FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Nani, RR
Shaum, JB
Gorka, AP
Schnermann, MJ
AF Nani, Roger R.
Shaum, James B.
Gorka, Alexander P.
Schnermann, Martin J.
TI Electrophile-Integrating Smiles Rearrangement Provides Previously
Inaccessible C4 '-O-Alkyl Heptamethine Cyanine Fluorophores
SO ORGANIC LETTERS
LA English
DT Article
ID DYES; FLUORESCENCE; CHROMOPHORE; PARADIGM; PROBES; AGENTS
AB New synthetic methods to rapidly access useful fluorophores are needed to advance modern molecular imaging techniques. A new variant of the classical Smiles rearrangement is reported that enables the efficient synthesis of previously inaccessible C4'-O-alkyl heptamethine cyanines. The key reaction involves N- to O- transposition with selective electrophile incorporation on nitrogen. A representative fluorophore exhibits excellent resistance to thiol nucleophiles, undergoes productive bioconjugation, and can be used in near-IR fluorescence imaging applications.
C1 [Nani, Roger R.; Shaum, James B.; Gorka, Alexander P.; Schnermann, Martin J.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
RP Schnermann, MJ (reprint author), NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
EM martin.schnermann@nih.gov
FU National Institutes of Health, Center for Cancer Research; National
Cancer Institute, National Institutes of Health
FX We thank Dr. Joseph Barchi (NIH/NCI) for NMR assistance and Dr. James
Kelley (NTH/NCI) for mass spectrometric analysis. Dr. Sibaprasad
Bhattacharyya (Leidos) is gratefully acknowledged for advice regarding
the antibody conjugation reactions. We also acknowledge the Frederick
CCR Flow Cytometry Core (Cancer and Inflammation Program, NCI,
Frederick) for flow cytometry analysis. This work was supported by the
Intramural Research Program of the National Institutes of Health, Center
for Cancer Research, and the National Cancer Institute, National
Institutes of Health.
NR 29
TC 7
Z9 7
U1 4
U2 23
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1523-7060
EI 1523-7052
J9 ORG LETT
JI Org. Lett.
PD JAN 16
PY 2015
VL 17
IS 2
BP 302
EP 305
DI 10.1021/ol503398f
PG 4
WC Chemistry, Organic
SC Chemistry
GA AZ6LR
UT WOS:000348331800034
PM 25562683
ER
PT J
AU Hristovski, D
Dinevski, D
Kastrin, A
Rindflesch, TC
AF Hristovski, Dimitar
Dinevski, Dejan
Kastrin, Andrej
Rindflesch, Thomas C.
TI Biomedical question answering using semantic relations
SO BMC BIOINFORMATICS
LA English
DT Article
ID CLINICAL QUESTIONS; MICROARRAY DATA; TEXT; INFORMATION; KNOWLEDGE;
DOCTORS; DISEASE; NEED
AB Background: The proliferation of the scientific literature in the field of biomedicine makes it difficult to keep abreast of current knowledge, even for domain experts. While general Web search engines and specialized information retrieval (IR) systems have made important strides in recent decades, the problem of accurate knowledge extraction from the biomedical literature is far from solved. Classical IR systems usually return a list of documents that have to be read by the user to extract relevant information. This tedious and time-consuming work can be lessened with automatic Question Answering (QA) systems, which aim to provide users with direct and precise answers to their questions. In this work we propose a novel methodology for QA based on semantic relations extracted from the biomedical literature.
Results: We extracted semantic relations with the SemRep natural language processing system from 122,421,765 sentences, which came from 21,014,382 MEDLINE citations (i.e., the complete MEDLINE distribution up to the end of 2012). A total of 58,879,300 semantic relation instances were extracted and organized in a relational database. The QA process is implemented as a search in this database, which is accessed through a Web-based application, called SemBT (available at http://sembt.mf.uni-lj.si). We conducted an extensive evaluation of the proposed methodology in order to estimate the accuracy of extracting a particular semantic relation from a particular sentence. Evaluation was performed by 80 domain experts. In total 7,510 semantic relation instances belonging to 2,675 distinct relations were evaluated 12,083 times. The instances were evaluated as correct 8,228 times (68%).
Conclusions: In this work we propose an innovative methodology for biomedical QA. The system is implemented as a Web-based application that is able to provide precise answers to a wide range of questions. A typical question is answered within a few seconds. The tool has some extensions that make it especially useful for interpretation of DNA microarray results.
C1 [Hristovski, Dimitar] Univ Ljubljana, Fac Med, Inst Biostat & Med Informat, SI-1104 Ljubljana, Slovenia.
[Kastrin, Andrej] Univ Maribor, Fac Med, SI-2000 Maribor, Slovenia.
[Kastrin, Andrej] Fac Informat Studies, Novo Mesto, Slovenia.
[Rindflesch, Thomas C.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
RP Hristovski, D (reprint author), Univ Ljubljana, Fac Med, Inst Biostat & Med Informat, Vrazov Trg 2, SI-1104 Ljubljana, Slovenia.
EM dimitar.hristovski@mf.uni-lj.si
OI Hristovski, Dimitar/0000-0001-6908-0246
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Library of Medicine.
NR 32
TC 5
Z9 5
U1 2
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JAN 16
PY 2015
VL 16
AR 6
DI 10.1186/s12859-014-0365-3
PG 14
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA AZ8PM
UT WOS:000348477400001
PM 25592675
ER
PT J
AU van Beers, EJ
Yang, YQ
Raghavachari, N
Tian, X
Allen, DT
Nichols, JS
Mendelsohn, L
Nekhai, S
Gordeuk, VR
Taylor, JG
Kato, GJ
AF van Beers, Eduard J.
Yang, Yanqin
Raghavachari, Nalini
Tian, Xin
Allen, Darlene T.
Nichols, James S.
Mendelsohn, Laurel
Nekhai, Sergei
Gordeuk, Victor R.
Taylor, James G.
Kato, Gregory J.
TI Iron, Inflammation, and Early Death in Adults With Sickle Cell Disease
SO CIRCULATION RESEARCH
LA English
DT Article
DE gene expression; inflammation; iron; mortality; sickle cell disease
ID PULMONARY-HYPERTENSION; HEMOLYTIC DISEASES; RISK-FACTORS; HEME;
ACTIVATION; MORTALITY; HEMOCHROMATOSIS; MACROPHAGES; RECOGNITION;
METABOLISM
AB Rationale: Patients with sickle cell disease (SCD) have markers of chronic inflammation, but the mechanism of inflammation and its relevance to patient survival are unknown.
Objective: To assess the relationship between iron, inflammation, and early death in SCD.
Methods and Results: Using peripheral blood mononuclear cell transcriptome profile hierarchical clustering, we classified 24 patients and 10 controls in clusters with significantly different expression of genes known to be regulated by iron. Subsequent gene set enrichment analysis showed that many genes associated with the high iron cluster were involved in the toll-like receptor system (TLR4, TLR7, and TLR8) and inflammasome complex pathway (NLRP3, NLRC4, and CASP1). Quantitative PCR confirmed this classification and showed that ferritin light chain, TLR4, and interleukin-6 expression were >100-fold higher in patients than in controls (P<0.001). Further linking intracellular iron and inflammation, 14 SCD patients with a ferroportin Q248H variant that causes intracellular iron accumulation had significantly higher levels of interleukin-6 and C-reactive protein compared with 14 matched SCD patients with the wild-type allele (P<0.05). Finally, in a cohort of 412 patients followed for a median period of 47 months (interquartile range, 24-82), C-reactive protein was strongly and independently associated with early death (hazard ratio, 3.0; 95% confidence interval, 1.7-5.2; P<0.001).
Conclusions: Gene expression markers of high intracellular iron in patients with SCD are associated with markers of inflammation and mortality. The results support a model in which intracellular iron promotes inflammatory pathways, such as the TLR system and the inflammasome, identifying important new pathways for additional investigation.
C1 [van Beers, Eduard J.; Allen, Darlene T.; Nichols, James S.; Mendelsohn, Laurel; Taylor, James G.; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Yang, Yanqin; Raghavachari, Nalini] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Nekhai, Sergei] Howard Univ, Dept Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
[Gordeuk, Victor R.] Univ Illinois, Ctr Comprehens Sickle Cell, Dept Med, Sect Hematol Oncol, Chicago, IL USA.
[Kato, Gregory J.] Univ Pittsburgh, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15260 USA.
[Kato, Gregory J.] Univ Pittsburgh, Heart Lung Blood & Vasc Med Inst, Pittsburgh, PA 15260 USA.
RP Kato, GJ (reprint author), 200 Lothrop St,BST E1240, Pittsburgh, PA 15261 USA.
EM katogj@upmc.edu
RI Kato, Gregory/I-7615-2014;
OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809
FU National Heart, Lung and Blood Institute Division of Intramural Research
[1ZIAHL006012-02, 1 ZIA HL006013-03, 1 ZIA HL006023-03]; Novartis
FX This research was funded by the National Heart, Lung and Blood Institute
Division of Intramural Research (1ZIAHL006012-02, 1 ZIA HL006013-03, and
1 ZIA HL006023-03). E.J. van Beers received financial research support
from Novartis to the University of Amsterdam. The funding organizations
had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation,
review, or approval of the article; and decision to submit the article
for publication.
NR 53
TC 9
Z9 9
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JAN 16
PY 2015
VL 116
IS 2
BP 298
EP U255
DI 10.1161/CIRCRESAHA.116.304577
PG 19
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AZ0MI
UT WOS:000347939000015
PM 25378535
ER
PT J
AU Penaloza-MacMaster, P
Barber, DL
Wherry, EJ
Provine, NM
Teigler, JE
Parenteau, L
Blackmore, S
Borducchi, EN
Larocca, RA
Yates, KB
Shen, H
Haining, WN
Sommerstein, R
Pinschewer, DD
Ahmed, R
Barouch, DH
AF Penaloza-MacMaster, Pablo
Barber, Daniel L.
Wherry, E. John
Provine, Nicholas M.
Teigler, Jeffrey E.
Parenteau, Lily
Blackmore, Stephen
Borducchi, Erica N.
Larocca, Rafael A.
Yates, Kathleen B.
Shen, Hao
Haining, W. Nicholas
Sommerstein, Rami
Pinschewer, Daniel D.
Ahmed, Rafi
Barouch, Dan H.
TI Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV
infection
SO SCIENCE
LA English
DT Article
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; CHRONIC VIRAL-INFECTION; CD8-T-CELL
MEMORY; CD4-T-CELL HELP; CD8(+); RESPONSES; PERSISTENCE; EPITOPE;
IDENTIFICATION; ACTIVATION
AB CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology.
C1 [Penaloza-MacMaster, Pablo; Provine, Nicholas M.; Teigler, Jeffrey E.; Parenteau, Lily; Blackmore, Stephen; Borducchi, Erica N.; Larocca, Rafael A.; Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Barber, Daniel L.] NIAID, Lab Parasit Dis, Bethesda, MD 20892 USA.
[Wherry, E. John; Shen, Hao] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Wherry, E. John; Shen, Hao] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Yates, Kathleen B.; Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Sommerstein, Rami; Pinschewer, Daniel D.] Univ Geneva, WHO Collaborating Ctr Vaccine Immunol, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland.
[Pinschewer, Daniel D.] Univ Basel, Div Expt Virol, Dept Biomed Haus Peterspl, CH-4009 Basel, Switzerland.
[Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
RP Barouch, DH (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
EM dbarouch@bidmc.harvard.edu
OI Sommerstein, Rami/0000-0003-1011-6878
FU NIH [AI007245, AI07387, AI078526, AI096040, AI030048]; Bill and Melinda
Gates Foundation [OPP1033091]; Swiss National Science Foundation
[310030_149340/1]; European Research Council; Ragon Institute; NIAID
Intramural Research Program
FX We thank A. Wieland, M. Rasheed, A. Kamphorst, K. Araki, S. Crotty, B.
Walker, C. Bricault, P. Abbink, and F. Ball for generous advice,
assistance, and reagents. The data presented in this manuscript are
tabulated in the main paper and the supplementary materials. Supported
by NIH grants AI007245 and AI07387 (P.P.M.), AI078526 and AI096040
(D.H.B.), and AI030048 (R.A.); Bill and Melinda Gates Foundation grant
OPP1033091 (D.H.B.); Swiss National Science Foundation grant
310030_149340/1 (D.D.P.); the European Research Council (D.D.P.) the
Ragon Institute (D.H.B.); and the NIAID Intramural Research Program
(D.L.B.). Gene expression data have been uploaded to GEO (accession no.
GSE63825). The authors declare no financial conflicts of interest.
NR 29
TC 13
Z9 13
U1 0
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JAN 16
PY 2015
VL 347
IS 6219
BP 278
EP 283
DI 10.1126/science.aaa2148
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ0DA
UT WOS:000347915300037
PM 25593185
ER
PT J
AU Natarajan, P
Punta, M
Kumar, A
Yeh, AP
Godzik, A
Aravind, L
AF Natarajan, Padmaja
Punta, Marco
Kumar, Abhinav
Yeh, Andrew P.
Godzik, Adam
Aravind, L.
TI Structure and sequence analyses of Bacteroides proteins BVU_4064 and
BF1687 reveal presence of two novel predominantly-beta domains,
predicted to be involved in lipid and cell surface interactions
SO BMC BIOINFORMATICS
LA English
DT Article
DE DUF3869; DUF3870; Domain of unknown function; Protein structure;
Beta-sandwich; Membrane-associated protein; Transthyretin superfamily;
Bacterial pore-forming toxins
ID HUMAN MICROBIOME; SIGNAL PEPTIDES; GUT MICROBIOME; DIVERSITY; SERVER;
PORE; AEROLYSIN; SOFTWARE; BACTERIA; DISEASE
AB Background: N-terminal domains of BVU_4064 and BF1687 proteins from Bacteroides vulgatus and Bacteroides fragilis respectively are members of the Pfam family PF12985 (DUF3869). Proteins containing a domain from this family can be found in most Bacteroides species and, in large numbers, in all human gut microbiome samples. Both BVU_4064 and BF1687 proteins have a consensus lipobox motif implying they are anchored to the membrane, but their functions are otherwise unknown. The C-terminal half of BVU_4064 is assigned to protein family PF12986 (DUF3870); the equivalent part of BF1687 was unclassified.
Results: Crystal structures of both BVU_4064 and BF1687 proteins, solved at the JCSG center, show strikingly similar three-dimensional structures. The main difference between the two is that the two domains in the BVU_4064 protein are connected by a short linker, as opposed to a longer insertion made of 4 helices placed linearly along with a strand that is added to the C-terminal domain in the BF1687 protein. The N-terminal domain in both proteins, corresponding to the PF12985 (DUF3869) domain is a beta-sandwich with pre-albumin-like fold, found in many proteins belonging to the Transthyretin clan of Pfam. The structures of C-terminal domains of both proteins, corresponding to the PF12986 (DUF3870) domain in BVU_4064 protein and an unclassified domain in the BF1687 protein, show significant structural similarity to bacterial pore-forming toxins. A helix in this domain is in an analogous position to a loop connecting the second and third strands in the toxin structures, where this loop is implicated to play a role in the toxin insertion into the host cell membrane. The same helix also points to the groove between the N- and C-terminal domains that are loosely held together by hydrophobic and hydrogen bond interactions. The presence of several conserved residues in this region together with these structural determinants could make it a functionally important region in these proteins.
Conclusions: Structural analysis of BVU_4064 and BF1687 points to possible roles in mediating multiple interactions on the cell-surface/extracellular matrix. In particular the N-terminal domain could be involved in adhesive interactions, the C-terminal domain and the inter-domain groove in lipid or carbohydrate interactions.
C1 [Natarajan, Padmaja; Kumar, Abhinav; Yeh, Andrew P.; Godzik, Adam] Joint Ctr Struct Gen, San Diego, CA USA.
[Natarajan, Padmaja; Godzik, Adam] Sanford Burnham Med Res Inst, Program Bioinformat & Syst Biol, La Jolla, CA USA.
[Punta, Marco] Wellcome Trust Genome Campus, European Mol Biol Lab, European Bioinformat Inst, Hinxton CB10 1SD, Cambs, England.
[Kumar, Abhinav; Yeh, Andrew P.] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA.
[Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 38A, Bethesda, MD 20894 USA.
RP Natarajan, P (reprint author), Joint Ctr Struct Gen, San Diego, CA USA.; Natarajan, P (reprint author), Sanford Burnham Med Res Inst, Program Bioinformat & Syst Biol, La Jolla, CA USA.; Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 38A, Bethesda, MD 20894 USA.
EM pnatarajan@sanfordburnham.org; aravind@ncbi.nlm.nih.gov
OI Godzik, Adam/0000-0002-2425-852X
FU Wellcome Trust [WT077044/Z/05/Z]; Howard Hughes Medical Institute; NIH
[U54 GM094586]; National Science Foundation [IIS-0646708, IIS-1153617];
U.S. Department of Energy, Office of Basic Energy Sciences
[DE-AC02-76SF00515]; DOE Office of Biological and Environmental
Research; National Institutes of Health, National Institute of General
Medical Sciences [P41GM103393]
FX Wellcome Trust (grant numbers WT077044/Z/05/Z); Howard Hughes Medical
Institute (R.D.F.); NIH U54 GM094586; National Science Foundation
(IIS-0646708 and IIS-1153617). Funding for open access charge: Wellcome
Trust (grant numbers WT077044/Z/05/Z). Use of the Stanford Synchrotron
Radiation Lightsource, SLAC National Accelerator Laboratory, is
supported by the U.S. Department of Energy, Office of Basic Energy
Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural
Molecular Biology Program is supported by the DOE Office of Biological
and Environmental Research, and by the National Institutes of Health,
National Institute of General Medical Sciences (including P41GM103393).
The contents of this publication are solely the responsibility of the
authors and do not necessarily represent the official views of DOE, NSF,
NIGMS, NCRR or NIH.
NR 52
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 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JAN 16
PY 2015
VL 16
AR 7
DI 10.1186/s12859-014-0434-7
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DD0KF
UT WOS:000369608200001
PM 25592227
ER
PT J
AU Ouyang, M
Su, WJ
Xiao, L
Rao, JN
Jiang, LP
Li, YW
Turner, DJ
Gorospe, M
Wang, JY
AF Ouyang, Miao
Su, Weijie
Xiao, Lan
Rao, Jaladanki N.
Jiang, Liping
Li, Yanwu
Turner, Douglas J.
Gorospe, Myriam
Wang, Jian-Ying
TI Modulation by miR-29b of intestinal epithelium homoeostasis through the
repression of menin translation
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE intestinal epithelial cell; intestinal epithelium homoeostasis; menin;
microRNA; post-transcriptional regulation
ID BINDING PROTEIN HUR; MESSENGER-RNA STABILITY; TUMOR-SUPPRESSOR MENIN;
C-MYC EXPRESSION; POLYAMINE DEPLETION; GENE-EXPRESSION;
COMPETITIVE-BINDING; CELL-PROLIFERATION; TRANSCRIPTION; APOPTOSIS
AB Menin regulates distinct cellular functions by regulating gene transcription through its interaction with partner transcription factors, but the exact mechanisms that controlmenin levels remain largely unknown. In the present study we report that Men1 mRNA, encoding menin, is a novel target of miR-29b and that miR-29b/Men1 mRNA association regulates menin expression post-transcriptionally in rat intestinal epithelial cells (IECs). Overexpression of a miR-29b precursor lowered the levels of Men1 mRNA modestly, but reduced new synthesis of menin robustly; conversely, antagonism of miR-29b enhanced menin protein synthesis and steady-state levels. The repressive effect of miR-29b on menin expression was mediated through a single binding site in the coding region of Men1 mRNA, because point mutation of this site prevented miR-29b-induced repression of menin translation. Increasing cellular polyamines due to overexpression of ornithine decarboxylase (ODC) enhanced menin translation by reducing miR-29b, whereas polyamine depletion by inhibiting ODC increased it, thus suppressing menin expression. Moreover, an increase in menin abundance in an miR-29b-silenced population of IECs led to increased sensitivity to apoptosis, which was prevented by silencing menin. These findings indicate that miR-29b represses translation of Men1 mRNA, in turn affecting intestinal epithelial homoeostasis by altering IEC apoptosis.
C1 [Ouyang, Miao; Su, Weijie; Xiao, Lan; Rao, Jaladanki N.; Jiang, Liping; Li, Yanwu; Turner, Douglas J.; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
[Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Ouyang, Miao; Su, Weijie; Xiao, Lan; Rao, Jaladanki N.; Jiang, Liping; Li, Yanwu; Turner, Douglas J.; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Gorospe, Myriam] Natl Inst Aging IRP, Genet Lab, NIH, Baltimore, MD USA.
RP Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
EM jwang@smail.umaryland.edu
FU US Department of Veterans Affairs; National Institutes of Health
[DK57819, DK61972, DK68491]; National Institute on Aging - Intramural
Research Program, National Institutes of Health
FX This work was supported by Merit Review Awards (to J.-Y.W., J.N.R. and
D.J.T.) from the US Department of Veterans Affairs and by grants from
National Institutes of Health (DK57819, DK61972 and DK68491 to J.-Y.W.).
M.G. is supported by the National Institute on Aging - Intramural
Research Program, National Institutes of Health. J-Y.W. is a Senior
Research Career Scientist, Biomedical Laboratory Research and
Development Service, US Department of Veterans Affairs.
NR 58
TC 5
Z9 5
U1 0
U2 2
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD JAN 15
PY 2015
VL 465
BP 315
EP 323
DI 10.1042/BJ20141028
PN 2
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CE2XR
UT WOS:000351685700012
PM 25317587
ER
PT J
AU Schick, UM
Auer, PL
Bis, JC
Lin, HH
Wei, P
Pankrate, N
Lange, LA
Brody, J
Stitziel, NO
Kim, D
Carlson, CS
Fornage, M
Haessler, J
Hsu, L
Jackson, RD
Kooperberg, C
Leal, SM
Psaty, BM
Boerwinkle, E
Tracy, R
Ardissino, D
Shah, S
Willer, C
Loos, R
Melander, O
Mcpherson, R
Hovingh, K
Reilly, M
Watkins, H
Girelli, D
Fontanillas, P
Chasman, DI
Gabriel, SB
Gibbs, R
Nickerson, DA
Kathiresan, S
Peters, U
Dupuis, J
Wilson, JG
Rich, SS
Morrison, AC
Benjamin, EJ
Gross, MD
Reiner, AP
AF Schick, Ursula M.
Auer, Paul L.
Bis, Joshua C.
Lin, Honghuang
Wei, Peng
Pankrate, Nathan
Lange, Leslie A.
Brody, Jennifer
Stitziel, Nathan O.
S. Kim, Daniel
Carlson, Christopher S.
Fornage, Myriam
Haessler, Jeffery
Hsu, Li
Jackson, Rebecca D.
Kooperberg, Charles
Leal, Suzanne M.
Psaty, Bruce M.
Boerwinkle, Eric
Tracy, Russell
Ardissino, Diego
Shah, Svati
Willer, Cristen
Loos, Ruth
Melander, Olle
Mcpherson, Ruth
Hovingh, Kees
Reilly, Muredach
Watkins, Hugh
Girelli, Domenico
Fontanillas, Pierre
Chasman, Daniel I.
Gabriel, Stacey B.
Gibbs, Richard
Nickerson, Deborah A.
Kathiresan, Sekar
Peters, Ulrike
Dupuis, Josee
Wilson, James G.
Rich, Stephen S.
Morrison, Alanna C.
Benjamin, Emelia J.
Gross, Myron D.
Reiner, Alex P.
CA Cohorts Heart Aging Res Genomic Ep
Natl Heart Lung Blood Inst GO Exom
TI Association of exome sequences with plasma C-reactive protein levels in
> 9000 participants
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CORONARY-HEART-DISEASE; GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS;
GENETIC-VARIATION; MENDELIAN RANDOMIZATION; CARDIOVASCULAR-DISEASE;
LDL-CHOLESTEROL; CRP LEVELS; METABOLIC-SYNDROME; AFRICAN-AMERICANS
AB C-reactive protein (CRP) concentration is a heritable systemic marker of inflammation that is associated with cardiovascular disease risk. Genome-wide association studies have identified CRP-associated common variants associated in 25 genes. Our aims were to apply exome sequencing to (1) assess whether the candidate loci contain rare coding variants associated with CRP levels and (2) perform an exome-wide search for rare variants in novel genes associated with CRP levels. We exome-sequenced 6050 European-Americans (EAs) and 3109 African-Americans (AAs) from the NHLBI-ESP and the CHARGE consortia, and performed association tests of sequence data with measured CRP levels. In single-variant tests across candidate loci, a novel rare (minor allele frequency = 0.16%) CRP-coding variant (rs77832441-A; p.Thr59Met) was associated with 53% lower mean CRP levels (P = 2.9 x 10(-6)). We replicated the association of rs77832441 in an exome array analysis of 11 414 EAs (P = 3.0 x 10(-15)). Despite a strong effect on CRP levels, rs77832441 was not associated with inflammation-related phenotypes including coronary heart disease. We also found evidence for an AA-specific association of APOE-epsilon 2 rs7214 with higher CRP levels. At the exome-wide significance level (P<5.0 x 10(-8)), we confirmed associations for reported common variants of HNF1A, CRP, IL6R and TOMM40-APOE. In gene-based tests, a burden of rare/lower frequency variation in CRP in EAs (P <= 6.8 x 10(-4)) and in retinoic acid receptor-related orphan receptor alpha (RORA) in AAs (P = 1.7 x 10(-3)) were associated with CRP levels at the candidate gene level (P < 2.0 x 10(-3)). This inquiry did not elucidate novel genes, but instead demonstrated that variants distributed across the allele frequency spectrum within candidate genes contribute to CRP levels.
C1 [Schick, Ursula M.; Auer, Paul L.; Carlson, Christopher S.; Haessler, Jeffery; Hsu, Li; Kooperberg, Charles; Peters, Ulrike; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Auer, Paul L.] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53201 USA.
[Bis, Joshua C.; Brody, Jennifer] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Lin, Honghuang; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Wei, Peng; Fornage, Myriam; Boerwinkle, Eric; Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, Houston, TX 77030 USA.
[Pankrate, Nathan; Gross, Myron D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Lange, Leslie A.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO 63110 USA.
[S. Kim, Daniel; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98105 USA.
[Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98105 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98105 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98105 USA.
[Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, Houston, TX 77030 USA.
[Boerwinkle, Eric; Gibbs, Richard] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Tracy, Russell] Univ Vermont, Dept Biochem, Burlington, VT 05401 USA.
[Tracy, Russell] Univ Vermont, Dept Pathol, Burlington, VT 05401 USA.
[Ardissino, Diego] Azienda Osped Univ Parma, Div Cardiol, Parma, Italy.
[Shah, Svati] Duke Univ, Dept Med, Div Cardiol, Durham, NC USA.
[Shah, Svati] Duke Univ, Ctr Human Genet, Durham, NC USA.
[Willer, Cristen] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Willer, Cristen] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Willer, Cristen] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Loos, Ruth] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Loos, Ruth] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
[Mcpherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON, Canada.
[Hovingh, Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Hovingh, Kees] Univ Amsterdam, Acad Med Ctr, Dept Expt Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Reilly, Muredach] Univ Penn, Perleman Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Reilly, Muredach] Univ Penn, Perleman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Cardiovasc Med, Oxford, England.
[Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Girelli, Domenico] Univ Verona, Sch Med, Dept Med, I-37100 Verona, Italy.
[Fontanillas, Pierre; Gabriel, Stacey B.; Kathiresan, Sekar] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Chasman, Daniel I.] Brigham & Womens Hosp, Div Preventat Med, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Dupuis, Josee; Benjamin, Emelia J.] Boston Univ, NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
RP Reiner, AP (reprint author), 1100 Fairview Ave N M3-A410, Seattle, WA 98109 USA.
EM apreiner@u.washington.edu
OI Lin, Honghuang/0000-0003-3043-3942; Stitziel,
Nathan/0000-0002-4963-8211; Benjamin, Emelia/0000-0003-4076-2336;
Watkins, Hugh/0000-0002-5287-9016
FU NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2
HL-102926]; NIH [5RC2HL 102419, U01DK085526]; National Heart, Lung, and
Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268
201100007C, HHSN268201100008C, HHSN268201100009C, HHSN2682011000010C,
HHSN2682011000011C, HHSN 2682011000012C]; Boston University
[N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; National Institutes on
Aging (NIA) [AG023629]; National Cancer Institute [R25CA094880];
National Heart, Lung, and Blood Institute (NHLBI). [HHSN268201200036C,
HHSN268 200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756,
R01HL071862]; [R01HL087641]; [R01HL59367]; [R01HL 086694]
FX The authors wish to acknowledge the support of the National Heart, Lung,
and Blood Institute (NHLBI) and the contributions of the research
institutions, study investigators, field staff and study participants in
creating this resource for biomedical research. Funding for GO ESP was
provided by NHLBI grants RC2 HL-103010 (HeartGO), RC2 HL-102923 (LungGO)
and RC2 HL-102924 (WHISP). The exome sequencing was performed through
NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO).
Funding support for 'Building on GWAS for NHLBI-diseases: the US CHARGE
consortium' was provided by the NIH through the American Recovery and
Reinvestment Act of 2009 (ARRA) (5RC2HL 102419). Data for 'Building on
GWAS for NHLBI-diseases: the US CHARGE consortium' were provided by Eric
Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC)
Study, L. Adrienne Cupples, principal investigator for the Framingham
Heart Study, and Bruce Psaty, principal investigator for the
Cardiovascular Health Study. Sequencing was carried out at the Baylor
Genome Center (U54 HG003273). The ARIC Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268 201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN2682011000010C, HHSN2682011000011C and HHSN 2682011000012C),
R01HL087641, R01HL59367 and R01HL 086694. The authors thank the staff
and participants of the ARIC study for their important contributions.
The Framingham Heart Study is conducted and supported by the NHLBI in
collaboration with Boston University (Contract No. N01-HC-25195), and
its contract with Affymetrix, Inc., for genome-wide genotyping services
(contract no. N02-HL-6-4278), for quality control by Framingham Heart
Study investigators using genotypes in the SNP Health Association
Resource (SHARe) project. A portion of this research was conducted using
the Linux Cluster for Genetic Analysis (LinGA) computing resources at
Boston University Medical Campus. This CHS research was supported by
contracts HHSN268201200036C, HHSN268 200800007C, N01 HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086
and grants HL080295, HL087652, HL105756 from the National Heart, Lung,
and Blood Institute (NHLBI) with additional contribution from National
Institute of Neurological Disorders and Stroke (NINDS). Additional
support was provided through AG023629 from the National Institutes on
Aging (NIA). A full list of CHS principal investigators and institutions
can be found at CHS-NHLBI.org. Supported in part by grant R25CA094880
from the National Cancer Institute and by R01HL071862 from NHLBI. The
Type 2 Diabetes Genetic Exploration by Next-generation sequencing in
multi-Ethnic Samples (T2D-GENES) project was supported by NIH grant
U01DK085526.
NR 87
TC 9
Z9 9
U1 1
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 JAN 15
PY 2015
VL 24
IS 2
BP 559
EP 571
DI 10.1093/hmg/ddu450
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CC1WV
UT WOS:000350137000021
PM 25187575
ER
PT J
AU Li, J
Lange, LA
Duan, Q
Lu, YR
Singleton, AB
Zonderman, AB
Evans, MK
Li, Y
Taylor, HA
Willis, MS
Nalls, M
Wilson, JG
Lange, EM
AF Li, Jin
Lange, Leslie A.
Duan, Qing
Lu, Yurong
Singleton, Andrew B.
Zonderman, Alan B.
Evans, Michele K.
Li, Yun
Taylor, Herman A.
Willis, Monte S.
Nalls, Mike
Wilson, James G.
Lange, Ethan M.
TI Genome-wide admixture and association study of serum iron, ferritin,
transferrin saturation and total iron binding capacity in African
Americans
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CATARACT; POPULATION; HEMOGLOBIN; DEFICIENCY; VARIANTS; MUTATION;
TMPRSS6; FAMILY; STORES; DOMAIN
AB Iron is an essential component of many important proteins and enzymes, including hemoglobin, which is responsible for carrying oxygen to the cells. African Americans (AAs) have a greater prevalence of iron deficiency compared with European Americans. We conducted genome-wide admixture-mapping and association studies for serum iron, serum ferritin, transferrin saturation (SAT) and total iron binding capacity (TIBC) in 2347 AAs participating in the Jackson Heart Study (JHS). Follow-up replication analyses for JHS iron-trait associated SNPs were conducted in 329 AA participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS). Higher estimated proportions of global African ancestry were significantly associated with lower levels of iron (P = 2.4 x 10(-5)), SAT (P = 0.0019) and TIBC (P = 0.042). We observed significant associations (P < 5 x 10(-8)) between serum TIBC levels and two independent SNPs around TFon chromosome 3, the first report of a genome-wide significant second independent signal in this region, and SNPs near two novel genes: HDGFL1 on chromosome 6 and MAF on chromosome 16. We also observed significant associations between ferritin levels and SNPs near GAB3 on chromosome X. We replicated our two independent associations at TFand our association at GAB3 in HANDLS. Our study provides evidence for both shared and unique genetic risk factors that are associated with iron-related measures in AAs. The top two variants in TFexplain 11.2% of the total variation in TIBC levels in AAs after accounting forage, gender, body mass index and background ancestry.
C1 [Li, Jin; Lange, Leslie A.; Duan, Qing; Lu, Yurong; Li, Yun; Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Li, Yun; Lange, Ethan M.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Willis, Monte S.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Singleton, Andrew B.; Nalls, Mike] NIA, Lab Neurogenet, NIH, Bethesda, MD 21225 USA.
[Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Bethesda, MD 21225 USA.
[Evans, Michele K.] NIA, Hlth Dispar Unit, NIH, Bethesda, MD 21225 USA.
[Taylor, Herman A.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Taylor, Herman A.] Jackson State Univ, Sch Hlth Sci, Jackson, MS 39217 USA.
[Taylor, Herman A.] Tougaloo Coll, Div Nat Sci, Tougaloo, MS 39174 USA.
RP Lange, EM (reprint author), Univ N Carolina, Dept Genet, 5111 Genet Med Bldg, Chapel Hill, NC 27599 USA.
EM elange@med.unc.edu
RI Singleton, Andrew/C-3010-2009;
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Heart, Lung, and Blood Institute; National Institute on
Minority Health and Health Disparities; National Institute on Biomedical
Imaging and Bioengineering [HHSN268201300046C, HHSN268201300047C,
HHSN26820 1300048C, HHSN268201300049C, HHSN268201300050C]; National
Institute of Health, National Institute on Aging; National Center on
Minority Health and Health Disparities [Z01-AG000513, 2009-149];
[R01HG006703]
FX JHS is supported by the National Heart, Lung, and Blood Institute and
the National Institute on Minority Health and Health Disparities, with
additional support from the National Institute on Biomedical Imaging and
Bioengineering (grant numbers HHSN268201300046C, HHSN268201300047C,
HHSN26820 1300048C, HHSN268201300049C, HHSN268201300050C). HANDLS is
supported by the Intramural Research Program of the National Institute
of Health, National Institute on Aging and the National Center on
Minority Health and Health Disparities (project # Z01-AG000513 and human
subjects protocol # 2009-149). E.M.L., Y.L. and Q.D. are partially
supported by R01HG006703.
NR 36
TC 5
Z9 5
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JAN 15
PY 2015
VL 24
IS 2
BP 572
EP 581
DI 10.1093/hmg/ddu454
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CC1WV
UT WOS:000350137000022
PM 25224454
ER
PT J
AU Kottyan, LC
Zoller, EE
Bene, J
Lu, XM
Kelly, JA
Rupert, AM
Lessard, CJ
Vaughn, SE
Marion, M
Weirauch, MT
Namjou, B
Adler, A
Rasmussen, A
Glenn, S
Montgomery, CG
Hirschfield, GM
Xie, G
Coltescu, C
Amos, C
Li, H
Ice, JA
Nath, SK
Mariette, X
Bowman, S
Rischmueller, M
Lester, S
Brun, JG
Goransson, LG
Harboe, E
Omdal, R
Cunninghame-Graham, DS
Vyse, T
Miceli-Richard, C
Brennan, MT
Lessard, JA
Wahren-Herlenius, M
Kvarnstrom, M
Illei, GG
Witte, T
Jonsson, R
Eriksson, P
Nordmark, G
Ng, WF
Anaya, JM
Rhodus, NL
Sega, BM
Merrill, JT
James, JA
Guthridge, JM
Scofield, RH
Alarcon-Riquelme, M
Bae, SC
Boackle, SA
Criswell, LA
Gilkeson, G
Kamen, DL
Jacob, CO
Kimberly, R
Brown, E
Edberg, J
Alarcon, GS
Reveille, JD
Vila, LM
Petri, M
Ramsey-Goldman, R
Freedman, BI
Niewold, T
Stevens, AM
Tsao, BP
Ying, J
Mayes, MD
Gorlova, OY
Wakeland, W
Radstake, T
Martin, E
Martin, J
Siminovitch, K
Sivils, KLM
Gaffney, PM
Langefeld, CD
Harley, JB
Kaufman, KM
AF Kottyan, Leah C.
Zoller, Erin E.
Bene, Jessica
Lu, Xiaoming
Kelly, Jennifer A.
Rupert, Andrew M.
Lessard, Christopher J.
Vaughn, Samuel E.
Marion, Miranda
Weirauch, Matthew T.
Namjou, Bahram
Adler, Adam
Rasmussen, Astrid
Glenn, Stuart
Montgomery, Courtney G.
Hirschfield, Gideon M.
Xie, Gang
Coltescu, Catalina
Amos, Chris
Li, He
Ice, John A.
Nath, Swapan K.
Mariette, Xavier
Bowman, Simon
Rischmueller, Maureen
Lester, Sue
Brun, Johan G.
Goransson, Lasse G.
Harboe, Erna
Omdal, Roald
Cunninghame-Graham, Deborah S.
Vyse, Tim
Miceli-Richard, Corinne
Brennan, Michael T.
Lessard, James A.
Wahren-Herlenius, Marie
Kvarnstrom, Marika
Illei, Gabor G.
Witte, Torsten
Jonsson, Roland
Eriksson, Per
Nordmark, Gunnel
Ng, Wan-Fai
Anaya, Juan-Manuel
Rhodus, Nelson L.
Sega, Barbara M.
Merrill, Joan T.
James, Judith A.
Guthridge, Joel M.
Scofield, R. Hal
Alarcon-Riquelme, Marta
Bae, Sang-Cheol
Boackle, Susan A.
Criswell, Lindsey A.
Gilkeson, Gary
Kamen, Diane L.
Jacob, Chaim O.
Kimberly, Robert
Brown, Elizabeth
Edberg, Jeffrey
Alarcon, Graciela S.
Reveille, John D.
Vila, Luis M.
Petri, Michelle
Ramsey-Goldman, Rosalind
Freedman, Barry I.
Niewold, Timothy
Stevens, Anne M.
Tsao, Betty P.
Ying, Jun
Mayes, Maureen D.
Gorlova, Olga Y.
Wakeland, Ward
Radstake, Timothy
Martin, Ezequiel
Martin, Javier
Siminovitch, Katherine
Sivils, Kathy L. Moser
Gaffney, Patrick M.
Langefeld, Carl D.
Harley, John B.
Kaufman, Kenneth M.
CA UK Primary Sjogrens Syndrome Regis
TI The IRF5-TNPO3 association with systemic lupus erythematosus has two
components that other autoimmune disorders variably share
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PRIMARY BILIARY-CIRRHOSIS; INTERFERON
REGULATORY FACTOR-5; IRF5 GENE POLYMORPHISMS; PRISTANE-INDUCED LUPUS;
STRONG RISK-FACTOR; SUSCEPTIBILITY LOCI; TRANSCRIPTION FACTORS; DISTINCT
POPULATIONS; JAPANESE POPULATION
AB Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-value(meta) = 6 x 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3(P-values(EU) = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjogren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
C1 [Kottyan, Leah C.; Zoller, Erin E.; Bene, Jessica; Lu, Xiaoming; Vaughn, Samuel E.; Weirauch, Matthew T.; Namjou, Bahram; Harley, John B.; Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Div Rheumatol, Cincinnati, OH 45229 USA.
[Rupert, Andrew M.; Weirauch, Matthew T.] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.
[Kottyan, Leah C.; Weirauch, Matthew T.; Harley, John B.; Kaufman, Kenneth M.] US Dept Vet Affairs Med Ctr, Cincinnati, OH USA.
[Kelly, Jennifer A.; Lessard, Christopher J.; Adler, Adam; Rasmussen, Astrid; Glenn, Stuart; Montgomery, Courtney G.; Li, He; Ice, John A.; Nath, Swapan K.; Merrill, Joan T.; James, Judith A.; Guthridge, Joel M.; Scofield, R. Hal; Alarcon-Riquelme, Marta; Sivils, Kathy L. Moser; Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Marion, Miranda; Langefeld, Carl D.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Marion, Miranda; Langefeld, Carl D.] Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA.
[Freedman, Barry I.] Wake Forest Sch Med, Winston Salem, NC USA.
[Hirschfield, Gideon M.] Univ Birmingham, NIHR Biomed Res Unit, Birmingham, W Midlands, England.
[Xie, Gang; Siminovitch, Katherine] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Coltescu, Catalina] Toronto Western Hosp, Ctr Liver, Toronto, ON M5T 2S8, Canada.
[Amos, Chris] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA.
[Lessard, Christopher J.; Li, He] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
[James, Judith A.; Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
[Mariette, Xavier; Miceli-Richard, Corinne] Hop Univ Paris Sud, Dept Rheumatol, INSERM U1012, Le Kremlin Bicetre, France.
[Bowman, Simon] Univ Hosp Birmingham, Dept Rheumatol, Birmingham, W Midlands, England.
[Rischmueller, Maureen; Lester, Sue] Queen Elizabeth Hosp, Adelaide, SA, Australia.
[Lester, Sue] Univ Adelaide, Adelaide, SA, Australia.
[Brun, Johan G.] Univ Bergen, Inst Internal Med, Bergen, Norway.
[Jonsson, Roland] Univ Bergen, Gade Inst, Broegelmann Res Lab, Bergen, Norway.
[Brun, Johan G.; Jonsson, Roland] Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway.
[Goransson, Lasse G.; Harboe, Erna; Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
[Cunninghame-Graham, Deborah S.; Vyse, Tim] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England.
[Brennan, Michael T.] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA.
[Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA.
[Wahren-Herlenius, Marie; Kvarnstrom, Marika] Karolinska Inst, Dept Med, Stockholm, Sweden.
[Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Witte, Torsten] Hannover Med Sch, Hannover, Germany.
[Eriksson, Per] Linkoping Univ, Fac Hlth Sci, Dept Rheumatol Clin & Expt Med, Linkoping, Sweden.
[Nordmark, Gunnel] Uppsala Univ, Dept Med Sci, Rheumatol, Uppsala, Sweden.
[Ng, Wan-Fai] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia.
[Rhodus, Nelson L.] Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA.
[Sega, Barbara M.] Univ Minnesota, Sch Med, Div Rheumatol, Minneapolis, MN 55455 USA.
[Scofield, R. Hal] Div Vet Affairs Med Ctr, Oklahoma City, OK USA.
[Alarcon-Riquelme, Marta] Pfizer Univ Granada Junta Andalucia, Genom Invest Oncol GENYO, Granada, Spain.
[Bae, Sang-Cheol] Hanyang Univ Hosp Rheumat Dis, Dept Rheumatol, Seoul, South Korea.
[Boackle, Susan A.] Univ Colorado, Sch Med, Div Rheumatol, Aurora, CO USA.
[Criswell, Lindsey A.] Univ Calif San Francisco, Div Rheumatol, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA.
[Gilkeson, Gary; Kamen, Diane L.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Mol Microbiol & Immunol, Los Angeles, CA 90033 USA.
[Kimberly, Robert; Brown, Elizabeth; Edberg, Jeffrey; Alarcon, Graciela S.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Div Rheumatol & Clin Immunogenet, Houston, TX 77030 USA.
[Vila, Luis M.] Univ Puerto Rico, San Juan, PR 00936 USA.
[Petri, Michelle] Johns Hopkins, Div Rheumatol, Baltimore, MD USA.
[Ramsey-Goldman, Rosalind] Northwestern Univ, Div Rheumatol, Chicago, IL 60611 USA.
[Niewold, Timothy] Mayo Clin, Div Rheumatol & Immunol, Rochester, MN USA.
[Stevens, Anne M.] Univ Washington, Seattle, WA 98195 USA.
[Stevens, Anne M.] Seattle Childrens Hosp, Seattle, WA USA.
[Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Ying, Jun; Mayes, Maureen D.; Gorlova, Olga Y.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wakeland, Ward] Univ Texas Southwestern Med Sch, Dallas, TX USA.
[Radstake, Timothy] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands.
[Martin, Ezequiel; Martin, Javier] Inst Parasitol & Biomed Lopez Neyra Avda, Granada, Spain.
[Siminovitch, Katherine] Univ Toronto, Dept Med, Toronto, ON, Canada.
RP Kottyan, LC (reprint author), Cincinnati Childrens Hosp, 3333 Burnet Ave,Mail Locat 15012, Cincinnati, OH 45229 USA.
EM leah.kottyan@cchmc.org
RI Hirschfield, Gideon/M-2143-2015; Witte, Torsten/B-5783-2016; Martin,
Javier/B-8141-2008; Siminovitch, Katherine/K-1475-2013; Anaya,
Juan-Manuel/J-1960-2016;
OI Hirschfield, Gideon/0000-0002-6736-2255; Anaya,
Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario,
Biblioteca/0000-0003-3491-9392; Kimberly, Robert/0000-0002-5330-3086;
Niewold, Timothy/0000-0003-3532-6660; Wahren-Herlenius,
Marie/0000-0002-0915-7245
FU National Institutes of Health [AI024717, AR042460, AI031584, DE015223,
AR057172, AR043418, AR065626, AR049084, AI082714, AR052300, AR062277,
AR060366]; U.S. Department of Defense [PR094002]; U.S. Department of
Veterans Affairs [IMMA 9]; General Center Research Center [RR-000079];
Alliance for Lupus Research; Korea Healthcare technology RD Project;
Ministry for Health and Welfare, Republic of Korea [HI12C1834]; Swedish
Rheumatism Association; American College of Rheumatology Research and
Education Foundation/Abbott Healthy Professional Graduate Student
Preceptorship Award; Oklahoma Medical Research Foundation; Sjogren's
Syndrome Foundation [4434]; Phileona Foundation; French Ministry of
Health (PHRC) [2006-AOM06133]; Strategic Research Program at Helse
Bergen; Western Norway Regional Health Authority; Broegelmann Foundation
[TP03, WI 1031/6-1, KFO 250, Z1]; Medical Research Council (UK)
[G0800629]; Northumberland, Tyne Wear CLRN; Canadian Institutes for
Health Research [MOP74621]; Ontario Research Fund [REO-061]; PBC Society
of Canada; Canadian Institutes of Health Research; Canada Research
Chair; Sherman Family Chair in Genomic Medicine; National Institutes of
Health. [AI094377, AR062755, AR30692, AR048940, RR026314, RR029882,
1RR025741, TR000165, AR 002138, AI070304, AR43727, AR0608040, AR058959,
AR053483, DE018209-02, DE018209, RR020143, AI083194, RR027190, AI101934,
GM103510]
FX This work has been supported by National Institutes of Health grants and
contracts (AI024717, AR042460, AI031584, DE015223, AR057172, AI083194,
AR043418, AR065626, AR049084, AI082714, AR052300, AR062277, AR060366,
AI094377, GM103510, RR020143, AR062755, AR30692, AR048940, RR027190,
RR026314, RR029882, 1RR025741, TR000165, AR 002138, AI070304, AR43727,
AR0608040, DE015223, AR058959, AR049084, AR053483 AI082714, DE018209-02,
DE018209, RR020143, AI083194, RR027190, AI101934, and GM103510); the
U.S. Department of Defense (PR094002); the U.S. Department of Veterans
Affairs (IMMA 9); the General Center Research Center (RR-000079);
Alliance for Lupus Research; the Korea Healthcare technology R&D
Project; Ministry for Health and Welfare, Republic of Korea (HI12C1834);
Mary Kirkland Scholar (J.B.H. and L.A.C.); the Swedish Rheumatism
Association, American College of Rheumatology Research and Education
Foundation/Abbott Healthy Professional Graduate Student Preceptorship
Award 2009; Oklahoma Medical Research Foundation, Sjogren's Syndrome
Foundation (4434); Phileona Foundation, French Ministry of Health (PHRC
No2006-AOM06133); The Strategic Research Program at Helse Bergen,
Western Norway Regional Health Authority and The Broegelmann Foundation
(KFO 250, TP03, WI 1031/6-1", "KFO 250, Z1); Medical Research Council
(UK G0800629); Northumberland, Tyne & Wear CLRN; the Canadian Institutes
for Health Research (MOP74621); the Ontario Research Fund (REO-061); the
PBC Society of Canada; Canadian Institutes of Health Research; and the
Canada Research Chair and the Sherman Family Chair in Genomic Medicine.
