyang Technol Univ, Sch Chem & Biomed Engn, 70 Nanyang Dr, Singapore 637457, Singapore.
EM hduan@ntu.edu.sg; shawn.chen@nih.gov
RI Huang, Peng/R-2480-2016
OI Huang, Peng/0000-0003-3651-7813
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB);
   Singapore Ministry of Education [RG47/13, MOE2013-T3-1-002]
FX We thank the intramural research program of the National Institute of
   Biomedical Imaging and Bioengineering (NIBIB) for support of this work.
   H.D. is grateful to Singapore Ministry of Education for financial
   support (Tier 1 project RG47/13 and Tier3 project MOE2013-T3-1-002).
NR 53
TC 35
Z9 37
U1 48
U2 252
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0001-4842
EI 1520-4898
J9 ACCOUNTS CHEM RES
JI Accounts Chem. Res.
PD SEP
PY 2015
VL 48
IS 9
BP 2506
EP 2515
DI 10.1021/acs.accounts.5b00059
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA CR7AX
UT WOS:000361501400003
PM 26134093
ER

PT J
AU Tian, Q
   Simonsick, EM
   Resnick, SM
   Shardell, MD
   Ferrucci, L
   Studenski, SA
AF Tian, Qu
   Simonsick, Eleanor M.
   Resnick, Susan M.
   Shardell, Michelle D.
   Ferrucci, Luigi
   Studenski, Stephanie A.
TI Lap time variation and executive function in older adults: the Baltimore
   Longitudinal Study of Aging
SO AGE AND AGEING
LA English
DT Article
DE lap time variation; psychomotor speed; cognitive flexibility; older
   people
ID GAIT VARIABILITY; PERFORMANCE; SPEED; DEMENTIA; STANDARD; DECLINE;
   MEMORY; RISK
AB Objective: examine the cross-sectional association between a clinically accessible measure of variable walking and executive function.
   Methods: older adults aged 60 or older from the Baltimore Longitudinal Study of Aging (n = 811) with data on the 400-m walk test and cognition. Based on ten 40-m laps, we calculated mean lap time (MLT) and variation in time across ten 40-m laps (lap time variation, LTV). Executive function tests assessed attention and short-term memory (digit span forward and backward), psychomotor speed [Trail Making Test (TMT) part A] and multicomponent tasks requiring cognitive flexibility [TMT part B, part B-A (Delta TMT) and digit symbol substitution test (DSST)]. Multivariate linear regression analysis examined the cross-sectional association between LTV and executive function, adjusted for MLT, age, sex and education, as well as the LTV x MLT interaction.
   Results: the LTV was univariately associated with all executive function tests except digit span (P < 0.001); after adjustment, the association with TMT part A remained (standardised beta = 0.142, P = 0.002). There was an interaction between MLT and LTV; among fast walkers, greater LTV was associated with a greater Delta TMT (beta for LTV x MLT = -1.121, P = 0.016) after adjustment.
   Conclusion: at any walking speed, greater LTV is associated with psychomotor slowing. Among persons with faster walking speed, variation is associated with worse performance on a complex measure of cognitive flexibility. A simple measure of variability in walking time is independently associated with psychomotor slowing.
C1 [Tian, Qu; Simonsick, Eleanor M.; Shardell, Michelle D.; Ferrucci, Luigi; Studenski, Stephanie A.] NIA, NIH, Translat Gerontol Branch, Baltimore, MD 21224 USA.
   [Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA.
RP Tian, Q (reprint author), NIA, NIH, Translat Gerontol Branch, Baltimore, MD 21224 USA.
EM qu.tian@nih.gov
FU Intramural Research Program of the National Institute on Aging
FX This research was supported by the Intramural Research Program of the
   National Institute on Aging.
NR 26
TC 3
Z9 3
U1 4
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
EI 1468-2834
J9 AGE AGEING
JI Age Ageing
PD SEP
PY 2015
VL 44
IS 5
BP 796
EP 800
DI 10.1093/ageing/afv076
PG 5
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA CR5MY
UT WOS:000361388400014
PM 26082177
ER

PT J
AU Guevara, AB
   Knutson, KM
   Wassermann, EM
   Pulaski, S
   Grafman, J
   Krueger, F
AF Guevara, Andrea Brioschi
   Knutson, Kristine M.
   Wassermann, Eric M.
   Pulaski, Sarah
   Grafman, Jordan
   Krueger, Frank
TI Theory of mind impairment in patients with behavioural variant
   fronto-temporal dementia (bv-FTD) increases caregiver burden
SO AGE AND AGEING
LA English
DT Article
DE caregiver burden; theory of mind; faux-pas task; frontal cortex;
   voxel-based morphometry; older people
ID ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; FRONTAL VARIANT; PREMOTOR CORTEX;
   EMPATHY; CHILDREN; SYSTEMS; BASES
AB Setting: National Institute of Neurological Disorders and Stroke, National Institutes of Health.
   Subjects: bv-FTDp (n = 28), a subgroup of their caregivers (n = 20) and healthy controls (n = 32).
   Methods: we applied a faux-pas (FP) task as a ToM measure in bv-FTDp and healthy controls and the Zarit Burden Interview as a measure of burden in patients' caregivers. Patients underwent structural MRI; we used voxel-based morphometry to examine relationships between regional atrophy and ToM impairment and caregiver burden.
   Results: FP task performance was impaired in bv-FTDp and negatively associated with caregiver burden. Atrophy was found in areas involved in ToM. Caregiver burden increased with greater atrophy in left lateral premotor cortex, a region associated in animal models with the presence of mirror neurons, possibly involved in empathy.
   Conclusion: ToM impairment in bv-FTDp is associated with increased caregiver burden.
C1 [Guevara, Andrea Brioschi] Univ Lausanne, Fac Biol & Med, Lausanne, VD, Switzerland.
   [Guevara, Andrea Brioschi; Knutson, Kristine M.; Wassermann, Eric M.; Pulaski, Sarah] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA.
   [Grafman, Jordan] Rehabil Inst Chicago, Brain Injury Res, Chicago, IL 60611 USA.
   [Krueger, Frank] George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA.
RP Krueger, F (reprint author), George Mason Univ, Mol Neurosci Dept, 4400 Univ Dr,Mail Stop 2A1, Fairfax, VA 22030 USA.