NR 75
TC 18
Z9 18
U1 2
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JAN 15
PY 2015
VL 24
IS 2
BP 582
EP 596
DI 10.1093/hmg/ddu455
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CC1WV
UT WOS:000350137000023
PM 25205108
ER
PT J
AU Aka, PV
Kemp, TJ
Rabkin, CS
Shiels, MS
Polizzotto, MN
Lauria, C
Vitale, F
Pinto, LA
Goedert, JJ
AF Aka, Peter V.
Kemp, Troy J.
Rabkin, Charles S.
Shiels, Meredith S.
Polizzotto, Mark N.
Lauria, Carmela
Vitale, Francesco
Pinto, Ligia A.
Goedert, James J.
TI A Multiplex Panel of Plasma Markers of Immunity and Inflammation in
Classical Kaposi Sarcoma
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE classical Kaposi sarcoma; IP-10; sIL-1RII; human herpesvirus 8
ID RISK-FACTORS
AB Kaposi sarcoma (KS) risk is affected by perturbed immunity. Herein, we compared plasma from 15 human immunodeficiency virus (HIV)-negative classic KS cases to plasma from 29 matched controls, using a multiplex panel of immunity markers. Of 70 markers, CXCL10 (IP-10), sIL-1RII, sIL-2RA, and CCL3 (MIP-1A) were strongly and significantly associated with KS, after adjustment for age and smoking status. These and previous observations are consistent with a tumor-promoting role for these cytokines, particularly CXCL10, but the small sample size and case-control design preclude firm conclusions on KS risk or pathogenesis. Larger, well-designed prospective studies are needed to better assess the association of these markers with KS.
C1 [Aka, Peter V.; Kemp, Troy J.; Rabkin, Charles S.; Shiels, Meredith S.; Pinto, Ligia A.; Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Polizzotto, Mark N.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lauria, Carmela] Lega Italiana Lotta Contro & Tumori Sez Ragusa, Ragusa, Italy.
[Vitale, Francesco] Univ Palermo, Dipartimento Sci Promoz Salute & Materno Infantil, I-90133 Palermo, Italy.
RP Goedert, JJ (reprint author), NCI, NIH, DCEG, Infect & Immunoepidemiol Branch, 9609 Med Ctr Dr,Rm 6E106 MSC 9704, Bethesda, MD 20892 USA.
EM goedertj@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health [Z01-CP-010214]
FX This work was supported by the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health
(intramural research program Z01-CP-010214).
NR 15
TC 2
Z9 2
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2015
VL 211
IS 2
BP 226
EP 229
DI 10.1093/infdis/jiu410
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CC3CC
UT WOS:000350221000009
PM 25149762
ER
PT J
AU Ndour, PA
Lopera-Mesa, TM
Diakite, SAS
Chiang, S
Mouri, O
Roussel, C
Jaureguiberry, S
Biligui, S
Kendjo, E
Claessens, A
Ciceron, L
Mazier, D
Thellier, M
Diakite, M
Fairhurst, RM
Buffet, PA
AF Ndour, Papa Alioune
Lopera-Mesa, Tatiana M.
Diakite, Seidina A. S.
Chiang, Serena
Mouri, Oussama
Roussel, Camille
Jaureguiberry, Stephane
Biligui, Sylvestre
Kendjo, Eric
Claessens, Antoine
Ciceron, Liliane
Mazier, Dominique
Thellier, Marc
Diakite, Mahamadou
Fairhurst, Rick M.
Buffet, Pierre A.
TI Plasmodium falciparum Clearance Is Rapid and Pitting Independent in
Immune Malian Children Treated With Artesunate for Malaria
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE malaria; Plasmodium falciparum; parasite clearance; artemisinin;
pitting; acquired immunity; spleen
ID PARASITE CLEARANCE; INFECTED ERYTHROCYTES; MEROZOITE ANTIGENS;
ACQUIRED-IMMUNITY; RANDOMIZED-TRIAL; SURFACE-ANTIGEN; SPLEEN;
ANTIBODIES; VACCINE; QUININE
AB Background. In Plasmodium falciparum-infected patients treated with artemisinins, parasitemia declines through so-called pitting, an innate splenic process that transforms infected red blood cells (iRBCs) into once-infected RBCs (O-iRBCs).
Methods. We measured pitting in 83 French travelers and 42 Malian children treated for malaria with artesunate.
Results. In travelers, O-iRBCs peaked at 107.7% initial parasitemia. In Malian children aged 1.5-4 years, O-iRBCs peaked at higher concentrations than in children aged 9-13 years (91.60% vs 31.95%; P = .0097). The parasite clearance time in older children was shorter than in younger children (P = .0001), and the decline in parasitemia in children aged 1.5-4 years often started 6 hours after treatment initiation, a lag phase generally absent in infants and older children. A 6-hour lag phase in artificial pitting of artesunate-exposed iRBCs was also observed in vitro. The proportion of iRBCs recognized by autologous immunoglobulin G(IgG) correlated with the parasite clearance time (r = -0.501; P = .0006) and peak O-iRBC concentration (r = -0.420; P = .0033).
Conclusions. Antimalarial immunity correlates with fast artemisinin-induced parasite clearance and low pitting rates. In nonimmune populations, artemisinin-induced P. falciparum clearance is related to pitting and starts after a 6-hour lag phase. In immune populations, passively and naturally acquired immune mechanisms operating faster than pitting may exist. This mechanism may mitigate the emergence of artemisinin-resistant P. falciparum in Africa.
C1 [Ndour, Papa Alioune; Roussel, Camille; Biligui, Sylvestre; Kendjo, Eric; Ciceron, Liliane; Mazier, Dominique; Thellier, Marc; Buffet, Pierre A.] UPMC CR7, CIMI PARIS, INSERM U1135, CNRS ERL 8255, F-75651 Paris 13, France.
[Ndour, Papa Alioune; Jaureguiberry, Stephane; Biligui, Sylvestre; Kendjo, Eric; Ciceron, Liliane; Mazier, Dominique; Thellier, Marc; Buffet, Pierre A.] Ctr Natl Reference Paludisme Site Pitie Salpetrie, Paris, France.
[Ndour, Papa Alioune; Buffet, Pierre A.] Lab Excellence GR Ex, Paris, France.
[Mouri, Oussama; Jaureguiberry, Stephane; Mazier, Dominique; Thellier, Marc; Buffet, Pierre A.] Hop La Pitie Salpetriere, AP HP, Serv Parasitol Mycol, Paris, France.
[Mouri, Oussama; Jaureguiberry, Stephane; Mazier, Dominique; Thellier, Marc; Buffet, Pierre A.] Serv Malad Infect & Trop, Paris, France.
[Lopera-Mesa, Tatiana M.; Chiang, Serena; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Diakite, Seidina A. S.; Diakite, Mahamadou] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Odontostomatol, Bamako, Mali.
[Claessens, Antoine] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH8 9YL, Midlothian, Scotland.
RP Ndour, PA (reprint author), UPMC CR7, CIMI PARIS, INSERM U1135, CNRS ERL 8255, 47 Blvd Hop, F-75651 Paris 13, France.
EM ndourmail@yahoo.fr
OI Thellier, Marc/0000-0003-4867-2423; Claessens,
Antoine/0000-0002-4277-0914; NDOUR, PAPA ALIOUNE/0000-0001-7203-9754
FU DIM Mal Inf Region Ile de France; Worldwide Antimalarial Resistance
Network; National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Bill and Melinda Gates Foundation; Follereau
Foundation; INSERM-APHP France; University of Oxford
FX This work was supported by the DIM Mal Inf Region Ile de France; the
Worldwide Antimalarial Resistance Network; the Intramural Research
Program, National Institute of Allergy and Infectious Diseases, National
Institutes of Health; the Bill and Melinda Gates Foundation (to P. A.
N.); the Follereau Foundation (to L. C.); INSERM-APHP France (to S. J.);
and the University of Oxford.
NR 31
TC 17
Z9 17
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2015
VL 211
IS 2
BP 290
EP 297
DI 10.1093/infdis/jiu427
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CC3CC
UT WOS:000350221000017
PM 25183768
ER
PT J
AU Smiley, ST
Singh, A
Read, SW
Sharma, OK
Finzi, D
Lane, C
Rice, JS
AF Smiley, Stephen T.
Singh, Anjali
Read, Sarah W.
Sharma, Opendra K.
Finzi, Diana
Lane, Clifford
Rice, Jeffrey S.
TI Progress Toward Curing HIV Infections With Hematopoietic Stem Cell
Transplantation
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
DE HIV; transplantation; latency; reservoirs
ID VERSUS-HOST-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS;
BONE-MARROW-TRANSPLANTATION; ANTIRETROVIRAL THERAPY; T-CELLS;
REPLICATION; RESERVOIR; CCR5; CURE; CYCLOPHOSPHAMIDE
AB Combination antiretroviral therapy can suppress human immunodeficiency virus (HIV) infection but cannot completely eradicate the virus. A major obstacle in the quest for a cure is the difficulty in targeting and measuring latently infected cells. To date, a single person seems to have been cured of HIV. Hematopoietic stem cell transplantation (HSCT) preceded this cancer patient's long-term sustained HIV remission, but researchers have been unable to replicate this cure, and the mechanisms that led to HIV remission remain to be established. In February 2014, the National Institute of Allergy and Infectious Diseases sponsored a workshop that provided a venue for in-depth discussion of whether HSCT could be exploited to cure HIV in cancer patients requiring such procedures. Participants also discussed how HSCT might be applied to a broader community of HIV-infected persons in whom the risks of HSCT currently outweigh the likelihood and benefits of HIV cure.
C1 [Smiley, Stephen T.; Singh, Anjali; Read, Sarah W.; Sharma, Opendra K.; Finzi, Diana] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Lane, Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Rice, Jeffrey S.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
RP Smiley, ST (reprint author), NIAID, Div Aids, 5601 Fishers Lane,Room 9E45, Bethesda, MD 20892 USA.
EM stephen.smiley@nih.gov
NR 40
TC 2
Z9 2
U1 1
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JAN 15
PY 2015
VL 60
IS 2
BP 292
EP 297
DI 10.1093/cid/ciu766
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CB6TR
UT WOS:000349760100021
PM 25273081
ER
PT J
AU Miller, Y
Ma, BY
Nussinov, R
AF Miller, Yifat
Ma, Buyong
Nussinov, Ruth
TI Polymorphism in Self-Assembly of Peptide-Based beta-Hairpin Contributes
to Network Morphology and Hydrogel Mechanical Rigidity
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID PARTICLE MESH EWALD; MOLECULAR-DYNAMICS; DESIGNED PEPTIDE; POTENTIAL
FUNCTIONS; LIQUID WATER; FLOW-CONTROL; PROTEINS; AGGREGATION; FIBRILS;
RELEASE
AB Hydrogels are proving to be an excellent class of materials for biomedical applications. The molecular self-assembly of designed MAX1 beta-hairpin peptides into fibrillar networks has emerged as a novel route to form responsive hydrogels. Herein, computational modeling techniques are used to investigate the relative arrangements of individual hairpins within the fibrils that constitute the gel. The modeling provides insight into the morphology of the fibril network, which defines the gels mechanical properties. Our study suggests polymorphic arrangements of the hairpins within the fibrils; however, the relative populations and the relative conformational energies of the polymorphic arrangements show a preference toward an arrangement of hairpins where their turn regions are not capable of forming intermolecular interaction. Repulsive intramolecular electrostatic interactions appear to dictate the formation of fibrils with shorter, rather than longer, persistent lengths. These repulsive intramolecular interactions also disfavor the formation of fibril entanglements. Taken together, the modeling predicts that MAX1 forms a network containing a large number of branch points, a network morphology supported by the formation of short fibril segments. We posit that, under static conditions, the preferred branched structures of the MAX1 peptide assembly result in a cross-linked hydrogel organization. At the same time, the shear stress leads to short fibrillar structures, thus fluidic hydrogel states.
C1 [Miller, Yifat] Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel.
[Miller, Yifat] Ben Gurion Univ Negev, Ilse Katz Inst Nanoscale Sci & Technol, IL-84105 Beer Sheva, Israel.
[Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Miller, Y (reprint author), Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel.
EM ymiller@bgu.ac.il; NussinoR@hekix.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU Federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; Israel Binational Science Foundation
[2011128]; Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research
FX We thank Yoav Atsmon-Raz for the RMSD analysis for all models. All
simulations have been performed using the high-performance computational
facilities of the Miller lab in the BGU HPC computational center and the
Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda,
MD (http://biowulf.nih.gov). The support of the BGU HPC computational
center staff is greatly acknowledged. This project has been funded in
whole or in part with Federal funds from the National Cancer Institute,
National Institutes of Health, under contract number HHSN261200800001E
and by the Israel Binational Science Foundation Grant No. 2011128. 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 42
TC 5
Z9 5
U1 1
U2 32
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JAN 15
PY 2015
VL 119
IS 2
BP 482
EP 490
DI 10.1021/jp511485n
PG 9
WC Chemistry, Physical
SC Chemistry
GA AZ2XX
UT WOS:000348093700010
PM 25545881
ER
PT J
AU Chen, GZ
Xu, RF
Zhang, SS
Wang, YN
Wang, PH
Edin, ML
Zeldin, DC
Wang, DW
AF Chen, Guangzhi
Xu, Renfan
Zhang, Shasha
Wang, Yinna
Wang, Peihua
Edin, Matthew L.
Zeldin, Darryl C.
Wang, Dao Wen
TI CYP2J2 overexpression attenuates nonalcoholic fatty liver disease
induced by high-fat diet in mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE CYP2J2; EETs; nonalcoholic fatty liver disease; palmitic acid;
inflammation; oxidative stress
ID NF-KAPPA-B; OXIDATIVE STRESS; MURINE STEATOHEPATITIS;
INSULIN-RESISTANCE; DIABETES-MELLITUS; ACTIVATION; CELLS; INFLAMMATION;
PATHOGENESIS; DYSFUNCTION
AB Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress than wild-type control mice. These effects were associated with inhibition of NF-kappa B/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced inflammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-kappa B/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant effects that could aid in the design of new therapies for the prevention and treatment of NAFLD.
C1 [Chen, Guangzhi; Zhang, Shasha; Wang, Yinna; Wang, Peihua; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Internal Med, Wuhan 430030, Peoples R China.
[Chen, Guangzhi; Zhang, Shasha; Wang, Yinna; Wang, Peihua; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Gene Therapy Ctr, Wuhan 430030, Peoples R China.
[Xu, Renfan] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Med Ultrasound, Wuhan 430030, Peoples R China.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, 1095 Jiefang Ave, Wuhan 430030, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
FU NSFC [81400369, 31130031]; National Institutes of Health, National
Institute of Environmental Health Sciences [Z01 025034]
FX This work was supported by NSFC Grant (nos. 81400369 and 31130031) and
in part by the intramural research program of the National Institutes of
Health, National Institute of Environmental Health Sciences (Z01 025034
to D. C. Zeldin).
NR 45
TC 11
Z9 11
U1 1
U2 9
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 JAN 15
PY 2015
VL 308
IS 2
BP E97
EP E110
DI 10.1152/ajpendo.00366.2014
PG 14
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA CB0GD
UT WOS:000349302900001
PM 25389366
ER
PT J
AU Li, R
Xu, XZ
Chen, C
Wang, Y
Gruzdev, A
Zeldin, DC
Wang, DW
AF Li, Rui
Xu, Xizhen
Chen, Chen
Wang, Yan
Gruzdev, Artiom
Zeldin, Darryl C.
Wang, Dao Wen
TI CYP2J2 attenuates metabolic dysfunction in diabetic mice by reducing
hepatic inflammation via the PPAR gamma
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE cytochrome P450 epoxygenase 2J2; peroxisome proliferator-activated
receptor-gamma
ID SOLUBLE EPOXIDE HYDROLASE; IMPROVES INSULIN SENSITIVITY; ACTIVATED
PROTEIN-KINASE; DB/DB MICE; CYTOCHROME-P450 2J2; RECEPTOR-GAMMA; CELL
GROWTH; FATTY-ACIDS; RESISTANCE; OBESITY
AB Epoxyeicosatrienoic acids (EETs) and arachidonic acid-derived cytochrome P450 (CYP) epoxygenase metabolites have diverse biological effects, including anti-inflammatory properties in the vasculature. Increasing evidence suggests that inflammation in type 2 diabetes is a key component in the development of insulin resistance. In this study, we investigated whether CYP epoxygenase expression and exogenous EETs can attenuate insulin resistance in diabetic db/db mice and in cultured hepatic cells (HepG2). In vivo, CYP2J2 expression and the accompanying increase in EETs attenuated insulin resistance, as determined by plasma glucose levels, glucose tolerance test, insulin tolerance test, and hyperinsulinemic euglycemic clamp studies. CYP2J2 expression reduced the production of proinflammatory cytokines in liver, including CRP, IL-6, IL-beta, and TNF alpha, and decreased the infiltration of macrophages in liver. CYP2J2 expression also decreased activation of proinflammatory signaling cascades by decreasing NF-kappa B and MAPK activation in hepatocytes. Interestingly, CYP2J2 expression and exogenous EET treatment increased glucose uptake and activated the insulin-signaling cascade both in vivo and in vitro, suggesting that CYP2J2 metabolites play a role in glucose homeostasis. Furthermore, CYP2J2 expression upregulated PPAR gamma, which has been shown to induce adipogenesis, which attenuates dyslipidemias observed in diabetes. All of the findings suggest that CYP2J2 expression attenuates the diabetic phenotype and insulin resistance via inhibition of NF-kappa B and MAPK signaling pathways and activation of PPAR gamma.
C1 [Li, Rui; Xu, Xizhen; Chen, Chen; Wang, Yan; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430030, Peoples R China.
[Li, Rui; Xu, Xizhen; Chen, Chen; Wang, Yan; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Hypertens, Wuhan 430030, Peoples R China.
[Gruzdev, Artiom; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430030, Peoples R China.
EM dwwang57@263.net.cn
FU National Science Foundation of China key projects [30930039, 31130031];
973 program [2012CB518004]; Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences [Z01 025034]
FX This work was supported by National Science Foundation of China key
projects (nos. 30930039 and 31130031), the 973 program (2012CB518004),
and in part by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (Z01 025034 to D. C. Zeldin).
NR 63
TC 9
Z9 9
U1 1
U2 12
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 JAN 15
PY 2015
VL 308
IS 4
BP E270
EP E282
DI 10.1152/ajpendo.00118.2014
PG 13
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA CB0GL
UT WOS:000349303800002
PM 25389363
ER
PT J
AU Hall, RH
Sack, DA
AF Hall, Robert H.
Sack, David A.
TI Introducing cholera vaccination in Asia, Africa and Haiti: A meeting
report
SO VACCINE
LA English
DT Article
DE Cholera; Cholera vaccination; Oral vaccine; Vaccine demonstration;
Vaccine stockpile; Acceptability; Feasibility
ID WHOLE-CELL; VIETNAM; IMMUNOGENICITY; KNOWLEDGE; VACCINES; SAFETY;
ADULTS; TRIAL; INDIA
AB Orally-administered cholera vaccine (OCV) has been increasingly examined as an additional tool to intervene against endemic and epidemic cholera. In 2013, short- and long-term field experience with OCV under nine distinctive field settings was reported from India, Bangladesh, Vietnam, Guinea, Haiti, and Thailand. Lead investigators from each of these projects presented their findings at a symposium chaired by Drs. David A. Sack and Robert H. Hall at the Vaccines for Enteric Diseases (VED) Conference in Bangkok on November 7, 2013. The objective of the symposium was to describe the unique features of each setting and project, share field experience of implementing cholera vaccination, discuss results, and identify constraints to the wider use of OCV. The VED provided a forum where >200 attendees engaged with this exciting and potentially decisive new development in the cholera field.
C1 [Hall, Robert H.] NIAID, Bethesda, MD 20892 USA.
[Sack, David A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
RP Hall, RH (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM robert.hall@nih.gov
FU DOVE project (Delivering Oral Vaccine Effectively); Vaccines for Enteric
Diseases Conference held in Bangkok, Thailand, from November 6-8; Bill
and Melinda Gates Foundation [OPP1053556]
FX The Symposium "Symposium on Implementing Oral Cholera Vaccines" was
sponsored in part by the DOVE project (Delivering Oral Vaccine
Effectively) and convened during the Vaccines for Enteric Diseases
Conference held in Bangkok, Thailand, from November 6-8, 2013. A list of
participants and abstracts can be found here. The speakers included
Dipika Sur (NICED, Kolkata, India), Firdausi Qadri (icddr,b; Dhaka,
Bangladesh), Sah Binod (International Vaccine Institute, Seoul, Republic
of Korea), Kashmira Date and Chris Phares (CDC, Atlanta, Georgia, USA),
Dang Duc Anh (NIHE, Hanoi, Vietnam), Francisco Luquero (Epicentre/MSF,
Paris France), Louise Ivers (Partners in Health, Boston, Massachusetts,
USA), and Stephen Martin (WHO, Geneva, Switzerland). The DOVE project is
based at the Johns Hopkins Bloomberg School of Public Health, Baltimore,
Maryland USA, and is funded the Bill and Melinda Gates Foundation
(OPP1053556).
NR 28
TC 1
Z9 1
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JAN 15
PY 2015
VL 33
IS 4
BP 487
EP 492
DI 10.1016/j.vaccine.2014.11.031
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CA8UJ
UT WOS:000349196100001
PM 25437100
ER
PT J
AU Jain, S
Farias, GG
Bonifacino, JS
AF Jain, Shweta
Farias, Ginny G.
Bonifacino, Juan S.
TI Polarized sorting of the copper transporter ATP7B in neurons mediated by
recognition of a dileucine signal by AP-1
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID TRANS-GOLGI NETWORK; CLATHRIN ADAPTER COMPLEX; WILSON DISEASE PROTEIN;
P-TYPE ATPASE; HIPPOCAMPAL-NEURONS; INTRACELLULAR-LOCALIZATION;
BIOCHEMICAL-CHARACTERIZATION; LIVER-TRANSPLANTATION; REGULATED
TRAFFICKING; MEMBRANE TRAFFICKING
AB Neurons are highly polarized cells having distinct somatodendritic and axonal domains. Here we report that polarized sorting of the Cu2+ transporter ATP7B and the vesicle-SNARE VAMP4 to the somatodendritic domain of rat hippocampal neurons is mediated by recognition of dileucine-based signals in the cytosolic domains of the proteins by the sigma 1 subunit of the clathrin adaptor AP-1. Under basal Cu2+ conditions, ATP7B was localized to the trans-Golgi network (TGN) and the plasma membrane of the soma and dendrites but not the axon. Mutation of a dileucine-based signal in ATP7B or overexpression of a dominant-negative sigma 1 mutant resulted in nonpolarized distribution of ATP7B between the somatodendritic and axonal domains. Furthermore, addition of high Cu2+ concentrations, previously shown to reduce ATP7B incorporation into AP-1-containing clathrin-coated vesicles, caused loss of TGN localization and somatodendritic polarity of ATP7B. These findings support the notion of AP-1 as an effector of polarized sorting in neurons and suggest that altered polarity of ATP7B in polarized cell types might contribute to abnormal copper metabolism in the MEDNIK syndrome, a neurocutaneous disorder caused by mutations in the sigma 1A subunit isoform of AP-1.
C1 [Jain, Shweta; Farias, Ginny G.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM bonifacinoj@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU Intramural Program of the National Institute of Child Health and Human
Development, National Institutes of Health [ZIA HD001607-22]
FX We thank X. Zhu and N. Tsai for expert technical assistance, X. Ren for
help with Figure 4A, S. Lutsenko, M. Krieger, W. Mothes, A. Sharma, and
J. Lippincott-Schwartz for kind gifts of reagents, and R. Mattera and S.
Kaler for helpful discussions and critical review of the manuscript.
This work was funded by the Intramural Program of the National Institute
of Child Health and Human Development, National Institutes of Health
(ZIA HD001607-22).
NR 60
TC 11
Z9 11
U1 0
U2 2
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JAN 15
PY 2015
VL 26
IS 2
BP 218
EP 228
DI 10.1091/mbc.E14-07-1177
PG 11
WC Cell Biology
SC Cell Biology
GA CA4EO
UT WOS:000348857200006
PM 25378584
ER
PT J
AU Naumiec, GR
Cai, LS
Pike, VW
AF Naumiec, Gregory R.
Cai, Lisheng
Pike, Victor W.
TI New N-aryl-N '-(3-(substituted)phenyl)-N '-methylguanidines as leads to
potential PET radioligands for imaging the open NMDA receptor
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE N-Methyl-D-aspartate receptor; Phencyclidine; Positron emission
tomography
ID IN-VITRO EVALUATION; SYNAPTIC PLASTICITY; CHANNEL; ION; ANTAGONISTS;
SUBUNIT; SITE; MICE
AB An expansive set of N-aryl-N'-(3-(substituted)phenyl)-N'-methylguanidines was prepared in a search for new leads to prospective PET ligands for imaging of the open channel of the N-methyl-D-aspartate (NMDA) receptor in vivo. The N-aryl rings and their substituents were varied, whereas the N-methyl group was maintained as a site for potential labeling with the positron-emitter, carbon-11 (t(1/2) = 20.4 min). At micromolar concentration, over half of the prepared compounds strongly inhibited the binding of [H-3] TCP to its binding site in the open NMDA receptor in vitro. Four ligands displayed affinities that are similar or superior to those of the promising SPECT radioligand ([I-123]CNS1261). The 30-dimethylamino (19; K-i 36.7 nM), 3'-trifluoromethyl (20; K-i 18.3 nM) and 3'-methylthio (2; K-i 39.8 nM) derivatives of N-1-naphthyl-N'-(phenyl)-N'-methylguanidine were identified as especially attractive leads for PET radioligand development. (C) 2014 Published by Elsevier Ltd.
C1 [Naumiec, Gregory R.; Cai, Lisheng; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH)
FX This study was supported by the Intramural Research Program of the
National Institutes of Health (NIH), specifically the National Institute
of Mental Health (NIMH).
NR 25
TC 3
Z9 3
U1 1
U2 6
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 JAN 15
PY 2015
VL 25
IS 2
BP 225
EP 228
DI 10.1016/j.bmcl.2014.11.066
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA AY9XQ
UT WOS:000347901400014
PM 25499436
ER
PT J
AU Etemadi, A
Kamangar, F
Islami, F
Poustchi, H
Pourshams, A
Brennan, P
Boffetta, P
Malekzadeh, R
Dawsey, SM
Abnet, CC
Emadi, A
AF Etemadi, Arash
Kamangar, Farin
Islami, Farhad
Poustchi, Hossein
Pourshams, Akram
Brennan, Paul
Boffetta, Paolo
Malekzadeh, Reza
Dawsey, Sanford M.
Abnet, Christian C.
Emadi, Ashkan
TI Mortality and cancer in relation to ABO blood group phenotypes in the
Golestan Cohort Study
SO BMC MEDICINE
LA English
DT Article
DE Blood group; ABO; Rh; Mortality; Cancer; Cardiovascular disease
ID VON-WILLEBRAND-FACTOR; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE;
ESOPHAGEAL CANCER; GASTRIC-CANCER; HEART-DISEASE; RISK-FACTORS;
ASSOCIATION; IRAN; ALLELES
AB Background: A few studies have shown an association between blood group alleles and vascular disease, including atherosclerosis, which is thought to be due to the higher level of von Willebrand factor in these individuals and the association of blood group locus variants with plasma lipid levels. No large population-based study has explored this association with overall and cause-specific mortality.
Methods: We aimed to study the association between ABO blood groups and overall and cause-specific mortality in the Golestan Cohort Study. In this cohort, 50,045 people 40- to 70-years old were recruited between 2004 and 2008, and followed annually to capture all incident cancers and deaths due to any cause. We used Cox regression models adjusted for age, sex, smoking, socioeconomic status, ethnicity, place of residence, education and opium use.
Results: During a total of 346,708 person-years of follow-up (mean duration 6.9 years), 3,623 cohort participants died. Non-O blood groups were associated with significantly increased total mortality (hazard ratio (HR) = 1.09; 95% confidence interval (CI): 1.01 to 1.17) and cardiovascular disease mortality (HR = 1.15; 95% CI: 1.03 to 1.27). Blood group was not significantly associated with overall cancer mortality, but people with group A, group B, and all non-O blood groups combined had increased risk of incident gastric cancer. In a subgroup of cohort participants, we also showed higher plasma total cholesterol and low-density lipoprotein (LDL) in those with blood group A.
Conclusions: Non-O blood groups have an increased mortality, particularly due to cardiovascular diseases, which may be due to the effect of blood group alleles on blood biochemistry or their effect on von Willebrand factor and factor VIII levels.
C1 [Etemadi, Arash; Islami, Farhad; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran, Iran.
[Etemadi, Arash; Dawsey, Sanford M.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
[Islami, Farhad] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30329 USA.
[Poustchi, Hossein; Pourshams, Akram] Univ Tehran Med Sci, Digest Dis Res Inst, Liver & Pancreatobiliary Res Ctr, Tehran, Iran.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Emadi, Ashkan] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Etemadi, A (reprint author), Univ Tehran Med Sci, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran, Iran.
EM arash.etemadi@nih.gov
RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016
OI Abnet, Christian/0000-0002-3008-7843; Etemadi, Arash/0000-0002-3458-1072
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute;
Digestive Disease Research Center of Tehran University of Medical
Sciences [82-603]; Cancer Research UK [C20/A5860]; International Agency
FX This work was supported in part by the intramural research program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute; the Digestive Disease Research Center of Tehran University of
Medical Sciences (grant No 82-603); Cancer Research UK (C20/A5860); and
by the International Agency for Research on Cancer.
NR 35
TC 12
Z9 12
U1 1
U2 4
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 JAN 15
PY 2015
VL 13
AR 8
DI 10.1186/s12916-014-0237-8
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AZ7HI
UT WOS:000348389800001
PM 25592833
ER
PT J
AU Crompton, JG
Sukumar, M
Roychoudhuri, R
Clever, D
Gros, A
Eil, RL
Tran, E
Hanada, K
Yu, ZY
Palmer, DC
Kerkar, SP
Michalek, RD
Upham, T
Leonardi, A
Acquavella, N
Wang, E
Marincola, FM
Gattinoni, L
Muranski, P
Sundrud, MS
Klebanoff, CA
Rosenberg, SA
Fearon, DT
Restifo, NP
AF Crompton, Joseph G.
Sukumar, Madhusudhanan
Roychoudhuri, Rahul
Clever, David
Gros, Alena
Eil, Robert L.
Eric Tran
Hanada, Ken-ichi
Yu, Zhiya
Palmer, Douglas C.
Kerkar, Sid P.
Michalek, Ryan D.
Upham, Trevor
Leonardi, Anthony
Acquavella, Nicolas
Wang, Ena
Marincola, Francesco M.
Gattinoni, Luca
Muranski, Pawel
Sundrud, Mark S.
Klebanoff, Christopher A.
Rosenberg, Steven A.
Fearon, Douglas T.
Restifo, Nicholas P.
TI Akt Inhibition Enhances Expansion of Potent Tumor-Specific Lymphocytes
with Memory Cell Characteristics
SO CANCER RESEARCH
LA English
DT Article
ID CD8(+) T-CELLS; SPARE RESPIRATORY CAPACITY; CANCER IMMUNOSURVEILLANCE;
METASTATIC MELANOMA; ADOPTIVE TRANSFER; DIFFERENTIATION; IMMUNOTHERAPY;
METABOLISM; EFFECTOR; AUTOIMMUNITY
AB Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) results in complete regression of advanced cancer in some patients, but the efficacy of this potentially curative therapy may be limited by poor persistence of TIL after adoptive transfer. Pharmacologic inhibition of the serine/threonine kinase Akt has recently been shown to promote immunologic memory in virus-specific murine models, but whether this approach enhances features of memory (e.g., long-term persistence) in TIL that are characteristically exhausted and senescent is not established. Here, we show that pharmacologicinhibition of Akt enables expansion of TIL with the transcriptional, metabolic, and functional properties characteristic of memory T cells. Consequently, Akt inhibition results in enhanced persistence of TIL after adoptive transfer into an immunodeficient animal model and augments antitumor immunity of CD8 T cells in a mouse model of cell-based immunotherapy. Pharmacologic inhibition of Akt represents a novel immunometabolomic approach to enhance the persistence of antitumor T cells and improve the efficacy of cell-based immunotherapy for metastatic cancer. (C) 2014 AACR.
C1 [Crompton, Joseph G.; Sukumar, Madhusudhanan; Roychoudhuri, Rahul; Clever, David; Gros, Alena; Eil, Robert L.; Eric Tran; Hanada, Ken-ichi; Yu, Zhiya; Palmer, Douglas C.; Kerkar, Sid P.; Upham, Trevor; Leonardi, Anthony; Acquavella, Nicolas; Gattinoni, Luca; Muranski, Pawel; Klebanoff, Christopher A.; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA.
[Crompton, Joseph G.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA USA.
[Crompton, Joseph G.; Clever, David; Fearon, Douglas T.] Univ Cambridge, Sch Clin Med, Dept Med, Cambridge, England.
[Michalek, Ryan D.] Metabolon Incorp, Durham, NC USA.
[Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
[Sundrud, Mark S.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA.
[Klebanoff, Christopher A.] NCI, Clin Investigator Dev Program, NIH, Bethesda, MD 20892 USA.
RP Crompton, JG (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA.
EM joe.crompton@nih.gov; sukumarm2@mail.nih.gov; restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Palmer, Douglas/B-9454-2008; Roychoudhuri,
Rahul/A-7442-2010;
OI Gattinoni, Luca/0000-0003-2239-3282; Palmer,
Douglas/0000-0001-5018-5734; Roychoudhuri, Rahul/0000-0002-5392-1853;
Restifo, Nicholas P./0000-0003-4229-4580; Gros,
Alena/0000-0002-1207-1880
FU Intramural Research Program of the NCI [ZIA BC010763]; Wellcome Trust
Translational Medicine and Therapeutics Programme
FX The authors were supported by a generous gift from Li Jinyuan and the
Tiens Charitable Foundation, the NIH-Center for Regenerative Medicine,
the Milstein Family Foundation and by the Intramural Research Program of
the NCI (ZIA BC010763), Center for Cancer Research, NIH (Bethesda, MD).
This work was done in partial fulfillment of J.G. Crompton's PhD degree
from Cambridge University, Cambridge, England and he gratefully
acknowledges funding support from the Wellcome Trust Translational
Medicine and Therapeutics Programme.
NR 39
TC 50
Z9 50
U1 0
U2 16
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2015
VL 75
IS 2
BP 296
EP 305
DI 10.1158/0008-5472.CAN-14-2277
PG 10
WC Oncology
SC Oncology
GA AZ0LT
UT WOS:000347937600008
PM 25432172
ER
PT J
AU Boufraqech, M
Nilubol, N
Zhang, LS
Gara, SK
Sadowski, SM
Mehta, A
He, M
Davis, S
Dreiling, J
Copland, JA
Smallridge, RC
Quezado, MM
Kebebew, E
AF Boufraqech, Myriem
Nilubol, Naris
Zhang, Lisa
Gara, Sudheer Kumar
Sadowski, Samira M.
Mehta, Amit
He, Mei
Davis, Sean
Dreiling, Jennifer
Copland, John A.
Smallridge, Robert C.
Quezado, Martha M.
Kebebew, Electron
TI miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression
SO CANCER RESEARCH
LA English
DT Article
ID LYSYL OXIDASE; DOWN-REGULATION; BETA-AMINOPROPIONITRILE; MESENCHYMAL
TRANSITION; MICRORNAS; CARCINOMA; CELLS; METASTASIS; DIFFERENTIATION;
MALIGNANCY
AB Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, but its genetic drivers remain little understood. In this study, we report losses in expression of the miRNA miR30a, which is downregulated in ATC compared with differentiated thyroid cancer and normal tissue. miR30a downregulation was associated with advanced differentiated thyroid cancer and higher mortality. Mechanistically, we found miR30a decreased cellular invasion and migration, epithelial-mesenchymal transition marker levels, lysyl oxidase (LOX) expression, and metastatic capacity. LOX was identified as a direct target of miR30a that was overexpressed in ATC and associated with advanced differentiated thyroid cancer and higher mortality rate. Consistent with its role in other cancers, we found that LOX inhibited cell proliferation, cellular invasion, and migration and metastasis in vitro and in vivo. Together, our findings establish a critical functional role for miR30a downregulation in mediating LOX upregulation and thyroid cancer progression, with implications for LOX targeting as a rational therapeutic strategy in ATC.
C1 [Boufraqech, Myriem; Nilubol, Naris; Zhang, Lisa; Gara, Sudheer Kumar; Sadowski, Samira M.; Mehta, Amit; He, Mei; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Mehta, Amit] Geisel Sch Med Dartmouth, Hanover, NH USA.
[Davis, Sean] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dreiling, Jennifer; Quezado, Martha M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Copland, John A.; Smallridge, Robert C.] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA.
[Smallridge, Robert C.] Mayo Clin, Div Endocrinol, Dept Internal Med, Jacksonville, FL 32224 USA.
RP Kebebew, E (reprint author), NCI, Room 4-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Gara, Sudheer Kumar/E-8084-2016; Boufraqech, Myriem/E-4823-2016;
OI Davis, Sean/0000-0002-8991-6458
FU intramural research program of the Center for Cancer Research, NCI, NIH
FX This research was supported by the intramural research program of the
Center for Cancer Research, NCI, NIH.
NR 35
TC 11
Z9 12
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2015
VL 75
IS 2
BP 367
EP 377
DI 10.1158/0008-5472.CAN-14-2304
PG 11
WC Oncology
SC Oncology
GA AZ0LT
UT WOS:000347937600014
PM 25488748
ER
PT J
AU Iida, J
Dorchak, J
Clancy, R
Slavik, J
Ellsworth, R
Katagiri, Y
Pugacheva, EN
van Kuppevelt, TH
Mural, RJ
Cutler, ML
Shriver, CD
AF Iida, Joji
Dorchak, Jesse
Clancy, Rebecca
Slavik, Juliana
Ellsworth, Rachel
Katagiri, Yasuhiro
Pugacheva, Elena N.
van Kuppevelt, Toin H.
Mural, Richard J.
Cutler, Mary Lou
Shriver, Craig D.
TI Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast
cancer cell growth
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE NEDD9; Breast cancer; Migration; Growth; Chondroitin sulfate; CD44
ID HUMAN-MELANOMA INVASION; MOLECULAR-INTERACTIONS; HYALURONAN SYNTHESIS;
ANTIBODY GD3G7; PROTEOGLYCANS; MATRIX; PROGRESSION; METASTASIS; BINDING;
INTEGRIN
AB There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the mechanisms of NEDD9-mediated cancer migration and growth, stable cells overexpressing NEDD9 were generated using HCC38 as a parental cell line which expresses low level of endogenous NEDD9. Microarray studies demonstrated that core proteins of CD44 and Serglycin were markedly upregulated in HCC38(NEDD9) cells compared to HCC38(Vector) cells, while those of Syndecan-1, Syndecan-2, and Versican were downregulated in HCC38(NEDD9). Importantly, enzymes generating chondroitin sulfate glycosaminoglycans (CS) such as CHST11, CHST15, and CSGALNACT1 were upregulated in HCC38(NEDD9) compared to HCC38(Vector). Immunofluorescence studies using specific antibody, GD3G7, confirmed the enhanced expression of CS-E subunit in HCC38(NEDD9). Immunoprecipitation and western blotting analysis demonstrated that CS-E was attached to CD44 core protein. We demonstrated that removing CS by chondroitinase ABC significantly inhibited anchorage-independent colony formation of HCC38 (NEDD9) in methylcellulose. Importantly, the fact that GD3G7 significantly inhibited colony formation of HCC38(NEDD9) cells suggests that CS-E subunit plays a key role in this process. Furthermore, treatment of HCC38(NEDD9) cells with chondroitinase ABC or GD3G7 significantly inhibited mammosphere formation. Exogenous addition of CS-E enhanced colony formation and mammosphere formation of HCC38 parental and HCC38(Vector) cells. These results suggest that NEDD9 regulates the synthesis and expression of tumor associated glycocalyx structures including CS-E, which plays a key role in promoting and regulating breast cancer progression and metastasis and possibly stem cell phenotypes. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Iida, Joji; Dorchak, Jesse; Clancy, Rebecca; Slavik, Juliana; Mural, Richard J.] Windber Res Inst, Dept Cell Biol, Windber, PA 15963 USA.
[Ellsworth, Rachel] Henry M Jackson Fdn Adv Mil Med, Clin Breast Care Project, Windber, PA 15963 USA.
[Katagiri, Yasuhiro] NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Pugacheva, Elena N.] W Virginia Univ, Sch Med, Dept Biochem, Morgantown, WV 26506 USA.
[van Kuppevelt, Toin H.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Biochem, NL-6525 ED Nijmegen, Netherlands.
[Cutler, Mary Lou] Univ Hlth Sci, Uniformed Serv, Dept Pathol, Bethesda, MD 20814 USA.
[Shriver, Craig D.] Walter Reed Natl Mil Med Ctr, Dept Surg, Bethesda, MD 20814 USA.
RP Iida, J (reprint author), Windber Res Inst, Dept Cell Biol, Windber, PA 15963 USA.
EM g.iida@wriwindber.org
RI Kuppevelt, A.H.M.S.M./L-4463-2015
FU United States Army Medical Research Acquisition Activity (USAMRAA)
(Breast Cancer Translational Research) [W81XWH-12-2-0050]; United States
Military Cancer Institute (USMCI) [MDA905-02-2-0005]
FX During preparation of this manuscript Dr. Richard J Mural passed away
after two years of battle with cancer. We greatly appreciate his
continuous support and encouragement with dedicating this article to Dr.
Richard J Mural. We thank Mrs. Sue Lubert for sequencing DNA and Mrs.
Allyson Valente for performing micro-array studies. This research was
supported by a grant from the United States Army Medical Research
Acquisition Activity (USAMRAA) (Breast Cancer Translational Research:
W81XWH-12-2-0050) and the United States Military Cancer Institute
(USMCI) (MDA905-02-2-0005). The opinion and assertions contained herein
are the private views of the authors and are not to be construed as
official or as representing the views of the Department of the Army or
the Department of Defense.
NR 70
TC 9
Z9 10
U1 1
U2 15
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD JAN 15
PY 2015
VL 330
IS 2
BP 358
EP 370
DI 10.1016/j.yexcr.2014.11.002
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AZ5FN
UT WOS:000348245900012
PM 25445787
ER
PT J
AU Ming, M
Soltani, K
Shea, CR
Li, X
He, YY
AF Ming, M.
Soltani, K.
Shea, C. R.
Li, X.
He, Y. Y.
TI Dual role of SIRT1 in UVB-induced skin tumorigenesis
SO ONCOGENE
LA English
DT Article
DE SIRT1; UVB; skin tumorigenesis; DNA repair; apoptosis
ID DNA-DAMAGE RESPONSE; CELL-SURVIVAL; CALORIE RESTRICTION; MAMMALIAN
SIRTUINS; CANCER; MICE; P53; DEACETYLASE; PROTEIN; REPAIR
AB The protein deacetylase SIRT1 regulates various pathways in metabolism, aging and cancer. However, the role of SIRT1 in skin cancer remains unclear. Here, using mice with targeted deletions of SIRT1 in their epidermis in both resistant B6 and sensitive SKH1 hairless backgrounds, we show that the role of SIRT1 in skin cancer development induced by ultraviolet B (UVB) radiation is dependent on its gene dose. Keratinocyte-specific heterozygous deletion of SIRT1 promotes UVB-induced skin tumorigenesis, whereas homozygous deletion of SIRT1 suppresses skin tumor development but sensitizes the B6 mice to chronic solar injury. In mouse skin, SIRT1 is haploinsufficient for UVB-induced DNA damage repair and expression of xeroderma pigmentosum C (XPC), a protein critical for repairing UVB-induced DNA damage. As compared with normal human skin, downregulation of SIRT1 is in parallel with downregulation of XPC in human cutaneous squamous cell carcinoma at both the protein and mRNA levels. In contrast, homozygous SIRT1 deletion in mouse skin augments p53 acetylation and expression of its transcriptional target Noxa, and sensitizes the epidermis to UVB-induced apoptosis in vivo, while heterozygous SIRT1 deletion has no such effect. The gene dosage-dependent function of SIRT1 in DNA repair and cell survival is consistent with the dual roles of SIRT1 in UVB-induced skin tumorigenesis. Our results reveal the gene dosage-dependent in vivo functions of SIRT1 in skin tumorigenesis and may shed light on the role of SIRT1 in epithelial cancer induced by DNA damage.
C1 [Ming, M.; Soltani, K.; Shea, C. R.; He, Y. Y.] Univ Chicago, Dermatol Sect, Dept Med, Chicago, IL 60637 USA.
[Li, X.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC USA.
RP He, YY (reprint author), Univ Chicago, Dermatol Sect, Dept Med, Chicago, IL 60637 USA.
EM yyhe@medicine.bsd.uchicago.edu
FU NIH/NIEHS [ES016936]; American Cancer Society (ACS) [RSG-13-078-01];
University of Chicago Cancer Research Center [P30 CA014599]; CTSA [NIH
UL1RR024999]; University of Chicago Friends of Dermatology Endowment
Fund
FX This work was supported by the NIH/NIEHS Grant ES016936 (to YYH), the
American Cancer Society (ACS) Grant RSG-13-078-01 (to YYH), the
University of Chicago Cancer Research Center (P30 CA014599), the CTSA
(NIH UL1RR024999) and the University of Chicago Friends of Dermatology
Endowment Fund. We thank Terri Li for Ki67 and TUNEL and XPC
immunohistochemical analysis, and Dr Xiaobing Shi for kindly providing
the WT and K382R mutant p53 plasmids.
NR 45
TC 10
Z9 10
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JAN 15
PY 2015
VL 34
IS 3
BP 281
EP 287
DI 10.1038/onc.2013.583
PG 7
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AZ3RY
UT WOS:000348145500002
PM 24441046
ER
PT J
AU Sales, KU
Friis, S
Konkel, JE
Godiksen, S
Hatakeyama, M
Hansen, KK
Rogatto, SR
Szabo, R
Vogel, LK
Chen, W
Gutkind, JS
Bugge, TH
AF Sales, K. U.
Friis, S.
Konkel, J. E.
Godiksen, S.
Hatakeyama, M.
Hansen, K. K.
Rogatto, S. R.
Szabo, R.
Vogel, L. K.
Chen, W.
Gutkind, J. S.
Bugge, T. H.
TI Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant
progression and potentiation of ras-mediated squamous cell
carcinogenesis
SO ONCOGENE
LA English
DT Article
DE epithelial carcinogenesis; inflammation; keratinocyte stem cells;
pericellular proteolysis
ID PROTEINASE-ACTIVATED RECEPTOR-2; SERINE-PROTEASE MATRIPTASE; TISSUE
MICROARRAY ANALYSIS; HUMAN KERATINOCYTES; CLINICOPATHOLOGICAL
PARAMETERS; GENE-EXPRESSION; OVARIAN-CANCER; ENDOTHELIAL-CELLS;
EPITHELIAL-CELLS; IN-VITRO
AB The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)kappa B through G alpha i. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NF kappa B inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis.
C1 [Sales, K. U.; Friis, S.; Konkel, J. E.; Godiksen, S.; Hansen, K. K.; Szabo, R.; Chen, W.; Gutkind, J. S.; Bugge, T. H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Sales, K. U.] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD 20892 USA.
[Friis, S.; Godiksen, S.; Vogel, L. K.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Cellular & Mol Med, Copenhagen, Denmark.
[Godiksen, S.] Univ Copenhagen, Fac Sci, Dept Biol, Copenhagen, Denmark.
[Hatakeyama, M.; Rogatto, S. R.] Sao Paulo State Univ UNESP, Fac Med, Dept Urol, Botucatu, SP, Brazil.
[Hatakeyama, M.; Rogatto, S. R.] AC Camargo Canc Ctr, Sao Paulo, Brazil.
RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
RI Rogatto, Silvia/E-6535-2012
FU NIDCR Intramural Research Program; Augustinus Foundation, Kobmand
Kristian Kjaer og hustrus Foundation; Kjaer-Foundation; Dagmar Marshalls
Foundation; Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens
Foundation; Grosserer Valdemar Foersom og Hustru Thyra Foersoms
Foundation; Fabrikant Einar Willumsens Mindelegat; Sao Paulo Research
Foundation (FAPESP)
FX We thank Dr Mary Jo Danton for critically reviewing this manuscript.
Histology was performed by Histoserv, Germantown, MD, USA. We thank Dr
Allessia Gallo, Shyh-Ing Jang, Colleen Doci, Patricia Pilla, Zhiyong
Wang, Canstantinos Mikelis, Ramiro Iglesias-Bartolome and Morgan O'Hare
for technical assistance. The study was supported by the NIDCR
Intramural Research Program (THB, JSG, WC), the Augustinus Foundation,
Kobmand Kristian Kjaer og hustrus Foundation, the Kjaer-Foundation, the
Dagmar Marshalls Foundation, the Snedkermester Sophus Jacobsen og Hustru
Astrid Jacobsens Foundation, the Grosserer Valdemar Foersom og Hustru
Thyra Foersoms Foundation and Fabrikant Einar Willumsens Mindelegat (SG
and LKV), and the Sao Paulo Research Foundation (FAPESP) (MH, SRR).
NR 51
TC 10
Z9 11
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JAN 15
PY 2015
VL 34
IS 3
BP 288
EP 298
DI 10.1038/onc.2013.563
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AZ3RY
UT WOS:000348145500003
PM 24469043
ER
PT J
AU Earl, PL
Americo, JL
Cotter, CA
Moss, B
AF Earl, Patricia L.
Americo, Jeffrey L.
Cotter, Catherine A.
Moss, Bernard
TI Comparative live bioluminescence imaging of monkeypox virus
dissemination in a wild-derived inbred mouse (Mus musculus castaneus)
and outbred African dormouse (Graphiurus kelleni)
SO VIROLOGY
LA English
DT Article
DE Monkeypox virus pathogenesis; Monkeypox virus virulence;
Orthopoxviruses; Animal models; Smallpox
ID SMALL ANIMAL-MODELS; VACCINIA VIRUS; EXPERIMENTAL-INFECTION; PRAIRIE
DOGS; COMPARATIVE PATHOLOGY; SMALLPOX VACCINATION; CYNOMYS-LUDOVICIANUS;
STRAINS; DISEASE; PATHOGENESIS
AB Monkeypox virus belongs to the orthopoxvirus genus, infects rodents and monkeys in Africa, produces a smallpox-like zoonotic disease in humans, and has the potential for global spread and exploitation for bioterrorism. Several small animal models for studying monkeypox virus pathogenesis have been investigated. The African dormouse is a candidate natural host but is outbred and no immunological reagents exist. Although not a natural host, the CAST/EiJ mouse is inbred and animals and reagents are commercially available. We compared the dissemination of monkeypox virus by bioluminescence imaging in CAST/EiJ mice and dormice. In CAST/EiJ mice, intense replication occurred at the intranasal site of inoculation and virus spread rapidly to lungs and abdominal organs, which had a lower virus burden. Compared to CAST/EiJ mice, dormice exhibited a greater variation of virus spread, a slower time course, less replication in the head and chest, and more replication in abdominal organs prior to death. Published by Elsevier Inc.
C1 [Earl, Patricia L.; Americo, Jeffrey L.; Cotter, Catherine A.; Moss, Bernard] NIAID, Viral Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIH, Viral Dis Lab, 33 North Dr, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
OI Moss, Bernard/0000-0002-2154-8564
FU Division of Intramural Research, NIAID, NIH
FX We thank Gary Luker for advice regarding BLI and the NIAID Comparative
Medicine Branch for care of animals. The research was supported by the
Division of Intramural Research, NIAID, NIH.
NR 42
TC 1
Z9 1
U1 0
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JAN 15
PY 2015
VL 475
BP 150
EP 158
DI 10.1016/j.virol.2014.11.015
PG 9
WC Virology
SC Virology
GA AZ4FE
UT WOS:000348176500015
PM 25462355
ER
PT J
AU Itzel, T
Scholz, P
Maass, T
Krupp, M
Marquardt, JU
Strand, S
Becker, D
Staib, F
Binder, H
Roessler, S
Wang, XW
Thorgeirsson, S
Muller, M
Galle, PR
Teufel, A
AF Itzel, Timo
Scholz, Peter
Maass, Thorsten
Krupp, Markus
Marquardt, Jens U.
Strand, Susanne
Becker, Diana
Staib, Frank
Binder, Harald
Roessler, Stephanie
Wang, Xin Wei
Thorgeirsson, Snorri
Mueller, Martina
Galle, Peter R.
Teufel, Andreas
TI Translating bioinformatics in oncology: guilt-by-profiling analysis and
identification of KIF18B and CDCA3 as novel driver genes in
carcinogenesis
SO BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT 14th Annual Bioinformatics Open Source Conference (BOSC)
CY JUL 19-20, 2013
CL Special Interest Grp, Berlin, GERMANY
SP Open Bioinformat Fdn
HO Special Interest Grp
ID TUMOR-CELL GROWTH; HEPATOCELLULAR-CARCINOMA; MICROARRAY DATA; DATA SETS;
CANCER; PREDICTION; ASSOCIATION; DATABASE; SYSTEMS; TRANSFORMATION
AB Motivation: Co-regulated genes are not identified in traditional micro-array analyses, but may theoretically be closely functionally linked [guilt-by-association (GBA), guilt-by-profiling]. Thus, bioinformatics procedures for guilt-by-profiling/association analysis have yet to be applied to large-scale cancer biology.
We analyzed 2158 full cancer transcriptomes from 163 diverse cancer entities in regard of their similarity of gene expression, using Pearson's correlation coefficient (CC). Subsequently, 428 highly co-regulated genes (vertical bar CC vertical bar >= 0.8) were clustered unsupervised to obtain small co-regulated networks. A major subnetwork containing 61 closely co-regulated genes showed highly significant enrichment of cancer bio-functions. All genes except kinesin family member 18B (KIF18B) and cell division cycle associated 3 (CDCA3) were of confirmed relevance for tumor biology. Therefore, we independently analyzed their differential regulation in multiple tumors and found severe deregulation in liver, breast, lung, ovarian and kidney cancers, thus proving our GBA hypothesis. Overexpression of KIF18B and CDCA3 in hepatoma cells and subsequent microarray analysis revealed significant deregulation of central cell cycle regulatory genes. Consistently, RT-PCR and proliferation assay confirmed the role of both genes in cell cycle progression.
Finally, the prognostic significance of the identified KIF18B- and CDCA3-dependent predictors (P = 0.01, P = 0.04) was demonstrated in three independent HCC cohorts and several other tumors.
In summary, we proved the efficacy of large-scale guilt-by-profiling/association strategies in oncology. We identified two novel oncogenes and functionally characterized them. The strong prognostic importance of downstream predictors for HCC and many other tumors indicates the clinical relevance of our findings.
C1 [Itzel, Timo; Maass, Thorsten; Mueller, Martina; Teufel, Andreas] Univ Regensburg, Dept Med 1, D-93053 Regensburg, Germany.
[Scholz, Peter; Krupp, Markus; Marquardt, Jens U.; Strand, Susanne; Becker, Diana; Staib, Frank; Galle, Peter R.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, D-55131 Mainz, Germany.
[Binder, Harald] Johannes Gutenberg Univ Mainz, Univ Med Ctr, IMBEI, D-55131 Mainz, Germany.
[Roessler, Stephanie] Heidelberg Univ, Dept Pathol, D-69120 Heidelberg, Germany.
[Wang, Xin Wei; Thorgeirsson, Snorri] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
EM andreas.teufel@ukr.de
RI Binder, Harald/C-7413-2009; Wang, Xin/B-6162-2009
OI Binder, Harald/0000-0002-5666-8662;
FU German Cancer Aid [110989]; Intramural Research Program of the Center
for Cancer Research, National Cancer Institute (Bethesda, MD) [Z01 BC
010313]
FX TI, HB and AT were supported by the University Medical Center Mainz to
establish a bioinformatics core facility. JUM is supported by a grant
from the German Cancer Aid (110989). XWW was supported by a grant (Z01
BC 010313) from the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute (Bethesda, MD).
NR 40
TC 1
Z9 1
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JAN 15
PY 2015
VL 31
IS 2
BP 216
EP 224
DI 10.1093/bioinformatics/btu586
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA AY8WU
UT WOS:000347832300010
PM 25236463
ER
PT J
AU Wani, S
Das, A
Rastogi, A
Drahos, J
Ricker, W
Parsons, R
Bansal, A
Yen, R
Hosford, L
Jankowski, M
Sharma, P
Cook, MB
AF Wani, Sachin
Das, Ananya
Rastogi, Amit
Drahos, Jennifer
Ricker, Winifred
Parsons, Ruth
Bansal, Ajay
Yen, Roy
Hosford, Lindsay
Jankowski, Meghan
Sharma, Prateek
Cook, Michael B.
TI Endoscopic Ultrasonography in Esophageal Cancer Leads to Improved
Survival Rates: Results From a Population-Based Study
SO CANCER
LA English
DT Article
DE endoscopic ultrasonography; endoscopic ultrasound; esophageal cancer;
positron emission tomography and computed tomography; staging; survival
ID POSITRON-EMISSION-TOMOGRAPHY; CARCINOMA; ULTRASOUND; IMPACT;
ADENOCARCINOMA; ENDOSONOGRAPHY; METAANALYSIS; EUS
AB BACKGROUNDThe advantages of endoscopic ultrasound (EUS) and computed tomography (CT)-positron emission tomography (PET) with respect to survival for esophageal cancer patients are unclear. This study aimed to assess the effects of EUS, CT-PET, and their combination on overall survival with respect to cases not receiving these procedures.
METHODSPatients who were 66 years old when diagnosed with esophageal cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare linked database. Cases were split into 4 analytic groups: EUS only (n=318), CT-PET only (n=853), EUS+CT-PET (n=189), and no EUS or CT-PET (n=2439). Survival times were estimated with the Kaplan-Meier method and were compared with the log-rank test for each group versus the no EUS or CT-PET group. Multivariate Cox proportional hazards models were used to compare 1-, 3-, and 5-year survival rates.
RESULTSKaplan-Meier analyses showed that EUS, CT-PET, and EUS+CT-PET patients had improved survival for all stages (with the exception of stage 0 disease) in comparison with patients undergoing no EUS or CT-PET. Receipt of EUS increased the likelihood of receiving endoscopic therapies, esophagectomy, and chemoradiation. Multivariate Cox proportional hazards models showed that receipt of EUS was a significant predictor of improved 1- (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.39-0.59; P<.0001), 3- (HR, 0.57; 95% CI, 0.48-0.66; P<.0001), and 5-year survival (HR, 0.59; 95% CI, 0.50-0.68). Similar results were noted when the results were stratified on the basis of histology and for the CT-PET and EUS+CT-PET groups.
CONCLUSIONSReceipt of either EUS or CT-PET alone in esophageal cancer patients was associated with improved 1-, 3-, and 5-year survival. Future studies should identify barriers to the dissemination of these staging modalities. Cancer 2015;121:194-201. (c) 2014 American Cancer Society.
Patients undergoing endoscopic ultrasound (EUS), computed tomography (CT)-positron emission tomography (PET), or EUS and CT-PET have improved survival at all stages (with the exception of stage 0 disease) in comparison with patients undergoing no EUS or CT-PET. Receipt of EUS is a significant predictor for improved 1-, 3-, and 5-year survival. Similar results are noted when the results are stratified on the basis of histology and for groups undergoing CT-PET or EUS plus CT-PET.
C1 [Wani, Sachin; Yen, Roy; Hosford, Lindsay; Jankowski, Meghan] Univ Colorado, Anschutz Med Ctr, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA.
[Wani, Sachin] Vet Affairs Med Ctr, Div Gastroenterol & Hepatol, Denver, CO USA.
[Das, Ananya] Arizona Ctr Digest Hlth, Gilbert, AZ USA.
[Rastogi, Amit; Bansal, Ajay; Sharma, Prateek] Univ Kansas, Sch Med, Kansas City, MO USA.
[Rastogi, Amit; Bansal, Ajay; Sharma, Prateek] Vet Affairs Med Ctr, Kansas City, MO USA.
[Drahos, Jennifer; Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Ricker, Winifred; Parsons, Ruth] Informat Management Serv Inc, Rockville, MD USA.
RP Wani, S (reprint author), Univ Colorado, Anschutz Med Ctr, Div Gastroenterol & Hepatol, Mail Stop F735,1635 Aurora Court,Room 2-031, Aurora, CO 80045 USA.
EM sachinwani10@yahoo.com
RI Cook, Michael/A-5641-2009
OI Cook, Michael/0000-0002-0533-7302
FU AGA-Takeda Research Scholar Award in Gastroesophageal Reflux Disease and
Barrett's Esophagus; National Institutes of Health
FX Sachin Wani is supported by the AGA-Takeda Research Scholar Award in
Gastroesophageal Reflux Disease and Barrett's Esophagus. Jennifer Drahos
and Michael B. Cook are supported by the Intramural Program of the
National Institutes of Health.
NR 21
TC 10
Z9 11
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JAN 15
PY 2015
VL 121
IS 2
BP 194
EP 201
DI 10.1002/cncr.29043
PG 8
WC Oncology
SC Oncology
GA AY4IH
UT WOS:000347540900006
PM 25236485
ER
PT J
AU Messinger, YH
Stewart, DR
Priest, JR
Williams, GM
Harris, AK
Schultz, KAP
Yang, JD
Doros, L
Rosenberg, PS
Hill, DA
Dehner, LP
AF Messinger, Yoav H.
Stewart, Douglas R.
Priest, John R.
Williams, Gretchen M.
Harris, Anne K.
Schultz, Kris Ann P.
Yang, Jiandong
Doros, Leslie
Rosenberg, Philip S.
Hill, D. Ashley
Dehner, Louis P.
TI Pleuropulmonary Blastoma: A Report on 350 Central Pathology-Confirmed
Pleuropulmonary Blastoma Cases by the International Pleuropulmonary
Blastoma Registry
SO CANCER
LA English
DT Article
DE childhood cancer; DICER1; pleuropulmonary blastoma; rare cancer
ID PULMONARY BLASTOMA; PROGNOSTIC-FACTORS; DICER1 MUTATIONS; CHILDHOOD;
TUMOR; EXPERIENCE; CHILDREN
AB BACKGROUNDPleuropulmonary blastoma (PPB) has 3 subtypes on a tumor progression pathway ranging from type I (cystic) to type II (cystic/solid) and type III (completely solid). A germline mutation in DICER1 is the genetic cause in the majority of PPB cases.
METHODSPatients confirmed to have PPB by central pathology review were included, and their clinical characteristics and outcomes were reported. Germline DICER1 mutations were sought with Sanger sequencing.
RESULTSThere were 435 cases, and a central review confirmed 350 cases to be PPB; 85 cases (20%) were another entity. Thirty-three percent of the 350 PPB cases were type I or type I regressed (type Ir), 35% were type II, and 32% were type III or type II/III. The median ages at diagnosis for type I, type II, and type III patients were 8, 35, and 41 months, respectively. The 5-year overall survival (OS) rate for type I/Ir patients was 91%; all deaths in this group were due to progression to type II or III. OS was significantly better for type II versus type III (P=.0061); the 5-year OS rates were 71% and 53%, respectively. Disease-free survival (DFS) was also significantly better for type II versus type III (P=.0002); the 5-year DFS rates were 59% and 37%, respectively. The PPB type was the strongest predictor of outcome. Metastatic disease at the diagnosis of types II and III was also an independent unfavorable prognostic factor. Sixty-six percent of the 97 patients tested had a heterozygous germline DICER1 mutation. In this subset, the DICER1 germline mutation status was not related to the outcome.
CONCLUSIONSCystic type I/Ir PPB has a better prognosis than type II, and type II has a better outcome than type III. Surveillance of DICER1 carriers may allow the earlier detection of cystic PPB before its progression to type II or III PPB and thereby improve outcomes. Cancer 2015;121:276-85. (c) 2014 American Cancer Society.
Three hundred fifty centrally reviewed pleuropulmonary blastoma cases confirm that the outcomes of type I are better than the outcomes of type II and that the outcomes of type II are better than the outcomes of type III. Thus, the early detection of type I pleuropulmonary blastoma before its progression to type II or III may improve outcomes.
C1 [Messinger, Yoav H.; Priest, John R.; Williams, Gretchen M.; Harris, Anne K.; Schultz, Kris Ann P.] Childrens Hosp & Clin Minnesota, Int Pleuropulm Blastoma Registry, Minneapolis, MN 55404 USA.
[Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Yang, Jiandong; Hill, D. Ashley] Childrens Natl Med Ctr, Div Pathol, Washington, DC 20010 USA.
[Yang, Jiandong; Hill, D. Ashley] George Washington Univ, Sch Med, Dept Integrat Syst Biol, Med Genet Res Ctr, Washington, DC USA.
[Doros, Leslie] Childrens Natl Med Ctr, Div Oncol, Washington, DC 20010 USA.
[Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Dehner, Louis P.] Washington Univ, Lauren V Ackerman Lab Surg Pathol, Barnes Jewish Childrens Hosp, Dept Pathol & Immunol,Med Ctr, St Louis, MO USA.
[Dehner, Louis P.] Washington Univ, St Louis Childrens Hosp, Lauren V Ackerman Lab Surg Pathol, Dept Pathol & Immunol,Med Ctr, St Louis, MO 63110 USA.
RP Messinger, YH (reprint author), Childrens Hosp & Clin Minnesota, Int Pleuropulm Blastoma Registry, 2545 Chicago Ave South, Minneapolis, MN 55404 USA.
EM yoav.messinger@childrensmn.org
FU Division of Cancer Epidemiology and Genetics of the National Cancer
Institute's Intramural Research Program; Pine Tree Apple Tennis Classic;
M. Schutt Foundation; Children's Hospitals of Minnesota Foundation; St.
Baldrick's Foundation; Hyundai Hope on Wheels; National Institutes of
Health
FX This work was supported by the Division of Cancer Epidemiology and
Genetics of the National Cancer Institute's Intramural Research Program.
Charitable foundation grant support for this research was received from
Pine Tree Apple Tennis Classic, the M. Schutt Foundation, and the
Children's Hospitals of Minnesota Foundation. Kris Ann P. Schultz
reports grants from St. Baldrick's Foundation, Hyundai Hope on Wheels,
the National Institutes of Health (loan repayment program) during the
conduct of the study.
NR 32
TC 20
Z9 22
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JAN 15
PY 2015
VL 121
IS 2
BP 276
EP 285
DI 10.1002/cncr.29032
PG 10
WC Oncology
SC Oncology
GA AY4IH
UT WOS:000347540900015
PM 25209242
ER
PT J
AU Alderfer, MA
Zelley, K
Lindell, RB
Novokmet, A
Mai, PL
Garber, JE
Nathan, D
Scollon, S
Chun, NM
Patenaude, AF
Ford, JM
Plon, SE
Schiffman, JD
Diller, LR
Savage, SA
Malkin, D
Ford, CA
Nichols, KE
AF Alderfer, Melissa A.
Zelley, Kristin
Lindell, Robert B.
Novokmet, Ana
Mai, Phuong L.
Garber, Judy E.
Nathan, Deepika
Scollon, Sarah
Chun, Nicolette M.
Patenaude, Andrea F.
Ford, James M.
Plon, Sharon E.
Schiffman, Joshua D.
Diller, Lisa R.
Savage, Sharon A.
Malkin, David
Ford, Carol A.
Nichols, Kim E.
TI Parent Decision-Making Around the Genetic Testing of Children for
Germline TP53 Mutations
SO CANCER
LA English
DT Article
DE genetic testing; Li-Fraumeni syndrome; decision-making; pediatrics;
cancer
ID LI-FRAUMENI-SYNDROME; CANCER PREDISPOSITION; ISSUES; UPDATE; RISK
AB BACKGROUNDLi-Fraumeni syndrome is a rare genetic cancer predisposition syndrome caused by germline TP53 mutations. Up to 20% of mutation carriers develop cancer during childhood. The benefits of TP53 mutation testing of children are a matter of debate and knowledge of parent decision-making around such testing is limited. The current study examined how parents make decisions regarding TP53 testing for their children.
METHODSFamilies offered and those pursuing TP53 testing for their children were identified across the study sites. Qualitative interviews with 46 parents (39 families) were analyzed to describe decision-making styles and perceived advantages and disadvantages of testing.
RESULTSTP53 mutation testing uptake was high (92%). Three decision-making styles emerged. Automatic decisions (44% of decisions) involved little thought and identified immediate benefit(s) in testing (100% pursued testing). Considered decisions (49%) weighed the risks and benefits but were made easily (77% pursued testing). Deliberated decisions (6%) were difficult and focused on psychosocial concerns (25% pursued testing). Perceived advantages of testing included promoting child health, satisfying a need to know, understanding why cancer(s) occurred, suggesting family member risk, and benefiting research. Disadvantages included psychosocial risks and privacy/discrimination/insurance issues.
CONCLUSIONSAlthough empirical evidence regarding the benefits and risks of TP53 testing during childhood are lacking, the majority of parents in the current study decided easily in favor of testing and perceived a range of advantages. The authors conclude that in the context of a clinical diagnosis of Li-Fraumeni syndrome, parents should continue to be offered TP53 testing for their children, counseled regarding potential risks and benefits, and supported in their decision-making process. Cancer 2015;121:286-93. (c) 2014 American Cancer Society.
Li-Fraumeni Syndrome (LFS) is a rare genetic cancer predisposition syndrome caused by germline TP53 mutations in which up to 20% of mutation carriers develop cancer during childhood. Although empirical evidence regarding benefits and risks of TP53 testing during childhood are lacking, most parents in our study decided easily in favor of testing and perceived a range of advantages that outweighed risks.
C1 [Alderfer, Melissa A.; Zelley, Kristin; Lindell, Robert B.; Nichols, Kim E.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Alderfer, Melissa A.; Ford, Carol A.; Nichols, Kim E.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Novokmet, Ana; Malkin, David] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada.
[Mai, Phuong L.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Garber, Judy E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA.
[Garber, Judy E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Nathan, Deepika; Schiffman, Joshua D.] Univ Utah, Huntsman Canc Inst, High Risk Canc Clin, Salt Lake City, UT USA.
[Nathan, Deepika; Schiffman, Joshua D.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Scollon, Sarah; Plon, Sharon E.] Texas Childrens Canc Ctr, Canc Genet & Genom Program, Houston, TX USA.
[Scollon, Sarah; Plon, Sharon E.] Texas Childrens Hematol Ctr, Canc Genet & Genom Program, Houston, TX USA.
[Chun, Nicolette M.; Ford, James M.] Stanford Univ, Med Ctr, Canc Genet Program, Stanford, CA 94305 USA.
[Patenaude, Andrea F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA.
[Patenaude, Andrea F.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Ford, James M.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Ford, James M.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Plon, Sharon E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Plon, Sharon E.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Schiffman, Joshua D.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Diller, Lisa R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childhood Canc Survivor Program, Boston, MA 02115 USA.
[Diller, Lisa R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Malkin, David] Univ Toronto, Dept Pediat, Toronto, ON, Canada.
[Ford, Carol A.] Childrens Hosp Philadelphia, Div Adolescent Med, Philadelphia, PA 19104 USA.
RP Alderfer, MA (reprint author), Nemours Alfred I duPont Hosp Children, Ctr Healthcare Delivery Sci, 1600 Rockland Rd, Wilmington, DE 19803 USA.
EM melissa.alderfer@nemours.org
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU University of Pennsylvania Center for the Integration of Genetic
Healthcare Technologies (Penn-CIGHT); Center for Childhood Cancer
Research at The Children's Hospital of Philadelphia; Alex's Lemonade
Stand Foundation
FX Supported by grants from The University of Pennsylvania Center for the
Integration of Genetic Healthcare Technologies (Penn-CIGHT), the Center
for Childhood Cancer Research at The Children's Hospital of
Philadelphia, and Alex's Lemonade Stand Foundation.
NR 14
TC 5
Z9 5
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JAN 15
PY 2015
VL 121
IS 2
BP 286
EP 293
DI 10.1002/cncr.29027
PG 8
WC Oncology
SC Oncology
GA AY4IH
UT WOS:000347540900016
PM 25223899
ER
PT J
AU Mandl, JN
Ahmed, R
Barreiro, LB
Daszak, P
Epstein, JH
Virgin, HW
Feinberg, MB
AF Mandl, Judith N.
Ahmed, Rafi
Barreiro, Luis B.
Daszak, Peter
Epstein, Jonathan H.
Virgin, Herbert W.
Feinberg, Mark B.
TI Reservoir Host Immune Responses to Emerging Zoonotic Viruses
SO CELL
LA English
DT Review
ID AFRICAN-GREEN MONKEYS; NONPATHOGENIC SIV INFECTION; ACUTE RESPIRATORY
SYNDROME; EBOLA HEMORRHAGIC-FEVER; CHRONIC VIRAL-INFECTION; CD4(+)
T-CELLS; INFLUENZA-VIRUS; NIPAH VIRUS; PTEROPID BATS; RISK-FACTORS
AB Zoonotic viruses, such as HIV, Ebola virus, coronaviruses, influenza A viruses, hantaviruses, or henipaviruses, can result in profound pathology in humans. In contrast, populations of the reservoir hosts of zoonotic pathogens often appear to tolerate these infections with little evidence of disease. Why are viruses more dangerous in one species than another? Immunological studies investigating quantitative and qualitative differences in the host-virus equilibrium in animal reservoirs will be key to answering this question, informing new approaches for treating and preventing zoonotic diseases. Integrating an understanding of host immune responses with epidemiological, ecological, and evolutionary insights into viral emergence will shed light on mechanisms that minimize fitness costs associated with viral infection, facilitate transmission to other hosts, and underlie the association of specific reservoir hosts with multiple emerging viruses. Reservoir host studies provide a rich opportunity for elucidating fundamental immunological processes and their underlying genetic basis, in the context of distinct physiological and metabolic constraints that contribute to host resistance and disease tolerance.
C1 [Mandl, Judith N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Barreiro, Luis B.] Univ Montreal, St Justine Hosp Res Ctr, Dept Pediat, Montreal, PQ H3T 1J4, Canada.
[Daszak, Peter; Epstein, Jonathan H.] EcoHlth Alliance, New York, NY 10001 USA.
[Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Feinberg, Mark B.] Merck & Co Inc, Merck Vaccines, West Point, PA 19486 USA.
RP Mandl, JN (reprint author), McGill Univ, Dept Physiol, Montreal, PQ H3G 0B1, Canada.
EM mandlj@niaid.nih.gov
RI Barreiro, Luis/I-7772-2015
FU Intramural Research Program of NIAID, NIH
FX We would like to thank Nienke Vrisekoop, Roland Regoes, and Ronald
Germain for insightful comments, support, and advice during the
preparation of this manuscript. We are also extremely grateful to Tony
Schountz and our anonymous reviewers for their reading of the manuscript
and their very thoughtful feedback. This work was supported, in part, by
the Intramural Research Program of NIAID, NIH.
NR 124
TC 20
Z9 20
U1 4
U2 89
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JAN 15
PY 2015
VL 160
IS 1-2
BP 20
EP 35
DI 10.1016/j.cell.2014.12.003
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AZ0GD
UT WOS:000347923200006
PM 25533784
ER
PT J
AU Zhang, Y
Shen, J
AF Zhang, Yan
Shen, Jun
TI Regional and tissue-specific differences in brain glutamate
concentration measured by in vivo single voxel MRS
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Human brain; Glutamate; H-1 MRS; Averaged echo time; Regional
difference; Tissue composition; Metabolite quantification
ID REGULARIZED LINESHAPE DECONVOLUTION; METABOLITE RELAXATION-TIMES;
TE-AVERAGED PRESS; T-2 RELAXATION; WHITE-MATTER; 3 TESLA; SPECTROSCOPY;
WATER; DISTRIBUTIONS; QUANTITATION
AB Background: There is growing interest in characterizing spatial distribution of glutamate (Glu) in brain disorders. Comparing the differences in Glu concentration using magnetic resonance spectroscopy (MRS) is hampered by the confounding effects of different anatomical regions and tissue composition.
New method: Effect of tissue composition on Glu concentrations was studied by selecting closely adjacent voxels within a designated cortical region. Glu regional differences were assessed using voxels comprising essentially the same tissue composition from different cortical regions.
Results: Using point-resolved-spectroscopy (PRESS)-based averaged echo time method, Glu concentration in the anterior cingulate cortex (ACC) was found to correlate strongly with tissue gray matter (GM) fraction (r = 0.87, p = 10(-5)). No significant regional difference in Glu concentration was found between frontal and occipital lobes (p = 0.23) when the two measured voxels had essentially the same tissue composition.
Comparison with existing methods: The method of the current study is aimed to circumvent the difficulties in differentiating anatomical region from tissue composition, given that both can lead to Glu variations in brain. Glu concentration versus tissue composition was measured in the same anatomical region, while the comparison of regional differences was performed with the two regions that had essentially the same tissue composition.
Conclusions: In brain cortices, Glu level is significantly higher in GM than in WM. Glu level difference between frontal lobe and occipital lobe is insignificant. Published by Elsevier B.V.
C1 [Zhang, Yan; Shen, Jun] NIMH, MR Spect Core Facil, NIH, Bethesda, MD 20892 USA.
[Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Zhang, Y (reprint author), NIMH, MR Spect Core Facil, Bldg 10 Room 2D50,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM zhangya@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH) [ZIC MH002894-08]
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH) (grant no. ZIC MH002894-08). The NIMH had no further role
in study design; in the collection, analysis, or interpretation of data;
in the writing of the report; or in the decision to submit the paper for
publication.
NR 36
TC 5
Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
EI 1872-678X
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD JAN 15
PY 2015
VL 239
BP 94
EP 99
DI 10.1016/j.jneumeth.2014.09.021
PG 6
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AY6GE
UT WOS:000347664400011
PM 25261738
ER
PT J
AU Williams, KE
Miroshnychenko, O
Johansen, EB
Niles, RK
Sundaram, R
Kannan, K
Albertolle, M
Zhou, Y
Prasad, N
Drake, PM
Giudice, LC
Hall, SC
Witkowska, HE
Louis, GMB
Fisher, SJ
AF Williams, Katherine E.
Miroshnychenko, Olga
Johansen, Eric B.
Niles, Richard K.
Sundaram, Rajeshwari
Kannan, Kurunthachalam
Albertolle, Matthew
Zhou, Yan
Prasad, Namrata
Drake, Penelope M.
Giudice, Linda C.
Hall, Steven C.
Witkowska, H. Ewa
Louis, Germaine M. Buck
Fisher, Susan J.
TI Urine, peritoneal fluid and omental fat proteomes of reproductive age
women: Endometriosis-related changes and associations with endocrine
disrupting chemicals
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE Endometriosis; Peritoneal fluid; Urine; Omental fat; Mass spectrometry;
Environmental chemicals
ID PHTHALATE-ESTERS; ADIPOSE-TISSUE; BISPHENOL-A; BIOMARKERS; PROTEIN;
CELLS; CHROMATOGRAPHY; PROGRESSION; DISCOVERY; DIAGNOSIS
AB Endometriosis, ectopic growth of the uterine lining (endometrium), which affects 6-11% of reproductive age women, is associated with pelvic pain and infertility. We investigated the peritoneal fluid (PF), urine and omental fat (OF) proteomes of women with endometriosis vs. individuals with no surgically visualized endometriosis. All participants were enrolled in the NICHD-funded ENDO Study. A two-step proteomic study was performed. The first, a broad survey, employed a semi-quantitative gel LC-mass spectrometry (MS) workflow: SDS PAGE fractionation, trypsin digestion and LC MS/MS. The results showed sample integrity but failed to detect any differences between women with and without endometriosis. The second step was a quantitative analysis of OF samples. We employed another sample set (n = 30) from women +/- disease and isobaric mass-tag (iTRAQ) chemistry to label peptides and 2D LC MS/MS for protein identification and quantification. Three proteins matrix metalloproteinase-9, neutrophil elastase, and FAM49B-were significantly lower in abundance in samples from women with endometriosis. Interestingly, neutrophil elastase and FAM49B levels were associated with higher levels of a subset of endocrine disrupting chemicals (EDCs) that were previously measured in the same samples. The results of these experiments showed the feasibility of associating endometriosis with changes in the OF protein repertoire and EDC levels.
Biological significance
Endometriosis, pathological growth of the uterine lining, is associated with significant morbidities, including pain and infertility. However, the causes of this common condition are poorly understood. This study determined whether endometriosis was associated with changes in the protein composition of peritoneal fluid, urine and/or omental fat. A protein of unknown function (FAM49B) and two proteinases (metalloproteinase-9, neutrophil elastase) were down regulated in OF samples from women with versus without endometriosis. These findings suggested proteinase imbalances at sites that were distant from the endometriotic lesions. Additionally, FAM49B and neutrophil elastase levels were associated with higher levels of a subset of environmental chemicals that were quantified in the same samples, suggesting other possible associations. Thus, this work generated hypotheses that will be tested in further studies. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Williams, Katherine E.; Miroshnychenko, Olga; Johansen, Eric B.; Niles, Richard K.; Albertolle, Matthew; Prasad, Namrata; Drake, Penelope M.; Hall, Steven C.; Witkowska, H. Ewa; Fisher, Susan J.] Univ Calif San Francisco, Sandler Moore Mass Spectrometry Core Facil, San Francisco, CA 94143 USA.
[Williams, Katherine E.; Prasad, Namrata; Giudice, Linda C.; Hall, Steven C.; Witkowska, H. Ewa; Fisher, Susan J.] Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA.
[Williams, Katherine E.; Zhou, Yan; Prasad, Namrata; Giudice, Linda C.; Hall, Steven C.; Witkowska, H. Ewa; Fisher, Susan J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
[Sundaram, Rajeshwari; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA.
[Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Fisher, Susan J.] Univ Calif San Francisco, Div Maternal Fetal Med, San Francisco, CA 94143 USA.
[Zhou, Yan; Fisher, Susan J.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
[Fisher, Susan J.] Univ Calif San Francisco, Human Embryon Stem Cell Program, San Francisco, CA 94143 USA.
[Fisher, Susan J.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
RP Fisher, SJ (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
EM sfisher@cgl.ucsf.edu
OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis,
Germaine/0000-0002-1774-4490
FU NIH/NCI Cancer Center Support Grant [P30 CA082103]; Sandler New
Technology Award; Intramural Research Program, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health [NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02]
FX Funded by the Intramural Research Program, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health (contracts NO1-DK-6-3428; NO1-DK-6-3427;
10001406-02). Ethicon Endo-Surgery, LLC, kindly donated the HARMONIC ACE
36P shears and scalpel blades for use in the study through a signed
Materials Transfer Agreement with the University of Utah and the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development. The UCSF Sandler-Moore Mass Spectrometry Core Facility
acknowledges support from a Sandler New Technology Award, a gift from
the Gordon and Betty Moore Foundation, and NIH/NCI Cancer Center Support
Grant P30 CA082103.
NR 61
TC 3
Z9 4
U1 5
U2 25
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
EI 1876-7737
J9 J PROTEOMICS
JI J. Proteomics
PD JAN 15
PY 2015
VL 113
BP 194
EP 205
DI 10.1016/j.jprot.2014.09.015
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA AY4ZA
UT WOS:000347582200014
PM 25284053
ER
PT J
AU Gurdasani, D
Carstensen, T
Tekola-Ayele, F
Pagani, L
Tachmazidou, I
Hatzikotoulas, K
Karthikeyan, S
Iles, L
Pollard, MO
Choudhury, A
Ritchie, GS
Xue, YL
Asimit, J
Nsubuga, RN
Young, EH
Pomilla, C
Kivinen, K
Rockett, K
Kamali, A
Doumatey, AP
Asiki, G
Seeley, J
Sisay-Joof, F
Jallow, M
Tollman, S
Mekonnen, E
Ekong, R
Oljira, T
Bradman, N
Bojang, K
Ramsay, M
Adeyemo, A
Bekele, E
Motala, A
Norris, SA
Pirie, F
Kaleebu, P
Kwiatkowski, D
Tyler-Smith, C
Rotimi, C
Zeggini, E
Sandhu, MS
AF Gurdasani, Deepti
Carstensen, Tommy
Tekola-Ayele, Fasil
Pagani, Luca
Tachmazidou, Ioanna
Hatzikotoulas, Konstantinos
Karthikeyan, Savita
Iles, Louise
Pollard, Martin O.
Choudhury, Ananyo
Ritchie, GrahamR. S.
Xue, Yali
Asimit, Jennifer
Nsubuga, Rebecca N.
Young, Elizabeth H.
Pomilla, Cristina
Kivinen, Katja
Rockett, Kirk
Kamali, Anatoli
Doumatey, Ayo P.
Asiki, Gershim
Seeley, Janet
Sisay-Joof, Fatoumatta
Jallow, Muminatou
Tollman, Stephen
Mekonnen, Ephrem
Ekong, Rosemary
Oljira, Tamiru
Bradman, Neil
Bojang, Kalifa
Ramsay, Michele
Adeyemo, Adebowale
Bekele, Endashaw
Motala, Ayesha
Norris, Shane A.
Pirie, Fraser
Kaleebu, Pontiano
Kwiatkowski, Dominic
Tyler-Smith, Chris
Rotimi, Charles
Zeggini, Eleftheria
Sandhu, Manjinder S.
TI The African Genome Variation Project shapes medical genetics in Africa
SO NATURE
LA English
DT Article
ID POPULATION-GENETICS; WIDE ASSOCIATION; MALARIA; SELECTION; HYPERTENSION;
HISTORY; SUSCEPTIBILITY; REVEALS; DIVERSITY; EVOLUTION
AB Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.
C1 [Gurdasani, Deepti; Carstensen, Tommy; Pagani, Luca; Tachmazidou, Ioanna; Hatzikotoulas, Konstantinos; Karthikeyan, Savita; Iles, Louise; Pollard, Martin O.; Ritchie, GrahamR. S.; Xue, Yali; Asimit, Jennifer; Young, Elizabeth H.; Pomilla, Cristina; Kivinen, Katja; Adeyemo, Adebowale; Kwiatkowski, Dominic; Tyler-Smith, Chris; Zeggini, Eleftheria; Sandhu, Manjinder S.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Gurdasani, Deepti; Carstensen, Tommy; Karthikeyan, Savita; Iles, Louise; Young, Elizabeth H.; Pomilla, Cristina; Sandhu, Manjinder S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Tekola-Ayele, Fasil; Doumatey, Ayo P.; Adeyemo, Adebowale; Rotimi, Charles] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20891 USA.
[Pagani, Luca] Univ Bologna, Dept Biol Geol & Environm Sci, I-40126 Bologna, Italy.
[Iles, Louise] Univ York, Dept Archaeol, York YO1 7EP, N Yorkshire, England.
[Choudhury, Ananyo; Ramsay, Michele] Univ Witwatersrand, SBIMB, Johannesburg, Gauteng, South Africa.
[Ritchie, GrahamR. S.] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
[Nsubuga, Rebecca N.; Kamali, Anatoli; Asiki, Gershim; Seeley, Janet; Kaleebu, Pontiano] Uganda Virus Res Inst, MRC, Entebbe, Uganda.
[Rockett, Kirk; Kwiatkowski, Dominic] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Sisay-Joof, Fatoumatta; Jallow, Muminatou; Bojang, Kalifa] MRC Unit, Banjul, Gambia.
[Tollman, Stephen] MRC, Sch Publ Hlth, Wits Rural Publ Hlth & Hlth Transit Unit, Johannesburg, Gauteng, South Africa.
[Tollman, Stephen] INDEPTH Network, Accra, Ghana.
[Mekonnen, Ephrem] Univ Addis Ababa, Inst Biotechnol, Addis Ababa, Ethiopia.
[Ekong, Rosemary] UCL, Dept Genet Evolut & Environm, London, England.
[Oljira, Tamiru] Univ Haramaya, Dept Biol, Dire Dawa, Ethiopia.
[Bradman, Neil] Henry Stewart Grp, London WC1A 2HN, England.
[Ramsay, Michele] Natl Hlth Lab Serv, Div Human Genet, ZA-2000 Johannesburg, South Africa.
[Ramsay, Michele] Univ Witwatersrand, Fac Hlth Sci, Sch Pathol, ZA-2000 Johannesburg, South Africa.
[Bekele, Endashaw] Univ Addis Ababa, Coll Nat Sci, Dept Microbial Cellular & Mol Biol, Addis Ababa, Ethiopia.
[Motala, Ayesha; Pirie, Fraser] Univ KwaZulu Natal, Dept Endocrinol & Diabet, ZA-4013 Durban, South Africa.
[Norris, Shane A.] Univ Witwatersrand, Dept Paediat, Johannesburg, Gauteng, South Africa.
RP Sandhu, MS (reprint author), Wellcome Trust Sanger Inst, Genome Campus, Cambridge CB10 1SA, England.
EM dg11@sanger.ac.uk; cts@sanger.ac.uk; rotimic@mail.nih.gov;
eleftheria@sanger.ac.uk; ms23@sanger.ac.uk
RI Pollard, Martin/G-7205-2012;
OI Pollard, Martin/0000-0001-8738-0920; Seeley, Janet/0000-0002-0583-5272;
Asimit, Jennifer/0000-0002-4857-2249; Pagani, Luca/0000-0002-6639-524X;
Adeyemo, Adebowale/0000-0002-3105-3231; Zeggini,
Eleftheria/0000-0003-4238-659X; Kivinen, Katja/0000-0002-1135-7625;
Kwiatkowski, Dominic/0000-0002-5023-0176; Tekola-Ayele,
Fasil/0000-0003-4194-9370
FU Wellcome Trust [WT077383/Z/05/Z]; Wellcome Trust Sanger Institute
[WT098051]; Bill and Melinda Gates Foundation; Foundation for the
National Institutes of Health [566]; UK Medical Research Council
[G0901213-92157, G0801566, G0600718, MR/K013491/1]; South African Sugar
Association; Servier South Africa; Victor Daitz Foundation; National
Institute on Minority Health and Health Disparities; National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK); National Human
Genome Research Institute (NHGRI); Intramural Research Program of the
Center for Research on Genomics and Global Health (CRGGH) [Z01HG200362];
MRC Centre for Genomics and Global Health; Cambridge Commonwealth
Scholarship
FX This project was funded in part by the Wellcome Trust (grant number
WT077383/Z/05/Z), The Wellcome Trust Sanger Institute (grant number
WT098051), the Bill and Melinda Gates Foundation, the Foundation for the
National Institutes of Health (grant number 566), and the UK Medical
Research Council (grant numbers G0901213-92157, G0801566, G0600718 and
MR/K013491/1). We also acknowledge the National Institute for Health
Research Cambridge Biomedical Research Centre and the Wellcome Trust
Cambridge Centre for Global Health Research. We are very grateful to J.
Pickrell for sharing human origins data and MALDER code, and for useful
input on interpretations of these analyses. We also thank E. Garrison
for his suggestions on using Genome in a bottle sets
(ftp://ftp-trace.ncbi.nih.gov/giab/ftp/data/NA12878/variant_calls/NIST/R
EADME.NIST.v2.18.txt) for validation of whole-genome sequencing data. We
also thank the African Partnership for Chronic Disease Research
(APCDR)for providing a network to support this study as well as a
repository for deposition of curated data. Sample collections from South
Africa were funded by The South African Sugar Association, Servier South
Africa and The Victor Daitz Foundation. The Kenyan samples were
collected by D. Ngare of Moi University, Eldoret, Kenya, as part of the
Africa America Diabetes Mellitus (AADM) study and the International
HapMap project (D. Ngare, who is now deceased, was a great supporter of
genomics in Africa,as exemplified by his leadership in engaging the
Luhya and Maasai communities for the HapMap project). The Igbo samples
were collected by J. Oli of the University of Nigeria, Enugu, Nigeria.
The Ga-Adangbe samples were collected by the laboratories of A. Amoah of
the University of Ghana, Accra, Ghana, and J. Acheampong of the
University of Science and Technology, Kumasi, Ghana. Support for the
AADM study is provided by the National Institute on Minority Health and
Health Disparities, the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) and the National Human Genome Research Institute
(NHGRI). The Gambian samples were collected by M. Jallow and colleagues
at the MRC Unit, The Gambia and form part of the MalariaGEN Consortial
Resource. This research was supported in part by the Intramural Research
Program of the Center for Research on Genomics and Global Health (CRGGH;
grant number Z01HG200362) and by the MRC Centre for Genomics and Global
Health. D.G. was funded by the Cambridge Commonwealth Scholarship. We
thank the 1000 Genomes Project for sharing genotype data that were
analysed as part of this project. We also thank all study participants
who contributed to this study.