EM fkrueger@gmu.edu
FU National Institute of Neurological Disorders and Stroke at the National
   Institutes of Health, Bethesda, MD
FX This work was supported by the National Institute of Neurological
   Disorders and Stroke at the National Institutes of Health, Bethesda, MD.
NR 24
TC 1
Z9 1
U1 3
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
EI 1468-2834
J9 AGE AGEING
JI Age Ageing
PD SEP
PY 2015
VL 44
IS 5
BP 891
EP 895
DI 10.1093/ageing/afv059
PG 5
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA CR5MY
UT WOS:000361388400031
ER

PT J
AU Fowke, JH
   McLerran, DF
   Gupta, PC
   He, J
   Shu, XO
   Ramadas, K
   Tsugane, S
   Inoue, M
   Tamakoshi, A
   Koh, WP
   Nishino, Y
   Tsuji, I
   Ozasa, K
   Yuan, JM
   Tanaka, H
   Ahn, YO
   Chen, CJ
   Sugawara, Y
   Yoo, KY
   Ahsan, H
   Pan, WH
   Pednekar, M
   Gu, DF
   Xiang, YB
   Sauvaget, C
   Sawada, N
   Wang, RW
   Kakizaki, M
   Tomata, Y
   Ohishi, W
   Butler, LM
   Oze, I
   Kim, DH
   You, SL
   Park, SK
   Parvez, F
   Chuang, SY
   Chen, Y
   Lee, JE
   Grant, E
   Rolland, B
   Thornquist, M
   Feng, ZD
   Zheng, W
   Boffetta, P
   Sinha, R
   Kang, D
   Potter, JD
AF Fowke, Jay H.
   McLerran, Dale F.
   Gupta, Prakash C.
   He, Jiang
   Shu, Xiao-Ou
   Ramadas, Kunnambath
   Tsugane, Shoichiro
   Inoue, Manami
   Tamakoshi, Akiko
   Koh, Woon-Puay
   Nishino, Yoshikazu
   Tsuji, Ichiro
   Ozasa, Kotaro
   Yuan, Jian-Min
   Tanaka, Hideo
   Ahn, Yoon-Ok
   Chen, Chien-Jen
   Sugawara, Yumi
   Yoo, Keun-Young
   Ahsan, Habibul
   Pan, Wen-Harn
   Pednekar, Mangesh
   Gu, Dongfeng
   Xiang, Yong-Bing
   Sauvaget, Catherine
   Sawada, Norie
   Wang, Renwei
   Kakizaki, Masako
   Tomata, Yasutake
   Ohishi, Waka
   Butler, Lesley M.
   Oze, Isao
   Kim, Dong-Hyun
   You, San-Lin
   Park, Sue K.
   Parvez, Faruque
   Chuang, Shao-Yuan
   Chen, Yu
   Lee, Jung Eun
   Grant, Eric
   Rolland, Betsy
   Thornquist, Mark
   Feng, Ziding
   Zheng, Wei
   Boffetta, Paolo
   Sinha, Rashmi
   Kang, Daehee
   Potter, John D.
TI Associations of Body Mass Index, Smoking, and Alcohol Consumption With
   Prostate Cancer Mortality in the Asia Cohort Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE alcohol drinking; Asia; mortality; obesity; prostate cancer;
   prostate-specific antigen; smoking
ID RISK-FACTORS; RADICAL PROSTATECTOMY; PREVENTION TRIAL; AFRICAN-AMERICAN;
   SCREENING TRIAL; CAUCASIAN MEN; OBESITY; CHINA; ANTIGEN; METAANALYSIS
AB Many potentially modifiable risk factors for prostate cancer are also associated with prostate cancer screening, which may induce a bias in epidemiologic studies. We investigated the associations of body mass index (weight (kg)/height (m)(2)), smoking, and alcohol consumption with risk of fatal prostate cancer in Asian countries where prostate cancer screening is not widely utilized. Analysis included 18 prospective cohort studies conducted during 1963-2006 across 6 countries in southern and eastern Asia that are part of the Asia Cohort Consortium. Body mass index, smoking, and alcohol intake were determined by questionnaire at baseline, and cause of death was ascertained through death certificates. Analysis included 522,736 men aged 54 years, on average, at baseline. During 4.8 million person-years of follow-up, there were 634 prostate cancer deaths (367 prostate cancer deaths across the 11 cohorts with alcohol data). In Cox proportional hazards analyses of all cohorts in the Asia Cohort Consortium, prostate cancer mortality was not significantly associated with obesity (body mass index > 25: hazard ratio (HR) = 1.08, 95% confidence interval (CI): 0.85, 1.36), ever smoking (HR = 1.00, 95% CI: 0.84, 1.21), or heavy alcohol intake (HR = 1.00, 95% CI: 0.74, 1.35). Differences in prostate cancer screening and detection probably contribute to differences in the association of obesity, smoking, or alcohol intake with prostate cancer risk and mortality between Asian and Western populations and thus require further investigation.
C1 [Fowke, Jay H.; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37203 USA.
   [McLerran, Dale F.; Rolland, Betsy; Thornquist, Mark; Potter, John D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Gupta, Prakash C.; Pednekar, Mangesh] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai, India.
   [He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA.
   [Ramadas, Kunnambath] Reg Canc Ctr, Div Radiat Oncol, Trivandrum 695011, Kerala, India.
   [Tsugane, Shoichiro; Inoue, Manami; Sawada, Norie] Natl Canc Ctr, Epidemiol & Prevent Div, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan.
   [Inoue, Manami] Univ Tokyo, Grad Sch Med, AXA Dept Hlth & Human Secur, Tokyo, Japan.
   [Tamakoshi, Akiko] Hokkaido Univ, Sch Med, Dept Publ Hlth, Sapporo, Hokkaido 060, Japan.
   [Koh, Woon-Puay] Natl Univ Singapore, Duke NUS Grad Med Sch Singapore, Singapore 117548, Singapore.
   [Koh, Woon-Puay] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
   [Nishino, Yoshikazu] Miyagi Canc Ctr Res Inst, Div Canc Epidemiol & Prevent, Sendai, Miyagi, Japan.