NR 50
TC 75
Z9 75
U1 5
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2015
VL 517
IS 7534
BP 327
EP U397
DI 10.1038/nature13997
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY8NK
UT WOS:000347810300037
PM 25470054
ER
PT J
AU Barretto, RPJ
Gillis-Smith, S
Chandrashekar, J
Yarmolinsky, DA
Schnitzer, MJ
Ryba, NJP
Zuker, CS
AF Barretto, Robert P. J.
Gillis-Smith, Sarah
Chandrashekar, Jayaram
Yarmolinsky, David A.
Schnitzer, Mark J.
Ryba, Nicholas J. P.
Zuker, Charles S.
TI The neural representation of taste quality at the periphery
SO NATURE
LA English
DT Article
ID FLUORESCENCE MICROENDOSCOPY; MAMMALIAN BRAIN; CHORDA TYMPANI; UMAMI
TASTE; RECEPTORS; STIMULI; SWEET; CELLS; MICE; BUDS
AB The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and palate epithelium(1). To understand how TRCs transmit information to higher neural centres, we examined the tuning properties of large ensembles of neurons in the first neural station of the gustatory system. Here, we generated and characterized a collection of transgenic mice expressing a genetically encoded calcium indicator' in central and peripheral neurons, and used a gradient refractive index microendoscope combined with high-resolution two-photon microscopy to image taste responses from ganglion neurons buried deep at the base of the brain. Our results reveal fine selectivity in the taste preference of ganglion neurons; demonstrate a strong match between TRCs in the tongue and the principal neural afferents relaying taste information to the brain; and expose the highly specific transfer of taste information between taste cells and the central nervous system.
C1 [Barretto, Robert P. J.; Gillis-Smith, Sarah; Yarmolinsky, David A.; Zuker, Charles S.] Columbia Univ, Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA.
[Barretto, Robert P. J.; Gillis-Smith, Sarah; Yarmolinsky, David A.; Zuker, Charles S.] Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Barretto, Robert P. J.; Gillis-Smith, Sarah; Yarmolinsky, David A.; Zuker, Charles S.] Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
[Chandrashekar, Jayaram; Zuker, Charles S.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Schnitzer, Mark J.] Stanford Univ, James H Clark Ctr, Stanford, CA 94305 USA.
[Ryba, Nicholas J. P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Zuker, CS (reprint author), Columbia Univ, Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA.
EM nick.ryba@nih.gov; cz2195@columbia.edu
FU NIDCR
FX We thank the National Institute of Dental and Craniofacial Research
(NIDCR) transgenic-core and C. Guo at Janelia Farms for help in
generating the Thy1-GCaMP3 mouse lines, B. Shields for histology
support, and Y. Oka and M. Butnaru for nerve recording and
pharmacological advice. We also thank members of the Zuker laboratory
for helpful comments. This research was supported in part by the
intramural research program of NIDCR (N.J.P.R.). C.S.Z. is an
investigator of the Howard Hughes Medical Institute and a Senior Fellow
at Janelia Farms.
NR 30
TC 23
Z9 23
U1 5
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 15
PY 2015
VL 517
IS 7534
BP 373
EP U511
DI 10.1038/nature13873
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY8NK
UT WOS:000347810300047
PM 25383521
ER
PT J
AU Wang, H
Ferraris, JD
Klein, JD
Sands, JM
Burg, MB
Zhou, XM
AF Wang, Hong
Ferraris, Joan D.
Klein, Janet D.
Sands, Jeff M.
Burg, Maurice B.
Zhou, Xiaoming
TI PKC-alpha contributes to high NaCl-induced activation of NFAT5
(TonEBP/OREBP) through MAPK ERK1/2
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE inner medulla; hypertonicity; Src homology 2 domain-containing
phosphatase 1; serine-591-phosphorylated Src homology 2
domain-containing phosphatase 1; urinary concentration; nuclear factor
of activated T cells 5; tonicity-responsive enhancer-binding protein;
osmotic response element-binding protein
ID KINASE-C-ALPHA; TRANSCRIPTION FACTOR TONEBP/OREBP; MEDULLARY COLLECTING
DUCTS; PATHOGENIC T(H)17 CELLS; THICK ASCENDING LIMB;
TYROSINE-PHOSPHATASE; GENE-EXPRESSION; PROTEIN; HYPERTONICITY; KIDNEY
AB High NaCl in the renal medullary interstitial fluid powers the concentration of urine but can damage cells. The transcription factor nuclear factor of activated T cells 5 (NFAT5) activates the expression of osmoprotective genes. We studied whether PKC-alpha contributes to the activation of NFAT5. PKC-alpha protein abundance was greater in the renal medulla than in the cortex. Knockout of PKC-alpha reduced NFAT5 protein abundance and expression of its target genes in the inner medulla. In human embryonic kidney (HEK)-293 cells, high NaCl increased PKC-alpha activity, and small interfering RNA-mediated knockdown of PKC-alpha attenuated high NaCl-induced NFAT5 transcriptional activity. Expression of ERK1/2 protein and phosphorylation of ERK1/2 were higher in the renal inner medulla than in the cortex. Knockout of PKC-alpha decreased ERK1/2 phosphorylation in the inner medulla, as did knockdown of PKC-alpha in HEK-293 cells. Also, knockdown of ERK2 reduced high NaCl-dependent NFAT5 transcriptional activity in HEK-293 cells. Combined knockdown of PKC-alpha and ERK2 had no greater effect than knockdown of either alone. Knockdown of either PKC-alpha or ERK2 reduced the high NaCl-induced increase of NFAT5 transactivating activity. We have previously found that the high NaCl-induced increase of phosphorylation of Ser(591) on Src homology 2 domain-containing phosphatase 1 (SHP-1-S591-P) contributes to the activation of NFAT5 in cell culture, and here we found high levels of SHP-1-S591-P in the inner medulla. PKC-alpha has been previously shown to increase SHP-1-S591-P, which raised the possibility that PKC-alpha might be acting through SHP-1. However, we did not find that knockout of PKC-alpha in the renal medulla or knockdown in HEK-293 cells affected SHP-1-S591-P. We conclude that PKC-alpha contributes to high NaCl-dependent activation of NFAT5 through ERK1/2 but not through SHP-1-S591.
C1 [Wang, Hong; Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Ferraris, Joan D.; Burg, Maurice B.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Klein, Janet D.; Sands, Jeff M.] Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA.
RP Zhou, XM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM xiaoming.zhou@usuhs.edu
FU Uniformed Services University [R083ZY]; National Institutes of Health
(NIH) [HL-006134-04, R01-DK-89828]
FX This work was funded in part by Uniformed Services University Grant
R083ZY (to X. Zhou) and National Institutes of Health (NIH) Grant
HL-006134-04 (to M. B. Burg). J. D. Klein and J. M. Sands were supported
by NIH Grant R01-DK-89828.
NR 51
TC 7
Z9 7
U1 1
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JAN 15
PY 2015
VL 308
IS 2
BP F140
EP F148
DI 10.1152/ajprenal.00471.2014
PG 9
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA AY3DC
UT WOS:000347463700009
PM 25391900
ER
PT J
AU Lugrin, J
Parapanov, R
Rosenblatt-Velin, N
Rignault-Clerc, S
Feihl, F
Waeber, B
Muller, O
Vergely, C
Zeller, M
Tardivel, A
Schneider, P
Pacher, P
Liaudet, L
AF Lugrin, Jerome
Parapanov, Roumen
Rosenblatt-Velin, Nathalie
Rignault-Clerc, Stephanie
Feihl, Francois
Waeber, Bernard
Mueller, Olivier
Vergely, Catherine
Zeller, Marianne
Tardivel, Aubry
Schneider, Pascal
Pacher, Pal
Liaudet, Lucas
TI Cutting Edge: IL-1 alpha Is a Crucial Danger Signal Triggering Acute
Myocardial Inflammation during Myocardial Infarction
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NLRP3 INFLAMMASOME; CELLS; INJURY; FIBROBLASTS; REPAIR
AB Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-kappa B in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88(-/-) fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1 alpha, but not IL-1 beta, and the immune activation of cardiac fibroblasts was abrogated by an IL-1R antagonist and an IL-1 alpha-blocking Ab. Moreover, immune responses triggered by necrotic Il1a(-/-) cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1 alpha in the plasma, and postischemic inflammation was attenuated in Il1a(-/-) mice. Thus, our findings identify IL-1 alpha as a crucial early danger signal triggering post-MI inflammation.
C1 [Lugrin, Jerome; Parapanov, Roumen; Liaudet, Lucas] Univ Lausanne, Univ Hosp Med Ctr, Dept Intens Care Med, CH-1011 Lausanne, Switzerland.
[Rosenblatt-Velin, Nathalie; Rignault-Clerc, Stephanie; Feihl, Francois; Waeber, Bernard; Liaudet, Lucas] Univ Lausanne, Univ Hosp Med Ctr, Dept Clin Pathophysiol, CH-1011 Lausanne, Switzerland.
[Mueller, Olivier] Univ Lausanne, Univ Hosp Med Ctr, Dept Cardiol, CH-1011 Lausanne, Switzerland.
[Vergely, Catherine; Zeller, Marianne] Univ Bourgogne, Fac Med & Pharm, INSERM Unite Mixte Rech 866, Lab Physiopathol & Pharmacol Cardiometabol, F-21000 Dijon, France.
[Tardivel, Aubry; Schneider, Pascal] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
[Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
RP Liaudet, L (reprint author), Univ Hosp Med Ctr, Fac Biol & Med, Dept Intens Care Med, CH-1010 Lausanne, Switzerland.
EM lucas.liaudet@chuv.ch
RI Pacher, Pal/B-6378-2008; Vergely, Catherine/L-9534-2015; Lugrin,
Jerome/F-8739-2011; Liaudet, Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Lugrin, Jerome/0000-0002-1178-2752;
Liaudet, Lucas/0000-0003-2670-4930
FU Swiss National Foundation for Scientific Research [310030_135394/1,
310030_132491]; Muschamp Foundation; National Institutes of
Health/National Institute on Alcohol Abuse and Alcoholism
FX This work was supported by the Swiss National Foundation for Scientific
Research (Grants 310030_135394/1 to L.L. and 310030_132491 to N.R.-V.),
the Muschamp Foundation (to L.L.), and the Intramural Program of the
National Institutes of Health/National Institute on Alcohol Abuse and
Alcoholism (to P.P.). Breeding of Nlrp3-/- mice was supported
by the Institute for Arthritis Research at Lausanne University.
NR 16
TC 16
Z9 17
U1 1
U2 8
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 JAN 15
PY 2015
VL 194
IS 2
BP 499
EP 503
DI 10.4049/jimmunol.1401948
PG 5
WC Immunology
SC Immunology
GA AX8RR
UT WOS:000347176700002
PM 25505286
ER
PT J
AU Saunders, PM
Vivian, JP
Baschuk, N
Beddoe, T
Widjaja, J
O'Connor, GM
Hitchen, C
Pymm, P
Andrews, DM
Gras, S
McVicar, DW
Rossjohn, J
Brooks, AG
AF Saunders, Philippa M.
Vivian, Julian P.
Baschuk, Nikola
Beddoe, Travis
Widjaja, Jacqueline
O'Connor, Geraldine M.
Hitchen, Corinne
Pymm, Phillip
Andrews, Daniel M.
Gras, Stephanie
McVicar, Daniel W.
Rossjohn, Jamie
Brooks, Andrew G.
TI The Interaction of KIR3DL1*001 with HLA Class I Molecules Is Dependent
upon Molecular Microarchitecture within the Bw4 Epitope
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX;
IMMUNOGLOBULIN-LIKE RECEPTOR; INHIBITORY RECEPTOR; CRYSTAL-STRUCTURE;
MEDIATED LYSIS; NK CELLS; T-CELLS; RECOGNITION; KIR3DL1
AB The killer cell Ig-like receptor 3DL1 (KIR3DL1) inhibits activation of NK cells upon interaction with HLA class I molecules such as HLA-B*57:01, which contains the Bw4 epitope spanning residues 77-83 (e.g., NLRIALR), and not with HLA allomorphs that possess the Bw6 motif (e.g., HLA-B*08:01), which differ at residues 77, 80, 81, 82, and 83. Although Bw4 residues Ile(80) and Arg(83) directly interact with KIR3DL1*001, their precise role in determining KIR3DL1-HLA-Bw4 specificity remains unclear. Recognition of HLA-B*57:01 by either KIR3DL1(+) NK cells or the NK cell line YTS transfected with KIR3DL1*001 was impaired by mutation of residues 80 and 83 of HLA-B*57:01 to the corresponding amino acids within the Bw6 motif. Conversely, the simultaneous introduction of three Bw4 residues at positions 80, 82, and 83 into HLA-B*08: 01 conferred an interaction with KIR3DL1*001. Structural analysis of HLA-B*57:01, HLA-B*08:01, and mutants of each bearing substitutions at positions 80 and 83 revealed that Ile(80) and Arg(83) within the Bw4 motif constrain the conformation of Glu(76), primarily through a salt bridge between Arg(83) and Glu(76). This salt bridge was absent in HLA-Bw6 molecules as well as position 83 mutants of HLA-B*57:01. Mutation of the Bw4 residue Ile(80) also disrupted this salt bridge, providing further insight into the role that position 80 plays in mediating KIR3DL1 recognition. Thus, the strict conformation of HLA-Bw4 allotypes, held in place by the Glu(76)-Arg(83) interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha 1 helix that is less permissive for KIR3DL1 binding.
C1 [Saunders, Philippa M.; Widjaja, Jacqueline; Brooks, Andrew G.] Univ Melbourne, Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
[Vivian, Julian P.; Beddoe, Travis; Hitchen, Corinne; Pymm, Phillip; Gras, Stephanie; Rossjohn, Jamie] Monash Univ, Dept Biochem & Mol Biol, Sch Biomed Sci, Clayton, Vic 3800, Australia.
[Vivian, Julian P.; Rossjohn, Jamie] Monash Univ, Australian Res Council, Ctr Excellence Adv Mol Imaging, Clayton, Vic 3800, Australia.
[Baschuk, Nikola; Andrews, Daniel M.] Peter McCallum Canc Inst, Canc Immunol Program, Melbourne, Vic 3002, Australia.
[O'Connor, Geraldine M.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
RP Rossjohn, J (reprint author), Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
EM jamie.rossjohn@monash.edu; agbrooks@unimelb.edu.au
RI McVicar, Daniel/G-1970-2015;
OI Brooks, Andrew/0000-0002-4085-9683; Rossjohn, Jamie/0000-0002-2020-7522
FU National Health and Medical Research Council; Association for
International Cancer Research; Intramural Research Program of the
National Institutes of Health, National Cancer Institute, National
Institute of Allergy and Infectious Diseases; Frederick National
Laboratory for Cancer Research, National Institutes of Health
[HHSN26120080001E]; National Health and Medical Research Council Career
Development Award
FX This work was supported by grants from the National Health and Medical
Research Council and the Association for International Cancer Research
(to A.G.B. and J.R.), and the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, National
Institute of Allergy and Infectious Diseases, and federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health Contract HHSN26120080001E. J.P.V. is an Australian Research
Council Discovery Early Career Researcher Award Fellow; D.M.A. is the
recipient of a National Health and Medical Research Council Career
Development Award; and J.R. is a National Health and Medical Research
Council of Australia Fellow.
NR 41
TC 6
Z9 6
U1 0
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 JAN 15
PY 2015
VL 194
IS 2
BP 781
EP 789
DI 10.4049/jimmunol.1402542
PG 9
WC Immunology
SC Immunology
GA AX8RR
UT WOS:000347176700029
PM 25480565
ER
PT J
AU Kumar, S
Sarkar, P
Sim, MJW
Rajagopalan, S
Vogel, SS
Long, EO
AF Kumar, Santosh
Sarkar, Pabak
Sim, Malcolm J. W.
Rajagopalan, Sumati
Vogel, Steven S.
Long, Eric O.
TI A Single Amino Acid Change in Inhibitory Killer Cell Ig-like Receptor
Results in Constitutive Receptor Self-Association and Phosphorylation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID BIMOLECULAR FLUORESCENCE COMPLEMENTATION; TARGET-CELLS; DIRECT BINDING;
NK CELLS; ACTIVATION; COMPLEX; CYTOTOXICITY; RECOGNITION; LYMPHOCYTES;
MOLECULES
AB Signaling by immunoreceptors is often initiated by phosphorylation of cytosolic tyrosines, which then recruit effector molecules. In the case of MHC class I-specific inhibitory receptors, phosphorylation of cytosolic tyrosine residues within ITIMs results in recruitment of a protein tyrosine phosphatase that blocks activation signals. Recent work showed that signaling by an HLA-C-specific killer cell Ig-like receptor (KIR) is independent of signaling by activation receptors. It is not known how ITIM phosphorylation is initiated and regulated. In this article, we show that substitution of His-36 in the first Ig domain of KIR2DL1 with alanine (KIR2DL1-H36A) resulted in constitutive KIR2DL1 self-association and phosphorylation, as well as recruitment of tyrosine phosphatase SHP-1. Furthermore, substitution of His-36 with a similar bulky amino acid, phenylalanine, maintained the receptor in its unphosphorylated state, suggesting that steric hindrance by the His-36 side chain prevents constitutive KIR2DL1 self-association and ITIM phosphorylation. The equally strong phosphorylation of KIR2DL1 and KIR2DL1-H36A after inhibition of tyrosine phosphatase by pervanadate suggested that KIR2DL1-H36A is selectively protected from dephosphorylation. We propose that KIR phosphorylation is controlled by the accessibility of ITIM to tyrosine phosphatases and that KIR binding to HLA-C must override the hindrance that His-36 puts on KIR2DL1 self-association. Expression of KIR2DL1-H36A on NK cells led to stronger inhibition of lysis of HLA-C+ target cells than did expression of wild-type KIR2DL1. These results revealed that ITIM phosphorylation is controlled by self-association of KIR and that His-36 serves as a gatekeeper to prevent unregulated signaling through KIR2DL1.
C1 [Kumar, Santosh; Sim, Malcolm J. W.; Rajagopalan, Sumati; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Sarkar, Pabak; Vogel, Steven S.] NIAAA, Lab Mol Physiol, NIH, Rockville, MD 20892 USA.
[Sim, Malcolm J. W.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Med, Lung Immunol Grp, London W12 0NN, England.
RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr,Room 201E, Rockville, MD 20852 USA.
EM elong@nih.gov
OI Vogel, Steven/0000-0002-3005-2667; Sim, Malcolm/0000-0003-3407-9661
FU Intramural Research Program at the National Institutes of Health,
National Institute of Allergy and Infectious Diseases; National
Institute on Alcohol Abuse and Alcoholism; National Institutes of
Health-Wellcome Trust studentship
FX This work was supported by the Intramural Research Program at the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, and National Institute on Alcohol Abuse and
Alcoholism. M.J.W.S. is supported by a National Institutes of
Health-Wellcome Trust studentship.
NR 38
TC 4
Z9 4
U1 0
U2 7
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 JAN 15
PY 2015
VL 194
IS 2
BP 817
EP 826
DI 10.4049/jimmunol.1401830
PG 10
WC Immunology
SC Immunology
GA AX8RR
UT WOS:000347176700033
PM 25505289
ER
PT J
AU Cannon, TD
Chung, Y
He, G
Sun, DQ
Jacobson, A
van Erp, TGM
McEwen, S
Addington, J
Bearden, CE
Cadenhead, K
Cornblatt, B
Mathalon, DH
McGlashan, T
Perkins, D
Jeffries, C
Seidman, LJ
Tsuang, M
Walker, E
Woods, SW
Heinssen, R
AF Cannon, Tyrone D.
Chung, Yoonho
He, George
Sun, Daqiang
Jacobson, Aron
van Erp, Theo G. M.
McEwen, Sarah
Addington, Jean
Bearden, Carrie E.
Cadenhead, Kristin
Cornblatt, Barbara
Mathalon, Daniel H.
McGlashan, Thomas
Perkins, Diana
Jeffries, Clark
Seidman, Larry J.
Tsuang, Ming
Walker, Elaine
Woods, Scott W.
Heinssen, Robert
CA North Amer Prodrome Longitudinal S
TI Progressive Reduction in Cortical Thickness as Psychosis Develops: A
Multisite Longitudinal Neuroimaging Study of Youth at Elevated Clinical
Risk
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Inflammation; MRI; Prefrontal cortex; Prodromal; Psychosis;
Schizophrenia
ID ULTRA-HIGH-RISK; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX;
MAGNETIC-RESONANCE; NEUROANATOMICAL ABNORMALITIES; ANTIPSYCHOTIC
TREATMENT; HIPPOCAMPAL VOLUME; INDIVIDUALS; SCHIZOPHRENIA; BRAIN
AB BACKGROUND: Individuals at clinical high risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with individuals without symptomatic progression and with healthy control subjects. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown.
METHODS: In this multisite study, 274 CHR cases, including 35 individuals who converted to psychosis, and 135 healthy comparison subjects were scanned with magnetic resonance imaging at baseline, 12-month follow-up, or the point of conversion for the subjects who developed fully psychotic symptoms.
RESULTS: In a traveling subjects substudy, excellent reliability was observed for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR subjects who converted to psychosis showed a steeper rate of gray matter loss in the right superior frontal, middle frontal, and medial orbitofrontal cortical regions as well as a greater rate of expansion of the third ventricle compared with CHR subjects who did not convert to psychosis and healthy control subjects. Differential tissue loss was present in subjects who had not received antipsychotic medications during the interscan interval and was predicted by baseline levels of an aggregate measure of proinflammatory cytokines in plasma.
CONCLUSIONS: These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced in subjects with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acuteonset forms of psychosis.
C1 [Cannon, Tyrone D.; Chung, Yoonho; He, George; Jacobson, Aron] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Cannon, Tyrone D.; McGlashan, Thomas; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Sun, Daqiang; McEwen, Sarah; Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA.
[Sun, Daqiang; McEwen, Sarah; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[van Erp, Theo G. M.] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA.
[Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Cadenhead, Kristin; Tsuang, Ming] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Cornblatt, Barbara] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA.
[Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Perkins, Diana] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Jeffries, Clark] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC USA.
[Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Walker, Elaine] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Heinssen, Robert] NIMH, Div Treatment & Prevent Res, Rockville, MD 20857 USA.
RP Cannon, TD (reprint author), Yale Univ, Dept Psychol, 2 Hillhouse Ave,POB 208205, New Haven, CT 06520 USA.
EM tyrone.cannon@yale.edu
FU National Institute of Mental Health (NIMH) at the National Institutes of
Health [MH081902, MH081857, MH081988, MH081928, MH082004, MH082022,
MH081984, MH066160]; NIMH [P50 MH066286, P50 MH080272]; Commonwealth of
Massachusetts [SCDMH82101008006]
FX This work was supported by a collaborative U01 award from the National
Institute of Mental Health (NIMH) at the National Institutes of Health
(Grant Nos. MH081902 [TDC], MH081857 [BC], MH081988 [EW], MH081928
[LJS], MH082004 [DP], MH082022 [KC], MH081984 [JA], and MH066160 [SWW])
and NIMH Grant No. P50 MH066286 (CEB), NIMH Grant No. P50 MH080272, and
the Commonwealth of Massachusetts (Grant No. SCDMH82101008006 [LJS]).
NR 64
TC 74
Z9 74
U1 15
U2 41
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JAN 15
PY 2015
VL 77
IS 2
BP 147
EP 157
DI 10.1016/j.biopsych.2014.05.023
PG 11
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AW6NQ
UT WOS:000346386600010
PM 25034946
ER
PT J
AU Evans, JW
Kundu, P
Horovitz, SG
Bandettini, PA
AF Evans, Jennifer W.
Kundu, Prantik
Horovitz, Silvina G.
Bandettini, Peter A.
TI Separating slow BOLD from non-BOLD baseline drifts using multi-echo fMRI
SO NEUROIMAGE
LA English
DT Article
DE fMRI; Multi-echo; Denoising; Slow drift; Non-BOLD; BOLD
ID EVENT-RELATED FMRI; LOW-FREQUENCY DRIFT; FUNCTIONAL CONNECTIVITY;
PERFUSION FMRI; HUMAN BRAIN; CONTRAST SENSITIVITY; EMPIRICAL ANALYSES;
NULL-HYPOTHESIS; EPI; CORTEX
AB The functional magnetic resonance (fMRI) baseline is known to drift over the course of an experiment and is often attributed to hardware instability. These ultraslow fMRI fluctuations are inseparable from blood oxygenation level dependent (BOLD) changes in standard single echo fMRI and they are therefore typically removed before further analysis in both resting-state and task paradigms. However, some part of these fluctuations may be of neuronal origin, as neural activity can indeed fluctuate at the scale of several minutes or even longer, such as after the administration of drugs or during the ultradian rhythms. Here, we show that it is possible to separate the slow BOLD and non-BOLD drifts automatically using multi-echo fMRI and multi-echo independent components analysis (ME-ICA) denoising by demonstrating the detection of a visual signal evoked from a flickering checkerboard with slowly changing contrast. Published by Elsevier Inc.
C1 [Evans, Jennifer W.; Kundu, Prantik; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, LBC, NIH, Bethesda, MD 20892 USA.
[Horovitz, Silvina G.] NINDS, Human Motor Control Sect, MNB, NIH, Bethesda, MD 20892 USA.
RP Evans, JW (reprint author), 10 Ctr Dr,Bldg 10,Rm 1D73, Bethesda, MD 20892 USA.
EM jennifer.evans@nih.gov
OI Kundu, Prantik/0000-0001-9367-3068
FU Intramural NIH HHS [Z99 MH999999]
NR 38
TC 9
Z9 9
U1 3
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2015
VL 105
BP 189
EP 197
DI 10.1016/j.neuroimage.2014.10.051
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AW1LG
UT WOS:000346050300018
PM 25449746
ER
PT J
AU Collins, J
Huynh, M
AF Collins, John
Minh Huynh
TI Integrative modeling of multi-platform genomic data under the framework
of mediation analysis Reply
SO STATISTICS IN MEDICINE
LA English
DT Editorial Material
C1 [Collins, John] George Mason Univ, Dept Rehabil Sci, Coll Hlth & Human Serv, Fairfax, VA 22030 USA.
[Minh Huynh] NIH, Epidemiol & Biostat Sect, RMD, Mark O Hatfield Clin Res Ctr, Rockville, MD 20852 USA.
RP Collins, J (reprint author), George Mason Univ, Dept Rehabil Sci, Coll Hlth & Human Serv, 4400 Univ Dr,2G7, Fairfax, VA 22030 USA.
EM jcolli22@gmu.edu; minh.huynh@nih.gov
FU Intramural NIH HHS [Z99 CL999999]
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 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD JAN 15
PY 2015
VL 34
IS 1
BP 179
EP 180
DI 10.1002/sim.6328
PG 2
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AW3CI
UT WOS:000346162700015
PM 25492618
ER
PT J
AU Consonni, D
De Matteis, S
Pesatori, AC
Bertazzi, PA
Olsson, AC
Kromhout, H
Peters, S
Vermeulen, RCH
Pesch, B
Bruning, T
Kendzia, B
Behrens, T
Stucker, I
Guida, F
Wichmann, HE
Bruske, I
Landi, MT
Caporaso, NE
Gustavsson, P
Plato, N
Tse, LA
Yu, ITS
Jockel, KH
Ahrens, W
Pohlabeln, H
Merletti, F
Richiardi, L
Simonato, L
Forastiere, F
Siemiatycki, J
Parent, ME
Tardon, A
Boffetta, P
Zaridze, D
Chen, Y
Field, JK
't Mannetje, A
Pearce, N
McLaughlin, J
Demers, P
Lissowska, J
Szeszenia-Dabrowska, N
Bencko, V
Foretova, L
Janout, V
Rudnai, P
Fabianova, E
Dumitru, RS
Bueno-de-Mesquita, HB
Schuz, J
Straif, K
AF Consonni, Dario
De Matteis, Sara
Pesatori, Angela C.
Bertazzi, Pier Alberto
Olsson, Ann C.
Kromhout, Hans
Peters, Susan
Vermeulen, Roel C. H.
Pesch, Beate
Bruening, Thomas
Kendzia, Benjamin
Behrens, Thomas
Stuecker, Isabelle
Guida, Florence
Wichmann, Heinz-Erich
Brueske, Irene
Landi, Maria Teresa
Caporaso, Neil E.
Gustavsson, Per
Plato, Nils
Tse, Lap Ah
Yu, Ignatius Tak-sun
Joeckel, Karl-Heinz
Ahrens, Wolfgang
Pohlabeln, Hermann
Merletti, Franco
Richiardi, Lorenzo
Simonato, Lorenzo
Forastiere, Francesco
Siemiatycki, Jack
Parent, Marie-Elise
Tardon, Adonina
Boffetta, Paolo
Zaridze, David
Chen, Ying
Field, John K.
't Mannetje, Andrea
Pearce, Neil
McLaughlin, John
Demers, Paul
Lissowska, Jolanta
Szeszenia-Dabrowska, Neonila
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Rudnai, Peter
Fabianova, Eleonora
Dumitru, Rodica Stanescu
Bueno-de-Mesquita, H. B(as)
Schuez, Joachim
Straif, Kurt
TI Lung cancer risk among bricklayers in a pooled analysis of case-control
studies
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE lung neoplasms; case-control studies; bricklayers; occupational health;
epidemiology
ID CRYSTALLINE SILICA DUST; OCCUPATIONAL-EXPOSURE; CONSTRUCTION-INDUSTRY;
NORDIC COUNTRIES; UNITED-STATES; POPULATION; MORTALITY; WORKERS; MEN;
CARCINOGENS
AB Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p<0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos.
What's new? In their work, bricklayers can be exposed to various airborne carcinogens, including crystalline silica and asbestos. Previous studies of cancer risk have not accounted for full employment history or smoking status, and failed to establish a firm relationship between bricklaying and lung cancer. In this study, the authors used data from the largest collection of case-control studies on lung cancer with complete occupational and smoking history existing today, the SYNERGY project. They found clear evidence that lung cancer risk increases in proportion to the length of time spent working as a bricklayer, paving the way for better protection and compensation for those in this occupation.
C1 [Consonni, Dario; Pesatori, Angela C.; Bertazzi, Pier Alberto] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, I-20122 Milan, Italy.
[De Matteis, Sara] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[De Matteis, Sara; Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Olsson, Ann C.; Schuez, Joachim; Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon, France.
[Olsson, Ann C.; Gustavsson, Per; Plato, Nils] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Kromhout, Hans; Peters, Susan; Vermeulen, Roel C. H.] Inst Risk Assessment Sci, Utrecht, Netherlands.
[Peters, Susan] Univ Western Australia, Sch Populat Hlth, Perth, WA 6009, Australia.
[Pesch, Beate; Bruening, Thomas; Kendzia, Benjamin; Behrens, Thomas] Ruhr Univ Bochum IPA, German Social Accid Insurance Inst, Inst Prevent & Occupat Med, Bochum, Germany.
[Stuecker, Isabelle; Guida, Florence] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Environm Epidemiol Canc Team, Paris, France.
[Stuecker, Isabelle; Guida, Florence] Univ Paris 11, UMRS 1018, Paris, France.
[Wichmann, Heinz-Erich; Brueske, Irene] Deutsch Forschungszentrum Gesundheit & Umwelt, Inst Epidemiol 1, Neuherberg, Germany.
[Landi, Maria Teresa; Caporaso, Neil E.] NCI, NIH, Bethesda, MD 20892 USA.
[Tse, Lap Ah; Yu, Ignatius Tak-sun] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China.
[Joeckel, Karl-Heinz] Univ Duisburg Essen, Univ Hosp, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Ahrens, Wolfgang; Pohlabeln, Hermann] Leibniz Inst Prevent Res & Epidemiol BIPS, Bremen, Germany.
[Ahrens, Wolfgang] Univ Bremen, Inst Stat, D-28359 Bremen, Germany.
[Merletti, Franco; Richiardi, Lorenzo] Univ Turin, CPO Piemonte, Dept Med Sci, Canc Epidemiol Unit, Turin, Italy.
[Simonato, Lorenzo] Univ Padua, Dept Mol Med, Padua, Italy.
[Forastiere, Francesco] ASL Roma E, Dept Epidemiol, Rome, Italy.
[Siemiatycki, Jack] Univ Montreal, Hosp Res Ctr CRCHUM, Montreal, PQ, Canada.
[Siemiatycki, Jack] Sch Publ Hlth, Montreal, PQ, Canada.
[Parent, Marie-Elise] INRS Inst Armand Frappier, Epidemiol & Biostat Unit, Laval, PQ, Canada.
[Tardon, Adonina] Univ Oviedo, Oviedo, Spain.
[Tardon, Adonina] Ciber Epidemiol & Salud Publ CIBERESP, Oviedo, Spain.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Zaridze, David] Russian Canc Res Ctr, Moscow, Russia.
[Chen, Ying; Field, John K.] Univ Liverpool, Canc Res Ctr, Dept Mol & Clin Canc Med, Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England.
[Chen, Ying] Keele Univ, Res Inst Primary Care & Hlth Sci, Arthrit Res UK Primary Care Ctr, Keele, Staffs, England.
['t Mannetje, Andrea] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Pearce, Neil] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England.
[McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Demers, Paul] Canc Care Ontario, Occupat Canc Res Ctr, Toronto, ON, Canada.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Dumitru, Rodica Stanescu] Inst Publ Hlth, Bucharest, Romania.
[Bueno-de-Mesquita, H. B(as)] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. B(as)] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. B(as)] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
RP Consonni, D (reprint author), Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Via San Barnaba 8, I-20122 Milan, Italy.
EM Dario.Consonni@unimi.it
RI Janout, Vladimir/M-5133-2014; Chen, Ying/I-4349-2013; Yu, Ignatius Tak
Sun/A-9936-2008; Szeszenia-Dabrowska, Neonila/F-7190-2010; Bruning,
Thomas/G-8120-2015; Forastiere, Francesco/J-9067-2016; Consonni,
Dario/K-7943-2016; Vermeulen, Roel/F-8037-2011; bertazzi, pietro
alberto/D-5039-2017
OI richiardi, lorenzo/0000-0003-0316-9402; pesatori,
angela/0000-0002-0261-3252; Ahrens, Wolfgang/0000-0003-3777-570X; Field,
John/0000-0003-3951-6365; Peters, Susan/0000-0001-5662-1971; Pearce,
Neil/0000-0002-9938-7852; Bruning, Thomas/0000-0001-9560-5464;
Forastiere, Francesco/0000-0002-9162-5684; Consonni,
Dario/0000-0002-8935-3843; Vermeulen, Roel/0000-0003-4082-8163;
bertazzi, pietro alberto/0000-0003-3475-2449
FU German Social Accident Insurance (DGUV) [FP 271]; Canadian Institutes
for Health Research; Guzzo-SRC Chair in Environment and Cancer; National
Cancer Institute of Canada; Canadian Cancer Society; Occupational Cancer
Research Centre; Workplace Safety and Insurance Board; Cancer Care
Ontario; European Commission's INCO Copernicus program [IC15-CT96-0313];
European Union Nuclear Fission Safety Program [F14P-CT96-0055]; French
Agency of Health Security (ANSES); Fondation de France; French National
Research Agency (ANR); National Institute of Cancer (INCA); Fondation
pour la Recherche Medicale; French Institute for Public Health
Surveillance (InVS); Health Ministry (DGS); Organization for the
Research on Cancer (ARC); French Ministry of work, solidarity, and
public function (DGT); Federal Ministry of Education, Science, Research,
and Technology [01 HK 173/0]; Federal Ministry of Science [01 HK 546/8];
Ministry of Labour and Social Affairs [IIIb7-27/13]; Research Grants
Council of the Hong Kong Special Administrative Region, China
[CUHK4460/03M]; Environmental Epidemiology Program of the Lombardy
Region; INAIL; Italian Association for Cancer Research; Region Piedmont;
Compagnia di San Paolo; Lazio Region; Health Research Council of New
Zealand; New Zealand Department of Labour; Lottery Health Research;
Cancer Society of New Zealand; Polish State Committee for Scientific
Research [SPUB-M-COPERNICUS/P-05/DZ-30/99/2000]; Instituto Universitario
de Oncologia; Universidad de Oviedo; Asturias; Fondo de Investigacion
Sanitaria (FIS); Ciber de Epidemiologia y Salud Publica (CIBERESP);
Swedish Council for Work Life Research; Swedish Environmental Protection
Agency; Dutch Ministry of Health, Welfare and Sports; National Institute
of Public Health and the Environment; Europe Against Cancer Program; Roy
Castle Foundation; Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Division of Cancer
Epidemiology and Genetics, Bethesda, Maryland
FX Grant sponsor: German Social Accident Insurance (DGUV); Grant number: FP
271; Grant sponsors: Canadian Institutes for Health Research and
Guzzo-SRC Chair in Environment and Cancer, National Cancer Institute of
Canada, Canadian Cancer Society, Occupational Cancer Research Centre,
Workplace Safety and Insurance Board, Canadian Cancer Society, and
Cancer Care Ontario; Grant sponsor: European Commission's INCO
Copernicus program; Grant number: IC15-CT96-0313; Grant sponsor:
European Union Nuclear Fission Safety Program; Grant number:
F14P-CT96-0055; Grant sponsors: French Agency of Health Security
(ANSES), Fondation de France, French National Research Agency (ANR),
National Institute of Cancer (INCA), Fondation pour la Recherche
Medicale, French Institute for Public Health Surveillance (InVS), Health
Ministry (DGS), Organization for the Research on Cancer (ARC), and
French Ministry of work, solidarity, and public function (DGT); Grant
sponsor: Federal Ministry of Education, Science, Research, and
Technology; Grant number: 01 HK 173/0); Grant sponsor: Federal Ministry
of Science; Grant number: 01 HK 546/8; Grant sponsor: Ministry of Labour
and Social Affairs; Grant number: IIIb7-27/13; Grant sponsor: Research
Grants Council of the Hong Kong Special Administrative Region, China;
Grant number: CUHK4460/03M; Grant sponsors: Environmental Epidemiology
Program of the Lombardy Region, INAIL, Italian Association for Cancer
Research, Region Piedmont, Compagnia di San Paolo, Lazio Region, Health
Research Council of New Zealand, New Zealand Department of Labour,
Lottery Health Research, Cancer Society of New Zealand; Grant sponsor:
Polish State Committee for Scientific Research; Grant number:
SPUB-M-COPERNICUS/P-05/DZ-30/99/2000; Grant sponsors: Instituto
Universitario de Oncologia, Universidad de Oviedo, Asturias, Fondo de
Investigacion Sanitaria (FIS) and Ciber de Epidemiologia y Salud Publica
(CIBERESP), Swedish Council for Work Life Research and Swedish
Environmental Protection Agency, Dutch Ministry of Health, Welfare and
Sports, National Institute of Public Health and the Environment, and
Europe Against Cancer Program, Roy Castle Foundation, and Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Division of Cancer Epidemiology and Genetics, Bethesda,
Maryland.
NR 56
TC 5
Z9 5
U1 2
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JAN 15
PY 2015
VL 136
IS 2
BP 360
EP 371
DI 10.1002/ijc.28986
PG 12
WC Oncology
SC Oncology
GA AS9ZK
UT WOS:000344596600014
PM 24861979
ER
PT J
AU Silver, J
Li, ZY
Neuman, K
AF Silver, Jonathan
Li, Zhenyu
Neuman, Keir
TI Tethered-bead, immune sandwich assay
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Tethered-bead immunoassay; DNA tethers; Flow-mediated DNA extension;
Opto- microfluidics; PSA immunoassay; Single-molecule immunoassay
ID SINGLE MOLECULES; RNA-POLYMERASE; DNA; BIOSENSORS; FLOW; MICROSCOPY;
ANTIGEN; SURFACE; CELLS; FIELD
AB We describe a proof-of-principle, immune sandwich assay in which immune complexes link micron-size beads via DNA tethers to a sensor surface. The number of tethered beads, counted using low-magnification microscopy, provides a measure of the concentration of analyte. The prototype assay was sensitive to pM concentration of analyte. In theory, the assay could be sensitive to sub-fM analyte because beads attached via single-immune complexes and DNA strands form tethers, and tether formation in the absence of analyte is extremely rare. The limiting step at present is binding of streptavidin at the end of DNA to biotin on capture beads. Potential advantages of this type of sensor are discussed. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Silver, Jonathan] George Washington Univ, Dept Mech & Aerosp Engn, Washington, DC 20052 USA.
[Silver, Jonathan; Neuman, Keir] NHLBI, Biophys Lab, NIH, Bethesda, MD 20902 USA.
[Li, Zhenyu] George Washington Univ, Dept Elect & Comp Engn, Washington, DC USA.
RP Silver, J (reprint author), George Washington Univ, Dept Mech & Aerosp Engn, Washington, DC 20052 USA.
EM jesilver@gwu.edu
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU Intramural Research Program of the National Heart, Lung, and Blood
Institute at the National Institutes of Health; Institute of
Bioengineering at George Washington University
FX We thank Liusongsen Yang for help constructing flow cells and image
analysis. This research was supported by the Intramural Research Program
of the National Heart, Lung, and Blood Institute at the National
Institutes of Health and by a grant from the Institute of Bioengineering
at George Washington University to ZL and JS.
NR 21
TC 1
Z9 1
U1 1
U2 39
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
EI 1873-4235
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD JAN 15
PY 2015
VL 63
BP 117
EP 123
DI 10.1016/j.bios.2014.07.011
PG 7
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA AR1HT
UT WOS:000343337000017
PM 25064819
ER
PT J
AU Motta, M
Ramadan, A
Hillis, AE
Gottesman, RF
Leigh, R
AF Motta, Melissa
Ramadan, Amanda
Hillis, Argye E.
Gottesman, Rebecca F.
Leigh, Richard
TI Diffusion-perfusion mismatch: an opportunity for improvement in cortical
function
SO FRONTIERS IN NEUROLOGY
LA English
DT Article
DE diffusion-perfusion mismatch; acute ischemic stroke; penumbra; NIHSS;
functional outcome
ID POSITRON-EMISSION-TOMOGRAPHY; ACUTE STROKE; ISCHEMIC PENUMBRA;
COMPUTED-TOMOGRAPHY; CEREBRAL-ISCHEMIA; TISSUE; MRI; NEGLECT; TIME
AB Objective: There has been controversy over whether diffusion-perfusion mismatch provides a biomarker for the ischemic penumbra. In the context of clinical stroke trials, regions of the diffusion-perfusion mismatch that do not progress to infarct in the absence of reperfusion are considered to represent "benign oligemia." However, at least in some cases (particularly large vessel stenosis), some of this hypoperfused tissue may remain dysfunctional for a prolonged period without progressing to infarct and may recover function if eventually reperfused. We hypothesized that patients with persistent diffusion-perfusion mismatch using a hypoperfusion threshold of 4-5.9 s delay on time-to-peak (TTP) maps at least sometimes have persistent cognitive deficits relative to those who show some reperfusion of this hypoperfused tissue.
Methods: We tested this hypothesis in 38 patients with acute ischemic stroke who had simple cognitive tests (naming or line cancelation) and MRI with diffusion and perfusion imaging within 24h of onset and again within 10 days, most of whom had large vessel stenosis or occlusion.
Results: A persistent perfusion deficit of 4-5.9 s delay in TIP on follow up MRI was associated with a persistent cognitive deficit at that time point (p < 0.001). When we evaluated only patients who did not have infarct growth (n = 14), persistent hypoperfusion (persistent mismatch) was associated with a lack of cognitive improvement compared with those who had reperfused. The initial volume of hypoperfusion did not correlate with the later infarct volume (progression to infarct), but change in volume of hypoperfusion correlated with change in cognitive performance (p = 0.0001). Moreover, multivariable regression showed that the change in volume of hypoperfused tissue of 4-5.9 s delay (p = 0.002), and change in volume of ischemic tissue on diffusion weighted imaging (p = 0.02) were independently associated with change in cognitive function.
Conclusion: Our results provide additional evidence that non-infarcted tissue with a TIP delay of 4-5.9 s may be associated with persistent deficits, even if it does not always result in imminent progression to infarct. This tissue may represent the occasional opportunity to intervene to improve function even days after onset of symptoms.
C1 [Motta, Melissa] Univ Maryland, Sch Med, R Adams Shock Trauma Ctr, Baltimore, MD 21201 USA.
[Ramadan, Amanda] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Hillis, Argye E.; Gottesman, Rebecca F.; Leigh, Richard] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
RP Leigh, R (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, NIH, 10 Ctr Dr,Bldg 10,B1D733 MSC 1063, Bethesda, MD 20892 USA.
EM richard.leigh@nih.gov
FU National Institutes of Health (National Institute of Deafness and
Communication Disorders) [R25NS065729, R01 NS047691, DC05375, R01
DC03681]; National Institutes of Health (National Institute of
Neurological Disorders and Stroke) [R25NS065729, R01 NS047691, DC05375,
R01 DC03681]
FX This research reported in this paper was supported by the National
Institutes of Health (National Institute of Deafness and Communication
Disorders and National Institute of Neurological Disorders and Stroke)
through awards R25NS065729 to authors Melissa Motta and Argye E. Hillis,
and R01 NS047691, DC05375, and R01 DC03681 to author Argye E. Hillis.
The content is solely the responsibility of the authors and does not
necessarily represent the views the National Institutes of Health.
NR 20
TC 2
Z9 2
U1 0
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-2295
J9 FRONT NEUROL
JI Front. Neurol.
PD JAN 14
PY 2015
VL 5
AR UNSP 280
DI 10.3389/fneur.2014.00280
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CU7WE
UT WOS:000363751700001
ER
PT J
AU Vandekar, SN
Shinohara, RT
Raznahan, A
Roalf, DR
Ross, M
DeLeo, N
Ruparel, K
Verma, R
Wolf, DH
Gur, RC
Gur, RE
Satterthwaite, TD
AF Vandekar, Simon N.
Shinohara, Russell T.
Raznahan, Armin
Roalf, David R.
Ross, Michelle
DeLeo, Nicholas
Ruparel, Kosha
Verma, Ragini
Wolf, Daniel H.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
TI Topologically Dissociable Patterns of Development of the Human Cerebral
Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cortex; cortical thickness; development; diffusion imaging; MRI; white
matter
ID SURFACE-BASED ANALYSIS; WHITE-MATTER VOLUME; MAGNETIC-RESONANCE;
DIFFUSION MRI; HUMAN BRAIN; FUNCTIONAL-ORGANIZATION;
COGNITIVE-DEVELOPMENT; TANGENTIAL EXPANSION; ONSET SCHIZOPHRENIA;
CORTICAL THICKNESS
AB Over 90 years ago, anatomists noted the cortex is thinner in sulci than gyri, suggesting that development may occur on a fine scale driven by local topology. However, studies of brain development in youth have focused on describing how cortical thickness varies over large-scale functional and anatomic regions. How the relationship between thickness and local sulcal topology arises in development is still not well understood. Here, we investigated the spatial relationships between cortical thickness, folding, and underlying white matter organization to elucidate the influence of local topology on human brain development. Our approach included using both T1-weighted imaging and diffusion tensor imaging (DTI) in a cross-sectional sample of 932 youths ages 8 - 21 studied as part of the Philadelphia Neurodevelopmental Cohort. Principal components analysis revealed separable development-related processes of regionally specific nonlinear cortical thickening (from ages 8 - 14) and widespread linear cortical thinning that have dissociable relationships with cortical topology. Whereas cortical thinning was most prominent in the depths of the sulci, early cortical thickening was present on the gyri. Furthermore, decline in mean diffusivity calculated from DTI in underlying white matter was correlated with cortical thinning, suggesting that cortical thinning is spatially associated with white matter development. Spatial permutation tests were used to assess the significance of these relationships. Together, these data demonstrate that cortical remodeling during youth occurs on a local topological scale and is associated with changes in white matter beneath the cortical surface.