   [Tsuji, Ichiro; Sugawara, Yumi; Kakizaki, Masako; Tomata, Yasutake] Tohoku Univ, Grad Sch Med, Dept Publ Hlth & Forens Med, Div Epidemiol, Sendai, Miyagi 980, Japan.
   [Ozasa, Kotaro; Ohishi, Waka; Grant, Eric] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan.
   [Yuan, Jian-Min; Wang, Renwei] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
   [Yuan, Jian-Min; Butler, Lesley M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
   [Tanaka, Hideo; Oze, Isao] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan.
   [Ahn, Yoon-Ok; Yoo, Keun-Young; Park, Sue K.; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
   [Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
   [Chen, Chien-Jen; Pan, Wen-Harn] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
   [Ahsan, Habibul] Univ Chicago, Ctr Comprehens Canc, Dept Hlth Studies, Chicago, IL 60637 USA.
   [Ahsan, Habibul] Univ Chicago, Ctr Comprehens Canc, Dept Med, Chicago, IL 60637 USA.
   [Ahsan, Habibul] Univ Chicago, Ctr Comprehens Canc, Dept Human Genet, Chicago, IL 60637 USA.
   [Pan, Wen-Harn; Chuang, Shao-Yuan] Natl Hlth Res Inst, Div Prevent Med & Hlth Serv Res, Inst Populat Hlth Sci, Miaoli, Taiwan.
   [Pan, Wen-Harn] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan.
   [Gu, Dongfeng] Chinese Acad Med Sci, Dept Evidence Based Med, Fu Wai Hosp, Beijing 100730, Peoples R China.
   [Gu, Dongfeng] Chinese Acad Med Sci, Dept Populat Genet & Prevent, Fu Wai Hosp, Beijing 100730, Peoples R China.
   [Gu, Dongfeng] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China.
   [Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
   [Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
   [Sauvaget, Catherine] Int Agcy Res Canc, Screening Grp, F-69372 Lyon, France.
   [Kim, Dong-Hyun] Hallym Univ, Coll Med, Dept Social & Prevent Med, Seoul, South Korea.
   [You, San-Lin] Fu Jen Catholic Univ, Dept Publ Hlth, Taipei, Taiwan.
   [Park, Sue K.; Kang, Daehee] Seoul Natl Univ, Grad Sch, Canc Res Inst, Dept Biomed Sci, Seoul, South Korea.
   [Parvez, Faruque] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
   [Chen, Yu] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
   [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea.
   [Feng, Ziding] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
   [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
   [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
   [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
   [Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
   [Potter, John D.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Fowke, JH (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, 2525 West End Ave,Suite 1200, Nashville, TN 37203 USA.
EM jay.fowke@vanderbilt.edu
RI Chen, Chien-Jen/C-6976-2008; Tanaka, Hideo/A-8145-2016; 
OI Potter, John/0000-0001-5439-1500; Kakizaki, Masako/0000-0001-6030-8953;
   Yuan, Jian-Min/0000-0002-4620-3108; Sauvaget,
   Catherine/0000-0002-8053-4963
FU National Cancer Institute (US National Institutes of Health)
   [RO3CA159398]
FX This research was funded by grant RO3CA159398 (Principal Investigator:
   J.H.F.) from the National Cancer Institute (US National Institutes of
   Health).
NR 62
TC 11
Z9 11
U1 1
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 1
PY 2015
VL 182
IS 5
BP 381
EP 389
DI 10.1093/aje/kwv089
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CR5NB
UT WOS:000361388700002
PM 26243736
ER

PT J
AU Garcia-Closas, M
   de Gonzalez, AB
AF Garcia-Closas, Montserrat
   de Gonzalez, Amy Berrington
TI Invited Commentary: Screening and the Elusive Etiology of Prostate
   Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE alcohol drinking; Asia; mortality; obesity; prostate cancer;
   prostate-specific antigen; smoking
ID DOSE-RESPONSE METAANALYSIS; BREAST-CANCER; MAMMOGRAPHIC DENSITY;
   ALCOHOL-CONSUMPTION; SUSCEPTIBILITY LOCI; RISK-FACTORS; OBESITY;
   EPIDEMIOLOGY; MORTALITY; THERAPY
AB The role of lifestyle risk factors in prostate cancer risk remains elusive despite a large number of epidemiologic studies. In a pooled analysis of data from South and East Asian countries published in this issue, Fowke et al. (Am J Epidemiol. 2015;182(5):381-389) found no evidence for an association between prostate cancer mortality and obesity, alcohol, or smoking. Prostate cancer screening is very uncommon in these countries, and previous evidence for associations with lifestyle factors comes primarily from studies carried out in North America, where screening is very common. Fowke et al. concluded that screening biases are likely to explain the differences in study results. In this commentary, we discuss the potential influence of population-based cancer screening programs in estimates of association from epidemiologic studies. This highlights the importance of carefully considering the impact of screening in the analysis and interpretation of results, in order to advance our understanding of the etiology of cancers that can be detected by screening.
C1 [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
   [Garcia-Closas, Montserrat; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, Shady Grove, MA USA.
RP Garcia-Closas, M (reprint author), Inst Canc Res, Div Genet & Epidemiol, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England.
EM Montse.GarciaClosas@icr.ac.uk
FU Intramural NIH HHS
NR 31
TC 4
Z9 4
U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 1
PY 2015
VL 182
IS 5
BP 390
EP 393
DI 10.1093/aje/kwv086
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CR5NB
UT WOS:000361388700003
PM 26243738
ER

PT J
AU Boghossian, NS
   Albert, PS
   Mendola, P
   Grantz, KL
   Yeung, E
AF Boghossian, Nansi S.
   Albert, Paul S.
   Mendola, Pauline
   Grantz, Katherine L.
   Yeung, Edwina
TI Delivery Blood Pressure and Other First Pregnancy Risk Factors in
   Relation to Hypertensive Disorders in Second Pregnancies
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; chronic hypertension; hypertension; gestational
   hypertension; preeclampsia
ID HEALTHY NULLIPAROUS WOMEN; POPULATION-BASED COHORT; GESTATIONAL
   HYPERTENSION; RENAL BIOPSY; PREECLAMPSIA; RECURRENCE; WEIGHT
AB BACKGROUND
   First pregnancy characteristics and blood pressure (BP) measures may be associated with second pregnancy hypertensive disorder risk. We examined the association between first pregnancy risk factors and second pregnancy hypertensive disorders.