C1 [Vandekar, Simon N.; Roalf, David R.; DeLeo, Nicholas; Ruparel, Kosha; Wolf, Daniel H.; Gur, Ruben C.; Gur, Raquel E.; Satterthwaite, Theodore D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Vandekar, Simon N.; Shinohara, Russell T.; Ross, Michelle] Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA.
[Verma, Ragini; Gur, Ruben C.; Gur, Raquel E.] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA.
[Raznahan, Armin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Gur, Ruben C.] Philadelphia Vet Adm Med Ctr, Philadelphia, PA 19104 USA.
RP Satterthwaite, TD (reprint author), Hosp Univ Penn, 10th Floor,Gates Bldg, Philadelphia, PA 19104 USA.
EM sattertt@upenn.edu
FU National Institute of Mental Health RC2 [MH089983, MH089924]; Center for
Biomedical Computing and Image Analysis at the University of
Pennsylvania; National Institute of Mental Health [K23MH098130,
K01MH102609, R01MH101111, T32MH065218-11]; Marc Rapport Family
Investigator grant through the Brain and Behavior Foundation; National
Institute of Neurological Disorders and Stroke [R01NS085211]; Sidney R.
Baer, Jr. Foundation through the Brain and Behavior Foundation
FX This work was supported by National Institute of Mental Health RC2
Grants MH089983 and MH089924. Support for developing statistical
analyses (to S.N.V., R.T.S., and T.D.S.) was provided by a seed grant
from the Center for Biomedical Computing and Image Analysis at the
University of Pennsylvania. T.D.S. was supported by Grant K23MH098130
from the National Institute of Mental Health and the Marc Rapport Family
Investigator grant through the Brain and Behavior Foundation. R.T.S. was
supported by Grant R01NS085211 from the National Institute of
Neurological Disorders and Stroke. D.R.R. was supported by Grant
K01MH102609 from the National Institute of Mental Health. D.H.W. was
supported by Grant R01MH101111 from the National Institute of Mental
Health and the Sidney R. Baer, Jr. Foundation through the Brain and
Behavior Foundation. S.N.V. was supported by Grant T32MH065218-11 from
the National Institute of Mental Health. We thank Madhura Ingalhalikar
and Alex Smith for assistance with data processing. We also thank the
acquisition and recruitment team: Jeff Valdez, Raphael Gerraty, Marisa
Riley, Jack Keefe, Elliott Yodh, and Rosetta Chiavacci. We thank Chad
Jackson for data management. We thank Scott Troyan for assistance with
figures. We sincerely thank Fabian Scheipl for help on hypothesis
testing in general additive models. We thank Aaron Alexander-Bloch and
Phil Reiss for advice on implementation of the general additive model.
NR 69
TC 13
Z9 13
U1 1
U2 10
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 14
PY 2015
VL 35
IS 2
BP 599
EP 609
DI 10.1523/JNEUROSCI.3628-14.2015
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CB1SW
UT WOS:000349409300016
PM 25589754
ER
PT J
AU Roberts, AM
Ware, JS
Herman, DS
Schafer, S
Baksi, J
Bick, AG
Buchan, RJ
Walsh, R
John, S
Wilkinson, S
Mazzarotto, F
Felkin, LE
Gong, SS
MacArthur, JAL
Cunningham, F
Flannick, J
Gabriel, SB
Altshuler, DM
Macdonald, PS
Heinig, M
Keogh, AM
Hayward, CS
Banner, NR
Pennell, DJ
O'Regan, DP
San, TR
De Marvao, A
Dawes, TJW
Gulati, A
Birks, EJ
Yacoub, MH
Radke, M
Gotthardt, M
Wilson, JG
O'Donnell, CJ
Prasad, SK
Barton, PJR
Fatkin, D
Hubner, N
Seidman, JG
Seidman, CE
Cook, SA
AF Roberts, Angharad M.
Ware, James S.
Herman, Daniel S.
Schafer, Sebastian
Baksi, John
Bick, Alexander G.
Buchan, Rachel J.
Walsh, Roddy
John, Shibu
Wilkinson, Samuel
Mazzarotto, Francesco
Felkin, Leanne E.
Gong, Sungsam
MacArthur, Jacqueline A. L.
Cunningham, Fiona
Flannick, Jason
Gabriel, Stacey B.
Altshuler, David M.
Macdonald, Peter S.
Heinig, Matthias
Keogh, Anne M.
Hayward, Christopher S.
Banner, Nicholas R.
Pennell, Dudley J.
O'Regan, Declan P.
San, Tan Ru
De Marvao, Antonio
Dawes, Timothy J. W.
Gulati, Ankur
Birks, Emma J.
Yacoub, Magdi H.
Radke, Michael
Gotthardt, Michael
Wilson, James G.
O'Donnell, Christopher J.
Prasad, Sanjay K.
Barton, Paul J. R.
Fatkin, Diane
Hubner, Norbert
Seidman, Jonathan G.
Seidman, Christine E.
Cook, Stuart A.
TI Integrated allelic, transcriptional, and phenomic dissection of the
cardiac effects of titin truncations in health and disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID CARDIOVASCULAR MAGNETIC-RESONANCE; FAMILIAL DILATED CARDIOMYOPATHY;
HEART-FAILURE; PROGNOSTIC VALUE; RISK-FACTORS; POPULATION; VARIANTS;
MUTATIONS; SEQUENCE; GENES
AB The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms (using the TTN transcript annotations available at http://cardiodb.org/titin), and demonstrate that these data, coupled with the position of the TTNtv, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause of DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses, we provide evidence for a length-dependent mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings.
C1 [Roberts, Angharad M.; O'Regan, Declan P.; De Marvao, Antonio; Dawes, Timothy J. W.; Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England.
[Roberts, Angharad M.; Ware, James S.; Baksi, John; Buchan, Rachel J.; Walsh, Roddy; John, Shibu; Wilkinson, Samuel; Mazzarotto, Francesco; Felkin, Leanne E.; Gong, Sungsam; Pennell, Dudley J.; Gulati, Ankur; Prasad, Sanjay K.; Barton, Paul J. R.] Royal Brompton & Harefield Natl Hlth Serv NHS Fdn, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London SW3 6NP, England.
[Roberts, Angharad M.; Ware, James S.; Baksi, John; Buchan, Rachel J.; Walsh, Roddy; John, Shibu; Wilkinson, Samuel; Mazzarotto, Francesco; Felkin, Leanne E.; Gong, Sungsam; Pennell, Dudley J.; Gulati, Ankur; Prasad, Sanjay K.; Barton, Paul J. R.] Univ London Imperial Coll Sci Technol & Med, London SW3 6NP, England.
[Ware, James S.; Mazzarotto, Francesco; Felkin, Leanne E.; Banner, Nicholas R.; Pennell, Dudley J.; Birks, Emma J.; Yacoub, Magdi H.; Barton, Paul J. R.; Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6NP, England.
[Ware, James S.; Herman, Daniel S.; Bick, Alexander G.; Seidman, Jonathan G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Ware, James S.; Herman, Daniel S.; Bick, Alexander G.; Flannick, Jason; Gabriel, Stacey B.; Altshuler, David M.; Seidman, Christine E.] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Ware, James S.; Herman, Daniel S.; Bick, Alexander G.; Flannick, Jason; Gabriel, Stacey B.; Altshuler, David M.; Seidman, Christine E.] MIT, Cambridge, MA 02142 USA.
[Herman, Daniel S.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Schafer, Sebastian; Heinig, Matthias] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
[MacArthur, Jacqueline A. L.; Cunningham, Fiona] Wellcome Trust Genome Campus, European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SD, Cambs, England.
[Flannick, Jason] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Altshuler, David M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Macdonald, Peter S.; Keogh, Anne M.; Hayward, Christopher S.; Fatkin, Diane] St Vincents Hosp, Dept Cardiol, Darlinghurst, NSW 2010, Australia.
[Macdonald, Peter S.; Keogh, Anne M.; Hayward, Christopher S.; Fatkin, Diane] Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia.
[Macdonald, Peter S.; Keogh, Anne M.; Hayward, Christopher S.; Fatkin, Diane] Univ New S Wales, Fac Med, Kensington, NSW 2052, Australia.
[Banner, Nicholas R.] Harefield Hosp, Royal Brompton & Harefield NHS Fdn Trust, Harefield UB9 6JH, Middx, England.
[San, Tan Ru; Cook, Stuart A.] Natl Heart Ctr, Singapore 169609, Singapore.
[Birks, Emma J.] Univ Louisville, Dept Med, Louisville, KY 40202 USA.
[Birks, Emma J.] Jewish Hosp, Louisville, KY 40202 USA.
[Radke, Michael; Gotthardt, Michael] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
[Gotthardt, Michael] German Ctr Cardiovasc Res, D-13347 Berlin, Germany.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[O'Donnell, Christopher J.] NHLBI, FraminghamHeart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Hubner, Norbert] Charite, D-10117 Berlin, Germany.
[Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Seidman, Christine E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Cook, Stuart A.] Duke Natl Univ Singapore, Singapore 169857, Singapore.
RP Cook, SA (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England.
EM cseidman@genetics.med.harvard.edu; stuart.cook@nhcs.com.sg
RI Mazzarotto, Francesco/E-1843-2017;
OI Mazzarotto, Francesco/0000-0002-6159-9980; Felkin,
Leanne/0000-0003-1402-8314; Barton, Paul/0000-0002-1165-7767; Schafer,
Sebastian/0000-0002-6909-8275; Gotthardt, Michael/0000-0003-1788-3172;
Gong, Sungsam/0000-0001-5796-4423; Walsh, Roddy/0000-0001-5092-8825; de
Marvao, Antonio/0000-0001-9095-5887; Ware, James/0000-0002-6110-5880
FU NIHR Biomedical Research Unit in Cardiovascular Disease at Royal
Brompton & Harefield NHS Foundation Trust; Imperial College London; NIHR
Imperial Biomedical Research Centre; British Heart Foundation UK
[SP/10/10/28431, PG/12/27/29489]; European Molecular Biology Laboratory;
MRC UK; Wellcome Trust UK [087183/Z/08/Z, 092854/Z/10/Z, WT095908];
Fondation Leducq; Tanoto Foundation; Goh Foundation; Academy of Medical
Sciences; Arthritis Research UK; Heart Research UK; CORDA; National
Medical Research Council (NMRC) Singapore; Rosetrees Trus; European
Community's Seventh Framework Programme (FP7 [GEN2PHEN project])
[CardioNeT-ITN-289600, 200754]; National Human Genome Research Institute
[U54 HG003067]; NIH [HL080494, 5-T32-GM007748-33]; Howard Hughes Medical
Institute; Australian National Health and Medical Research Council;
NHLBI [N01-HC-25195, 6R01-NS 17950, N01-HC-95170, N01-HC-95171,
N01-HC-95172, HL-102924]; National Institute for Minority Health and
Health Disparities; National Institute of Biomedical Imaging and
Bioengineering; U.S. Department of Health and Human Services
[N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
32118-32119, 32122, 42107-26, 42129-32, 44221]
FX The research was supported by the NIHR Biomedical Research Unit in
Cardiovascular Disease at Royal Brompton & Harefield NHS Foundation
Trust and Imperial College London, NIHR Imperial Biomedical Research
Centre, British Heart Foundation UK (SP/10/10/28431, PG/12/27/29489),
European Molecular Biology Laboratory, MRC UK, Wellcome Trust UK
(087183/Z/08/Z, 092854/Z/10/Z, WT095908), Fondation Leducq, Tanoto
Foundation, Goh Foundation, Academy of Medical Sciences, Arthritis
Research UK, Heart Research UK, CORDA, National Medical Research Council
(NMRC) Singapore, Rosetrees Trust, European Community's Seventh
Framework Programme (FP7) [CardioNeT-ITN-289600; 200754 - the GEN2PHEN
project], National Human Genome Research Institute (U54 HG003067), NIH
(HL080494, 5-T32-GM007748-33), Howard Hughes Medical Institute, and the
Australian National Health and Medical Research Council. The FHS was
supported by the NHLBI (N01-HC-25195, 6R01-NS 17950), and genotyping
services from Affymetrix Inc. (N02-HL-6-4278). The JHS is supported by
NHLBI (N01-HC-95170, N01-HC-95171, N01-HC-95172), the National Institute
for Minority Health and Health Disparities, and the National Institute
of Biomedical Imaging and Bioengineering. The WHI Sequencing Project is
supported by NHLBI (HL-102924), NIH, and U.S. Department of Health and
Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6,
32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and
44221. This publication reflects only the author's views, and the
funders are not liable for any use that may be made of the information
contained herein.
NR 67
TC 42
Z9 43
U1 5
U2 19
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JAN 14
PY 2015
VL 7
IS 270
AR 270ra6
DI 10.1126/scitranslmed.3010134
PG 14
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AZ6TN
UT WOS:000348353400004
PM 25589632
ER
PT J
AU Rifkind, JM
Mohanty, JG
Nagababu, E
AF Rifkind, Joseph M.
Mohanty, Joy G.
Nagababu, Enika
TI The pathophysiology of extracellular hemoglobin associated with enhanced
oxidative reactions
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Review
DE extracellular hemoglobin; hemoglobin autoxidation; oxidative reactions;
hydrogen peroxide; heme; Fe(IV)hemoglobins; proinflammatory reactions
ID RED-BLOOD-CELLS; LOW-DENSITY-LIPOPROTEIN; HYDROGEN-PEROXIDE; HEME
DEGRADATION; GLUTATHIONE-PEROXIDASE; ENDOTHELIAL-CELLS;
AUTO-TRANSFUSION; HEMOLYTIC-ANEMIA; FENTON REAGENT; DISEASE
AB Hemoglobin (Hb) continuously undergoes autoxidation producing superoxide which dismutates into hydrogen peroxide (H2O2) and is a potential source for subsequent oxidative reactions. Autoxidation is most pronounced under hypoxic conditions in the microcirculation and for unstable dimers formed at reduced Hb concentrations. In the red blood cell (RBC), oxidative reactions are inhibited by an extensive antioxidant system. For extracellular Hb, whether from hemolysis of RBCs and/or the infusion of Hb-based blood substitutes, the oxidative reactions are not completely neutralized by the available antioxidant system. Un-neutralized H2O2 oxidizes ferrous and ferric Hbs to Fe(IV)-ferrylHb and OxyferrylHb, respectively. FerrylHb further reacts with H2O2 producing heme degradation products and free iron. OxyferrylHb, in addition to Fe(IV) contains a free radical that can undergo additional oxidative reactions. Fe(III)Hb produced during Hb autoxidation also readily releases heme, an additional source for oxidative stress. These oxidation products are a potential source for oxidative reactions in the plasma, but to a greater extent when the lower molecular weight Hb dimers are taken up into cells and tissues. Heme and oxyferryl have been shown to have a proinflammatory effect further increasing their potential for oxidative stress. These oxidative reactions contribute to a number of pathological situations including atherosclerosis, kidney malfunction, sickle cell disease, and malaria. The toxic effects of extracellular Hb are of particular concern with hemolytic anemia where there is an increase in hemolysis. Hemolysis is further exacerbated in various diseases and their treatments. Blood transfusions are required whenever there is an appreciable decrease in RBCs due to hemolysis or blood loss. It is, therefore, essential that the transfused blood, whether stored RBCs or the blood obtained by an Autologous Blood Recovery System from the patient, do not further increase extracellular Hb.
C1 [Rifkind, Joseph M.; Mohanty, Joy G.] NIH, Mol Dynam Sect, Lab Mol Gerontol, Baltimore, MD 21224 USA.
[Nagababu, Enika] Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
RP Mohanty, JG (reprint author), NIH, Mol Dynam Sect, Lab Mol Gerontol, NIH,Biomed Res Ctr, 251 Bayview Blvd,Rm 05B0131, Baltimore, MD 21224 USA.
EM mohantyj@mail.nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging
FX This research was supported (in part) by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 52
TC 3
Z9 4
U1 3
U2 14
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PD JAN 14
PY 2015
VL 5
AR 500
DI 10.3389/fphys.2014.00500
PG 7
WC Physiology
SC Physiology
GA AZ4UP
UT WOS:000348219000001
ER
PT J
AU Fairhurst, RM
AF Fairhurst, Rick M.
TI PfEMP1' s Magical Embrace of EPCR
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID FALCIPARUM-INFECTED ERYTHROCYTES; MALARIA; RECEPTOR
C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20852 USA.
EM rfairhurst@niaid.nih.gov
FU Intramural NIH HHS
NR 10
TC 0
Z9 0
U1 0
U2 2
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 JAN 14
PY 2015
VL 17
IS 1
BP 11
EP 13
DI 10.1016/j.chom.2014.12.010
PG 3
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AZ1YB
UT WOS:000348030100005
PM 25590756
ER
PT J
AU Douglas, AD
Baldeviano, GC
Lucas, CM
Lugo-Roman, LA
Crosnier, C
Bartholdson, SJ
Diouf, A
Miura, K
Lambert, LE
Ventocilla, JA
Leiva, KP
Milne, KH
Illingworth, JJ
Spencer, AJ
Hjerrild, KA
Alanine, DGW
Turner, AV
Moorhead, JT
Edgel, KA
Wu, YM
Long, CA
Wright, GJ
Lescano, AG
Draper, SJ
AF Douglas, Alexander D.
Baldeviano, G. Christian
Lucas, Carmen M.
Lugo-Roman, Luis A.
Crosnier, Cecile
Bartholdson, S. Josefin
Diouf, Ababacar
Miura, Kazutoyo
Lambert, Lynn E.
Ventocilla, Julio A.
Leiva, Karina P.
Milne, Kathryn H.
Illingworth, Joseph J.
Spencer, Alexandra J.
Hjerrild, Kathryn A.
Alanine, Daniel G. W.
Turner, Alison V.
Moorhead, Jeromy T.
Edgel, Kimberly A.
Wu, Yimin
Long, Carole A.
Wright, Gavin J.
Lescano, Andres G.
Draper, Simon J.
TI A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain
Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys
SO CELL HOST & MICROBE
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1; IN-ADJUVANT
VACCINES; MALARIA VACCINE; NANCYMAI MONKEYS; PFRH5 POLYMORPHISMS;
ANTIBODY TITER; PROTECTION; INVASION; IMMUNIZATION
AB Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans.
C1 [Douglas, Alexander D.; Milne, Kathryn H.; Illingworth, Joseph J.; Spencer, Alexandra J.; Hjerrild, Kathryn A.; Alanine, Daniel G. W.; Turner, Alison V.; Draper, Simon J.] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
[Baldeviano, G. Christian; Lucas, Carmen M.; Lugo-Roman, Luis A.; Ventocilla, Julio A.; Leiva, Karina P.; Moorhead, Jeromy T.; Edgel, Kimberly A.; Lescano, Andres G.] US Naval Med Res Unit 6 NAMRU 6, Lima, Peru.
[Crosnier, Cecile; Bartholdson, S. Josefin; Wright, Gavin J.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
[Diouf, Ababacar; Miura, Kazutoyo; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Lambert, Lynn E.; Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
RP Douglas, AD (reprint author), Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
EM sandy.douglas@ndm.ox.ac.uk
RI Douglas, Alexander/E-7040-2012; Lescano, Andres/B-8479-2008;
OI Douglas, Alexander/0000-0002-5410-7562; Lescano,
Andres/0000-0001-9779-633X; Spencer, Alexandra/0000-0001-7958-6961;
Draper, Simon/0000-0002-9415-1357
FU Wellcome Trust [089455/2/09/z, 092873/z/10/z, 098051]; PATH Malaria
Vaccine Initiative; Intramural Program of the National Institutes of
Health, National Institute of Allergy and Infectious Diseases;
University Challenge Seed Fund (Isis Innovation, University of Oxford);
European Community's Seventh Framework Programme (FP7) [242095 -
EVIMalaR]; NIH/FIC by the Fogarty International Center of the US
National Institutes of Health [2D43 TW007393]; MRC Career Development
Fellowship - UK Medical Research Council [MRC] [G1000527]; MRC Career
Development Fellowship - UK Department for International Development
[DFID] [G1000527]
FX The authors are grateful for the assistance of Adrian Hill, Julie Furze,
the Viral Vector Core Facility and Adjuvant Bank (Jenner Institute,
University of Oxford); David Staunton (Biophysical Instrument Facility,
Department of Biochemistry, University of Oxford); Ly-Mee Yu and Doug
Altman (Centre for Statistics in Medicine, University of Oxford); Julian
Rayner (Wellcome Trust Sanger Institute, UK); Carmen Franco, Roxana
Lescano, Jorge Nunez, Meddly Santolalla, and Lorena Tapia (NAMRU-6,
Peru); Olivo Miotto (Mahidol-Oxford Research Unit, Thailand); Yves
Durocher for provision of HEK293E cells (CNRC-NRC, Canada); and Alfredo
Nicosia (Okairos, Italy) for provision of the ChAd63 vector. A.D.D. held
a Wellcome Trust Training Fellowship for Clinicians in Basic Sciences
(grant number 089455/2/09/z). J.J.I. is a Wellcome Trust funded student
on the Infection, Immunology and Translational Medicine PhD Programme
(grant number 092873/z/10/z). C.C., S.J. B., and G.J.W. are supported by
the Wellcome Trust (grant number 098051). The GIA work was supported by
the PATH Malaria Vaccine Initiative and the Intramural Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases. This work was also funded in part by the University
Challenge Seed Fund (Isis Innovation, University of Oxford) and by the
European Community's Seventh Framework Programme (FP7/2007-2013) under
grant agreement number 242095 - EVIMalaR. A.G.L. is supported by
training grant NIH/FIC 2D43 TW007393 awarded to NAMRU-6 by the Fogarty
International Center of the US National Institutes of Health. S.J.D.
holds a MRC Career Development Fellowship (grant number G1000527; this
fellowship is jointly funded by the UK Medical Research Council [MRC]
and the UK Department for International Development [DFID] under the
MRC/DFID Concordat agreement) and is a Jenner Investigator and Lister
Institute Research Prize Fellow. A.D.D., J.J.I., C.C., S.J. B., G.J.W.,
and S.J.D. are named on patent applications relating to PfRH5 and/or
other malaria vaccines. Some of the listed authors are either military
service members (K.A.E., L.A.L.-R., J.T.M.) or employees of the US
Government (G.C.B., C.M.L., J.A.V., K.P.L., A.G.L.). This work was
prepared as part of their official duties. Title 17 U.S.C. 105 provides
that ''Copyright protection under this title is not available for any
work of the United States Government.'' Title 17 U.S.C. 101 defines a
U.S. Government work as a work prepared by a military service member or
employee of the US Government as part of that person's official duties.
The views expressed in this article are those of the authors and do not
necessarily reflect the official policy or position of the Department of
the Navy, Department of Defense, or the US Government.
NR 60
TC 42
Z9 42
U1 2
U2 11
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 JAN 14
PY 2015
VL 17
IS 1
BP 130
EP 139
DI 10.1016/j.chom.2014.11.017
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AZ1YB
UT WOS:000348030100016
PM 25590760
ER
PT J
AU Kim, DH
Xiao, Z
Kwon, S
Sun, XX
Ryerson, D
Tkac, D
Ma, P
Wu, SY
Chiang, CM
Zhou, E
Xu, HE
Palvimo, JJ
Chen, LF
Kemper, B
Kemper, JK
AF Kim, Dong-Hyun
Xiao, Zhen
Kwon, Sanghoon
Sun, Xiaoxiao
Ryerson, Daniel
Tkac, David
Ma, Ping
Wu, Shwu-Yuan
Chiang, Cheng-Ming
Zhou, Edward
Xu, H. Eric
Palvimo, Jorma J.
Chen, Lin-Feng
Kemper, Byron
Kemper, Jongsook Kim
TI A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation
in obesity
SO EMBO JOURNAL
LA English
DT Article
DE acetylation; NF-B; PIASy; steatosis; SUMO2
ID FARNESOID X RECEPTOR; PPAR-GAMMA; METABOLIC DISEASE; LYSINE ACETYLATION;
LIPID-METABOLISM; RESPONSE GENES; LXR-BETA; SIRT1; SUMOYLATION; PATHWAYS
AB Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and acetylation-defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-B but blocked that with RXR, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXR target genes. A dysregulated acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders.
C1 [Kim, Dong-Hyun; Kwon, Sanghoon; Ryerson, Daniel; Tkac, David; Kemper, Byron; Kemper, Jongsook Kim] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA.
[Xiao, Zhen] NCI, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, Frederick, MD 21701 USA.
[Sun, Xiaoxiao; Ma, Ping] Univ Georgia, Dept Stat, Athens, GA 30602 USA.
[Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas Dallas, SW Med Ctr, Dept Biochem, Simmons Comprehens Canc Ctr, Dallas, TX 75235 USA.
[Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas Dallas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA.
[Zhou, Edward; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI USA.
[Palvimo, Jorma J.] Univ Eastern Finland, Inst Biomed, Kuopio, Finland.
[Chen, Lin-Feng] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.
RP Kemper, JK (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA.
EM jongsook@illinois.edu
RI Ma, Ping/M-7746-2015
OI Ma, Ping/0000-0002-5728-3596
FU AHA post-doctoral fellowship [14POST20420006]; NSF [DMS-1440037,
DMS-1228288]; NIH [CA103867, DK62777, DK95842]; CPRIT [RP110471,
RP140367]; Welch Foundation [I-1805]; Academy of Finland
FX We thank Ron Hay at University of Dundee for kindly providing SUMO
expression plasmids and Peter Tontonoz at UCLA for (NF-kappa B
site)3-tk-luc plasmid. This study was supported by grants
from an AHA post-doctoral fellowship to DHK (14POST20420006), NSF grants
(DMS-1440037 and DMS-1228288) to PM, NIH (CA103867), CPRIT (RP110471 and
RP140367), and Welch Foundation (I-1805) to CMC, the Academy of Finland
to JP, and NIH grants (DK62777 and DK95842) to JKK.
NR 47
TC 15
Z9 15
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD JAN 14
PY 2015
VL 34
IS 2
BP 184
EP 199
DI 10.15252/embj.201489527
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AY9NY
UT WOS:000347878900007
PM 25425577
ER
PT J
AU Cerbini, T
Funahashl, R
Luo, YQ
Liu, CY
Park, K
Rao, M
Malik, N
Zou, JH
AF Cerbini, Trevor
Funahashl, Ray
Luo, Yongquan
Liu, Chengyu
Park, Kyeyoon
Rao, Mahendra
Malik, Nasir
Zou, Jizhong
TI Transcription Activator-Like Effector Nuclease (TALEN)-Mediated CLYBL
Targeting Enables Enhanced Transgene Expression and One-Step Generation
of Dual Reporter Human Induced Pluripotent Stem Cell (iPSC) and Neural
Stem Cell (NSC) Lines
SO PLOS ONE
LA English
DT Article
ID GENE CORRECTION; DISEASE; TALEN; SPECIFICITY; MUTATIONS; CLONES; CAS9
AB Targeted genome engineering to robustly express transgenes is an essential methodology for stem cell-based research and therapy. Although designer nucleases have been used to drastically enhance gene editing efficiency, targeted addition and stable expression of transgenes to date is limited at single gene/locus and mostly PPP1R12C/AAVS1 in human stem cells. Here we constructed transcription activator-like effector nucleases (TALENs) targeting the safe-harbor like gene CLYBL to mediate reporter gene integration at 38%-58% efficiency, and used both AAVS1-TALENs and CLYBL-TALENs to simultaneously knock-in multiple reporter genes at dual safe-harbor loci in human induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs). The CLYBL-TALEN engineered cell lines maintained robust reporter expression during self-renewal and differentiation, and revealed that CLYBL targeting resulted in stronger transgene expression and less perturbation on local gene expression than PPP1R12C/AAVS1. TALEN-mediated CLYBL engineering provides improved transgene expression and options for multiple genetic modification in human stem cells.
C1 [Cerbini, Trevor; Funahashl, Ray; Luo, Yongquan; Rao, Mahendra; Malik, Nasir; Zou, Jizhong] NIAMSD, NIH, Ctr Regenerat Med, Lab Stem Cell Biol, Bethesda, MD 20892 USA.
[Liu, Chengyu; Zou, Jizhong] NHLBI, Ctr Mol Med, Div Intramural Res, Bethesda, MD 20892 USA.
[Park, Kyeyoon] NINDS, Stem Cell Unit, Bethesda, MD 20892 USA.
RP Zou, JH (reprint author), NIAMSD, NIH, Ctr Regenerat Med, Lab Stem Cell Biol, Bethesda, MD 20892 USA.
EM zouj2@mail.nih.gov
FU National Institutes of Health Common Fund; National Heart, Lung, and
Blood Institute; National Institute of Neurological Disorders and Stroke
FX This research was supported by the National Institutes of Health Common
Fund and Intramural Research Programs of the National Heart, Lung, and
Blood Institute and National Institute of Neurological Disorders and
Stroke. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 32
TC 5
Z9 5
U1 1
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 14
PY 2015
VL 10
IS 1
AR e0116032
DI 10.1371/journal.pone.0116032
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ0ID
UT WOS:000347928300008
PM 25587899
ER
PT J
AU Costello, RB
Lentino, CV
Saldanha, L
Engler, MM
Engler, MB
Srinivas, P
Sempos, CT
AF Costello, Rebecca B.
Lentino, Cynthia V.
Saldanha, Leila
Engler, Marguerite M.
Engler, Mary B.
Srinivas, Pothur
Sempos, Christopher T.
TI A select review reporting the quality of studies measuring endothelial
dysfunction in randomised diet intervention trials
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Dietary supplements; Dietary ingredients; Vascular function;
Flow-mediated dilation; Systematic reviews
ID CORONARY-ARTERY-DISEASE; FLOW-MEDIATED DILATION; HEALTHY POSTMENOPAUSAL
WOMEN; FLAVANOL-RICH COCOA; CARDIOVASCULAR RISK-FACTORS; PURIFIED
EICOSAPENTAENOIC ACID; TYPE-2 DIABETES-MELLITUS; FISH-OIL
SUPPLEMENTATION; REDUCES BLOOD-PRESSURE; N-3 FATTY-ACIDS
AB A quality assessment of the primary studies reported in the literature carried out using SElect dietary ingredients (DI) purported to affect vascular endothelial function was conducted through a systematic PubMed SEarch from January 2000 to August 2012. A total of SEventy randomiSEd controlled trials with defined DI (folic acid (fifteen), n-3 fatty acids (twenty), cocoa (fifteen) and isoflavones (twenty)) and standardiSEd measures of vascular endothelial function were evaluated. Jadad scores, quality scoring parameters for DI and flow-mediated dilation (FMD) methodology uSEd were ascertained. A total of 3959 randomiSEd subjects, mean age 51 (SE 0.21) years (range 9-79 years), were repreSEnted in the dataSEt. The mean Jadad scores did not differ statistically among the DI studies, with the majority of the studies being of good quality. Higher DI quality scores were achieved by studies using the botanical ingredients cocoa and isoflavones than by thoSE using the nutrient ingredients folic acid and n-3 fatty acids. The mean DI quality scores were 4.13 (SE 0.34), 5.20 (SE 0.47), 6.13 (SE 0.41) and 6.00 (SE 0.59) for the folic acid, n-3 fatty acid, cocoa and isoflavone intervention studies, respectively (and significantly different). The mean Corretti FMD scores were 7.27 (SE 0.56), 7.46 (SE 0.79), 6.29 (SE 0.61) and 7.11 (SE 0.56) for the folic acid, n-3 fatty acid, cocoa and isoflavone intervention studies, respectively (NS). FMD studies failed to adequately describe the equipment uSEd and more than half failed to provide an adequate description of the procedures uSEd for vascular image acquisition and measurement. DI can be utiliSEd for dietary intervention studies; however, the methodology should be clearly reported using the guidelines for assessment for both DI and FMD.
C1 [Costello, Rebecca B.; Lentino, Cynthia V.; Saldanha, Leila; Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Engler, Marguerite M.; Engler, Mary B.] NINR, Bethesda, MD 20892 USA.
[Srinivas, Pothur] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Costello, RB (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA.
EM costellb@od.nih.gov
FU Office of Dietary Supplements, National Institutes of Health
FX The Office of Dietary Supplements, National Institutes of Health, funded
and sponsored this work.
NR 132
TC 1
Z9 1
U1 0
U2 11
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
EI 1475-2662
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JAN 14
PY 2015
VL 113
IS 1
BP 89
EP 99
DI 10.1017/S0007114514003353
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AX7OM
UT WOS:000347105000009
PM 25374114
ER
PT J
AU Swoboda, RK
Somasundaram, R
Caputo-Gross, L
Marincola, FM
Robbins, P
Herlyn, M
Herlyn, D
AF Swoboda, Rolf K.
Somasundaram, Rajasekharan
Caputo-Gross, Laura
Marincola, Francesco M.
Robbins, Paul
Herlyn, Meenhard
Herlyn, Dorothee
TI Antimelanoma CTL recognizes peptides derived from an ORF transcribed
from the antisense strand of the 3 ' untranslated region of TRIT1
SO Molecular Therapy-Oncolytics
LA English
DT Article
ID TRANSFER-RNA MODIFICATIONS; CYTOLYTIC T-LYMPHOCYTES; MALIGNANT-MELANOMA;
NONCODING RNAS; CANCER; CELLS; GENE; CD4(+); CLONE; IMMUNOTHERAPY
AB Noncoding regions of the genome play an important role in tumorigenesis of cancer. Using expression cloning, we have identified a cytotoxic T lymphocyte (CTL)-defined antigen that recognizes a protein sequence derived from an open reading frame transcribed from the reverse strand in the 3' untranslated region of tRNA isopentenyltransferase 1 (TRIT1). A peptide derived from this open reading frame (ORF) sequence and predicted to bind to HLA-B57, sensitized HLA-B57(+) tumor cells to lysis by CTL793. The peptide also induced a CTL response in peripheral blood mononuclear cells (PBMC) of patient 793 and in two other melanoma patients. The CTL lysed peptide-pulsed HLA-B57(+) target cells and melanoma cells with endogenous antigen expression. The recognition of this antigen is not limited to HLA-B57-restricted CTLs. An HLA-A2 peptide derived from the ORF was able to induce CTLs in PBMC of 2 HLA-A2(+) patients. This study describes for the first time a CTL-defined melanoma antigen that is derived from an ORF on the reverse strand of the putative tumor suppressor gene TRIT1. This antigen has potential use as a vaccine or its ability to induce CTLs in vitro could be used as a predictive biomarker.
C1 [Swoboda, Rolf K.; Somasundaram, Rajasekharan; Caputo-Gross, Laura; Herlyn, Meenhard; Herlyn, Dorothee] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Robbins, Paul] NCI, Surg Branch, NIH, Bethesda, MD USA.
[Swoboda, Rolf K.] Abzyme Therapeut, Pottstown, PA USA.
[Caputo-Gross, Laura] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
RP Swoboda, RK (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM rolf@wistar.org
FU [CA60975]; [CA88193]; [CA25874]; [CA10815]
FX The research was funded in part by grants CA60975, CA88193, CA25874, and
CA10815. We thank Ling Li for supplying melanocytes. The authors declare
no conflict of interest.
NR 42
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2372-7705
J9 Mol Ther-Oncolytics
JI Mol. Ther.-Oncolytics
PD JAN 14
PY 2015
VL 2
AR UNSP 14009
DI 10.1038/mto.2014.9
PG 8
WC Oncology; Medicine, Research & Experimental
SC Oncology; Research & Experimental Medicine
GA EE2PX
UT WOS:000389427800001
ER
PT J
AU Tang, BW
Raviv, A
Esposito, D
Flanders, KC
Daniel, C
Nghiem, BT
Garfield, S
Lim, L
Mannan, P
Robles, AI
Smith, WI
Zimmerberg, J
Ravin, R
Wakefield, LM
AF Tang, Binwu
Raviv, Asaf
Esposito, Dominic
Flanders, Kathleen C.
Daniel, Catherine
Nghiem, Bao Tram
Garfield, Susan
Lim, Langston
Mannan, Poonam
Robles, Ana I.
Smith, William I., Jr.
Zimmerberg, Joshua
Ravin, Rea
Wakefield, Lalage M.
TI A Flexible Reporter System for Direct Observation and Isolation of
Cancer Stem Cells
SO STEM CELL REPORTS
LA English
DT Article
ID TUMOR-INITIATING CELLS; PROGENITOR CELLS; GENE-EXPRESSION; ADULT STEM;
TGF-BETA; GENERATION; OCT4; PROGRESSION; LINES; DIFFERENTIATION
AB Many tumors are hierarchically organized with a minority cell population that has stem-like properties and enhanced ability to initiate tumorigenesis and drive therapeutic relapse. These cancer stem cells (CSCs) are typically identified by complex combinations of cell-surface markers that differ among tumor types. Here, we developed a flexible lentiviral-based reporter system that allows direct visualization of CSCs based on functional properties. The reporter responds to the core stem cell transcription factors OCT4 and SOX2, with further selectivity and kinetic resolution coming from use of a proteasome-targeting degron. Cancer cells marked by this reporter have the expected properties of self-renewal, generation of heterogeneous offspring, high tumor-and metastasis-initiating activity, and resistance to chemotherapeutics. With this approach, the spatial distribution of CSCs can be assessed in settings that retain microenvironmental and structural cues, and CSC plasticity and response to therapeutics can be monitored in real time.
C1 [Tang, Binwu; Raviv, Asaf; Flanders, Kathleen C.; Daniel, Catherine; Nghiem, Bao Tram; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Esposito, Dominic] Frederick Natl Lab Canc Res, Adv Technol Program, Prot Express Lab, Frederick, MD 21701 USA.
[Garfield, Susan; Lim, Langston; Mannan, Poonam] NCI, Confocal Microscopy Core, Bethesda, MD 20892 USA.
[Robles, Ana I.] NCI, Lab Human Carcinogenesis, Bethesda, MD 20892 USA.
[Smith, William I., Jr.] Suburban Hosp, Dept Pathol, Bethesda, MD 20814 USA.
[Zimmerberg, Joshua; Ravin, Rea] NICHHD, Program Phys Biol, Bethesda, MD 20892 USA.
RP Wakefield, LM (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM lw34g@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research [Z01 BC 005785]
FX We thank Barbara Taylor, Karen Wolcott, and Suphadra Banerjee of the CCR
FACS core facility, Dr. Mario Anzano and Anthony Vieira of the LCBG
Animal Core, and Sam Dengler of the LCBG and Jen Mehalko of the Protein
Expression Laboratory for their excellent technical assistance. We thank
Dr. Brid Ryan for expert guidance with the asymmetric cell division
assays. This work was supported by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research (grant
Z01 BC 005785, to L.M.W.).
NR 41
TC 15
Z9 15
U1 0
U2 5
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 JAN 13
PY 2015
VL 4
IS 1
BP 155
EP 169
DI 10.1016/j.stemcr.2014.11.002
PG 15
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA AZ2AK
UT WOS:000348036800014
PM 25497455
ER
PT J
AU Athwal, RK
Walkiewicz, MP
Baek, S
Fu, S
Bui, M
Camps, J
Ried, T
Sung, MH
Dalal, Y
AF Athwal, Rajbir K.
Walkiewicz, Marcin P.
Baek, Songjoon
Fu, Song
Bui, Minh
Camps, Jordi
Ried, Thomas
Sung, Myong-Hee
Dalal, Yamini
TI CENP-A nucleosomes localize to transcription factor hotspots and
subtelomeric sites in human cancer cells
SO EPIGENETICS & CHROMATIN
LA English
DT Article
ID CENTROMERE PROTEIN-A; HISTONE H3 VARIANT; I-HYPERSENSITIVE SITES; E3
UBIQUITIN LIGASE; COLORECTAL-CANCER; CRYSTAL-STRUCTURE; BREAST-CANCER;
GLUCOCORTICOID-RECEPTOR; GENOME INSTABILITY; CHROMATIN REQUIRES
AB Background: The histone H3 variant CENP-A is normally tightly regulated to ensure only one centromere exists per chromosome. Native CENP-A is often found overexpressed in human cancer cells and a range of human tumors. Consequently, CENP-A misregulation is thought to contribute to genome instability in human cancers. However, the consequences of such overexpression have not been directly elucidated in human cancer cells.
Results: To investigate native CENP-A overexpression, we sought to uncover CENP-A-associated defects in human cells. We confirm that CENP-A is innately overexpressed in several colorectal cancer cell lines. In such cells, we report that a subset of structurally distinct CENP-A-containing nucleosomes associate with canonical histone H3, and with the transcription-coupled chaperones ATRX and DAXX. Furthermore, such hybrid CENP-A nucleosomes localize to DNase I hypersensitive and transcription factor binding sites, including at promoters of genes across the human genome. A distinct class of CENP-A hotspots also accumulates at subtelomeric chromosomal locations, including at the 8q24/Myc region long-associated with genomic instability. We show this 8q24 accumulation of CENP-A can also be seen in early stage primary colorectal tumors.
Conclusions: Our data demonstrate that excess CENP-A accumulates at noncentromeric locations in the human cancer genome. These findings suggest that ectopic CENP-A nucleosomes could alter the state of the chromatin fiber, potentially impacting gene regulation and chromosome fragility.
C1 [Athwal, Rajbir K.; Walkiewicz, Marcin P.; Fu, Song; Bui, Minh; Dalal, Yamini] NCI, Ctr Canc Res, Chromatin Struct & Epigenet Mech Unit, NIH, Bethesda, MD 20892 USA.
[Athwal, Rajbir K.; Walkiewicz, Marcin P.; Baek, Songjoon; Fu, Song; Bui, Minh; Sung, Myong-Hee] NCI, Ctr Canc Res, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Camps, Jordi; Ried, Thomas] NCI, Ctr Canc Res, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Dalal, Y (reprint author), NCI, Ctr Canc Res, Chromatin Struct & Epigenet Mech Unit, NIH, 41 Ctr Dr, Bethesda, MD 20892 USA.
EM dalaly@mail.nih.gov
FU National Cancer Institute
FX The Intramural Research Program of the National Cancer Institute
supported all authors in this study. SF volunteered as a guest
researcher for the bulk of this study and was subsequently supported by
the NCI post-baccalaureate program.
NR 82
TC 13
Z9 13
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8935
J9 EPIGENET CHROMATIN
JI Epigenetics Chromatin
PD JAN 13
PY 2015
VL 8
AR 2
DI 10.1186/1756-8935-8-2
PG 23
WC Genetics & Heredity
SC Genetics & Heredity
GA CA6TE
UT WOS:000349047900001
PM 25788983
ER
PT J
AU Posokhova, E
Shukla, A
Seaman, S
Volate, S
Hilton, MB
Wu, BF
Morris, H
Swing, DA
Zhou, M
Zudaire, E
Rubin, JS
St Croix, B
AF Posokhova, Ekaterina
Shukla, Animesh
Seaman, Steven
Volate, Suresh
Hilton, Mary Beth
Wu, Bofan
Morris, Holly
Swing, Deborah A.
Zhou, Ming
Zudaire, Enrique
Rubin, Jeffrey S.
St Croix, Brad
TI GPR124 Functions as a WNT7-Specific Coactivator of Canonical
beta-Catenin Signaling
SO CELL REPORTS
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; PROTEIN-COUPLED RECEPTOR; MOUSE; LIMB; CNS;
ANGIOGENESIS; GENE; POLARITY; MODELS; MARKER
AB G protein-coupled receptor 124 (GPR124) is an orphan receptor in the adhesion family of GPCRs, and previous global or endothelial-specific disruption of Gpr124 in mice led to defective CNS angiogenesis and blood-brain barriergenesis. Similar developmental defects were observed following dual deletion of Wnt7a/Wnt7b or deletion of beta-catenin in endothelial cells, suggesting a possible relationship between GPR124 and canonical WNT signaling. Here, we show using in vitro reporter assays, mutation analysis, and genetic interaction studies in vivo that GPR124 functions as a WNT7A/WNT7B-specific costimulator of beta-catenin signaling in brain endothelium. WNT7-stimulated beta-catenin signaling was dependent upon GPR124's intracellular PDZ binding motif and a set of leucine-rich repeats in its extracellular domain. This study reveals a vital role for GPR124 in potentiation of WNT7-induced canonical beta-catenin signaling with important implications for understanding and manipulating CNS-specific angiogenesis and blood-brain barriergenesis.
C1 [Posokhova, Ekaterina; Shukla, Animesh; Seaman, Steven; Volate, Suresh; Hilton, Mary Beth; Wu, Bofan; Zudaire, Enrique; St Croix, Brad] NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
[Hilton, Mary Beth] Leidos Inc, Basic Res Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Morris, Holly; Swing, Deborah A.] NCI, Transgen Core Facil, MCGP, Frederick, MD 21702 USA.
[Zhou, Ming] Leidos Inc, Lab Prote & Analyt Technol, FNLCR, Frederick, MD 21702 USA.
[Rubin, Jeffrey S.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP St Croix, B (reprint author), NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
EM stcroix@ncifcrf.gov
FU Center for Cancer Research Intramural Program, NCI, NIH, a part of the
U.S. Department of Health and Human Services (DHHS)
FX We thank Terry P. Yamaguchi for helpful discussions during our studies
and expression vectors for constitutively active beta-catenin and
Renilla luciferase. We are grateful to the Open Source WNT project for
providing the panel of human WNT plasmids. This work was supported by
the Center for Cancer Research Intramural Program, NCI, NIH, a part of
the U.S. Department of Health and Human Services (DHHS). The content of
this publication does not necessarily reflect the views or policies of
the DHHS.
NR 24
TC 18
Z9 20
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 JAN 13
PY 2015
VL 10
IS 2
BP 123
EP 130
DI 10.1016/j.celrep.2014.12.020
PG 8
WC Cell Biology
SC Cell Biology
GA AZ2AI
UT WOS:000348036600001
PM 25558062
ER
PT J
AU Collins, FS
AF Collins, Francis S.
TI Exceptional Opportunities in Medical Science A View From the National
Institutes of Health
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
RP Collins, FS (reprint author), NIH, Off Director, 1 Ctr Dr, Bethesda, MD 20892 USA.
EM collinsf@mail.nih.gov
NR 8
TC 31
Z9 32
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 13
PY 2015
VL 313
IS 2
BP 131
EP 132
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AY6MC
UT WOS:000347679300006
PM 25585318
ER
PT J
AU Ji, Y
Wrzesinski, C
Yu, ZY
Hu, JH
Gautam, S
Hawk, NV
Telford, WG
Palmer, DC
Franco, Z
Sukumar, M
Roychoudhuri, R
Clever, D
Klebanoff, CA
Surh, CD
Waldmann, TA
Restifo, NP
Gattinoni, L
AF Ji, Yun
Wrzesinski, Claudia
Yu, Zhiya
Hu, Jinhui
Gautam, Sanjivan
Hawk, Nga V.
Telford, William G.
Palmer, Douglas C.
Franco, Zulmarie
Sukumar, Madhusudhanan
Roychoudhuri, Rahul
Clever, David
Klebanoff, Christopher A.
Surh, Charles D.
Waldmann, Thomas A.
Restifo, Nicholas P.
Gattinoni, Luca
TI miR-155 augments CD8(+) T-cell antitumor activity in lymphoreplete hosts
by enhancing responsiveness to homeostatic gamma(c) cytokines
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE microRNA-155; adoptive immunotherapy; lymphodepletion; homeostatic
cytokines
ID INCREASED INTENSITY LYMPHODEPLETION; METASTATIC MELANOMA; ADOPTIVE
IMMUNOTHERAPY; IMMUNE-SYSTEM; STEM-CELLS; THERAPY; CANCER; MICRORNA-155;
RESPONSES; EFFECTOR
AB Lymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic "cytokine sinks." These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enabled tumor-specific CD8(+) T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic gamma c cytokines, resulting in delayed cellular contraction and sustained cytokine production. miR-155 restrained the expression of the inositol 5-phosphatase Ship1, an inhibitor of the serine-threonine protein kinase Akt, and multiple negative regulators of signal transducer and activator of transcription 5 (Stat5), including suppressor of cytokine signaling 1 (Socs1) and the protein tyrosine phosphatase Ptpn2. Expression of constitutively active Stat5a recapitulated the survival advantages conferred by miR-155, whereas constitutive Akt activation promoted sustained effector functions. Our results indicate that overexpression of miR-155 in tumor-specific T cells can be used to increase the effectiveness of adoptive immunotherapies in a cell-intrinsic manner without the need for life-threatening, lymphodepleting maneuvers.
C1 [Ji, Yun; Hu, Jinhui; Gautam, Sanjivan; Hawk, Nga V.; Telford, William G.; Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wrzesinski, Claudia; Yu, Zhiya; Palmer, Douglas C.; Franco, Zulmarie; Sukumar, Madhusudhanan; Roychoudhuri, Rahul; Clever, David; Klebanoff, Christopher A.; Restifo, Nicholas P.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Surh, Charles D.] Acad Immunol & Microbiol, Inst Basic Sci, Pohang 790784, South Korea.
[Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Waldmann, TA (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov; tawald@helix.nih.gov; gattinol@mail.nih.gov
RI Gattinoni, Luca/A-2281-2008; Palmer, Douglas/B-9454-2008; Ji,
Yun/B-7245-2009; Roychoudhuri, Rahul/A-7442-2010;
OI Gattinoni, Luca/0000-0003-2239-3282; Palmer,
Douglas/0000-0001-5018-5734; Ji, Yun/0000-0001-6340-7009; Roychoudhuri,
Rahul/0000-0002-5392-1853; Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural Research Program of the National Cancer Institute, Center for
Cancer Research, National Institutes of Health
FX We thank A. Mixon and S. Farid for flow cytometry sorting. We thank Dr.
Hand for providing the AktCA and Stat5aCA constructs. This work was
supported by the Intramural Research Program of the National Cancer
Institute, Center for Cancer Research, National Institutes of Health.
NR 40
TC 11
Z9 12
U1 0
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 13
PY 2015
VL 112
IS 2
BP 476
EP 481
DI 10.1073/pnas.1422916112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY7HS
UT WOS:000347732300056
PM 25548153
ER
PT J
AU Ong, HL
de Souza, LB
Zheng, CY
Cheng, KT
Liu, XB
Goldsmith, CM
Feske, S
Ambudkar, IS
AF Ong, Hwei Ling
de Souza, Lorena Brito
Zheng, Changyu
Cheng, Kwong Tai
Liu, Xibao
Goldsmith, Corinne M.
Feske, Stefan
Ambudkar, Indu S.
TI STIM2 enhances receptor-stimulated Ca2+ signaling by promoting
recruitment of STIM1 to the endoplasmic reticulum-plasma membrane
junctions
SO SCIENCE SIGNALING
LA English
DT Article
ID OPERATED CALCIUM-ENTRY; STORE DEPLETION; CRAC CHANNELS; FLUID SECRETION;
DIRECT BINDING; SAM DOMAIN; ACTIVATION; ORAI1; OLIGOMERIZATION;
OSCILLATIONS
AB A central component of receptor-evoked Ca2+ signaling is store-operated Ca2+ entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca2+. We report that STIM2 enhances agonist-mediated activation of SOCE by promoting STIM1 clustering in ER-PM junctions at low stimulus intensities. Targeted deletion of STIM2 in mouse salivary glands diminished fluid secretion in vivo and SOCE activation in dispersed salivary acinar cells stimulated with low concentrations of muscarinic receptor agonists. STIM2 knockdown in human embryonic kidney (HEK) 293 cells diminished agonist-induced Ca2+ signaling and nuclear translocation of NFAT (nuclear factor of activated T cells). STIM2 lacking five carboxyl-terminal amino acid residues did not promote formation of STIM1 puncta at low concentrations of agonist, whereas coexpression of STIM2 with STIM1 mutant lacking the polybasic region STIM1 Delta K resulted in co-clustering of both proteins. Together, our findings suggest that STIM2 recruits STIM1 to ER-PM junctions at low stimulus intensities when ER Ca2+ stores are mildly depleted, thus increasing the sensitivity of Ca2+ signaling to agonists.
C1 [Ong, Hwei Ling; de Souza, Lorena Brito; Liu, Xibao; Ambudkar, Indu S.] NIDCR, Mol Physiol & Therapeut Branch, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Zheng, Changyu; Goldsmith, Corinne M.] NIDCR, Mol Physiol & Therapeut Branch, Translat Res Core, NIH, Bethesda, MD 20892 USA.
[Cheng, Kwong Tai] Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA.
[Feske, Stefan] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10016 USA.
RP Ambudkar, IS (reprint author), NIDCR, Mol Physiol & Therapeut Branch, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA.
EM indu.ambudkar@nih.gov
RI Brito de Souza, Lorena/N-3385-2014;
OI Brito de Souza, Lorena/0000-0002-2462-6759; Feske,
Stefan/0000-0001-5431-8178
FU NIDCR-Division of Intramural Research; NIH [AI097302]
FX We also acknowledge grant support from the NIDCR-Division of Intramural
Research for I.S.A. and from NIH (grant no. AI097302) for S.F.
NR 42
TC 10
Z9 10
U1 1
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 JAN 13
PY 2015
VL 8
IS 359
AR ra3
DI 10.1126/scisignal.2005748
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AZ0EY
UT WOS:000347920200002
PM 25587190
ER
PT J
AU Zhang, X
An, X
Liu, HX
Peng, J
Cai, SS
Wang, W
Lin, DT
YupengYang
AF Zhang, Xian
An, Xu
Liu, Hanxiao
Peng, Jing
Cai, Shanshan
Wang, Wei
Lin, Da-Ting
YupengYang
TI The Topographical Arrangement of Cutoff Spatial Frequencies across Lower
and Upper Visual Fields in Mouse V1
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RETINAL GANGLION-CELLS; RECEPTIVE-FIELD; FUNCTIONAL SPECIALIZATION;
DIRECTION SELECTIVITY; SUPERIOR COLLICULUS; INTRINSIC SIGNAL; VERNIER
ACUITY; CORTICAL AREAS; GRATING ACUITY; CORTEX
AB The visual response to spatial frequency (SF), a characteristic of spatial structure across position in space, is of particular importance for animal survival. A natural challenge for rodents is to detect predators as early as possible while foraging. Whether neurons in mouse primary visual cortex (V1) are functionally organized to meet this challenge remains unclear. Combining intrinsic signal optical imaging and single-unit recording, we found that the cutoff SF was much greater for neurons whose receptive fields were located above the mouse. Specifically, we discovered that the cutoff SF increased in a gradient that was positively correlated with the elevation in the visual field. This organization was present at eye opening and persisted through adulthood. Dark rearing delayed the maturation of the cutoff SF globally, but had little impact on the topographical organization of the cutoff SF, suggesting that this regional distribution is innately determined. This form of cortical organization of different SFs may benefit the mouse for detection of airborne threats in the natural environment.
C1 [Zhang, Xian; An, Xu; Liu, Hanxiao; Peng, Jing; Cai, Shanshan; YupengYang] Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Brain Funct & Dis, Hefei 230027, Peoples R China.
[Wang, Wei] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China.
[Wang, Wei] Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.
[Lin, Da-Ting] Natl Inst Drug Abuse, Intramural Res Programme, NIH, Baltimore, MD 21224 USA.
RP YupengYang (reprint author), Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Brain Funct & Dis, Hefei 230027, Peoples R China.
EM yangyp@ustc.edu.cn
FU National '973' Programmes [2009CB941303, 2011CBA00400]; National Natural
Science Foundation of China [31371112]
FX This work was supported by National '973' Programmes 2009CB941303 and
2011CBA00400, the National Natural Science Foundation of China (Nos.
31371112). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript. We
thank Drs. Nigel Daw, Michael Stryker, Yifeng Zhang, Jianzhong Jin, Ian
Andolina and Niall McLoughlin for comments and suggestions on the data
analysis and manuscript writing.
NR 61
TC 1
Z9 1
U1 9
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 13
PY 2015
VL 5
AR 7734
DI 10.1038/srep07734
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY8WT
UT WOS:000347832200003
PM 25583266
ER
PT J
AU Damsky, W
Micevic, G
Meeth, K
Muthusamy, V
Curley, DP
Santhanakrishnan, M
Erdelyi, I
Platt, JT
Huang, L
Theodosakis, N
Zaidi, MR
Tighe, S
Davies, MA
Dankort, D
McMahon, M
Merlino, G
Bardeesy, N
Bosenberg, M
AF Damsky, William
Micevic, Goran
Meeth, Katrina
Muthusamy, Viswanathan
Curley, David P.
Santhanakrishnan, Manjula
Erdelyi, Ildiko
Platt, James T.
Huang, Laura
Theodosakis, Nicholas
Zaidi, M. Raza
Tighe, Scott
Davies, Michael A.
Dankort, David
McMahon, Martin
Merlino, Glenn
Bardeesy, Nabeel
Bosenberg, Marcus
TI mTORC1 Activation Blocks Braf(V600E)-Induced Growth Arrest but Is
Insufficient for Melanoma Formation
SO CANCER CELL
LA English
DT Article
ID ONCOGENE-INDUCED SENESCENCE; MALIGNANT MELANOMAS; CUTANEOUS MELANOMA;
MELANOCYTIC TUMORS; MOUSE MODEL; COMPLEX 2; PTEN LOSS; EXPRESSION;
CANCER; NEVI
AB Braf(V600E) induces benign, growth-arrested melanocytic nevus development, but also drives melanoma formation. Cdkn2a loss in Braf(V600E) melanocytes in mice results in rare progression to melanoma, but only after stable growth arrest as nevi. Immediate progression to melanoma is prevented by upregulation of miR-99/100, which downregulates mTOR and IGF1R signaling. mTORC1 activation through Stk11 (Lkb1) loss abrogates growth arrest of Braf(V600E) melanocytic nevi, but is insufficient for complete progression to melanoma. Cdkn2a loss is associated with mTORC2 and Akt activation in human and murine melanocytic neoplasms. Simultaneous Cdkn2a and Lkb1 inactivation in Braf(V600E) melanocytes results in activation of both mTORC1 and mTORC2/Akt, inducing rapid melanoma formation in mice. In this model, activation of both mTORC1/2 is required for Braf-induced melanomagenesis.
C1 [Damsky, William; Micevic, Goran; Platt, James T.; Huang, Laura; Bosenberg, Marcus] Yale Univ, Dept Dermatol, New Haven, CT 06510 USA.
[Micevic, Goran; Meeth, Katrina; Theodosakis, Nicholas; Bosenberg, Marcus] Yale Univ, Dept Pathol, New Haven, CT 06510 USA.
[Muthusamy, Viswanathan] Yale Univ, Dept Chem, New Haven, CT 06510 USA.
[Curley, David P.] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Santhanakrishnan, Manjula] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
[Erdelyi, Ildiko] Yale Univ, Sch Med, Sect Comparat Med, New Haven, CT 06510 USA.
[Zaidi, M. Raza] Temple Univ, Fels Inst Canc Res & Mol Biol, Sch Med, Philadelphia, PA 19140 USA.
[Tighe, Scott] Univ Vermont, Coll Med, Vermont Canc Ctr, NextGen Sequencing Facil, Burlington, VT 05405 USA.
[Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Dankort, David] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
[McMahon, Martin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
[McMahon, Martin] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Merlino, Glenn] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
RP Damsky, W (reprint author), Yale Univ, Dept Dermatol, New Haven, CT 06510 USA.
EM william.damsky@gmail.com; marcus.bosenberg@yale.edu
RI Zaidi, M. Raza/H-1386-2016;
OI Zaidi, M. Raza/0000-0003-0480-3188; Dankort, David/0000-0002-5862-6829
FU National Cancer Institute [NCI] Cancer Center Support Grant [CCSG]
[CA-16672]; NCI [R01 CA112054, P50 CA121974, P01 CA128814]; Hevery
Foundation; Joanna M. Nicolay Melanoma Foundation; GlaxoSmithKline;
Genentech; Merck; Myriad; AstraZeneca; Sanofi-Aventis
FX The authors thank all members of the M.B. lab. We also thank Z. Zhao for
FACS sort assistance, the Yale Dermatopathology lab for tissue
processing, the University of Vermont Microarray Core Facility for
assistance with microarray analyses, and the RPPA Core Facility at MD
Anderson Cancer Center for the RPPA analyses (supported by National
Cancer Institute [NCI] Cancer Center Support Grant [CCSG] CA-16672).
Special thanks to R. Halaban for providing human melanoma cell lines and
to D. Stern and his lab for the human melanoma RPPA analyses. This work
was supported by grants from the NCI (R01 CA112054, P50 CA121974, and
P01 CA128814) and the Hevery and Joanna M. Nicolay Melanoma Foundations.
The results in part are based on data generated by the TCGA Research
Network. M. A. D. has served on advisory boards for GlaxoSmithKline,
Genentech, Novartis, and Sanofi-Aventis and has received research
funding from GlaxoSmithKline, Genentech, Merck, Myriad, AstraZeneca, and
Sanofi-Aventis.
NR 51
TC 18
Z9 19
U1 4
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 JAN 12
PY 2015
VL 27
IS 1
BP 41
EP 56
DI 10.1016/j.ccell.2014.11.014
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AY9ZS
UT WOS:000347906900009
PM 25584893
ER
PT J
AU Arem, H
Pfeiffer, RM
Engels, EA
Alfano, CM
Hollenbeck, A
Park, Y
Matthews, CE
AF Arem, Hannah
Pfeiffer, Ruth M.
Engels, Eric A.
Alfano, Catherine M.
Hollenbeck, Albert
Park, Yikyung
Matthews, Charles E.
TI Pre- and Postdiagnosis Physical Activity, Television Viewing, and
Mortality Among Patients With Colorectal Cancer in the National
Institutes of Health-AARP Diet and Health Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID GROWTH-FACTOR-I; IGF-BINDING-PROTEINS; BODY-MASS INDEX; QUALITY-OF-LIFE;
SEDENTARY BEHAVIOR; ACTIVITY QUESTIONNAIRE; INSULIN-RESISTANCE; FACTOR
(IGF)-I; COLON-CANCER; SURVIVAL
AB Purpose
Physical inactivity has been associated with higher mortality risk among survivors of colorectal cancer (CRC), but the independent effects of pre- versus postdiagnosis activity are unclear, and the association between watching television (TV) and mortality in survivors of CRC is previously undefined.
Methods
We analyzed the associations between prediagnosis (n = 3,797) and postdiagnosis (n = 1,759) leisure time physical activity (LTPA) and TV watching and overall and disease-specific mortality among patients with CRC. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs, adjusting for known mortality risk factors.
Results
Comparing survivors of CRC reporting more than 7 hours per week (h/wk) of prediagnosis LTPA with those reporting no LTPA, we found a 20% lower risk of all-cause mortality (HR, 0.80; 95% CI, 0.68 to 0.95; P for trend = .021). Postdiagnosis LTPA of >= 7 h/wk, compared with none, was associated with a 31% lower all-cause mortality risk (HR, 0.69; 95% CI, 0.49 to 0.98; P for trend = .006), independent of prediagnosis activity. Compared with 0 to 2 TV hours per day (h/d) before diagnosis, those reporting >= 5 h/d of TV before diagnosis had a 22% increased all-cause mortality risk (HR, 1.22; 95% CI, 1.06 to 1.41; P trend = .002), and more postdiagnosis TV watching was associated with a nonsignificant 25% increase in all-cause mortality risk (HR, 1.25; 95% CI, 0.93 to 1.67; P for trend = .126).
Conclusion
LTPA was inversely associated with all-cause mortality, whereas more TV watching was associated with increased mortality risk. For both LTPA and TV watching, postdiagnosis measures independently explained the association with mortality. Clinicians should promote both minimizing TV time and increasing physical activity for longevity among survivors of CRC, regardless of previous behaviors. (C) 2014 by American Society of Clinical Oncology
C1 [Arem, Hannah; Pfeiffer, Ruth M.; Engels, Eric A.; Alfano, Catherine M.; Matthews, Charles E.] NCI, Bethesda, MD 20892 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
[Park, Yikyung] Washington Univ Sch Med, St Louis, MO USA.
RP Arem, H (reprint author), 9609 Med Ctr Dr,Rm 6E324, Rockville, MD 20892 USA.
EM Aremhe2@mail.nih.gov
OI Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health, National Cancer Institute (Bethesda, MD)
FX Supported, in part, by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute (Bethesda, MD).
NR 37
TC 19
Z9 19
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 JAN 10
PY 2015
VL 33
IS 2
BP 180
EP U87
DI 10.1200/JCO.2014.58.1355
PG 10
WC Oncology
SC Oncology
GA CF2ZX
UT WOS:000352418100012
PM 25488967
ER
PT J
AU Naghavi, M
Wang, HD
Lozano, R
Davis, A
Liang, XF
Zhou, MG
Vollset, SE
Ozgoren, AA
Abdalla, S
Abd-Allah, F
Aziz, MIA
Abera, SF
Aboyans, V
Abraham, B
Abraham, JP
Abuabara, KE
Abubakar, I
Abu-Raddad, LJ
Abu-Rmeileh, NME
Achoki, T
Adelekan, A
Ademi, ZN
Adofo, K
Adou, AK
Adsuar, JC
Aernlov, J
Agardh, EE
Akena, D
Al Khabouri, MJ
Alasfoor, D
Albittar, M
Alegretti, MA
Aleman, AV
Alemu, ZA
Alfonso-Cristancho, R
Alhabib, S
Ali, MK
Ali, R
Alla, F
Al Lami, F
Allebeck, P
AlMazroa, MA
Salman, RAS
Alsharif, U
Alvarez, E
Alviz-Guzman, N
Amankwaa, AA
Amare, AT
Ameli, O
Amini, H
Ammar, W
Anderson, HR
Anderson, BO
Antonio, CAT
Anwari, P
Apfel, H
Cunningham, SA
Arsenijevic, VSA
Al Artaman
Asad, MM
Asghar, RJ
Assadi, R
Atkins, LS
Atkinson, C
Badawi, A
Bahit, MC
Bakfalouni, T
Balakrishnan, K
Balalla, S
Banerjee, A
Barber, RM
Barker-Collo, SL
Barquera, S
Barregard, L
Barrero, LH
Barrientos-Gutierrez, T
Basu, A
Basu, S
Basulaiman, MO
Beardsley, J
Bedi, N
Beghi, E
Bekele, T
Bell, ML
Benjet, C
Bennett, DA
Bensenor, IM
Benzian, H
Bertozzi-Villa, A
Beyene, TJ
Bhala, N
Bhalla, A
Bhutta, ZA
Bikbov, B
Bin Abdulhak, A
Biryukov, S
Blore, JD
Blyth, FM
Bohensky, MA
Borges, G
Bose, D
Boufous, S
Bourne, RR
Boyers, LN
Brainin, M
Brauer, M
Brayne, CEG
Brazinova, A
Breitborde, N
Brenner, H
Briggs, ADM
Brown, JC
Brugha, TS
Buckle, GC
Bui, LN
Bukhman, G
Burch, M
Nonato, IRC
Carabin, H
Cardenas, R
Carapetis, J
Carpenter, DO
Caso, V
Castaneda-Orjuela, CA
Castro, RE
Catala-Lopez, F
Cavalleri, F
Chang, JC
Charlson, FC
Che, X
Chen, HL
Chen, YY
Chen, JS
Chen, ZM
Chiang, PPC
Chimed-Ochir, O
Chowdhury, R
Christensen, H
Christophi, CA
Chuang, TW
Chugh, SS
Cirillo, M
Coates, MM
Coffeng, LE
Coggeshall, MS
Cohen, A
Colistro, V
Colquhoun, SM
Colomar, M
Cooper, LT
Cooper, C
Coppola, LM
Cortinovis, M
Courville, K
Cowie, BC
Criqui, MH
Crump, JA
Cuevas-Nasu, L
Leite, IDC
Dabhadkar, KC
Dandona, L
Dandona, R
Dansereau, E
Dargan, PI
Dayama, A
De la Cruz-Gongora, V
de la Vega, SF
De Leo, D
Degenhardt, L
del Pozo-Cruz, B
Dellavalle, RP
Deribe, K
Jarlais, DCD
Dessalegn, M
deVeber, GA
Dharmaratne, SD
Dherani, M
Diaz-Ortega, JL
Diaz-Torne, C
Dicker, D
Ding, EL
Dokova, K
Dorsey, ER
Driscoll, TR
Duan, LL
Duber, HC
Durrani, AM
Ebel, BE
Edmond, KM
Ellenbogen, RG
Elshrek, Y
Ermakov, SP
Erskine, HE
Eshrati, B
Esteghamati, A
Estep, K
Furst, T
Fahimi, S
Fahrion, AS
Faraon, EJA
Farzadfar, F
Fay, DFJ
Feigl, AB
Feigin, VL
Felicio, MM
Fereshtehnejad, SM
Fernandes, JG
Ferrari, AJ
Fleming, TD
Foigt, N
Foreman, K
Forouzanfar, MH
Fowkes, FGR
Paleo, UF
Franklin, RC
Futran, ND
Gaffikin, L
Gambashidze, K
Gankpe, FG
Garcia-Guerra, FA
Garcia, AC
Geleijnse, JM
Gessner, BD
Gibney, KB
Gillum, RF
Gilmour, S
Abdelmageem, I
Ginawi, M
Giroud, M
Glaser, EL
Goenka, S
Dantes, HG
Gona, P
Gonzalez-Medina, D
Guinovart, C
Gupta, R
Gupta, R
Gosselin, RA
Gotay, CC
Goto, A
Gowda, HN
Graetz, N
Greenwell, KF
Gugnani, HC
Gunnell, D
Gutierrez, RA
Haagsma, J
Hafezi-Nejad, N
Hagan, H
Hagstromer, M
Halasa, YA
Hamadeh, RR
Hamavid, H
Hammami, M
Hancock, J
Hankey, GJ
Hansen, GM
Harb, HL
Harewood, H
Haro, JM
Havmoeller, R
Hay, RJ
Hay, SI
Hedayati, MT
Pi, IBH
Heuton, KR
Heydarpour, P
Higashi, H
Hijar, M
Hoek, HW
Hoffman, HJ
Hornberger, JC
Hosgood, HD
Hossain, M
Hotez, PJ
Hoy, DG
Hsairi, M
Hu, GQ
Huang, JJ
Huffman, MD
Hughes, AJ
Husseini, A
Huynh, C
Iannarone, M
Iburg, KM
Idrisov, BT
Ikeda, N
Innos, K
Inoue, M
Islami, F
Ismayilova, S
Jacobsen, KH
Jassal, S
Jayaraman, SP
Jensen, PN
Jha, V
Jiang, GH
Jiang, Y
Jonas, JB
Joseph, J
Juel, K
Kabagambe, EK
Kan, HD
Karch, A
Karimkhani, C
Karthikeyan, G
Kassebaum, N
Kaul, A
Kawakami, N
Kazanjan, K
Kazi, DS
Kemp, AH
Kengne, AP
Keren, A
Kereselidze, M
Khader, YS
Khalifa, SEAH
Khan, EA
Khan, G
Khang, YH
Kieling, C
Kinfu, Y
Kinge, JM
Kim, D
Kim, S
Kivipelto, M
Knibbs, L
Knudsen, AK
Kokubo, Y
Kosen, S
Kotagal, M
Kravchenko, MA
Krishnaswami, S
Krueger, H
Defo, BK
Kuipers, EJ
Bicer, BK
Kulkarni, C
Kulkarni, VS
Kumar, K
Kumar, RB
Kwan, GF
Kyu, H
Lai, T
Balaji, AL
Lalloo, R
Lallukka, T
Lam, H
Lan, Q
Lansingh, VC
Larson, HJ
Larsson, A
Lavados, PM
Lawrynowicz, AEB
Leasher, JL
Lee, JT
Leigh, J
Leinsalu, M
Leung, R
Levitz, C
Li, B
Li, YC
Li, YM
Liddell, C
Lim, SS
de Lima, GMF
Lind, ML
Lipshultz, SE
Liu, SW
Liu, Y
Lloyd, BK
Lofgren, KT
Logroscino, G
London, SJ
Lortet-Tieulent, J
Lotufo, PA
Lucas, RM
Lunevicius, R
Lyons, RA
Ma, S
Machado, VMP
MacIntyre, MF
Mackay, MT
MacLachlan, JH
Magis-Rodriguez, C
Mahdi, AA
Majdan, M
Malekzadeh, R
Mangalam, S
Mapoma, CC
Marape, M
Marcenes, W
Margono, C
Marks, GB
Marzan, MB
Masci, JR
Mashal, MTQ
Masiye, F
Mason-Jones, AJ
Matzopolous, R
Mayosi, BM
Mazorodze, TT
McGrath, JJ
Mckay, AC
Mckee, M
McLain, A
Meaney, PA
Mehndiratta, MM
Mejia-Rodriguez, F
Melaku, YA
Meltzer, M
Memish, ZA
Mendoza, W
Mensah, GA
Meretoja, A
Mhimbira, FA
Miller, TR
Mills, EJ
Misganaw, A
Mishra, SK
Mock, CN
Moffitt, TE
Ibrahim, NM
Mohammad, KA
Mokdad, AH
Mola, GL
Monasta, L
Monis, JD
Hernandez, JCM
Montico, M
Montine, TJ
Mooney, MD
Moore, AR
Moradi-Lakeh, M
Moran, AE
Mori, R
Moschandreas, J
Moturi, WN
Moyer, ML
Mozaffarian, D
Mueller, UO
Mukaigawara, M
Mullany, EC
Murray, J
Mustapha, A
Naghavi, P
Naheed, A
Naidoo, KS
Naldi, L
Nand, D
Nangia, V
Narayan, KMV
Nash, D
Nasher, J
Nejjari, C
Nelson, RG
Neuhouser, M
Neupane, SP
Newcomb, PA
Newman, L
Newton, CR
Ng, M
Ngalesoni, FN
Nguyen, G
Nguyen, NTT
Nisar, MI
Nolte, S
Norheim, OF
Norman, RE
Norrving, B
Nyakarahuka, L
Odell, S
O'Donnell, M
Ohkubo, T
Ohno, SL
Olusanya, BO
Omer, SB
Opio, JN
Orisakwe, OE
Ortblad, KF
Ortiz, A
Otayza, MLK
Pain, AW
Pandian, JD
Panelo, CI
Panniyammakal, J
Papachristou, C
Caicedo, AJP
Patten, SB
Patton, GC
Paul, VK
Pavlin, B
Pearce, N
Pellegrini, CA
Pereira, DM
Peresson, SC
Perez-Padilla, R
Perez-Ruiz, FP
Perico, N
Pervaiz, A
Pesudovs, K
Peterson, CB
Petzold, M
Phillips, BK
Phillips, DE
Phillips, MR
Plass, D
Piel, FB
Poenaru, D
Polinder, S
Popova, S
Poulton, RG
Pourmalek, F
Prabhakaran, D
Qato, D
Quezada, AD
Quistberg, DA
Rabito, F
Rafay, A
Rahimi, K
Rahimi-Movaghar, V
Rahman, SUR
Raju, M
Rakovac, I
Rana, SM
Refaat, A
Remuzzi, G
Ribeiro, AL
Ricci, S
Riccio, PM
Richardson, L
Richardus, JH
Roberts, B
Roberts, DA
Robinson, M
Roca, A
Rodriguez, A
Rojas-Rueda, D
Ronfani, L
Room, R
Roth, GA
Rothenbacher, D
Rothstein, DH
Rowley, JT
Roy, N
Ruhago, GM
Rushton, L
Sambandam, S
Soreide, K
Saeedi, MY
Saha, S
Sahathevan, R
Sahraian, MA
Sahle, BW
Salomon, JA
Salvo, D
Samonte, GMJ
Sampson, U
Sanabria, JR
Sandar, L
Santos, IS
Satpathy, M
Sawhney, M
Saylan, M
Scarborough, P
Schottker, B
Schmidt, JC
Schneider, IJC
Schumacher, AE
Schwebel, DC
Scott, JG
Sepanlou, SG
Servan-Mori, EE
Shackelford, K
Shaheen, A
Shahraz, S
Shakh-Nazarova, M
Shangguan, S
She, J
Sheikhbahaei, S
Shepard, DS
Shibuya, K
Shinohara, Y
Shishani, K
Shiue, I
Shivakoti, R
Shrime, MG
Sigfusdottir, ID
Silberberg, DH
Silva, AP
Simard, EP
Sindi, S
Singh, JA
Singh, L
Sioson, E
Skirbekk, V
Sliwa, K
So, S
Soljak, M
Soneji, S
Soshnikov, SS
Sposato, LA
Sreeramareddy, CT
Stanaway, JRD
Stathopoulou, VK
Steenland, K
Stein, C
Steiner, C
Stevens, A
Stoeckl, H
Straif, K
Stroumpoulis, K
Sturua, L
Sunguya, BF
Swaminathan, S
Swaroop, M
Sykes, BL
Tabb, KM
Takahashi, K
Talongwa, RT
Tan, F
Tanne, D
Tanner, M
Tavakkoli, M
Ao, BT
Teixeira, CM
Templin, T
Tenkorang, EY
Terkawi, AS
Thomas, BA
Thorne-Lyman, AL
Thrift, AG
Thurston, GD
Tillmann, T
Tirschwell, DL
Tleyjeh, IM
Tonelli, M
Topouzis, F
Towbin, JA
Toyoshima, H
Traebert, J
Tran, BX
Truelsen, T
Trujillo, U
Trillini, M
Dimbuene, ZT
Tsilimbaris, M
Tuzcu, EM
Ubeda, C
Uchendu, US
Ukwaja, KN
Undurraga, EA
Vallely, AJ
van de Vijver, S
van Gool, CH
Varakin, YY
Vasankari, TJ
Vasconcelos, AMN
Vavilala, MS
Venketasubramanian, N
Vijayakumar, L
Villalpando, S
Violante, FS
Vlassov, VV
Wagner, GR
Waller, SG
Wang, JL
Wang, L
Wang, XR
Wang, YP
Warouw, TS
Weichenthal, S
Weiderpass, E
Weintraub, RG
Wenzhi, W
Werdecker, A
Wessells, KRR
Westerman, R
Whiteford, HA
Wilkinson, JD
Williams, TN
Woldeyohannes, SM
Wolfe, CDA
Wolock, TM
Woolf, AD
Wong, JQ
Wright, JL
Wulf, S
Wurtz, B
Xu, GL
Yang, YC
Yano, Y
Yatsuya, H
Yip, P
Yonemoto, N
Yoon, SJ
Younis, M
Yu, CH
Jin, KY
Zaki, MES
Zamakhshary, MF
Zeeb, H
Zhang, Y
Zhao, Y
Zheng, YF
Zhu, J
Zhu, S
Zonies, D
Zou, XN
Zunt, JR
Vos, T
Lopez, AD
Murray, CJL
AF Naghavi, Mohsen
Wang, Haidong
Lozano, Rafael
Davis, Adrian
Liang, Xiaofeng
Zhou, Maigeng
Vollset, Stein Emil
Ozgoren, Ayse Abbasoglu
Abdalla, Safa
Abd-Allah, Foad
Aziz, Muna I. Abdel
Abera, Semaw Ferede
Aboyans, Victor
Abraham, Biju
Abraham, Jerry P.
Abuabara, Katrina E.
Abubakar, Ibrahim
Abu-Raddad, Laith J.
Abu-Rmeileh, Niveen M. E.
Achoki, Tom
Adelekan, Ademola
Ademi, Zanfi Na
Adofo, Koranteng
Adou, Arsene Kouablan
Adsuar, Jose C.
Aernlov, Johan
Agardh, Emilie Elisabet
Akena, Dickens
Al Khabouri, Mazin J.
Alasfoor, Deena
Albittar, Mohammed
Alegretti, Miguel Angel
Aleman, Alicia V.
Alemu, Zewdie Aderaw
Alfonso-Cristancho, Rafael
Alhabib, Samia
Ali, Mohammed K.
Ali, Raghib
Alla, Francois
Al Lami, Faris
Allebeck, Peter
AlMazroa, Mohammad A.
Salman, Rustam Al-Shahi
Alsharif, Ubai
Alvarez, Elena
Alviz-Guzman, Nelson
Amankwaa, Adansi A.
Amare, Azmeraw T.
Ameli, Omid
Amini, Hassan
Ammar, Walid
Anderson, H. Ross
Anderson, Benjamin O.
Antonio, Carl Abelardo T.
Anwari, Palwasha
Apfel, Henry
Cunningham, Solveig Argeseanu
Arsenijevic, Valentina S. Arsic
Al Artaman
Asad, Majed Masoud
Asghar, Rana J.
Assadi, Reza
Atkins, Lydia S.
Atkinson, Charles
Badawi, Alaa
Bahit, Maria C.
Bakfalouni, Talal
Balakrishnan, Kalpana
Balalla, Shivanthi
Banerjee, Amitava
Barber, Ryan M.
Barker-Collo, Suzanne L.
Barquera, Simon
Barregard, Lars
Barrero, Lope H.
Barrientos-Gutierrez, Tonatiuh
Basu, Arindam
Basu, Sanjay
Basulaiman, Mohammed Omar
Beardsley, Justin
Bedi, Neeraj
Beghi, Ettore
Bekele, Tolesa
Bell, Michelle L.
Benjet, Corina
Bennett, Derrick A.
Bensenor, Isabela M.
Benzian, Habib
Bertozzi-Villa, Amelia
Beyene, Tariku Jibat
Bhala, Neeraj
Bhalla, Ashish
Bhutta, Zulfiqar A.
Bikbov, Boris
Bin Abdulhak, Aref
Biryukov, Stan
Blore, Jed D.
Blyth, Fiona M.
Bohensky, Megan A.
Borges, Guilherme
Bose, Dipan
Boufous, Soufiane
Bourne, Rupert R.
Boyers, Lindsay N.
Brainin, Michael
Brauer, Michael
Brayne, Carol E. G.
Brazinova, Alexandra
Breitborde, Nicholas
Brenner, Hermann
Briggs, Adam D. M.
Brown, Jonathan C.
Brugha, Traolach S.
Buckle, Geoffrey C.
Bui, Linh Ngoc
Bukhman, Gene
Burch, Michael
Nonato, Ismael Ricardo Campos
Carabin, Helesne
Cardenas, Rosario
Carapetis, Jonathan
Carpenter, David O.
Caso, Valeria
Castaneda-Orjuela, Carlos A.
Castro, Ruben Estanislao
Catala-Lopez, Ferrn
Cavalleri, Fiorella
Chang, Jung-Chen
Charlson, Fiona C.
Che, Xuan
Chen, Honglei
Chen, Yingyao
Chen, Jian Sheng
Chen, Zhengming
Chiang, Peggy Pei-Chia
Chimed-Ochir, Odgerel
Chowdhury, Rajiv
Christensen, Hanne
Christophi, Costas A.
Chuang, Ting-Wu
Chugh, Sumeet S.
Cirillo, Massimo
Coates, Matthew M.
Coffeng, Luc Edgar
Coggeshall, Megan S.
Cohen, Aaron
Colistro, Valentina
Colquhoun, Samantha M.
Colomar, Mercedes
Cooper, Leslie Trumbull
Cooper, Cyrus
Coppola, Luis M.
Cortinovis, Monica
Courville, Karen
Cowie, Benjamin C.
Criqui, Michael H.
Crump, John A.
Cuevas-Nasu, Lucia
Leite, Iuri da Costa
Dabhadkar, Kaustubh C.
Dandona, Lalit
Dandona, Rakhi
Dansereau, Emily
Dargan, Paul I.
Dayama, Anand
De la Cruz-Gongora, Vanessa
de la Vega, Shelley F.
De Leo, Diego
Degenhardt, Louisa
del Pozo-Cruz, Borja
Dellavalle, Robert P.
Deribe, Kebede
Jarlais, Don C. Des
Dessalegn, Muluken
deVeber, Gabrielle A.
Dharmaratne, Samath D.
Dherani, Mukesh
Diaz-Ortega, Jose-Luis
Diaz-Torne, Cesar
Dicker, Daniel
Ding, Eric L.
Dokova, Klara
Dorsey, E. Ray
Driscoll, Tim R.
Duan, Leilei
Duber, Herbert C.
Durrani, Adnan M.
Ebel, Beth E.
Edmond, Karen M.
Ellenbogen, Richard G.
Elshrek, Yousef
Ermakov, Sergey Petrovich
Erskine, Holly E.
Eshrati, Babak
Esteghamati, Alireza
Estep, Kara
Fuerst, Thomas
Fahimi, Saman
Fahrion, Anna S.
Faraon, Emerito Jose A.
Farzadfar, Farshad
Fay, Derek F. J.
Feigl, Andrea B.
Feigin, Valery L.
Felicio, Manuela Mendonca
Fereshtehnejad, Seyed-Mohammad
Fernandes, Jefferson G.
Ferrari, Alize J.
Fleming, Thomas D.
Foigt, Nataliya
Foreman, Kyle
Forouzanfar, Mohammad H.
Fowkes, F. Gerry R.
Fra Paleo, Urbano
Franklin, Richard C.
Futran, Neal D.
Gaffikin, Lynne
Gambashidze, Ketevan
Gankpe, Fortune Gbetoho
Garcia-Guerra, Francisco Armando
Garcia, Ana Cristina
Geleijnse, Johanna M.
Gessner, Bradford D.
Gibney, Katherine B.
Gillum, Richard F.
Gilmour, Stuart
Abdelmageem, Ibrahim
Ginawi, Mohamed
Giroud, Maurice
Glaser, Elizabeth L.
Goenka, Shifalika
Dantes, Hector Gomez
Gona, Philimon
Gonzalez-Medina, Diego
Guinovart, Caterina
Gupta, Rahul
Gupta, Rajeev
Gosselin, Richard A.
Gotay, Carolyn C.
Goto, Atsushi
Gowda, Hube N.
Graetz, Nicholas
Greenwell, K. Fern
Gugnani, Harish Chander
Gunnell, David
Gutierrez, Reyna A.
Haagsma, Juanita
Hafezi-Nejad, Nima
Hagan, Holly
Hagstromer, Maria
Halasa, Yara A.
Hamadeh, Randah Ribhi
Hamavid, Hannah
Hammami, Mouhanad
Hancock, Jamie
Hankey, Graeme J.
Hansen, Gillian M.
Harb, Hilda L.
Harewood, Heather
Haro, Josep Maria
Havmoeller, Rasmus
Hay, Roderick J.
Hay, Simon I.
Hedayati, Mohammad T.
Pi, Ileana B. Heredia
Heuton, Kyle R.
Heydarpour, Pouria
Higashi, Hideki
Hijar, Martha
Hoek, Hans W.
Hoffman, Howard J.
Hornberger, John C.
Hosgood, H. Dean
Hossain, Mazeda
Hotez, Peter J.
Hoy, Damian G.
Hsairi, Mohamed
Hu, Guoqing
Huang, John J.
Huffman, Mark D.
Hughes, Andrew J.
Husseini, Abdullatif
Huynh, Chantal
Iannarone, Marissa
Iburg, Kim M.
Idrisov, Bulat T.
Ikeda, Nayu
Innos, Kaire
Inoue, Manami
Islami, Farhad
Ismayilova, Samaya
Jacobsen, Kathryn H.
Jassal, Simerjot
Jayaraman, Sudha P.
Jensen, Paul N.
Jha, Vivekanand
Jiang, Guohong
Jiang, Ying
Jonas, Jost B.
Joseph, Jonathan
Juel, Knud
Kabagambe, Edmond Kato
Kan, Haidong
Karch, Andre
Karimkhani, Chante
Karthikeyan, Ganesan
Kassebaum, Nicholas
Kaul, Anil
Kawakami, Norito
Kazanjan, Konstantin
Kazi, Dhruv S.
Kemp, Andrew H.
Kengne, Andre Pascal
Keren, Andre
Kereselidze, Maia
Khader, Yousef Saleh
Khalifa, Shams Eldin Ali Hassan
Khan, Ejaz Ahmed
Khan, Gulfaraz
Khang, Young-Ho
Kieling, Christian
Kinfu, Yohannes
Kinge, Jonas M.
Kim, Daniel
Kim, Sungroul
Kivipelto, Miia
Knibbs, Luke
Knudsen, Ann Kristin
Kokubo, Yoshihiro
Kosen, Sowarta
Kotagal, Meera
Kravchenko, Michael A.
Krishnaswami, Sanjay
Krueger, Hans
Defo, Barthelemy Kuate
Kuipers, Ernst J.
Bicer, Burcu Kucuk
Kulkarni, Chanda
Kulkarni, Veena S.
Kumar, Kaushalendra
Kumar, Ravi B.
Kwan, Gene F.
Kyu, Hmwe
Lai, Taavi
Balaji, Arjun Lakshmana
Lalloo, Ratilal
Lallukka, Tea
Lam, Hilton
Lan, Qing
Lansingh, Van C.
Larson, Heidi J.
Larsson, Anders
Lavados, Pablo M.
Lawrynowicz, Alicia E. B.
Leasher, Janet L.
Lee, Jong-Tae
Leigh, James
Leinsalu, Mall
Leung, Ricky
Levitz, Carly
Li, Bin
Li, Yichong
Li, Yongmei
Liddell, Chelsea
Lim, Stephen S.
de Lima, Graca Maria Ferreira
Lind, Maggie L.
Lipshultz, Steven E.
Liu, Shiwei
Liu, Yang
Lloyd, Belinda K.
Lofgren, Katherine T.
Logroscino, Giancarlo
London, Stephanie J.
Lortet-Tieulent, Joannie
Lotufo, Paulo A.
Lucas, Robyn M.
Lunevicius, Raimundas
Lyons, Ronan Anthony
Ma, Stefan
Machado, Vasco Manuel Pedro
MacIntyre, Michael F.
Mackay, Mark T.
MacLachlan, Jennifer H.
Magis-Rodriguez, Carlos
Mahdi, Abbas A.
Majdan, Marek
Malekzadeh, Reza
Mangalam, Srikanth
Mapoma, Christopher Chabila
Marape, Marape
Marcenes, Wagner
Margono, Christopher
Marks, Guy B.
Marzan, Melvin Barrientos
Masci, Joseph R.
Mashal, Mohammad Taufi Q.
Masiye, Felix
Mason-Jones, Amanda J.
Matzopolous, Richard
Mayosi, Bongani M.
Mazorodze, Tasara T.
McGrath, John J.
Mckay, Abigail C.
Mckee, Martin
McLain, Abigail
Meaney, Peter A.
Mehndiratta, Man Mohan
Mejia-Rodriguez, Fabiola
Melaku, Yohannes Adama
Meltzer, Michele
Memish, Ziad A.
Mendoza, Walter
Mensah, George A.
Meretoja, Atte
Mhimbira, Francis A.
Miller, Ted R.
Mills, Edward J.
Misganaw, Awoke
Mishra, Santosh K.
Mock, Charles N.
Moffitt, Terrie E.
Ibrahim, Norlinah Mohamed
Mohammad, Karzan Abdulmuhsin
Mokdad, Ali H.
Mola, Glen Liddell
Monasta, Lorenzo
Monis, Jonathan de la Cruz
Hernandez, Julio C. Montaez
Montico, Marcella
Montine, Thomas J.
Mooney, Meghan D.
Moore, Ami R.
Moradi-Lakeh, Maziar
Moran, Andrew E.
Mori, Rintaro
Moschandreas, Joanna
Moturi, Wilkister Nyaora
Moyer, Madeline L.
Mozaffarian, Dariush
Mueller, Ulrich O.
Mukaigawara, Mitsuru
Mullany, Erin C.
Murray, Joseph
Mustapha, Adetoun
Naghavi, Paria
Naheed, Aliya
Naidoo, Kovin S.
Naldi, Luigi
Nand, Devina
Nangia, Vinay
Narayan, K. M. Venkat
Nash, Denis
Nasher, Jamal
Nejjari, Chakib
Nelson, Robert G.
Neuhouser, Marian
Neupane, Sudan Prasad
Newcomb, Polly A.
Newman, Lori
Newton, Charles R.
Ng, Marie
Ngalesoni, Frida Namnyak
Nguyen, Grant
Nhung Thi Trang Nguyen
Nisar, Muhammad Imran
Nolte, Sandra
Norheim, Ole F.
Norman, Rosana E.
Norrving, Bo
Nyakarahuka, Luke
Odell, Shaun
O'Donnell, Martin
Ohkubo, Takayoshi
Ohno, Summer Lockett
Olusanya, Bolajoko O.
Omer, Saad B.
Opio, John Nelson
Orisakwe, Orish Ebere
Ortblad, Katrina F.
Ortiz, Alberto
Otayza, Maria Lourdes K.
Pain, Amanda W.
Pandian, Jeyaraj D.
Panelo, Carlo Irwin
Panniyammakal, Jeemon
Papachristou, Christina
Paternina Caicedo, Angel J.
Patten, Scott B.
Patton, George C.
Paul, Vinod K.
Pavlin, Boris
Pearce, Neil
Pellegrini, Carlos A.
Pereira, David M.
Peresson, Sophie C.
Perez-Padilla, Rogelio
Perez-Ruiz, Fernando P.
Perico, Norberto
Pervaiz, Aslam
Pesudovs, Konrad
Peterson, Carrie B.
Petzold, Max
Phillips, Bryan K.
Phillips, David E.
Phillips, Michael R.
Plass, Dietrich
Piel, Frederic Bernard
Poenaru, Dan
Polinder, Suzanne
Popova, Svetlana
Poulton, Richie G.
Pourmalek, Farshad
Prabhakaran, Dorairaj
Qato, Dima
Quezada, Amado D.