   METHODS
   Electronic medical records of nulliparas (n = 26,787) delivering at least twice in Utah (2002-2010) were used. Polychotomous logistic regression models estimated the association of first pregnancy risk factors with second pregnancy hypertensive disorders (gestational hypertension, preeclampsia, or chronic hypertension) stratified by first pregnancy hypertensive status and adjusted for second characteristics.
   RESULTS
   Among normotensive women in their first pregnancy, preterm birth (<34 weeks) and elevated BP at delivery admission in the first pregnancy increased odds of all incident hypertensive disorders in the second. Even borderline admission BP (either systolic or diastolic BP: 130-139 or 85-89 mm Hg, respectively) was associated with a doubling of hypertensive disorder risk in a subsequent pregnancy. First pregnancy BP was also associated with recurrence risks for hypertensive disorders, but the relation was stronger for women with gestational hypertension in their first pregnancy with more than 2-fold elevated risk across all BP categories (odds ratios range: 2.32-12.6). However, the majority of women (75%) with a hypertensive disorder in the first pregnancy do not repeat this outcome in the second pregnancy.
   CONCLUSION
   Delivery admission BP of a first pregnancy was strongly related to hypertensive disorder incidence and recurrence in the subsequent pregnancy. Although crude, these measures may prove useful as a predictor of long-term maternal health and future pregnancy risk.
C1 [Boghossian, Nansi S.; Mendola, Pauline; Grantz, Katherine L.; Yeung, Edwina] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
   [Boghossian, Nansi S.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
   [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA.
RP Yeung, E (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
EM yeungedw@mail.nih.gov
RI Yeung, Edwina/F-5992-2015; 
OI Yeung, Edwina/0000-0002-3851-2613; Mendola, Pauline/0000-0001-5330-2844;
   Grantz, Katherine/0000-0003-0276-8534
FU Intramural Research Program of the Eunice Kennedy Shriver National
   Institute of Child Health and Human Development [HHSN275200800002I,
   HHSN27500004]
FX This work was supported by the Intramural Research Program of the Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   (contracts numbers: HHSN275200800002I, HHSN27500004).
NR 29
TC 2
Z9 2
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD SEP
PY 2015
VL 28
IS 9
BP 1172
EP 1179
DI 10.1093/ajh/hpv001
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CR5NR
UT WOS:000361390300015
PM 25673041
ER

PT J
AU Avila, C
   Willins, JL
   Jackson, M
   Mathai, J
   Jabsky, M
   Kong, A
   Callaghan, F
   Ishkin, S
   Shroyer, ALW
AF Avila, Cecilia
   Willins, Jennifer L.
   Jackson, Matthew
   Mathai, Jacob
   Jabsky, Marina
   Kong, Alex
   Callaghan, Fiona
   Ishkin, Selda
   Shroyer, A. Laurie W.
TI Usefulness of Two Clinical Chorioamnionitis Definitions in Predicting
   Neonatal Infectious Outcomes: A Systematic Review
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Review
DE chorioamnionitis; sepsis; fever; pregnancy complications
ID PRETERM PREMATURE RUPTURE; INTRA-AMNIOTIC INFECTION; B STREPTOCOCCAL
   DISEASE; BIRTH-WEIGHT INFANTS; BIOPHYSICAL PROFILE; MEMBRANES; TERM;
   EPIDEMIOLOGY; PREVENTION; GUIDELINES
AB Objective To assess the usefulness of two definitions of acute clinical chorioamnionitis (ACCA) in predicting risk of neonatal infectious outcomes (NIO) and mortality, the first definition requiring maternal fever alone (Fever), and the second requiring >= 1 Gibbs criterion besides fever (Fever + 1).
   Study Design PubMed, Web of Science, and the Cochrane Database of Systematic Reviews were searched from January 1, 1979 to April 9, 2013. Twelve studies were reviewed (of 316 articles identified): three studies with term patients, four with preterm premature rupture of membranes (PPROM) patients, and five mixed studies with mixed gestational ages and/or membrane status (intact and/or ruptured).
   Results Both definitions demonstrated an increased NIO risk for ACCA versus non-ACCA patients, with an odds ratio increase for the Fever + 1 definition that was about twofold larger than the Fever definition.
   Conclusion As the Fever definition demonstrated increased NIO risk for ACCA versus non-ACCA patients, the Fever alone ACCA definition should be used to trigger future clinical treatment in many clinical situations.
C1 [Avila, Cecilia; Willins, Jennifer L.; Mathai, Jacob; Jabsky, Marina; Kong, Alex; Ishkin, Selda] SUNY Stony Brook, Sch Med, Dept Obstet Gynecol & Reprod Med, Stony Brook, NY 11794 USA.
   [Jackson, Matthew] US FDA, CDER OTS OB DB6, Silver Spring, MD USA.
   [Callaghan, Fiona] Natl Lib Med, Lister Hill Ctr Biomed Commun, NIH, Bethesda, MD USA.
   [Shroyer, A. Laurie W.] SUNY Stony Brook, Sch Med, Dept Surg, Stony Brook, NY 11794 USA.
RP Avila, C (reprint author), SUNY Stony Brook, Sch Med, Dept Obstet & Gynecol, HSC T9-30,100 Nicholls Rd, Stony Brook, NY 11794 USA.
EM Cecilia.Avila@stonybrookmedicine.edu
RI Shroyer, Annie Laurie/B-8836-2016
OI Shroyer, Annie Laurie/0000-0001-6461-0623
FU Department of OB/GYN at Stony Brook University School of Medicine
   (Division of Maternal Fetal Medicine); Stony Brook University School of
   Medicine Dean's office Professional Development Program
FX This study was supported by the Department of OB/GYN at Stony Brook
   University School of Medicine (Division of Maternal Fetal Medicine) and
   by the Stony Brook University School of Medicine Dean's office
   Professional Development Program (Dr. Avila, PDP Scholar; Dr. Shroyer,
   PDP Mentor).
NR 37
TC 5
Z9 5
U1 1
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
EI 1098-8785
J9 AM J PERINAT
JI Am. J. Perinatol.