Quistberg, D. Alex
Rabito, Felicia
Rafay, Anwar
Rahimi, Kazem
Rahimi-Movaghar, Vafa
Rahman, Sajjad U. R.
Raju, Murugesan
Rakovac, Ivo
Rana, Saleem M.
Refaat, Amany
Remuzzi, Giuseppe
Ribeiro, Antonio L.
Ricci, Stefano
Riccio, Patricia M.
Richardson, Lee
Richardus, Jan Hendrik
Roberts, Bayard
Roberts, D. Allen
Robinson, Margaret
Roca, Anna
Rodriguez, Alina
Rojas-Rueda, David
Ronfani, Luca
Room, Robin
Roth, Gregory A.
Rothenbacher, Dietrich
Rothstein, David H.
Rowley, Jane Tf
Roy, Nobhojit
Ruhago, George M.
Rushton, Lesley
Sambandam, Sankar
Soreide, Kjetil
Saeedi, Mohammad Yahya
Saha, Sukanta
Sahathevan, Ramesh
Sahraian, Mohammad Ali
Sahle, Berhe Weldearegawi
Salomon, Joshua A.
Salvo, Deborah
Samonte, Genesis May J.
Sampson, Uchechukwu
Sanabria, Juan Ramon
Sandar, Logan
Santos, Itamar S.
Satpathy, Maheswar
Sawhney, Monika
Saylan, Mete
Scarborough, Peter
Schoettker, Ben
Schmidt, Juergen C.
Schneider, Ione J. C.
Schumacher, Austin E.
Schwebel, David C.
Scott, James G.
Sepanlou, Sadaf G.
Servan-Mori, Edson E.
Shackelford, Katya
Shaheen, Amira
Shahraz, Saeid
Shakh-Nazarova, Marina
Shangguan, Siyi
She, Jun
Sheikhbahaei, Sara
Shepard, Donald S.
Shibuya, Kenji
Shinohara, Yukito
Shishani, Kawkab
Shiue, Ivy
Shivakoti, Rupak
Shrime, Mark G.
Sigfusdottir, Inga Dora
Silberberg, Donald H.
Silva, Andrea P.
Simard, Edgar P.
Sindi, Shireen
Singh, Jasvinder A.
Singh, Lavanya
Sioson, Edgar
Skirbekk, Vegard
Sliwa, Karen
So, Samuel
Soljak, Michael
Soneji, Samir
Soshnikov, Sergey S.
Sposato, Luciano A.
Sreeramareddy, Chandrashekhar T.
Stanaway, Jeff Rey D.
Stathopoulou, Vasiliki Kalliopi
Steenland, Kyle
Stein, Claudia
Steiner, Caitlyn
Stevens, Antony
Stoeckl, Heidi
Straif, Kurt
Stroumpoulis, Konstantinos
Sturua, Lela
Sunguya, Bruno F.
Swaminathan, Soumya
Swaroop, Mamta
Sykes, Bryan L.
Tabb, Karen M.
Takahashi, Ken
Talongwa, Roberto Tchio
Tan, Feng
Tanne, David
Tanner, Marcel
Tavakkoli, Mohammad
Ao, Braden Te
Teixeira, Carolina Maria
Templin, Tara
Tenkorang, Eric Yeboah
Terkawi, Abdullah Sulieman
Thomas, Bernadette A.
Thorne-Lyman, Andrew L.
Thrift, Amanda G.
Thurston, George D.
Tillmann, Taavi
Tirschwell, David L.
Tleyjeh, Imad M.
Tonelli, Marcello
Topouzis, Fotis
Towbin, Jeffrey A.
Toyoshima, Hideaki
Traebert, Jefferson
Tran, Bach X.
Truelsen, Thomas
Trujillo, Ulises
Trillini, Matias
Dimbuene, Zacharie Tsala
Tsilimbaris, Miltiadis
Tuzcu, E. Murat
Ubeda, Clotilde
Uchendu, Uche S.
Ukwaja, Kingsley N.
Undurraga, Eduardo A.
Vallely, Andrew J.
van de Vijver, Steven
van Gool, Coen H.
Varakin, Yuri Y.
Vasankari, Tommi J.
Vasconcelos, Ana Maria Nogales
Vavilala, Monica S.
Venketasubramanian, N.
Vijayakumar, Lakshmi
Villalpando, Salvador
Violante, Francesco S.
Vlassov, Vasiliy Victorovich
Wagner, Gregory R.
Waller, Stephen G.
Wang, JianLi
Wang, Linhong
Wang, XiaoRong
Wang, Yanping
Warouw, Tati Suryati
Weichenthal, Scott
Weiderpass, Elisabete
Weintraub, Robert G.
Wenzhi, Wang
Werdecker, Andrea
Wessells, K. Ryan R.
Westerman, Ronny
Whiteford, Harvey A.
Wilkinson, James D.
Williams, Thomas Neil
Woldeyohannes, Solomon Meseret
Wolfe, Charles D. A.
Wolock, Timothy M.
Woolf, Anthony D.
Wong, John Q.
Wright, Jonathan L.
Wulf, Sarah
Wurtz, Brittany
Xu, Gelin
Yang, Yang C.
Yano, Yuichiro
Yatsuya, Hiroshi
Yip, Paul
Yonemoto, Naohiro
Yoon, Seok-Jun
Younis, Mustafa
Yu, Chuanhua
Jin, Kim Yun
Zaki, Maysaa El Sayed
Zamakhshary, Mohammed Fouad
Zeeb, Hajo
Zhang, Yong
Zhao, Yong
Zheng, Yingfeng
Zhu, Jun
Zhu, Shankuan
Zonies, David
Zou, Xiao Nong
Zunt, Joseph R.
Vos, Theo
Lopez, Alan D.
Murray, Christopher J. L.
CA GBD Mortal 2013 Causes Death Colla
TI Global, regional, and national age-sex specific all-cause and
cause-specific mortality for 240 causes of death, 1990-2013: a
systematic analysis for the Global Burden of Disease Study 2013
SO LANCET
LA English
DT Article
ID INFLUENZAE TYPE-B; PNEUMOCOCCAL CONJUGATE VACCINE;
PLACEBO-CONTROLLED-TRIAL; 187 COUNTRIES; RISK-FACTORS; ENTERIC
MULTICENTER; CHILDREN YOUNGER; CHILDHOOD PNEUMONIA; INTEGRATED APPROACH;
POPULATION HEALTH
AB Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.
Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.
Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.
Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
C1 [Naghavi, Mohsen; Wang, Haidong; Lozano, Rafael; Vollset, Stein Emil; Achoki, Tom; Apfel, Henry; Atkinson, Charles; Barber, Ryan M.; Bertozzi-Villa, Amelia; Biryukov, Stan; Brown, Jonathan C.; Catala-Lopez, Ferrn; Coates, Matthew M.; Coffeng, Luc Edgar; Coggeshall, Megan S.; Dandona, Lalit; Dansereau, Emily; Dicker, Daniel; Duber, Herbert C.; Estep, Kara; Fleming, Thomas D.; Forouzanfar, Mohammad H.; Gonzalez-Medina, Diego; Graetz, Nicholas; Haagsma, Juanita; Hamavid, Hannah; Hancock, Jamie; Hansen, Gillian M.; Heuton, Kyle R.; Higashi, Hideki; Huynh, Chantal; Iannarone, Marissa; Joseph, Jonathan; Kassebaum, Nicholas; Kyu, Hmwe; Levitz, Carly; Liddell, Chelsea; Lind, Maggie L.; Lofgren, Katherine T.; MacIntyre, Michael F.; Margono, Christopher; McLain, Abigail; Mokdad, Ali H.; Mooney, Meghan D.; Moradi-Lakeh, Maziar; Moyer, Madeline L.; Mullany, Erin C.; Naghavi, Paria; Ng, Marie; Nguyen, Grant; Odell, Shaun; Ohno, Summer Lockett; Ortblad, Katrina F.; Pain, Amanda W.; Phillips, Bryan K.; Phillips, David E.; Richardson, Lee; Roberts, D. Allen; Robinson, Margaret; Roth, Gregory A.; Sandar, Logan; Schumacher, Austin E.; Shackelford, Katya; Singh, Lavanya; Sioson, Edgar; Stanaway, Jeff Rey D.; Steiner, Caitlyn; Stevens, Antony; Templin, Tara; Thomas, Bernadette A.; Wolock, Timothy M.; Wulf, Sarah; Wurtz, Brittany; Vos, Theo; Murray, Christopher J. L.] Inst Hlth Metr & Evaluat, Seattle, WA USA.
[Ellenbogen, Richard G.; Wright, Jonathan L.] Univ Washington, Sch Med, Seattle, WA USA.
[Kassebaum, Nicholas] Childrens Hosp, Seattle, WA USA.
[Tirschwell, David L.] Dept Neurol, Seattle, WA USA.
[Ebel, Beth E.] Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA.
[Alfonso-Cristancho, Rafael; Anderson, Benjamin O.; Futran, Neal D.; Jensen, Paul N.; Kotagal, Meera; Mock, Charles N.; Montine, Thomas J.; Pellegrini, Carlos A.; Quistberg, D. Alex; Vavilala, Monica S.; Zunt, Joseph R.] Univ Washington, Seattle, WA 98195 USA.
[Lozano, Rafael; Barquera, Simon; Barrientos-Gutierrez, Tonatiuh; Nonato, Ismael Ricardo Campos; Cuevas-Nasu, Lucia; De la Cruz-Gongora, Vanessa; Diaz-Ortega, Jose-Luis; Garcia-Guerra, Francisco Armando; Dantes, Hector Gomez; Pi, Ileana B. Heredia; Mejia-Rodriguez, Fabiola; Hernandez, Julio C. Montaez; Perez-Padilla, Rogelio; Quezada, Amado D.; Salvo, Deborah; Servan-Mori, Edson E.; Villalpando, Salvador] Natl Inst Publ Hlth Mexico, Mexico City, DF, Mexico.
[Davis, Adrian; Fay, Derek F. J.; Schmidt, Juergen C.] Publ Hlth England, London, England.
[Zhou, Maigeng; Duan, Leilei; Li, Yichong; Liu, Shiwei; Wang, Linhong] Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China.
[Tan, Feng] Natl Inst Occupat Hlth & Control, Beijing, Peoples R China.
[Liang, Xiaofeng] China Ctr Dis Control Prevent, Beijing, Peoples R China.
[Vollset, Stein Emil; Kinge, Jonas M.; Knudsen, Ann Kristin; Skirbekk, Vegard] Norwegian Inst Publ Hlth, Oslo, Norway.
[Vollset, Stein Emil; Norheim, Ole F.] Univ Bergen, Bergen, Norway.
[Ozgoren, Ayse Abbasoglu; Bicer, Burcu Kucuk] Hacettepe Univ, Inst Populat Studies, Ankara, Turkey.
[Abdalla, Safa] Sudanese Publ Hlth Consultancy Grp, Solihull, W Midlands, England.
[Abd-Allah, Foad] Cairo Univ, Fac Med, Cairo, Egypt.
[Aziz, Muna I. Abdel] Inst Publ Hlth, Khartoum, Sudan.
[Abera, Semaw Ferede] Coll Hlth Sci, Sch Publ Hlth, Mekelle, Tigray, Ethiopia.
[Melaku, Yohannes Adama; Sahle, Berhe Weldearegawi] Mekelle Univ, Mekelle, Tigray, Ethiopia.
[Aboyans, Victor] Dupuytren Univ Hosp, Limoges, France.
[Abraham, Biju] Oslo & Akershus Univ, Coll Appl Sci HiOA, Oslo, Norway.
[Abraham, Jerry P.] Univ Texas San Antonio, Sch Med, San Antonio, TX USA.
[Abuabara, Katrina E.; Silberberg, Donald H.] Univ Penn, Philadelphia, PA 19104 USA.
[Benzian, Habib] Dept Epidemiol & Publ Hlth, London, England.
[Benzian, Habib] UCL, London, England.
[Abu-Raddad, Laith J.] Weill Cornell Med Coll Qatar, Doha, Qatar.
[Abu-Rmeileh, Niveen M. E.] Birzeit Univ, Inst Community & Publ Hlth, Ramallah, W Bank, Israel.
[Adelekan, Ademola] Publ Hlth Promot Alliance, Osogbp, Nigeria.
[Chiang, Peggy Pei-Chia] Beneral Practice & Primary Hlth Care Acad Ctr, Melbourne, Vic, Australia.
[Colquhoun, Samantha M.] Ctr Int Child Hlth, Melbourne, Vic, Australia.
[Ademi, Zanfi Na; Blore, Jed D.; Bohensky, Megan A.; Catala-Lopez, Ferrn; Balaji, Arjun Lakshmana; Patton, George C.; Weintraub, Robert G.] Univ Melbourne, Melbourne, Vic, Australia.
[Adofo, Koranteng] Kwame Nkrumah Univ Sci & Technol, Kumasi, Ashanti, Ghana.
[Adou, Arsene Kouablan] Assoc Ivoirienne Bien Etre Familial, Abidjan, Cote Ivoire.
[Adsuar, Jose C.; Fra Paleo, Urbano] Univ Extremadura, Caceres, Spain.
[Aernlov, Johan; Larsson, Anders] Uppsala Univ, Uppsala, Sweden.
[Agardh, Emilie Elisabet] Inst Publ Hlth Sci, Stockholm, Sweden.
[Akena, Dickens; Nyakarahuka, Luke] Makerere Univ, Kampala, Uganda.
[Al Khabouri, Mazin J.; Alasfoor, Deena] Minist Hlth, Muscat, Oman.
[Al Lami, Faris] Baghdad Coll Med, Baghdad, Iraq.
[Albittar, Mohammed] Independent, Damascus, Syria.
Grp Invest Ciencias Salud & Neurociencias CISNEUR, Cartagena De Indias, Bolivar, Colombia.
[Alegretti, Miguel Angel; Aleman, Alicia V.; Cavalleri, Fiorella; Colistro, Valentina] Univ Republica, Fac Med, Dept Prevent & Social Med, Montevideo, Uruguay.
[Alemu, Zewdie Aderaw] Debre Markos Univ, Debre Markos, Amhara, Ethiopia.
[Alhabib, Samia] Natl Guard Hlth Affairs, Riyadh, Saudi Arabia.
[Simard, Edgar P.; Steenland, Kyle] Rollins Sch Publ Hlth, Atlanta, GA USA.
[Ali, Mohammed K.; Cunningham, Solveig Argeseanu; Dabhadkar, Kaustubh C.; Liu, Yang; Narayan, K. M. Venkat; Omer, Saad B.; Phillips, Michael R.] Emory Univ, Atlanta, GA 30322 USA.
[Ali, Raghib; Bennett, Derrick A.; Briggs, Adam D. M.; Chen, Zhengming; Hay, Simon I.; Piel, Frederic Bernard; Rahimi, Kazem; Scarborough, Peter] Univ Oxford, Oxford, England.
[Alla, Francois] Univ Lorraine, Sch Publ Hlth, Nancy, France.
[Allebeck, Peter] Dept Publ Hlth Sci, Stockholm, Sweden.
[Fereshtehnejad, Seyed-Mohammad] Dept Neurobiol Care Sci & Soc NVS, Stockholm, Sweden.
[Kivipelto, Miia] Aging Res Ctr, Stockholm, Sweden.
[Weiderpass, Elisabete] Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hagstromer, Maria; Havmoeller, Rasmus; Sindi, Shireen] Karolinska Inst, Stockholm, Sweden.
[AlMazroa, Mohammad A.; Basulaiman, Mohammed Omar; Memish, Ziad A.; Saeedi, Mohammad Yahya] Saudi Minist Hlth, Riyadh, Saudi Arabia.
[Salman, Rustam Al-Shahi; Fowkes, F. Gerry R.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Alsharif, Ubai; Nolte, Sandra; Papachristou, Christina] Charite, D-13353 Berlin, Germany.
[Alvarez, Elena] Government, Madrid, Spain.
[Alviz-Guzman, Nelson; Paternina Caicedo, Angel J.] Univ Cartagena, Cartagena De Indias, Colombia.
[Amankwaa, Adansi A.] Albany State Univ, Albany, GA 31705 USA.
[Amare, Azmeraw T.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Amare, Azmeraw T.] Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar, Ethiopia.
[Ameli, Omid] Boston Univ, Boston, MA 02215 USA.
[Amini, Hassan] Kurdistan Univ Med Sci, Kurdistan Environm Hlth Res Ctr, Sanandaj, Kurdistan, Iran.
[Amini, Hassan] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.
[Tanner, Marcel] Univ Basel, Basel, Switzerland.
[Ammar, Walid] Minist Publ Hlth, Beirut, Lebanon.
[Anderson, H. Ross] St Georges Univ London, London, England.
[Antonio, Carl Abelardo T.; Faraon, Emerito Jose A.; Panelo, Carlo Irwin] Univ Philippines Manila, Coll Publ Hlth, Manila, Philippines.
[Anwari, Palwasha] UNFPA, Kabul, Afghanistan.
[Arsenijevic, Valentina S. Arsic] Univ Belgrade, Sch Med, Inst Microbiol & Immunol, Belgrade, Serbia.
[Al Artaman] Evidera Inc, Lexington, MA USA.
[Asad, Majed Masoud] Minist Hlth, Amman, Jordan.
[Asghar, Rana J.] South Asian Publ Hlth Forum, Islamabad, Pakistan.
[Assadi, Reza] Mashhad Univ Med Sci, Mashhad, Khorasan Razavi, Iran.
[Atkins, Lydia S.] Minist Hlth Wellness Human Serv & Gender Relat, Castries, St Lucia.
[Badawi, Alaa] Publ Hlth Agcy Canada, Toronto, ON, Canada.
[Bahit, Maria C.] INECO Neurociencias, Santa Fe, NM USA.
[Bakfalouni, Talal] Minist Hlth, Damascus, Syria.
[Balakrishnan, Kalpana] Sri Ramachandra Univ, Madras, Tamil Nadu, India.
[Balalla, Shivanthi; Feigin, Valery L.] Natl Inst Stroke & Appl Neurosciences, Auckland, New Zealand.
[Barker-Collo, Suzanne L.] Sch Psychol, Auckland, New Zealand.
[del Pozo-Cruz, Borja] Univ Auckland, Auckland 1, New Zealand.
[Banerjee, Amitava] Univ Birmingham, Birmingham, W Midlands, England.
[Barregard, Lars] Univ Gothenburg, Dept Environm & Occupat Hlth, Gothenburg, Sweden.
[Barrero, Lope H.] Pontificia Univ Javeriana, Dept Ind Engn, Bogota, Colombia.
[Basu, Arindam] Univ Canterbury, Sch Hlth Sci, Canterbury, New Zealand.
[So, Samuel] Asian Liver Ctr, Palo Alto, CA USA.
[Gaffikin, Lynne] Stanford Univ, Med Ctr, Sch Med, Stanford, CA 94305 USA.
[Basu, Sanjay] Stanford Univ, Stanford, CA 94305 USA.
[Beardsley, Justin] Univ Oxford, Ho Hi Minh City, Vietnam.
[Bedi, Neeraj] Coll Publ Hlth & Trop Med, Jazan, Saudi Arabia.
[Beghi, Ettore; Cortinovis, Monica; Perico, Norberto; Remuzzi, Giuseppe; Trillini, Matias] IRCCS Ist Ric Farmacol Mario Negri, Milan, Italy.
[Bekele, Tolesa] Madawalabu Univ, Bale Goba, Oromia, Ethiopia.
[Bell, Michelle L.; Huang, John J.] Yale Univ, New Haven, CT USA.
[Benjet, Corina; Gutierrez, Reyna A.] Natl Inst Psychiat Ramon de la Fuente, Mexico City, DF, Mexico.
[Bensenor, Isabela M.; Kemp, Andrew H.] Univ Hosp, Sao Paulo, Brazil.
[Lotufo, Paulo A.; Santos, Itamar S.] Univ Sao Paulo, Sao Paulo, Brazil.
[Beyene, Tariku Jibat; Deribe, Kebede] Univ Addis Ababa, Debre Zeit, Ethiopia.
[Bhala, Neeraj] Wellington Hosp, Wellington, New Zealand.
[Bhalla, Ashish] Postgrad Inst Med Educ & Res, Chandigarh 160012, UT, India.
[Bhutta, Zulfiqar A.] Med Ctr, Karachi, Pakistan.
[Nisar, Muhammad Imran] Aga Khan Univ, Karachi, Pakistan.
[Bikbov, Boris] I Evdokimov Moscow State Univ Med & Dent, Moscow, Russia.
[Bin Abdulhak, Aref] Univ Missouri, Kansas City, MO 64110 USA.
[Marks, Guy B.] Woolcock Inst Med Res, Sydney, NSW, Australia.
[Driscoll, Tim R.] Sydney Sch Publ Hlth, Sydney, NSW, Australia.
[Blyth, Fiona M.; Leigh, James] Univ Sydney, Sydney, NSW 2006, Australia.
[Borges, Guilherme] Inst Nacl Psiquiatria, Mexico City, DF, Mexico.
[Bose, Dipan] World Bank, Washington, DC 20433 USA.
[Boufous, Soufiane] Transport & Rd Safety TARS Res, Sydney, NSW, Australia.
[Vallely, Andrew J.] Kirby Inst, Sydney, NSW, Australia.
[Degenhardt, Louisa; Satpathy, Maheswar] Univ New S Wales, Sydney, NSW, Australia.
[Bourne, Rupert R.] Anglia Ruskin Univ, Vis & Eye Res Unit, Cambridge, England.
[Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA.
[Brainin, Michael] Danube Univ Krems, Krems, Austria.
[Krueger, Hans] Sch Populat & Publ Hlth, Vancouver, BC, Canada.
[Brauer, Michael; Gotay, Carolyn C.; Pourmalek, Farshad] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Brayne, Carol E. G.] Cambridge Inst Publ Hlth, Cambridge, England.
[Brazinova, Alexandra; Majdan, Marek] Trnava Univ, Fac Hlth Sci & Social Work, Trnava, Slovakia.
[Breitborde, Nicholas] Univ Arizona, Tucson, AZ USA.
[Brenner, Hermann] German Canc Res Ctr, Heidelberg, Germany.
[Brugha, Traolach S.] Univ Leicester, Leicester, Leics, England.
[Buckle, Geoffrey C.; Gona, Philimon] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Bui, Linh Ngoc; Nhung Thi Trang Nguyen] Hanoi Sch Publ Hlth, Hanoi, Vietnam.
[Bukhman, Gene] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Ding, Eric L.; Fahimi, Saman; Shangguan, Siyi] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Feigl, Andrea B.; Salomon, Joshua A.; Shrime, Mark G.] Harvard Univ, Cambridge, MA 02138 USA.
[Burch, Michael] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Cardenas, Rosario] Univ Autonoma Metropolitana, Mexico City, DF, Mexico.
[Carabin, Helesne] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA.
[Carapetis, Jonathan] Telethon Inst Child Hlth Res, Subiaco, WA, Australia.
[Carpenter, David O.] Univ Albany, Rensselaer, NY USA.
[Caso, Valeria] Univ Perugia, Stroke Unit, I-06100 Perugia, Italy.
[Castaneda-Orjuela, Carlos A.] Colombian Natl Hlth Observ, Inst Nacl Salud, Bogota, Colombia.
[Castro, Ruben Estanislao] Univ Diego Portales, Santiago, Chile.
[Catala-Lopez, Ferrn] Minist Hlth, Spanish Med & Healthcare Prod Agcy AEMPS, Div Pharmacoepidemiol & Pharmacovigilance, Madrid, Spain.
[Chang, Jung-Chen] Natl Taiwan Univ, Taipei 10764, Taiwan.
[Hoy, Damian G.] Univ Queensland, Sch Populat Hlth, Herston, Qld, Australia.
[Scott, James G.] Univ Queensland, Clin Res Ctr, Herston, Qld, Australia.
[Charlson, Fiona C.; Erskine, Holly E.; Ferrari, Alize J.; Knibbs, Luke; McGrath, John J.; Norman, Rosana E.; Whiteford, Harvey A.] Univ Queensland, Brisbane, Qld, Australia.
[Che, Xuan] NIH, Bethesda, MD 20892 USA.
[She, Jun] Zhongshan Hosp, Shanghai, Peoples R China.
[Chen, Yingyao; Kan, Haidong] Fudan Univ, Shanghai 200433, Peoples R China.
[Chen, Zhengming] CTSU, Nuffield Dept Populat Hlth, Oxford, England.
[Chen, Honglei; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv,RTP,NC USA, Res Triangle Pk, NC 27709 USA.
[Chen, Jian Sheng] Inst Bone & Joint Res, St Laonards, NSW, Australia.
[Chimed-Ochir, Odgerel] Univ Occupat & Environm Hlth, Dept Environm Epidemiol, Kitakyushu, Fukuoka 807, Japan.
[Chowdhury, Rajiv; Murray, Christopher J. L.] Univ Cambridge, Cambridge, England.
[Christensen, Hanne] Bispebjerg Hosp, Copenhagen, Denmark.
[Christophi, Costas A.] Cyprus Univ Technol, Limassol, Cyprus.
[Chang, Jung-Chen] Taipei Med Univ, Sch Med, Dept Mol Parasitol & Trop Dis, Taipei, Taiwan.
[Chuang, Ting-Wu] Taipei Med Univ, Ctr Int Trop Med, Coll Med, Taipei, Taiwan.
[Chugh, Sumeet S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Cirillo, Massimo] Univ Salerno, I-84081 Baronissi, SA, Italy.
[Cohen, Aaron] Hlth Effects Inst, Boston, MA USA.
[Colomar, Mercedes] UNICEM, Montevideo, Uruguay.
[Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Cooper, Cyrus; Tleyjeh, Imad M.] Mayo Clin, Rochester, MN USA.
[Coppola, Luis M.] Hosp Municipal Ramon Santamarina, Buenos Aires, DF, Argentina.
[Cowie, Benjamin C.; MacLachlan, Jennifer H.] Victorian Infect Dis Reference Lab, North Melbourne, Vic, Australia.
[Criqui, Michael H.; Jassal, Simerjot] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Crump, John A.] Dunedin Sch Med, Ctr Int Hlth, Dunedin, Otago, New Zealand.
[Poulton, Richie G.] Univ Otago, Dunedin, Otago, New Zealand.
[Leite, Iuri da Costa] Natl Sch Publ Hlth ENSP Fiocruz, Rio De Janeiro, Brazil.
[Dandona, Lalit; Dandona, Rakhi; Goenka, Shifalika] Publ Hlth Fdn India, New Delhi, India.
[Dandona, Rakhi; Goenka, Shifalika] Indian Inst Publ Hlth, New Delhi, India.
[Dargan, Paul I.] Guys & St Thomas NHS Fdn Trust, London, England.
[Dayama, Anand] Jacobi Med Ctr, Dept Surg, Atlanta, GA USA.
[de la Vega, Shelley F.] Univ Philippines, Inst Aging, Manila, Philippines.
[Lam, Hilton] Univ Philippines, Natl Inst Hlth, Inst Hlth Policy & Dev Studies, Manila, Philippines.
[De Leo, Diego] Griffith Univ, Brisbane, Qld 4111, Australia.
[Uchendu, Uche S.] US Dept Vet Affairs, Washington, DC USA.
[Dellavalle, Robert P.] Eastern Colorado Healthcare Syst, Denver, CO USA.
[Jarlais, Don C. Des] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Dessalegn, Muluken] Africa Med & Res Fdn Ethiopia, Addis Ababa, Ethiopia.
[deVeber, Gabrielle A.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Dharmaratne, Samath D.] Univ Peradeniya, Peradeniya, Sri Lanka.
[Dherani, Mukesh] Univ Liverpool, Liverpool L69 3BX, Merseyside, England.
[Diaz-Torne, Cesar] Hosp Santa Creu & Sant Pau, Barcelona, Spain.
[Dokova, Klara] Med Univ Varna, Fac Publ Hlth, Dept Social Med, Varna, Bulgaria.
[Dorsey, E. Ray] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Durrani, Adnan M.] NIH, Montgomery, MD USA.
[Hankey, Graeme J.] Sch Med & Pharmacol, Perth, WA, Australia.
[Kabagambe, Edmond Kato] Univ Western Australia, Perth, WA 6009, Australia.
[Elshrek, Yousef] Univ Tripoli, Fac Agr, Dept Food Sci, Tripoli, Libya.
[Ermakov, Sergey Petrovich] Russian Acad Sci, Inst Social & Econ Studies Populat, Moscow, Russia.
[Eshrati, Babak] Arak Univ Med Sci & Hlth Affairs, Arak, Markazi, Iran.
[Esteghamati, Alireza; Hafezi-Nejad, Nima; Sheikhbahaei, Sara] Endocrinol & Metab Res Ctr, Tehran, Iran.
[Farzadfar, Farshad] Noncommunicable Dis Reesearch Ctr, Tehran, Iran.
[Malekzadeh, Reza; Sepanlou, Sadaf G.] Digest Dis Res Ctr, Tehran, Iran.
[Rahimi-Movaghar, Vafa] Sina Trauma & Surg Res Ctr, Tehran, Iran.
[Sahraian, Mohammad Ali] Res Ctr, Tehran, Iran.
[Moradi-Lakeh, Maziar] Dept Community Med, Tehran, Iran.
[Heydarpour, Pouria] Univ Tehran Med Sci, Tehran, Iran.
[Fuerst, Thomas] Ctr Hlth Policy, London, England.
[Fuerst, Thomas] Dept Infect Dis Epidemiol, London, England.
[Mustapha, Adetoun] MRC PHE Ctr Hlth & Environm, London, England.
[Foreman, Kyle; Rodriguez, Alina; Rushton, Lesley; Soljak, Michael; Williams, Thomas Neil] Univ London Imperial Coll Sci Technol & Med, London, England.
[Vollset, Stein Emil] Div Informat Evidence Res & Innovat, Copenhagen, Denmark.
[Fahrion, Anna S.; Rakovac, Ivo] WHO, Reg Off Europe, DK-2100 Copenhagen, Denmark.
[Newman, Lori] WHO, CH-1211 Geneva, Switzerland.
[Teixeira, Carolina Maria] ARS Norte, Oporto, Portugal.
[Felicio, Manuela Mendonca; de Lima, Graca Maria Ferreira; Machado, Vasco Manuel Pedro] IP Dept Saude Publ, Oporto, Portugal.
[Fernandes, Jefferson G.] German Hosp Oswaldo Cruz, Inst Educ & Sci, Sao Paulo, Brazil.
[Foigt, Nataliya] Ukraine Acad Med Sci, Inst Gerontol, UA-252655 Kiev, Ukraine.
[Franklin, Richard C.] James Cook Univ, Townsville, Qld 4811, Australia.
[Gambashidze, Ketevan; Kazanjan, Konstantin; Kereselidze, Maia; Shakh-Nazarova, Marina; Sturua, Lela] Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia.
[Gankpe, Fortune Gbetoho] Clin Cooperat Parakou, Parakou, Borgou, Benin.
[Garcia, Ana Cristina] Publ Hlth Unit Primary Hlth Care Grp Almada Seixa, Almada, Setubal, Portugal.
[Geleijnse, Johanna M.] Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands.
[Gessner, Bradford D.] Agence Med Prevent, Paris, France.
[Lloyd, Belinda K.] Eastern Hlth Clin Sch, Melbourne, Vic, Australia.
[Gibney, Katherine B.; Thrift, Amanda G.] Monash Univ, Melbourne, Vic 3004, Australia.
[Gillum, Richard F.] Howard Univ, Washington, DC 20059 USA.
[Inoue, Manami] Grad Sch Med, Tokyo, Japan.
[Kawakami, Norito] Sch Publ Hlth, Tokyo, Japan.
[Gilmour, Stuart; Shibuya, Kenji] Univ Tokyo, Tokyo, Japan.
[Ginawi, Mohamed] Univ Hail, Coll Med, Hail, Saudi Arabia.
[Giroud, Maurice] Univ Hosp Dijon, Dijon France, Region Of Burgo, France.
[Glaser, Elizabeth L.; Halasa, Yara A.; Idrisov, Bulat T.; Shahraz, Saeid; Shepard, Donald S.; Undurraga, Eduardo A.] Brandeis Univ, Waltham, MA USA.
[Gosselin, Richard A.; Kazi, Dhruv S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Goto, Atsushi] Natl Ctr Global Hlth & Med, Dept Diabet Res, Tokyo, Japan.
[Gugnani, Harish Chander] St James Sch Med, Kralendijk, Bonaire, Netherlands.
[Guinovart, Caterina] PATH, Seattle, WA USA.
[Gunnell, David] Univ Bristol, Bristol, Avon, England.
[Gupta, Rahul] Fortis Escorts Hosp, Jaipur, Rajasthan, India.
[Gupta, Rajeev] Kanawha Charleston Hlth Dept, Charleston, WV USA.
[Thurston, George D.] NYU, Nelson Inst Environm Med, Tuxedo Pk, NY USA.
[Hagan, Holly] NYU, New York, NY USA.
[Hamadeh, Randah Ribhi] Arabian Gulf Univ, Manama, Bahrain.
[Hammami, Mouhanad] Wayne Cty Dept Hlth & Human Serv, Detroit, MI USA.
[Harewood, Heather] Eunice Gibson Polyclin, Bridgetown, St Michael, Barbados.
[Haro, Josep Maria] Univ Barcelona, CIBERSAM, Barcelona, Spain.
[Hay, Roderick J.] Int Fdn Dermatol, London, England.
[Hedayati, Mohammad T.] Mazandaran Univ Med Sci, Sari, Mazandaran, Iran.
[Hijar, Martha] Fdn Entornos AC, Cuernavaca, Morelos, Mexico.
[Hoek, Hans W.] Parnassia Psychiat Inst, The Hague, Netherlands.
[Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
[Hornberger, John C.] Cedar Associates, Menlo Pk, CA USA.
[Hosgood, H. Dean] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Hossain, Mazeda; Larson, Heidi J.; Mckee, Martin; Pearce, Neil; Roberts, Bayard; Stoeckl, Heidi; Tillmann, Taavi] London Sch Hyg & Trop Med, London WC1, England.
[Hotez, Peter J.] Baylor Coll Med, Houston, TX 77030 USA.
[Hoy, Damian G.] Secretariat Pacific Commun, Publ Hlth Div, Herston, Qld, Australia.
[Hsairi, Mohamed] Natl Inst Publ Hlth MOH, Tunis, Tunisia.
[Hu, Guoqing] Univ Toronto, Toronto, ON, Canada.
[Hu, Guoqing] Cent S Univ, Changsha, Hunan, Peoples R China.
[Huffman, Mark D.] Feinberg Sch Med, Chicago, IL USA.
[Swaroop, Mamta] Northwestern Univ, Chicago, IL 60611 USA.
[Husseini, Abdullatif] Qatar Univ, Publ Hlth Program, Birzeit, Ramallah, Israel.
[Iburg, Kim M.] Aarhus Univ, Aarhus, Denmark.
[Ikeda, Nayu] Natl Inst Hlth & Nutr, Bunkyo Ku, Tokyo 162, Japan.
[Innos, Kaire; Leinsalu, Mall] Natl Inst Hlth Dev, Tallinn, Estonia.
[Islami, Farhad] Amer Canc Soc, New York, NY USA.
[Ismayilova, Samaya] Self Employed, Baku, Azerbaijan.
[Jacobsen, Kathryn H.] George Mason Univ, Fairfax, VA 22030 USA.
[Jassal, Simerjot] VA San Diego, San Diego, CA USA.
[Jayaraman, Sudha P.] Virginia Commonwealth Univ, Richmond, VA USA.
[Jha, Vivekanand] Postgrad Inst Med Educ & Res, Chandigarh 160012, India.
[Jiang, Guohong] Tianjin Ctr Dis Control & Prevent, Tianjin, Peoples R China.
[Jiang, Ying] Univ Occupat & Environm Hlth, Inst Ind Ecol Sci, Dept Hlth Dev, Dept Environm Epidemiol, Kitakyushu, Fukuoka 807, Japan.
[Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
[Juel, Knud] Natl Inst Publ Hlth, Copenhagen, Denmark.
[Kabagambe, Edmond Kato; Sampson, Uchechukwu] Vanderbilt Univ, Nashville, TN 37235 USA.
Univ Balamand, Beirut, Lebanon.
[Karch, Andre] Helmholtz Ctr Infect Res, Braunschweig, Germany.
[Karch, Andre] German Ctr Infect Res DZIF, Braunschweig, Germany.
[Karimkhani, Chante] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Moran, Andrew E.] Columbia Univ, New York, NY USA.
[Karthikeyan, Ganesan; Paul, Vinod K.] All India Inst Med Sci, New Delhi, India.
[Kaul, Anil] Oklahoma State Univ, Tulsa, OK USA.
[Kengne, Andre Pascal; Matzopolous, Richard] South African Med Res Council, Cape Town, Western Cape, South Africa.
[Keren, Andre] Hadassah Kerem Univ Hosp, Jerusalem, Israel.
[Khader, Yousef Saleh] Jordan Univ Sci & Technol, Irbid, Jordan.
[Khalifa, Shams Eldin Ali Hassan] Supreme Council Hlth, Doha, Qatar.
[Khan, Ejaz Ahmed] Hlth Serv Acad, Islamabad, Punjab, Pakistan.
[Khan, Gulfaraz] UAE Univ, Abu Dhabi, U Arab Emirates.
[Khang, Young-Ho] Seoul Natl Univ, Coll Med, Inst Hlth Policy & Management, Seoul, South Korea.
[Kieling, Christian] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil.
[Kim, Daniel] Northeastern Univ, Boston, MA 02115 USA.
[Kim, Sungroul] Soonchunhyang Univ, Asan, South Korea.
[Kinfu, Yohannes] Univ Canberra, Canberra, ACT 2601, Australia.
[Kokubo, Yoshihiro] Natl Cerebral & Cardiovasc Ctr, Dept Prevent Cardiol, Suita, Osaka, Japan.
[Kosen, Sowarta] Ctr Community Empowerment Hlth Policy & Humanitie, Jakarta, Indonesia.
[Warouw, Tati Suryati] NIHRD, Jakarta, Special Provinc, Indonesia.
[Kravchenko, Michael A.; Varakin, Yuri Y.] Res Ctr Neurol, Moscow, Russia.
[Krishnaswami, Sanjay] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Krishnaswami, Sanjay] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Defo, Barthelemy Kuate] Univ Montreal, Montreal, PQ, Canada.
[Polinder, Suzanne] Dept Publ Hlth, Rotterdam, Netherlands.
[Kuipers, Ernst J.; Richardus, Jan Hendrik] Erasmus MC Univ Med Ctr, Rotterdam, Netherlands.
[Kulkarni, Chanda] Rajrajeshwari Med Coll & Hosp, Bangalore, Karnataka, India.
[Kulkarni, Veena S.] Arkansas State Univ, State Univ, AR 72467 USA.
[Kumar, Kaushalendra] Int Inst Populat Sci, Bombay, Maharashtra, India.
[Kwan, Gene F.] Boston Med Ctr, Boston, MA USA.
[Lai, Taavi] Fourth View Consulting, Tallinn, Estonia.
[Lalloo, Ratilal] Australian Res Ctr Populat Oral Hlth, Gold Coast, Qld, Australia.
[Lalloo, Ratilal] Univ Adelaide, Sch Dent, Gold Coast, Qld, Australia.
[Lallukka, Tea] Finnish Inst Occupat Hlth, Helsinki, Finland.
[Lallukka, Tea] Univ Helsinki, Fac Med, Hjelt Inst, FIN-00014 Helsinki, Finland.
[Lan, Qing] NCI, Rockville, MD USA.
[Lansingh, Van C.] IAPB & Vis 2020 LA, Weston, FL USA.
[Lavados, Pablo M.] Univ Desarrollo, Serv Neurol Clin Alemana, Santiago, RM, Chile.
[Lawrynowicz, Alicia E. B.; Silva, Andrea P.; Ubeda, Clotilde] Inst Nacl Epidemiol Dr Juan H Jara, Buenos Aires, DF, Argentina.
[Leasher, Janet L.] Nova SE Univ, Ft Lauderdale, FL 33314 USA.
[Lee, Jong-Tae; Yoon, Seok-Jun] Korea Univ, Seoul, South Korea.
[Leung, Ricky] SUNY Albany, Rensselaer, NY USA.
[Zhang, Yong] Dept Gerontol, Jinan, Shandong, Peoples R China.
[Li, Bin] Jinan Cent Hosp, Jinan, Shandong, Peoples R China.
[Li, Yichong] Genentech Inc, San Francisco, CA USA.
[Lipshultz, Steven E.] Wayne State Univ, Miami, FL USA.
[Lloyd, Belinda K.; Room, Robin] Eastern Hlth, Turning Point Alcohol & Drug Ctr, Fitzroy, Vic, Australia.
[Logroscino, Giancarlo] Univ Bari, Bari, Italy.
Australian Natl Univ, Canberra, ACT, Australia.
[Lunevicius, Raimundas] Aintree Univ Hosp NHS Fdn Trust, NHS Fdn Trust, Liverpool L9 7AL, Merseyside, England.
[Lyons, Ronan Anthony] Swansea Univ, swauni, Swansea, W Glam, Wales.
[Ma, Stefan] Minist Hlth Singapore, Singapore, Singapore.
[Mackay, Mark T.] Royal Childrens Hosp, Melbourne, Vic, Australia.
[Magis-Rodriguez, Carlos] Ctr Prevenc & Control VIH SIDA, Mexico City, DF, Mexico.
[Mahdi, Abbas A.] King Georges Med Univ, Lucknow, Uttar Pradesh, India.
[Mangalam, Srikanth] Tech Stand & Safety Author, Toronto, ON, Canada.
[Mapoma, Christopher Chabila; Masiye, Felix] Univ Zambia, Lusaka, Zambia.
[Marape, Marape] Botswana Baylor Childrens Clin Ctr Excellence, Gaborone, Botswana.
[Marcenes, Wagner] Univ London, London, England.
[Marzan, Melvin Barrientos] Univ East Ramon Magsaysay, Med Ctr, Quezon City, Metro Manila, Philippines.
[Masci, Joseph R.] Elmhurst Hosp Ctr, Mt Sinai Serv, Elmhurst, NY USA.
[Mashal, Mohammad Taufi Q.] Minist Publ Hlth, Kabul, Afghanistan.
[Mason-Jones, Amanda J.] Univ York, York YO10 5DD, N Yorkshire, England.
[Sliwa, Karen] Hatter Inst Cardiovasc Res Africa, Fac Hlth Sci, Cape Town, Western Cape, South Africa.
[Mayosi, Bongani M.] Univ Cape Town, Cape Town, Western Cape, South Africa.
[Mazorodze, Tasara T.] AIDC EC, Port Elizabeth, Eastern Cape, South Africa.
[Mckay, Abigail C.] EmergentCorp, Belize City, Belize District, Belize.
[Mehndiratta, Man Mohan] Janakpuri Superspecialty Hosp, Delhi, India.
[Meltzer, Michele] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Mendoza, Walter] UNFPA, Lima, Peru.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mhimbira, Francis A.] Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
[Miller, Ted R.] Pacific Inst Res & Evaluat, Calverton, MD USA.
[Miller, Ted R.] Curtin Univ, Ctr Populat Hlth Res, Perth, WA 6845, Australia.
[Mills, Edward J.] Univ Ottawa, Ottawa, ON, Canada.
[Mishra, Santosh K.] SNDT Womens Univ, Populat Educ Resource Ctr, Dept Continuing & Adult Educ & Extens, Bombay, Maharashtra, India.
[Moffitt, Terrie E.] Duke Univ, Durham, NC USA.
[Ibrahim, Norlinah Mohamed] Univ Kebangsaan Malaysia, Med Ctr, Dept Med, Kuala Lumpur, Malaysia.
[Mohammad, Karzan Abdulmuhsin] Univ Salahaddin, Erbil, Iraq.
[Mola, Glen Liddell] Univ Papua New Guinea, Port Moresby, NCD, Papua N Guinea.
[Monasta, Lorenzo; Montico, Marcella; Ronfani, Luca] Inst Maternal & Child Health IRCCS Burlo Garofolo, Trieste, Italy.
[Monis, Jonathan de la Cruz] Bur Int Hlth Cooperat, Manila, Philippines.
[Moore, Ami R.] Univ N Texas, Denton, TX 76203 USA.
[Mori, Rintaro] Natl Ctr Child Hlth & Dev, Tokyo, Japan.
[Tsilimbaris, Miltiadis] Dept Med, Iraklion, Greece.
[Moschandreas, Joanna] Univ Crete, Iraklion, NE, Greece.
[Moturi, Wilkister Nyaora] Egerton Univ, Egerton, Rift Valley, Kenya.
[Mozaffarian, Dariush] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Mueller, Ulrich O.] Univ Marburg, Marburg, Germany.
[Mukaigawara, Mitsuru] Tokyo Med & Dent Univ, Bunkyo Ku, Tokyo, Japan.
[Naheed, Aliya] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh.
[Naidoo, Kovin S.] Univ KwaZulu Natal, Durban, KwaZulu Natal, South Africa.
[Naldi, Luigi] Azienda Osped Papa Giovanni XXIII, Bergamo, Italy.
[Nand, Devina] Minist Hlth Fiji, Suva, Fiji.
[Nangia, Vinay] Suraj Eye Inst, Nagpur, Maharashtra, India.
[Nash, Denis] CUNY, Sch Publ Hlth, New York, NY 10021 USA.
[Nasher, Jamal] Minist Publ Hlth & Populat, Sanaa, Yemen.
[Nejjari, Chakib] Fac Med, Fes, Morocco.
[Nelson, Robert G.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA.
[Neuhouser, Marian; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Neupane, Sudan Prasad] Univ Oslo, Norwegian Ctr Addict Res SERAF, N-0316 Oslo, Norway.
[Ngalesoni, Frida Namnyak] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania.
[Norrving, Bo] Lund Univ, Fac Med, Dept Clin Sci, Lund, Sweden.
[O'Donnell, Martin] Natl Univ Ireland Galway, Galway, Ireland.
[Ohkubo, Takayoshi] Teikyo Univ, Sch Med, Tokyo 173, Japan.
[Olusanya, Bolajoko O.] Ctr Hlth Start Initiat, Lagos, Nigeria.
[Opio, John Nelson] Lira Municipal Council, Lira Dist Local Govt, Northern Uganda, Uganda.
[Orisakwe, Orish Ebere] Univ Port Harcourt, Fac Pharm, Toxicol Unit, Port Harcourt, Rivers State, Nigeria.
[Ortiz, Alberto] IIS Fdn Jimenez Diaz, Madrid, Spain.
[Otayza, Maria Lourdes K.] Mariano Marcos Mem Hosp, City Of Batac, Ilocos Norte, Philippines.
[Otayza, Maria Lourdes K.] Med Ctr, City Of Batac, Ilocos Norte, Philippines.
[Pandian, Jeyaraj D.] Christian Med Coll Ludhiana, Ludhiana, Punjab, India.
[Panniyammakal, Jeemon] Ctr Chron Dis Control, Delhi, India.
[Patten, Scott B.; Wang, JianLi] Univ Calgary, Calgary, AB, Canada.
[Pavlin, Boris] Independent Researcher, Waigani, NCD, Papua N Guinea.
[Pereira, David M.] Univ Porto, REQUIMTE, Fac Farm, Dept Quim,Lab Farmacognosia, P-4100 Oporto, Portugal.