PD SEP
PY 2015
VL 32
IS 11
BP 1001
EP 1009
DI 10.1055/s-0035-1547325
PG 9
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CR5UQ
UT WOS:000361410300001
PM 26007317
ER

PT J
AU Fernandez, E
   Watterberg, KL
   Faix, RG
   Yoder, BA
   Walsh, MC
   Lacy, CB
   Osborne, KA
   Das, A
   Kendrick, DE
   Stoll, BJ
   Poindexter, BB
   Laptook, AR
   Kennedy, KA
   Schibler, K
   Bell, EF
   Van Meurs, KP
   Frantz, ID
   Goldberg, RN
   Shankaran, S
   Carlo, WA
   Ehrenkranz, RA
   Sanchez, PJ
   Higgins, RD
AF Fernandez, Erika
   Watterberg, Kristi L.
   Faix, Roger G.
   Yoder, Bradley A.
   Walsh, Michele C.
   Lacy, Conra Backstrom
   Osborne, Karen A.
   Das, Abhik
   Kendrick, Douglas E.
   Stoll, Barbara J.
   Poindexter, Brenda B.
   Laptook, Abbot R.
   Kennedy, Kathleen A.
   Schibler, Kurt
   Bell, Edward F.
   Van Meurs, Krisa P.
   Frantz, Ivan D., III
   Goldberg, Ronald N.
   Shankaran, Seetha
   Carlo, Waldemar A.
   Ehrenkranz, Richard A.
   Sanchez, Pablo J.
   Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst C
TI Definitions of Cardiovascular Insufficiency and Relation to Outcomes in
   Critically III Newborn Infants
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE blood pressure; cardiovascular insufficiency; outcomes; newborn; infant
ID BIRTH-WEIGHT INFANTS; EXTREMELY PRETERM INFANTS; ARTERIAL
   BLOOD-PRESSURE; VENA-CAVA FLOW; INTRAVENTRICULAR HEMORRHAGE;
   INTENSIVE-CARE; PREMATURE-INFANTS; HYPOTENSION; MORBIDITY;
   NEURODEVELOPMENT
AB Background We previously reported on the overall incidence, management, and outcomes in infants with cardiovascular insufficiency (CVI). However, there are limited data on the relationship of the specific different definitions of CVI to short-term outcomes in term and late preterm newborn infants.
   Objective This study aims to evaluate how four definitions of CVI relate to short-term outcomes and death.
   Study Design The previously reported study was a multicenter, prospective cohort study of 647 infants >= 34 weeks gestation admitted to a Neonatal Research Network (NRN) newborn intensive care unit (NICU) and mechanically ventilated (MV) during their first 72 hours. The relationship of five short-term outcomes at discharge and four different definitions of CVI were further analyzed.
   Results All the four definitions were associated with greater number of days on MV and days on O-2. The definition using a threshold blood pressure (BP) measurement alone was not associated with days of full feeding, days in the NICU or death. The definition based on the treatment of CVI was associated with all the outcomes including death.
   Conclusions The definition using a threshold BP alone was not consistently associated with adverse short-term outcomes. Using only a threshold BP to determine therapy may not improve outcomes.
C1 [Fernandez, Erika; Watterberg, Kristi L.; Lacy, Conra Backstrom] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
   [Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
   [Yoder, Bradley A.; Walsh, Michele C.; Osborne, Karen A.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
   [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
   [Kendrick, Douglas E.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
   [Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
   [Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
   [Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
   [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
   [Kennedy, Kathleen A.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA.
   [Schibler, Kurt] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
   [Schibler, Kurt] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
   [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
   [Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA.
   [Van Meurs, Krisa P.] Lucile Packard Childrens Hosp, Palo Alto, CA USA.
   [Frantz, Ivan D., III] Tufts Med Ctr, Floating Hosp Children, Dept Pediat, Div Newborn Med, Boston, MA USA.
   [Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
   [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
   [Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
   [Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
   [Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Fernandez, E (reprint author), Univ Calif San Diego, Dept Pediat & Neonatol, 402 Dickinson St,MPF 1-140, San Diego, CA 92103 USA.
EM erfernandez@ucsd.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (NICHD)
FX The National Institutes of Health and the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development (NICHD)
   provided grant support for the Neonatal Research Network's Term
   Hypotension Study.
NR 25
TC 0
Z9 0
U1 1
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
EI 1098-8785
J9 AM J PERINAT
JI Am. J. Perinatol.
PD SEP
PY 2015
VL 32
IS 11
BP 1024
EP 1030
DI 10.1055/s-0035-1547321
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CR5UQ
UT WOS:000361410300004
PM 25825962
ER

PT J
AU Flood, P
   McKinley, P
   Monk, C
   Muntner, P
   Colantonio, LD
   Goetzl, L
   Hatch, M
   Sloan, RP
AF Flood, Pamela
   McKinley, Paula
   Monk, Catherine
   Muntner, Paul
   Colantonio, Lisandro D.
   Goetzl, Laura
   Hatch, Maureen
   Sloan, Richard P.
TI Beat-to-Beat Heart Rate and Blood Pressure Variability and Hypertensive
   Disease in Pregnancy
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE hypertensive diseases of pregnancy; autonomic function; heart rate
   variability; blood pressure variability
ID ARTERIAL-PRESSURE; SPECTRAL-ANALYSIS; PREECLAMPSIA; REDUCTION; WOMEN;
   ATHEROSCLEROSIS; REPRODUCIBILITY; ACTIVATION; DISCHARGE; RESPONSES
AB Objective The aim of this study is to determine the relationship between heart rate and/or blood pressure variability, measured at 28 weeks' gestation, and the incidence of pregnancy-induced hypertension or preeclampsia.
   Study Design Secondary analysis of data from a prospectively enrolled cohort of 385 active military women in whom spectral analysis of continuous heart rate and variability was measured at 28 weeks' gestation. The primary outcome was the predictive value of spectral analysis of heart rate and blood pressure for hypertensive diseases of pregnancy.
   Results High-frequency heart rate variability was reduced and low-frequency variability of systolic and diastolic blood pressure increased in women who would develop pregnancy-induced hypertension but not preeclampsia. Low-frequency variability of diastolic blood pressure remained a significant predictor of pregnancy-induced hypertension but not preeclampsia after adjustment for age, weight, and blood pressure in a multivariate model.
   Conclusion Early identification of pregnancy-induced hypertension can facilitate treatment to avoid maternal morbidity. Understanding the physiological underpinnings of the two very different diseases may lead to improved treatment and prevention. If proven effective in a broader population, the ability to differentiate pregnancy-induced hypertension from preeclampsia may reduce unnecessary iatrogenic interventions or inappropriate preterm delivery.
C1 [Flood, Pamela] Stanford Univ, Dept Anesthesia Perioperat & Pain Med, San Francisco, CA USA.
   [McKinley, Paula; Sloan, Richard P.] Columbia Univ, Dept Behav Med, New York, NY USA.
   [Monk, Catherine] Columbia Univ, Dept Psychiat Behav Med & Dev Neurosci, New York, NY USA.
   [Muntner, Paul; Colantonio, Lisandro D.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
   [Goetzl, Laura] Temple Univ, Dept Obstet & Gynecol, Philadelphia, PA 19122 USA.
   [Hatch, Maureen] NCI, NIH, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
RP Flood, P (reprint author), Stanford Univ, Dept Anesthesia Perioperat & Pain Med, 300 Pasteur Dr, Palo Alto, CA 94304 USA.
EM pflood@stanford.edu
OI Colantonio, Lisandro/0000-0001-8742-1788
NR 35
TC 2
Z9 2
U1 1
U2 4
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
EI 1098-8785
J9 AM J PERINAT
JI Am. J. Perinatol.
PD SEP
PY 2015
VL 32
IS 11
BP 1050
EP 1058
DI 10.1055/s-0035-1548542
PG 9
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CR5UQ
UT WOS:000361410300008
PM 25970272
ER

PT J
AU Hueper, K
   Vogel-Claussen, J
   Parikh, MA
   Austin, JHM
   Bluemke, DA
   Carr, J
   Choi, J
   Goldstein, TA
   Gomes, AS
   Hoffman, EA
   Kawut, SM
   Lima, J
   Michos, ED
   Post, WS
   Po, MJ
   Prince, MR
   Liu, K
   Rabinowitz, D
   Skrok, J
   Smith, BM
   Watson, K
   Yin, YB
   Zambeli-Ljepovic, AM
   Barr, RG
AF Hueper, Katja
   Vogel-Claussen, Jens
   Parikh, Megha A.
   Austin, John H. M.
   Bluemke, David A.
   Carr, James
   Choi, Jiwoong
   Goldstein, Thomas A.
   Gomes, Antoinette S.
   Hoffman, Eric A.
   Kawut, Steven M.
   Lima, Joao
   Michos, Erin D.
   Post, Wendy S.
   Po, Ming Jack
   Prince, Martin R.
   Liu, Kiang
   Rabinowitz, Dan
   Skrok, Jan
   Smith, Ben M.
   Watson, Karol
   Yin, Youbing
   Zambeli-Ljepovic, Alan M.
   Barr, R. Graham
TI Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary
   Disease and Emphysema The MESA COPD Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE pulmonary microvascular blood flow (PMBF); gadolinium-enhanced MRI;
   chronic obstructive pulmonary disease (COPD); lung emphysema; small
   airway disease
ID CIRCULATING ENDOTHELIAL MICROPARTICLES; QUANTITATIVE
   COMPUTED-TOMOGRAPHY; LEFT-VENTRICULAR MASS; CIGARETTE-SMOKE;
   LUNG-FUNCTION; ATHEROSCLEROSIS MESA; REFERENCE VALUES; VOLUME ANALYSIS;
   CELL APOPTOSIS; PERFUSION
AB Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease.
   Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema.
   Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units ( -950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output.
   Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema(-950HU) and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P vi 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers.
   Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.
C1 [Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Skrok, Jan] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
   [Lima, Joao; Michos, Erin D.; Post, Wendy S.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
   [Hueper, Katja; Vogel-Claussen, Jens] Endstage & Obstruct Lung Dis Hannover BREATH, Dept Radiol & Res, Hannover, Germany.
   [Parikh, Megha A.; Smith, Ben M.; Barr, R. Graham] Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
   [Austin, John H. M.; Prince, Martin R.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY USA.
   [Barr, R. Graham] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA.
   [Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
   [Carr, James] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA.
   [Liu, Kiang] Northwestern Univ, Dept Biostat, Chicago, IL 60611 USA.
   [Choi, Jiwoong; Hoffman, Eric A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
   [Choi, Jiwoong] Univ Iowa, IIHR Hydrosci & Engn, Iowa City, IA USA.
   [Hoffman, Eric A.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
   [Hoffman, Eric A.] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA.
   [Goldstein, Thomas A.] Stanford Univ, Dept Biomed Engn, Stanford, CA 94305 USA.
   [Gomes, Antoinette S.] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA.
   [Watson, Karol] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
   [Kawut, Steven M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
   [Po, Ming Jack; Zambeli-Ljepovic, Alan M.] Columbia Univ, Dept Biomed Engn, New York, NY USA.
   [Rabinowitz, Dan] Columbia Univ, Dept Stat, New York, NY USA.
   [Yin, Youbing] VIDA Diagnost, Coralville, IA USA.
RP Barr, RG (reprint author), Columbia Univ, Med Ctr, Presbyterian Hosp East 105 9, 630 West 168th St, New York, NY 10032 USA.
EM rgb9@columbia.edu
RI Hueper, Katja/J-9566-2016; Prince, Martin/S-6850-2016; 
OI Hueper, Katja/0000-0002-3195-4400; Bluemke, David/0000-0002-8323-8086;
   Prince, Martin/0000-0002-9883-0584
FU National Institutes of Health [R01-HL093081, R01-HL077612, R01-HL075476,
   R01-HL-112986, N01-HC95159-HC95169, UL1 RR024156]
FX Supported by National Institutes of Health grants R01-HL093081,
   R01-HL077612, R01-HL075476, R01-HL-112986, N01-HC95159-HC95169, and UL1
   RR024156.
NR 69
TC 16
Z9 16
U1 1
U2 4
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD SEP 1
PY 2015
VL 192
IS 5
BP 570
EP 580
DI 10.1164/rccm.201411-2120OC
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CR4XX
UT WOS:000361344500010
PM 26067761
ER

PT J
AU Szymanski, EP
   Leung, JM
   Fowler, CJ
   Haney, C
   Hsu, AP
   Chen, F
   Duggal, P
   Oler, AJ
   McCormack, R
   Podack, E
   Drummond, RA
   Lionakis, MS
   Browne, SK
   Prevots, DR
   Knowles, M
   Cutting, G
   Liu, XY
   Devine, SE
   Fraser, CM
   Tettelin, H
   Olivier, KN
   Holland, SM
AF Szymanski, Eva P.
   Leung, Janice M.
   Fowler, Cedar J.
   Haney, Carissa
   Hsu, Amy P.
   Chen, Fei
   Duggal, Priya
   Oler, Andrew J.
   McCormack, Ryan
   Podack, Eckhard
   Drummond, Rebecca A.
   Lionakis, Michail S.
   Browne, Sarah K.
   Prevots, D. Rebecca
   Knowles, Michael
   Cutting, Gary
   Liu, Xinyue
   Devine, Scott E.
   Fraser, Claire M.
   Tettelin, Herve
   Olivier, Kenneth N.
   Holland, Steven M.
TI Pulmonary Nontuberculous Mycobacterial Infection A Multisystem,
   Multigenic Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE bronchiectasis; cilia; genetics; immune system diseases; nontuberculous
   mycobacteria
ID EHLERS-DANLOS-SYNDROME; MACROPHAGE-STIMULATING PROTEIN; INHERITED CARD9
   DEFICIENCY; COMPLEX LUNG-DISEASE; CYSTIC-FIBROSIS; AVIUM COMPLEX;
   UNRELATED PATIENTS; GENETIC-VARIANTS; SEQUENCING DATA; RISK-FACTORS
AB Rationale: The clinical features of patients infected with pulmonary nontuberculous mycobacteria (PNTM) are well described, but the genetic components of infection susceptibility are not.
   Objectives: To examine genetic variants in patients with PNTM, their unaffected family members, and a control group.
   Methods: Whole-exome sequencing was done on 69 white patients with PNTM and 18 of their white unaffected family members. We performed a candidate gene analysis using immune, cystic fibrosis transmembrance conductance regulator (CFTR), cilia, and connective tissue gene sets. The numbers of patients, family members, and control subjects with variants in each category were compared, as was the average number of variants per person.
   Measurements and Main Results: A significantly higher number of patients with PNTM than the other subjects had low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue categories (35, 26, 90, and 90%, respectively). Patients with PNTM also had significantly more cilia and connective tissue variants per person than did control subjects (2.47 and 2.55 compared with 1.38 and 1.40, respectively; P= 1.4X 10(-6) and P = 2.7 X 10(-8) respectively). Patients with PNTM had an average of 5.26 variants across all categories (1.98 in control subjects; P = 2.8 X 10(-17)), and they were more likely than control subjects to have variants in multiple categories. We observed similar results for family members without PNTM infection, with the exception of the immune category.
   Conclusions: Patients with PNTM have more low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue genes than their unaffected family members and control subjects. We propose that PNTM infection is a multigenic disease in which combinations of variants across gene categories, plus environmental exposures, increase susceptibility to the infection.
C1 [Szymanski, Eva P.; Leung, Janice M.; Fowler, Cedar J.; Haney, Carissa; Hsu, Amy P.; Drummond, Rebecca A.; Lionakis, Michail S.; Browne, Sarah K.; Prevots, D. Rebecca; Holland, Steven M.] NHLBI, Lab Clin Infect Dis, NIH, Bethesda, MD USA.
   [Oler, Andrew J.] NHLBI, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Natl Inst Allergy & Infect Dis,NIH, Bethesda, MD USA.
   [Olivier, Kenneth N.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD USA.
   [Chen, Fei; Duggal, Priya] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Cutting, Gary] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD USA.
   [McCormack, Ryan; Podack, Eckhard] Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL USA.
   [Knowles, Michael] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
   [Liu, Xinyue; Devine, Scott E.; Fraser, Claire M.; Tettelin, Herve] Univ Maryland, Inst Genome Sci, Baltimore, MD 21201 USA.
   [Devine, Scott E.; Fraser, Claire M.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
   [Tettelin, Herve] Univ Maryland, Dept Microbiol & Immunol, Sch Med, Baltimore, MD 21201 USA.
RP Holland, SM (reprint author), Natl Inst Allergy & Infect Dis, Lab Clin Infect Dis, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
OI Drummond, Rebecca/0000-0001-5424-7074
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases (NIAID); Division of Intramural Research, NHLBI,
   National Institutes of Health (NIH); NIAID, NIH, U.S. Department of
   Health and Human Services [HHSN272200900009C]; NIH [5R01 HL071798, U54
   HL096458]; RDCRN through NCATS; RDCRN through NHLBI
FX Supported by Division of Intramural Research, National Institute of
   Allergy and Infectious Diseases (NIAID), and the Division of Intramural
   Research, NHLBI, National Institutes of Health (NIH); for exome
   sequencing and analyses, supported in part with federal funds to the
   Institute for Genome Sciences (C.M.F., principal investigator) from the
   NIAID, NIH, U.S. Department of Health and Human Services, under contract
   number HHSN272200900009C; and also supported by NIH grants 5R01 HL071798
   and U54 HL096458 (M.K.). The Genetic Disorders of Mucociliary Clearance
   (U54 HL096458) is a part of the National Center for Advancing
   Translational Studies (NCATS) Rare Diseases Clinical Research Network
   (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research,
   NCATS, funded through a collaboration between NCATS and NHLBI.
NR 49
TC 16
Z9 16
U1 1
U2 4
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD SEP 1
PY 2015
VL 192
IS 5
BP 618
EP 628
DI 10.1164/rccm.201502-0387OC
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CR4XX
UT WOS:000361344500015
PM 26038974
ER

PT J
AU Rao, MR
AF Rao, Malla R.
TI Foreword: International Centers of Excellence for Malaria Research
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Editorial Material
C1 [Rao, Malla R.] NIAID, NIH, Div Microbiol & Infect Dis, Bethesda, MD 20852 USA.
RP Rao, MR (reprint author), NIAID, NIH, Div Microbiol & Infect Dis, BG 5601F1 Room 8A38,5601 Fishers Lane, Rockville, MD 20852 USA.
EM mrao@niaid.nih.gov
NR 7
TC 3
Z9 3
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD SEP
PY 2015
VL 93
IS 3
SU S
BP 1
EP 4
DI 10.4269/ajtmh.15-0407
PG 4
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA CR3TC
UT WOS:000361255000001
PM 26574613
ER

PT J
AU Conn, JE
   Norris, DE
   Donnelly, MJ
   Beebe, NW
   Burkot, TR
   Coulibaly, MB
   Chery, L
   Eapen, A
   Keven, JB
   Kilama, M
   Kumar, A
   Lindsay, SW
   Moreno, M
   Quinones, M
   Reimer, LJ
   Russell, TL
   Smith, DL
   Thomas, MB
   Walker, ED
   Wilson, ML
   Yan, GY
AF Conn, Jan E.
   Norris, Douglas E.
   Donnelly, Martin J.
   Beebe, Nigel W.
   Burkot, Thomas R.
   Coulibaly, Mamadou B.
   Chery, Laura
   Eapen, Alex
   Keven, John B.
   Kilama, Maxwell
   Kumar, Ashwani
   Lindsay, Steve W.
   Moreno, Marta
   Quinones, Martha
   Reimer, Lisa J.
   Russell, Tanya L.
   Smith, David L.
   Thomas, Matthew B.
   Walker, Edward D.
   Wilson, Mark L.
   Yan, Guiyun
TI Entomological Monitoring and Evaluation: Diverse Transmission Settings
   of ICEMR Projects Will Require Local and Regional Malaria Elimination
   Strategies
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID PAPUA-NEW-GUINEA; DOMINANT ANOPHELES VECTORS; INSECTICIDE-TREATED NETS;
   DISTRIBUTION MAPS; BIONOMIC PRECIS; SOUTHERN ZAMBIA; CONTROL
   INTERVENTIONS; DARLINGI POPULATIONS; SPECIES COMPOSITION;
   DIPTERA-CULICIDAE
AB The unprecedented global efforts for malaria elimination in the past decade have resulted in altered vectorial systems, vector behaviors, and bionomics. These changes combined with increasingly evident heterogeneities in malaria transmission require innovative vector control strategies in addition to the established practices of long-lasting insecticidal nets and indoor residual spraying. Integrated vector management will require focal and tailored vector control to achieve malaria elimination. This switch of emphasis from universal coverage to universal coverage plus additional interventions will be reliant on improved entomological monitoring and evaluation. In 2010, the National Institutes for Allergies and Infectious Diseases (NIAID) established a network of malaria research centers termed ICEMRs (International Centers for Excellence in Malaria Research) expressly to develop this evidence base in diverse malaria endemic settings. In this article, we contrast the differing ecology and transmission settings across the ICEMR study locations. In South America, Africa, and Asia, vector biologists are already dealing with many of the issues of pushing to elimination such as highly focal transmission, proportionate increase in the importance of outdoor and crepuscular biting, vector species complexity, and "sub patent" vector transmission.
C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
   SUNY Albany, Dept Biomed Sci, Sch Publ Hlth, Albany, NY 12222 USA.
   Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Johns Hopkins Malaria Res Inst, Baltimore, MD USA.
   Univ Liverpool, Liverpool Sch Trop Med, Dept Vector Biol, Liverpool L3 5QA, Merseyside, England.
   Wellcome Trust Sanger Inst, Malaria Programme, Cambridge, England.
   Univ Queensland, Brisbane, Qld, Australia.
   CSIRO, Brisbane, Qld, Australia.
   James Cook Univ, Cairns, Australia.
   Univ Sci Tech & Technol Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali.
   Univ Washington, Dept Chem, Seattle, WA 98195 USA.
   Natl Inst Epidemiol Campus Chennai, Natl Inst Malaria Res, Madras, Tamil Nadu, India.
   Papua New Guinea Inst Med Res, Madang, Papua N Guinea.
   Infect Dis Res Collaborat, Kampala, Uganda.
   Natl Inst Malaria Res, Field Unit Goa, Panaji, Goa, India.
   Univ Durham, Sch Biol & Biomed Sci, Durham, England.
   Univ Calif, Div Infect Dis, San Diego Sch Med, La Jolla, CA USA.
   Univ Calif, George Palade Labs, San Diego Sch Med, La Jolla, CA USA.
   Univ Nacl Colombia, Dept Publ Hlth, Fac Med, Bogota, Colombia.
   Papua New Guinea Inst Med Res, Goroka, Papua N Guinea.
   Univ Queensland, Pacific Malaria Initiat Support Ctr, Sch Populat Hlth, Herston, Qld, Australia.
   Univ Queensland, Australian Ctr Trop & Int Hlth, Herston, Qld, Australia.
   James Cook Univ, Queensland Trop Hlth Alliance, Fac Med Hlth & Mol Sci, Cairns, Australia.
   Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
   Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
   Univ Oxford, Spatial Ecol & Epidemiol Grp, Dept Zool, Oxford, England.
   NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
   Michigan State Univ, Dept Entomol, E Lansing, MI 48824 USA.
   Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   Univ Calif Irvine, Program Publ Hlth, Coll Hlth Sci, Irvine, CA USA.
RP Conn, JE (reprint author), New York State Dept Hlth, Griffin Lab, Wadsworth Ctr, 5668 State Farm Rd, Slingerlands, NY 12159 USA.
EM jan.conn@health.ny.gov
RI Beebe, Nigel/C-5610-2008; 
OI Reimer, Lisa/0000-0002-9711-4981
FU National Institute of Allergy and Infectious Diseases
FX This study was supported by grants from the National Institute of
   Allergy and Infectious Diseases to each of the ICEMR sites whose
   research is represented in this report.
NR 94
TC 12
Z9 12
U1 1
U2 9
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD SEP
PY 2015
VL 93
IS 3
SU S
BP 28
EP 41
DI 10.4269/ajtmh.15-0009
PG 14
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA CR3TC
UT WOS:000361255000004
PM 26259942
ER

EF