[Peresson, Sophie C.] Int Diabet Federat, Brussels, Belgium.
[Perez-Ruiz, Fernando P.] Hosp Univ Cruces, Baracaldo, Spain.
[Pervaiz, Aslam] Postgrad Med Inst, Lahore, Punjab, Pakistan.
[Pesudovs, Konrad] Flinders Univ S Australia, Adelaide, SA 5001, Australia.
[Peterson, Carrie B.] Aalborg Univ, Aalborg, Denmark.
[Petzold, Max] Univ Gothenburg, Sahlgrenska Acad, Ctr Appl Biostat, Gothenburg, Sweden.
[Phillips, Michael R.] Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China.
[Plass, Dietrich] Fed Environm Agcy, Exposure Assessment & Environm Hlth Indicators, Bielefeld, North Rhine Wes, Germany.
[Poenaru, Dan] McMaster Univ, Hamilton, ON, Canada.
[Popova, Svetlana] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Prabhakaran, Dorairaj] Ctr Chron Dis Control, Delhi, India.
[Qato, Dima] Univ Illinois, Coll Pharm, Chicago, IL USA.
[Tabb, Karen M.] Univ Illinois, Chicago, IL USA.
[Rabito, Felicia] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Rafay, Anwar] Contech Intl, Lahore, Punjab, Pakistan.
[Rahman, Sajjad U. R.] Hamad Med Corp, Doha, Qatar.
[Raju, Murugesan] Univ Missouri, Columbia, MS USA.
[Rana, Saleem M.] Univ Punjab, Dept Publ Hlth, Lahore, Punjab, Pakistan.
[Refaat, Amany] Walden Univ, Minneapolis, MN USA.
[Ribeiro, Antonio L.] Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil.
[Ricci, Stefano] UO Neurol USL Umbria 1, Perugia, Italy.
[Riccio, Patricia M.] Univ Western Ontario, Dept Clin Neurol Sci, London Hlth Sci Ctr, London, ON, Canada.
[Roca, Anna] MRC Unit, Fajara, Gambia.
[Rojas-Rueda, David] Ctr Res Environm Epidemiol CREAL, Barcelona, Catalonia, Spain.
[Rothenbacher, Dietrich] Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany.
[Rothstein, David H.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Roy, Nobhojit] BARC Hosp, Bombay, Maharashtra, India.
[Ruhago, George M.; Sunguya, Bruno F.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
Rwanda Biomed Ctr, Kigali, Rwanda.
[Soreide, Kjetil] Stavanger Univ Hosp, Stavanger, Norway.
[Saha, Sukanta] Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
[Sahathevan, Ramesh] UKM Med Ctr, Kuala Lumpur, Malaysia.
[Samonte, Genesis May J.] Natl Epidemiol Ctr, HIV AIDS & STI Surveillance & Strateg Informat Un, Dept Hlth, Manila, National Capita, Philippines.
[Sanabria, Juan Ramon] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Sawhney, Monika] Marshall Univ, Huntington, WV USA.
[Saylan, Mete] Novartis, Istanbul, Turkey.
[Schoettker, Ben] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Baden Wurttembe, Switzerland.
[Schneider, Ione J. C.] Univ Fed Santa Catarina, Florianopolis, SC, Brazil.
[Schwebel, David C.; Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Shaheen, Amira] An Najah Univ, Nablus, Palestine, Israel.
[Shinohara, Yukito] Tachikawa Hosp, Tokyo, Japan.
[Shishani, Kawkab] Washington State Univ, Spokane, WA USA.
[Shiue, Ivy] Heriot Watt Univ, Edinburgh, Midlothian, Scotland.
[Shivakoti, Rupak] Ctr Clin Global Hlth Educ, Baltimore, MD USA.
[Tran, Bach X.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Sigfusdottir, Inga Dora] Reykjavik Univ, Reykjavik, Iceland.
[Soneji, Samir] Dartmouth Coll, Lebanon, NH 03756 USA.
[Soshnikov, Sergey S.] Minist Hlth Russian Federat, Fed Res Inst Hlth Org & Informat, Moscow, Russia.
[Sposato, Luciano A.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada.
[Sreeramareddy, Chandrashekhar T.] Univ Tunku Abdul Rahman, Fac Med & Hlth Sci, Kajang, Selangor, Malaysia.
[Stathopoulou, Vasiliki Kalliopi] Ctr Hosp Nord Deux Sevres, Bressuire, France.
[Straif, Kurt] IARC WHO, Lyon, France.
[Stroumpoulis, Konstantinos] Alexandra Gen Hosp Athens, KEELPNO, Ctr Dis Control, Athens, Greece.
[Swaminathan, Soumya] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Sykes, Bryan L.] Univ Calif Irvine, Dept Criminol Law & Soc & Sociol, Irvine, CA USA.
[Takahashi, Ken] Univ Occupat & Environm Hlth, Inst Ind Ecol Sci, Dept Environm Epidemiol, Kitakyushu, Fukuoka 807, Japan.
[Talongwa, Roberto Tchio] Minist Hlth MINSANTE, Yaounde, Cameroon.
[Tanne, David] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
[Tanne, David] Tel Aviv Univ, Tel Hashomer, Israel.
[Tavakkoli, Mohammad] Westchester Med Ctr, Valhalla, NY USA.
[Ao, Braden Te] Auckland Univ Technol, Auckland, New Zealand.
Jhpiego, Addis Ababa, Ethiopia.
[Tenkorang, Eric Yeboah] Mem Univ Newfoundland, St John, NF, Canada.
[Terkawi, Abdullah Sulieman] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA.
[Terkawi, Abdullah Sulieman; Tleyjeh, Imad M.] King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia.
[Thorne-Lyman, Andrew L.] WorldFish, New York, NY USA.
[Tleyjeh, Imad M.] Alfasial Univ, Coll Med, Riyadh, Saudi Arabia.
[Tonelli, Marcello] Univ Alberta, Edmonton, AB, Canada.
[Topouzis, Fotis] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece.
[Towbin, Jeffrey A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Toyoshima, Hideaki] Hlth Care Ctr Anjo Kosei Hosp, Anjo, Aichi, Japan.
[Traebert, Jefferson] Univ Southern Santa Catarina, Palhoca, SC, Brazil.
[Truelsen, Thomas] Univ Copenhagen, Herlev Hosp, Dept Neurol, Copenhagen, Denmark.
[Trujillo, Ulises] Serv Canario Salud, Tenerife, Spain.
[Dimbuene, Zacharie Tsala] Univ Kinshasa, Fac Econ & Management, Dept Populat Sci & Dev, Kinshasa, Zaire.
[Ukwaja, Kingsley N.] Fed Teaching Hosp Abakaliki, Dept Internal Med, Abakailiki, Ebonyi State, Nigeria.
[van de Vijver, Steven] African Populat & Hlth Res Ctr, Nairobi, Kenya.
[van Gool, Coen H.] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Vasankari, Tommi J.] UKK Inst Hlth Promot Res, Tampere, Finland.
[Vasconcelos, Ana Maria Nogales] Univ Brasilia, Brasilia, DF, Brazil.
[Venketasubramanian, N.] Raffles Hosp, Ctr Neurosci, Singapore, Singapore.
[Vijayakumar, Lakshmi] Voluntary Hlth Serv, Madras, Tamil Nadu, India.
[Violante, Francesco S.] Univ Bologna, Bologna, Italy.
[Vlassov, Vasiliy Victorovich] Higher Sch Econ, Moscow, Russia.
[Wagner, Gregory R.] Natl Inst Occupat Safety & Hlth, Washington, DC USA.
[Waller, Stephen G.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Wang, Yanping; Zhu, Jun] Natl Off Maternal & Childs Hlth Surveillance, Chengdu, Peoples R China.
[Weichenthal, Scott] Hlth Canada, Ottawa, ON K1A 0L2, Canada.
[Weintraub, Robert G.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Wenzhi, Wang] Beijing Neurosurg Inst, Beijing, Peoples R China.
[Werdecker, Andrea] Inst Med Sociol & Social Med, Marburg, Hessen, Germany.
[Wessells, K. Ryan R.] Univ Calif Davis, Davis, CA 95616 USA.
[Wilkinson, James D.] Univ Miami, Miami, FL USA.
[Woldeyohannes, Solomon Meseret] Univ Gondar, Inst Publ Hlth, Gondar, Amhara, Ethiopia.
[Wong, John Q.] Ateneo Sch Med & Publ Hlth, Pasig, Metro Manila, Philippines.
[Woolf, Anthony D.] Royal Cornwall Hosp, Truro, Cornwall, England.
[Xu, Gelin] Nanjing Univ, Sch Med, Jinling Hosp, Nanjing 210008, Jiangsu, Peoples R China.
[Yang, Yang C.] Univ N Carolina, Chapel Hill, NC USA.
[Yano, Yuichiro] Jichi Med Univ, Sch Med, Div Cardiovasc Med, Shimotsuke, Tochigi, Japan.
[Yatsuya, Hiroshi] Fujita Hlth Univ, Toyoake, Aichi, Japan.
[Yip, Paul] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
[Yonemoto, Naohiro] Natl Ctr Neurol & Psychiat, Tokyo, Japan.
[Younis, Mustafa] Jackson State Univ, Jackson, MS USA.
[Yu, Chuanhua] Wuhan Univ, Sch Publ Hlth, Global Hlth Inst, Dept Epidemiol & Biostat, Wuhan 430072, Hubei, Peoples R China.
[Jin, Kim Yun] TCM Med TK SDN BHD, Nusajaya, Johor Bahru, Malaysia.
[Zaki, Maysaa El Sayed] Mansoura Fac Med, Mansoura, Egypt.
[Zamakhshary, Mohammed Fouad] Minist Planning & Training, Riyadh, Saudi Arabia.
[Zeeb, Hajo] Leibniz Inst Prevent Res & Epidemiol BIPS, Bremen, Germany.
[Zhao, Yong] Chongqing Med Univ, Chongqing, Peoples R China.
[Zheng, Yingfeng] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Zhu, Shankuan] Zhejiang Univ, Sch Publ Hlth, Hangzhou 310003, Zhejiang, Peoples R China.
[Zonies, David] Landstuhl Reg Med Ctr, Landstuhl, NY USA.
[Zou, Xiao Nong] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China.
RP Murray, CJL (reprint author), 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
EM cjlm@uw.edu
RI Higashi, Hideki/D-3797-2011; Lavados, Pablo/E-9918-2016; Davis,
Adrian/E-6022-2015; Undurraga, Eduardo/I-3739-2014; Alsharif,
Ubai/C-6527-2017; Amini, Heresh/B-3076-2010; Lotufo, Paulo/A-9843-2008;
Karch, Andre/D-6973-2017; Hedayati, Mohammad T./E-2304-2017; Patten,
Scott/B-4434-2011; Scott, James/D-5900-2012; Franklin,
Richard/H-1731-2012; Ermakov, Sergey/G-1709-2016; Pereira,
David/M-9286-2013; Dokova, Klara/N-2448-2016; Montico,
Marcella/B-5290-2013; Jacobsen, Kathryn/B-5857-2008; Lalloo,
Ratilal/O-5624-2014; Tillmann, Taavi/R-6026-2016; Soshnikov,
Sergey/R-7352-2016; Salomon, Joshua/D-3898-2009; Beyene, Tariku
Jibat/A-6875-2017; Santos, Itamar/K-7055-2012; Patton,
George/B-5246-2013; Varakin, Yuriy/C-8634-2012; Brenner,
Hermann/B-4627-2017; Nolte, Sandra/B-7498-2008; Ribeiro,
Antonio/C-2707-2009; CSTFA, ResearcherID/P-1067-2014; Hankey, Graeme
/H-4968-2014; Research ID, CTBCC /O-3564-2014; Moffitt,
Terrie/D-5295-2011; Ronfani, Luca/B-6668-2013; Ameli, Omid/G-1583-2013;
Rakovac, Ivo/A-7678-2013; Tanne, David/F-2560-2010; Adsuar, Jose
C/C-6558-2008; Majdan, Marek/K-5017-2012; Castro, Ruben/J-1948-2015;
Balakrishnan, Kalpana/B-6653-2015; Whiteford, Harvey/A-4840-2009;
Charlson, Fiona/F-5290-2011; LOGROSCINO, GIANCARLO/K-5148-2016; McGrath,
John/G-5493-2010; wang, YA XING/K-9671-2016; Naldi, Luigi/K-6343-2016;
Osborne, Nicholas/N-4915-2015; Thrift, Amanda/I-6251-2012; Weiderpass,
Elisabete/M-4029-2016; Tonelli, Marcello/B-3028-2009; Rahimi,
Kazem/Q-1279-2015; Haro, Josep Maria/D-1423-2011; Degenhardt,
Louisa/D-4515-2012; Kaul, Anil/B-2075-2016; Carabin, Helene/B-7600-2016;
Monasta, Lorenzo/B-1388-2012; Sepanlou, Sadaf/H-9343-2016; Kravchenko,
Michael/B-2596-2012
OI Heydarpour, Pouria/0000-0001-5644-7555; Quistberg,
Alex/0000-0001-9730-2686; Liu, Zhi-Hong/0000-0001-6093-0726; Kieling,
Christian/0000-0001-7691-4149; Sindi, Shireen/0000-0002-3786-0552;
Husseini, Abdullatif/0000-0001-8767-5956; Benjet,
Corina/0000-0002-4569-6094; Mhimbira, Francis/0000-0001-8989-6832;
Olusanya, Bolajoko/0000-0002-3826-0583; Tabb Dina,
Karen/0000-0002-4722-9502; Higashi, Hideki/0000-0002-5534-0905; Vallely,
Andrew/0000-0003-1558-4822; Goenka, Shifalika/0000-0001-6993-2883; Xu,
Gelin/0000-0002-6194-0341; Goto, Atsushi/0000-0003-0669-654X; Naghavi,
Paria/0000-0002-8908-7952; Lavados, Pablo/0000-0002-9118-9093; Davis,
Adrian/0000-0001-7134-7528; Banerjee, Amitava/0000-0001-8741-3411;
Hotez, Peter/0000-0001-8770-1042; Abubakar, Ibrahim/0000-0002-0370-1430;
Schottker, Ben/0000-0002-1217-4521; Pourmalek,
Farshad/0000-0002-2134-0771; Undurraga, Eduardo/0000-0002-4425-1253;
Wessells, K. Ryan/0000-0002-5485-7144; Khan, Ejaz/0000-0002-7072-8035;
Hagstromer, Maria/0000-0002-4607-8677; Bikbov,
Boris/0000-0002-1925-7506; MacLachlan, Jennifer/0000-0002-7654-4536;
Gibney, Katherine/0000-0001-5851-5339; Stockl,
Heidi/0000-0002-0907-8483; Kwan, Gene/0000-0002-0929-6800; Piel,
Frederic B./0000-0001-8131-7728; Ukwaja, Kingsley
N./0000-0002-1974-8735; Alsharif, Ubai/0000-0002-4024-3950; Amini,
Heresh/0000-0002-4825-1322; Lotufo, Paulo/0000-0002-4856-8450; Karch,
Andre/0000-0003-3014-8543; Hedayati, Mohammad T./0000-0001-6415-4648;
Patten, Scott/0000-0001-9871-4041; Scott, James/0000-0002-0744-0688;
Franklin, Richard/0000-0003-1864-4552; Ermakov,
Sergey/0000-0003-1072-1162; Pereira, David/0000-0003-0384-7592;
Bohensky, Megan/0000-0001-8370-1408; Montico,
Marcella/0000-0003-0377-8232; Jacobsen, Kathryn/0000-0002-4198-6246;
Lalloo, Ratilal/0000-0001-5822-1269; Tillmann,
Taavi/0000-0002-8428-3719; Soshnikov, Sergey/0000-0002-6983-7066;
Salomon, Joshua/0000-0003-3929-5515; Beyene, Tariku
Jibat/0000-0002-7474-1966; Santos, Itamar/0000-0003-3212-8466; Patton,
George/0000-0001-5039-8326; Brenner, Hermann/0000-0002-6129-1572; Nolte,
Sandra/0000-0001-6185-9423; Ribeiro, Antonio/0000-0002-2740-0042;
Hankey, Graeme /0000-0002-6044-7328; Moffitt,
Terrie/0000-0002-8589-6760; Ronfani, Luca/0000-0001-5710-3914; Ameli,
Omid/0000-0001-7878-0551; Rakovac, Ivo/0000-0003-3462-2636; Tanne,
David/0000-0002-6699-2220; Adsuar, Jose C/0000-0001-7203-3168; Majdan,
Marek/0000-0001-8037-742X; NORMAN, ROSANA/0000-0002-9742-1957; Soreide,
Kjetil/0000-0001-7594-4354; Chen, Honglei/0000-0003-3446-7779;
Perez-Ruiz, Fernando/0000-0002-5268-1894; Catala-Lopez,
Ferran/0000-0002-3833-9312; Norheim, Ole F./0000-0002-5748-5956; London,
Stephanie/0000-0003-4911-5290; Hay, Simon/0000-0002-0611-7272;
Moradi-Lakeh, Maziar/0000-0001-7381-5305; Al-Shahi Salman,
Rustam/0000-0002-2108-9222; Prabhakaran, Dorairaj/0000-0002-3172-834X;
Deribe, Kebede/0000-0002-8526-6996; Khang, Young-Ho/0000-0002-9585-8266;
Ortiz Arduan, Alberto/0000-0002-9805-9523; Kemp,
Andrew/0000-0003-1146-3791; Erskine, Holly/0000-0003-3119-9211; Aboyans,
Victor/0000-0002-0322-9818; Brauer, Michael/0000-0002-9103-9343; Glaser,
Elizabeth/0000-0002-1918-057X; Balakrishnan,
Kalpana/0000-0002-5905-1801; Paternina-Caicedo,
Angel/0000-0002-6332-5174; Newton, Charles/0000-0002-6999-5507; Cowie,
Benjamin/0000-0002-7087-5895; O'Donnell, Martin/0000-0002-7347-7761;
O'donnell, Colm/0000-0002-8004-450X; Rodriguez,
Alina/0000-0003-1209-8802; Whiteford, Harvey/0000-0003-4667-6623;
Charlson, Fiona/0000-0003-2876-5040; LOGROSCINO,
GIANCARLO/0000-0003-0423-3242; McGrath, John/0000-0002-4792-6068; wang,
YA XING/0000-0003-2749-7793; Naldi, Luigi/0000-0002-3160-2835; Osborne,
Nicholas/0000-0002-6700-2284; Thrift, Amanda/0000-0001-8533-4170;
Weiderpass, Elisabete/0000-0003-2237-0128; Rahimi,
Kazem/0000-0002-4807-4610; Haro, Josep Maria/0000-0002-3984-277X;
Degenhardt, Louisa/0000-0002-8513-2218; Monasta,
Lorenzo/0000-0001-7774-548X; Sepanlou, Sadaf/0000-0002-3669-5129;
Kravchenko, Michael/0000-0001-5187-5518
FU British Heart Foundation [RG/08/014/24067]; Department of Health
[CDF-2013-06-012, RP-PG-0407-10184]; Medical Research Council
[MC_UP_A620_1014, G9806489, MC_U137686851, MC_U147585819, MC_UU_12011/1,
MR/K006525/1, MR/L003120/1]; NCATS NIH HHS [KL2 TR001088]; NIA NIH HHS
[P30 AG017253]; NIEHS NIH HHS [P30 ES000260]; Wellcome Trust [089276,
089963, 099876]
NR 122
TC 936
Z9 979
U1 232
U2 767
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JAN 10
PY 2015
VL 385
IS 9963
BP 117
EP 171
DI 10.1016/S0140-6736(14)61682-2
PG 55
WC Medicine, General & Internal
SC General & Internal Medicine
GA AY7BI
UT WOS:000347715900024
PM 25530442
ER
PT J
AU Burleigh, A
McKinney, S
Brimhall, J
Yap, D
Eirew, P
Poon, S
Ng, V
Wan, A
Prentice, L
Annab, L
Barrett, JC
Caldas, C
Eaves, C
Aparicio, S
AF Burleigh, Angela
McKinney, Steven
Brimhall, Jazmine
Yap, Damian
Eirew, Peter
Poon, Steven
Ng, Viola
Wan, Adrian
Prentice, Leah
Annab, Lois
Barrett, J. Carl
Caldas, Carlos
Eaves, Connie
Aparicio, Samuel
TI A co-culture genome-wide RNAi screen with mammary epithelial cells
reveals transmembrane signals required for growth and differentiation
SO BREAST CANCER RESEARCH
LA English
DT Article
ID CHARACTERIZATION IN-VITRO; HUMAN BREAST-TISSUE; ADULT HUMAN BREAST;
SERIAL PASSAGE; 3 DIMENSIONS; STEM-CELLS; CANCER; MORPHOGENESIS; GLAND;
FIBROBLASTS
AB Introduction: The extracellular signals regulating mammary epithelial cell growth are of relevance to understanding the pathophysiology of mammary epithelia, yet they remain poorly characterized. In this study, we applied an unbiased approach to understanding the functional role of signalling molecules in several models of normal physiological growth and translated these results to the biological understanding of breast cancer subtypes.
Methods: We developed and utilized a cytogenetically normal clonal line of hTERT immortalized human mammary epithelial cells in a fibroblast-enhanced co-culture assay to conduct a genome-wide small interfering RNA (siRNA) screen for evaluation of the functional effect of silencing each gene. Our selected endpoint was inhibition of growth. In rigorous postscreen validation processes, including quantitative RT-PCR, to ensure on-target silencing, deconvolution of pooled siRNAs and independent confirmation of effects with lentiviral short-hairpin RNA constructs, we identified a subset of genes required for mammary epithelial cell growth. Using three-dimensional Matrigel growth and differentiation assays and primary human mammary epithelial cell colony assays, we confirmed that these growth effects were not limited to the 184-hTERT cell line. We utilized the METABRIC dataset of 1,998 breast cancer patients to evaluate both the differential expression of these genes across breast cancer subtypes and their prognostic significance.
Results: We identified 47 genes that are critically important for fibroblast-enhanced mammary epithelial cell growth. This group was enriched for several axonal guidance molecules and G protein-coupled receptors, as well as for the endothelin receptor PROCR. The majority of genes (43 of 47) identified in two dimensions were also required for three-dimensional growth, with HSD17B2, SNN and PROCR showing greater than tenfold reductions in acinar formation. Several genes, including PROCR and the neuronal pathfinding molecules EFNA4 and NTN1, were also required for proper differentiation and polarization in three-dimensional cultures. The 47 genes identified showed a significant nonrandom enrichment for differential expression among 10 molecular subtypes of breast cancer sampled from 1,998 patients. CD79A, SERPINH1, KCNJ5 and TMEM14C exhibited breast cancer subtype-independent overall survival differences.
Conclusion: Diverse transmembrane signals are required for mammary epithelial cell growth in two-dimensional and three-dimensional conditions. Strikingly, we define novel roles for axonal pathfinding receptors and ligands and the endothelin receptor in both growth and differentiation.
C1 [Burleigh, Angela; McKinney, Steven; Brimhall, Jazmine; Yap, Damian; Eirew, Peter; Poon, Steven; Ng, Viola; Wan, Adrian; Prentice, Leah; Aparicio, Samuel] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1L3, Canada.
[Burleigh, Angela; McKinney, Steven; Brimhall, Jazmine; Yap, Damian; Eirew, Peter; Poon, Steven; Ng, Viola; Wan, Adrian; Prentice, Leah; Aparicio, Samuel] British Columbia Canc Agcy, Vancouver, BC V5Z 1L3, Canada.
[Prentice, Leah] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada.
[Annab, Lois] Chromatin & Gene Express Sect, Res Triangle Pk, NC 27709 USA.
[Barrett, J. Carl] NIEHS, Mol Carcinogenesis Lab, NIH, Durham, NC 27709 USA.
[Caldas, Carlos] Univ Cambridge, Li Ka Shin Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England.
[Caldas, Carlos] Univ Cambridge, Li Ka Shin Ctr, Dept Oncol, Cambridge CB2 0RE, England.
[Eaves, Connie] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
RP Aparicio, S (reprint author), Univ British Columbia, Dept Pathol & Lab Med, 675 West 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM saparicio@bccrc.ca
OI Yap, Damian/0000-0002-5370-4592
NR 70
TC 6
Z9 6
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD JAN 9
PY 2015
VL 17
AR 4
DI 10.1186/s13058-014-0510-y
PG 21
WC Oncology
SC Oncology
GA CE3JR
UT WOS:000351723100003
PM 25572802
ER
PT J
AU Yap, TL
Jiang, ZP
Heinrich, F
Gruschus, JM
Pfefferkorn, CM
Barros, M
Curtis, JE
Sidransky, E
Lee, JC
AF Yap, Thai Leong
Jiang, Zhiping
Heinrich, Frank
Gruschus, James M.
Pfefferkorn, Candace M.
Barros, Marilia
Curtis, Joseph E.
Sidransky, Ellen
Lee, Jennifer C.
TI Structural Features of Membrane-bound Glucocerebrosidase and
alpha-Synuclein Probed by Neutron Reflectometry and Fluorescence
Spectroscopy
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BILAYER-LIPID MEMBRANES; ACID-BETA-GLUCOSIDASE; SAPOSIN-C;
PARKINSONS-DISEASE; GAUCHER-DISEASE; LYSOSOMAL DEGRADATION; DEFECTIVE
ENZYME; PROTEIN; MUTATIONS; BINDING
AB Mutations in glucocerebrosidase (GCase), the enzyme deficient in Gaucher disease, are a common genetic risk factor for the development of Parkinson disease and related disorders, implicating the role of this lysosomal hydrolase in the disease etiology. A specific physical interaction exists between the Parkinson disease-related protein alpha-synuclein (alpha-syn) and GCase both in solution and on the lipid membrane, resulting in efficient enzyme inhibition. Here, neutron reflectometry was employed as a first direct structural characterization of GCase and alpha-syn.GCase complex on a sparsely-tethered lipid bilayer, revealing the orientation of the membrane-bound GCase. GCase binds to and partially inserts into the bilayer with its active site most likely lying just above the membrane-water interface. The interaction was further characterized by intrinsic Trp fluorescence, circular dichroism, and surface plasmon resonance spectroscopy. Both Trp fluorescence and neutron reflectometry results suggest a rearrangement of loops surrounding the catalytic site, where they extend into the hydrocarbon chain region of the outer leaflet. Taking advantage of contrasting neutron scattering length densities, the use of deuterated alpha-syn versus protiated GCase showed a large change in the membrane-bound structure of alpha-syn in the complex. We propose a model of alpha-syn.GCase on the membrane, providing structural insights into inhibition of GCase by alpha-syn. The interaction displaces GCase away from the membrane, possibly impeding substrate access and perturbing the active site. GCase greatly alters membrane-bound alpha-syn, moving helical residues away from the bilayer, which could impact the degradation of alpha-syn in the lysosome where these two proteins interact.
C1 [Yap, Thai Leong; Jiang, Zhiping; Gruschus, James M.; Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Heinrich, Frank; Barros, Marilia] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
[Heinrich, Frank; Curtis, Joseph E.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, NIH, 50 South Dr,Bldg 50 Rm 3513, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
RI Heinrich, Frank/A-5339-2010; Lee, Jennifer/E-9658-2015
OI Heinrich, Frank/0000-0002-8579-553X; Lee, Jennifer/0000-0003-0506-8349
FU Intramural Research Program at the National Institutes of Health; NHLBI;
NHGRI
FX This work was supported by the Intramural Research Program at the
National Institutes of Health, NHLBI, and NHGRI. Research was performed
in part at the NIST Center for Nanoscale Science and Technology and by
the NIST IMS program "Precision Measurements for Integral Membrane
Proteins."
NR 59
TC 6
Z9 6
U1 3
U2 20
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 9
PY 2015
VL 290
IS 2
BP 744
EP 754
DI 10.1074/jbc.M114.610584
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AY8BA
UT WOS:000347778200005
PM 25429104
ER
PT J
AU Groveman, BR
Kraus, A
Raymond, LD
Dolan, MA
Anson, KJ
Dorward, DW
Caughey, B
AF Groveman, Bradley R.
Kraus, Allison
Raymond, Lynne D.
Dolan, Michael A.
Anson, Kelsie J.
Dorward, David W.
Caughey, Byron
TI Charge Neutralization of the Central Lysine Cluster in Prion Protein
(PrP) Promotes PrPSc-like Folding of Recombinant PrP Amyloids
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID N-TERMINAL TRUNCATION; SCRAPIE PRION; IN-VITRO; MAMMALIAN PRIONS;
HYDROGEN/DEUTERIUM EXCHANGE; MOLECULAR-BASIS; NORMAL BRAIN; CONVERSION;
FIBRILS; FORM
AB The structure of the infectious form of prion protein, PrPSc, remains unclear. Most pure recombinant prion protein (PrP) amyloids generated in vitro are not infectious and lack the extent of the protease-resistant core and solvent exclusion of infectious PrPSc, especially within residues similar to 90-160. Polyanionic cofactors can enhance infectivity and PrPSc-like characteristics of such fibrils, but the mechanism of this enhancement is unknown. In considering structural models of PrPSc multimers, we identified an obstacle to tight packing that might be overcome with polyanionic cofactors, namely, electrostatic repulsion between four closely spaced cationic lysines within a central lysine cluster of residues 101-110. For example, in our parallel in-register intermolecular beta-sheet model of PrPSc, not only would these lysines be clustered within the 101-110 region of the primary sequence, but they would have intermolecular spacings of only similar to 4.8 between stacke beta-strands. We have now performed molecular dynamics simulations predicting that neutralization of the charges on these lysine residues would allow more stable parallel in-register packing in this region. We also show empirically that substitution of these clustered lysine residues with alanines or asparagines results in recombinant PrP amyloid fibrils with extended proteinase-K resistant beta-sheet cores and infrared spectra that are more reminiscent of bona fide PrPSc. These findings indicate that charge neutralization at the central lysine cluster is critical for the folding and tight packing of N-proximal residues within PrP amyloid fibrils. This charge neutralization may be a key aspect of the mechanism by which anionic cofactors promote PrPSc formation.
C1 [Groveman, Bradley R.; Kraus, Allison; Raymond, Lynne D.; Anson, Kelsie J.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Dorward, David W.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Dolan, Michael A.] NIAID, Computat Biol Sect, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM bcaughey@nih.gov
FU Intramural Program of the National Institute of Allergy and Infectious
Diseases
FX This work was supported, in whole or in part, by the Intramural Program
of the National Institute of Allergy and Infectious Diseases.
NR 57
TC 13
Z9 14
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 9
PY 2015
VL 290
IS 2
BP 1119
EP 1128
DI 10.1074/jbc.M114.619627
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AY8BA
UT WOS:000347778200043
PM 25416779
ER
PT J
AU Chen, HL
Zhao, EJ
Zhang, W
Lu, Y
Liu, R
Huang, XM
Ciesielski-Jones, AJ
Justice, MA
Cousins, DS
Peddada, S
AF Chen, Honglei
Zhao, Edward J.
Zhang, Wen
Lu, Yi
Liu, Rui
Huang, Xuemei
Ciesielski-Jones, Anna J.
Justice, Michele A.
Cousins, Deborah S.
Peddada, Shyamal
TI Meta-analyses on prevalence of selected Parkinson's nonmotor symptoms
before and after diagnosis
SO TRANSLATIONAL NEURODEGENERATION
LA English
DT Article
DE Parkinson's disease; Nonmotor symptoms; Meta-analysis; Prevalence;
Natural history
ID SLEEP BEHAVIOR DISORDER; BOWEL MOVEMENT FREQUENCY; RISK-FACTORS;
IDENTIFICATION TEST; PRODROMAL FEATURES; OLFACTORY FUNCTION; DUAL HIT;
DISEASE; CONSTIPATION; LIFE
AB Background: Nonmotor symptoms are common among patients with Parkinson's disease (PD) and some may precede disease diagnosis.
Methods: We conducted a meta-analysis on the prevalence of selected nonmotor symptoms before and after PD diagnosis, using random-effect models. We searched PubMed (1965 through October/November 2012) for the following symptoms: hyposmia, constipation, rapid eye movement sleep behavior disorder, excessive daytime sleepiness, depression, and anxiety. Eligible studies were publications in English with original data on one or more of these symptoms.
Results: The search generated 2,373 non-duplicated publications and 332 met the inclusion criteria, mostly (n = 320) on symptoms after PD diagnosis. For all symptoms, the prevalence was substantially higher in PD cases than in controls, each affecting over a third of the patients. Hyposmia was the most prevalent (75.5% in cases vs. 19.1% in controls), followed by constipation (50% vs. 17.7%), anxiety (39.9% vs. 19.1%), rapid eye movement sleep behavior disorder (37.0% vs. 7.0%), depression (36.6% vs. 14.9%), and excessive daytime sleepiness (33.9% vs. 10.5%). We observed substantial heterogeneities across studies and meta-regression analyses suggested that several factors might have contributed to this. However, the prevalence estimates were fairly robust in several sensitivity analyses. Only 20 studies had data on any symptoms prior to PD diagnosis, but still the analyses revealed higher prevalence in future PD cases than in controls.
Conclusion: These symptoms are common among PD patients both before and after diagnosis. Further studies are needed to understand the natural history of nonmotor symptoms in PD and their etiological and clinical implications.
C1 [Chen, Honglei; Zhao, Edward J.; Zhang, Wen; Liu, Rui] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Lu, Yi; Ciesielski-Jones, Anna J.; Justice, Michele A.; Cousins, Deborah S.] Social & Sci Syst Inc, Durham, NC USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Peddada, Shyamal] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Chen, Honglei/0000-0003-3446-7779
FU NIEHS NIH HHS [Z01 ES101986]
NR 39
TC 8
Z9 9
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2047-9158
J9 TRANSL NEURODEGENER
JI Transl. Neurodegener.
PD JAN 8
PY 2015
VL 4
AR UNSP 1
DI 10.1186/2047-9158-4-1
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA CY3MS
UT WOS:000366314500001
PM 25671103
ER
PT J
AU Sauna, ZE
Lozier, JN
Kasper, CK
Yanover, C
Nichols, T
Howard, TE
AF Sauna, Zuben E.
Lozier, Jay N.
Kasper, Carol K.
Yanover, Chen
Nichols, Timothy
Howard, Tom E.
TI The intron-22-inverted F8 locus permits factor VIII synthesis:
explanation for low inhibitor risk and a role for pharmacogenomics
SO BLOOD
LA English
DT Article
ID SEVERE HEMOPHILIA-A; ENDOGENOUS FACTOR-VIII; MHC CLASS-II; CENTRAL
TOLERANCE; GENE; MUTATION; MILD; CELLS; IMMUNOGENICITY; INVERSIONS
AB Intron-22-inversion patients express the entire Factor VIII (FVIII)-amino-acid sequence intracellularly as 2 non-secreted polypeptides and have a positive "intracellular (I)-FVIII-CRM" status. Mutations conferring a positive I-FVIII-CRM status are associated with low inhibitor risk and are pharmacogenetically relevant because inhibitor risk may be affected by the nature of the therapeutic FVIII-protein (tFVIII), the affinity of any tFVIII-derived foreign peptide (tFVIII-fp) for anyHLAclass-II isomer (HLA-II) comprising individual major histocompatibility complex (MHC) repertoires, and the stability of any tFVIII-fp/HLA-II complex. We hypothesize that mutations conferring a completely or substantially negative I-FVIII-CRM status are pharmacogenetically irrelevant because inhibitor risk is high with any tFVIII and individual MHC repertoire.
C1 [Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Lozier, Jay N.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kasper, Carol K.] Orthopaed Hemophilia Treatment Ctr, Los Angeles, CA USA.
[Kasper, Carol K.] Univ So Calif, Keck Sch Med, Dept Med, Div Hematol, Los Angeles, CA 90033 USA.
[Yanover, Chen] IBM Res Lab, Machine Learning Healthcare & Life Sci, Haifa, Israel.
[Nichols, Timothy] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Nichols, Timothy] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA.
[Howard, Tom E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Howard, Tom E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA.
RP Howard, TE (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Bldg 500,Room 1258, Los Angeles, CA 90073 USA.
EM zuben.sauna@fda.hhs.gov; Tom.Howard@va.gov
RI Yanover, Chen/A-3754-2012
OI Yanover, Chen/0000-0003-3663-4286
FU Modernization of Science Program of the Center for Biologics Evaluation
and Research, United States Food and Drug Administration; National
Heart, Lung and Blood Institute, National Institutes of Health
[1RC2-HL101851, HL-71130, HL-72533]; Bayer Healthcare Corporation; Bayer
Hemophilia Awards Program; Baxter Healthcare Corporation; Clinical
Translational Science Institute at the University of Southern California
FX This study was supported by the Modernization of Science Program of the
Center for Biologics Evaluation and Research, United States Food and
Drug Administration (Z.E.S.); and grants from the National Heart, Lung
and Blood Institute, National Institutes of Health (1RC2-HL101851,
HL-71130, HL-72533), the Bayer Healthcare Corporation, Bayer Hemophilia
Awards Program, Baxter Healthcare Corporation, and the Clinical
Translational Science Institute at the University of Southern California
(T.E.H.).
NR 31
TC 3
Z9 4
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 JAN 8
PY 2015
VL 125
IS 2
BP 223
EP 228
DI 10.1182/blood-2013-12-530113
PG 6
WC Hematology
SC Hematology
GA CD1CA
UT WOS:000350810200010
PM 25406352
ER
PT J
AU Sasaki, H
Kurotaki, D
Osato, N
Sato, H
Sasaki, I
Koizumi, S
Wang, HS
Kaneda, C
Nishiyama, A
Kaisho, T
Aburatani, H
Morse, HC
Ozato, K
Tamura, T
AF Sasaki, Haruka
Kurotaki, Daisuke
Osato, Naoki
Sato, Hideaki
Sasaki, Izumi
Koizumi, Shin-ichi
Wang, Hongsheng
Kaneda, Chika
Nishiyama, Akira
Kaisho, Tsuneyasu
Aburatani, Hiroyuki
Morse, Herbert C., III
Ozato, Keiko
Tamura, Tomohiko
TI Transcription factor IRF8 plays a critical role in the development of
murine basophils and mast cells
SO BLOOD
LA English
DT Article
ID CD8-ALPHA(+) DENDRITIC CELLS; SEQUENCE-BINDING-PROTEIN; IN-VIVO;
HEMATOPOIETIC LINEAGES; C/EBP-ALPHA; STEM-CELL; DIFFERENTIATION; ICSBP;
PROGENITORS; EXPRESSION
AB Basophils and mast cells play critical roles in host defense against pathogens and allergic disorders. However, the molecular mechanism by which these cells are generated is not completely understood. Here we demonstrate that interferon regulatory factor-8 (IRF8), a transcription factor essential for the development of several myeloid lineages, also regulates basophil and mast cell development. irf8(-/-) mice displayed a severe reduction in basophil counts, which was accounted for by the absence of pre-basophil and mast cell progenitors (pre-BMPs). Although Irf8(-/-) mice retained peripheral tissue mast cells, remaining progenitors from mice including granulocyte progenitors (GPs) were unable to efficiently generate either basophils or mast cells, indicating that IRF8 also contributes to the development of mast cells. IRF8 appeared to function at the GP stage, because IRF8 was expressed in GPs, but not in basophils, mast cells, and basophi/mast cell-restricted progenitor cells. Furthermore, we demonstrate that GATA2, a transcription factor known to promote basophil and mast cell differentiation, acts downstream of IRF8. These results shed light on the pathways and mechanism underlying the development of basophils and mast cells.
C1 [Sasaki, Haruka; Kurotaki, Daisuke; Sato, Hideaki; Koizumi, Shin-ichi; Kaneda, Chika; Nishiyama, Akira; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 2360004, Japan.
[Osato, Naoki; Aburatani, Hiroyuki] Univ Tokyo, Adv Sci & Technol Res Ctr, Genome Sci Div, Tokyo, Japan.
[Sasaki, Izumi; Kaisho, Tsuneyasu] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Lab Immune Regulat, Osaka, Japan.
[Wang, Hongsheng; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Lab Immunogenet, NIH, Rockville, MD USA.
[Kaisho, Tsuneyasu] RIKEN Res Ctr Allergy & Immunol, Lab Inflammatory Regulat, Yokohama, Kanagawa, Japan.
[Ozato, Keiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
RP Tamura, T (reprint author), Yokohama City Univ, Grad Sch Med, Dept Immunol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan.
EM tamurat@yokohama-cu.ac.jp
FU KAKENHI from the Japan Society for the Promotion of Science [24390246,
24118002, 24790322]; MEXT; Yokohama City University; National Institutes
of Health, National Institute of Allergy and Infectious Diseases; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX This work was supported by KAKENHI grants-in-aid (24390246 and 24118002)
(T.T.) and (24790322) (D.K.) from the Japan Society for the Promotion of
Science, the fund for Creation of Innovation Centers for Advanced
Interdisciplinary Research Areas Program in the Project for Developing
Innovation Systems from MEXT (T.T.), a grant for Strategic Research
Promotion from Yokohama City University (T.T.), and the Intramural
Research Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases (H.W., H.C.M.) and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (K.O.), and the supercomputing resource was provided by
Human Genome Center of the Institute of Medical Science at the
University of Tokyo.
NR 50
TC 18
Z9 19
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 JAN 8
PY 2015
VL 125
IS 2
BP 358
EP 369
DI 10.1182/blood-2014-02-557983
PG 12
WC Hematology
SC Hematology
GA CD1CA
UT WOS:000350810200024
PM 25398936
ER
PT J
AU Rosenberg, PS
Barker, KA
Anderson, WF
AF Rosenberg, Philip S.
Barker, Kimberly A.
Anderson, William F.
TI Future distribution of multiple myeloma in the United States by sex,
age, and race/ethnicity
SO BLOOD
LA English
DT Letter
ID SURVIVAL; CANCER; IMPROVEMENT
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 NIH HHS
NR 9
TC 3
Z9 3
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JAN 8
PY 2015
VL 125
IS 2
BP 410
EP 412
DI 10.1182/blood-2014-10-609461
PG 5
WC Hematology
SC Hematology
GA CD1CA
UT WOS:000350810200030
PM 25573972
ER
PT J
AU Glubb, DM
Maranian, MJ
Michailidou, K
Pooley, KA
Meyer, KB
Kar, S
Carlebur, S
O'Reilly, M
Betts, JA
Hillman, KM
Kaufmann, S
Beesley, J
Canisius, S
Hopper, JL
Southey, MC
Tsimiklis, H
Apicella, C
Schmidt, MK
Broeks, A
Hogervorst, FB
van der Schoot, CE
Muir, K
Lophatananon, A
Stewart-Brown, S
Siriwanarangsan, P
Fasching, PA
Ruebner, M
Ekici, AB
Beckmann, MW
Peto, J
Dos-Santos-Silva, I
Fletcher, O
Johnson, N
Pharoah, PDP
Bolla, MK
Wang, Q
Dennis, J
Sawyer, EJ
Tomlinson, I
Kerin, MJ
Miller, N
Burwinkel, B
Marme, F
Yang, RX
Surowy, H
Guenel, P
Truong, T
Menegaux, F
Sanchez, M
Bojesen, SE
Nordestgaard, BG
Nielsen, SF
Flyger, H
Gonzelez-Neira, A
Benitez, J
Zamora, MP
Perez, JIA
Anton-Culver, H
Neuhausen, SL
Brenner, H
Dieffenbach, AK
Arndt, V
Stegmaier, C
Meindl, A
Schmutzler, RK
Brauch, H
Ko, YD
Bruning, T
Nevanlinna, H
Muranen, TA
Aittomaki, K
Blomqvist, C
Matsuo, K
Ito, H
Iwata, H
Tanaka, H
Dork, T
Bogdanova, NV
Helbig, S
Lindblom, A
Margolin, S
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Wu, AH
Tseng, CC
Van den Berg, D
Stram, DO
Lambrechts, D
Zhao, H
Weltens, C
van Limbergen, E
Chang-Claude, J
Flesch-Janys, D
Rudolph, A
Seibold, P
Radice, P
Peterlongo, P
Barile, M
Capra, F
Couch, FJ
Olson, JE
Hallberg, E
Vachon, C
Giles, GG
Milne, RL
McLean, C
Haiman, CA
Henderson, BE
Schumacher, F
Le Marchand, L
Simard, J
Goldberg, MS
Labreche, F
Dumont, M
Teo, SH
Yip, CH
See, MH
Cornes, B
Cheng, CY
Ikram, MK
Kristensen, V
Zheng, W
Halverson, SL
Shrubsole, M
Long, J
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Kauppila, S
Andrulis, IL
Knight, JA
Glendon, G
Tchatchou, S
Devilee, P
Tollenaar, RAEM
Seynaeve, C
Van Asperen, CJ
Garcia-Closas, M
Figueroa, J
Chanock, SJ
Lissowska, J
Czene, K
Klevebring, D
Darabi, H
Eriksson, M
Hooning, MJ
Hollestelle, A
Martens, JWM
Collee, JM
Hall, P
Li, JM
Humphreys, K
Shu, XO
Lu, W
Gao, YT
Cai, H
Cox, A
Cross, SS
Reed, MWR
Blot, W
Signorello, LB
Cai, QY
Shah, M
Ghoussaini, M
Kang, D
Choi, JY
Park, SK
Noh, DY
Hartman, M
Miao, H
Lim, WY
Tang, A
Hamann, U
Torres, D
Jakubowska, A
Lubinski, J
Jaworska, K
Durda, K
Sangrajrang, S
Gaborieau, V
Brennan, P
McKay, J
Olswold, C
Slager, S
Toland, AE
Yannoukakos, D
Shen, CY
Wu, PE
Yu, JC
Hou, MF
Swerdlow, A
Ashworth, A
Orr, N
Jones, M
Pita, G
Alonso, MR
Alvarez, N
Herrero, D
Tessier, DC
Vincent, D
Bacot, F
Luccarini, C
Baynes, C
Ahmed, S
Healey, CS
Brown, MA
Ponder, BAJ
Chenevix-Trench, G
Thompson, DJ
Edwards, SL
Easton, DF
Dunning, AM
French, JD
AF Glubb, Dylan M.
Maranian, Mel J.
Michailidou, Kyriaki
Pooley, Karen A.
Meyer, Kerstin B.
Kar, Siddhartha
Carlebur, Saskia
O'Reilly, Martin
Betts, Joshua A.
Hillman, Kristine M.
Kaufmann, Susanne
Beesley, Jonathan
Canisius, Sander
Hopper, John L.
Southey, Melissa C.
Tsimiklis, Helen
Apicella, Carmel
Schmidt, Marjanka K.
Broeks, Annegien
Hogervorst, Frans B.
van der Schoot, C. Ellen
Muir, Kenneth
Lophatananon, Artitaya
Stewart-Brown, Sarah
Siriwanarangsan, Pornthep
Fasching, Peter A.
Ruebner, Matthias
Ekici, Arif B.
Beckmann, Matthias W.
Peto, Julian
Dos-Santos-Silva, Isabel
Fletcher, Olivia
Johnson, Nichola
Pharoah, Paul D. P.
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Sawyer, Elinor J.
Tomlinson, Ian
Kerin, Michael J.
Miller, Nicola
Burwinkel, Barbara
Marme, Frederik
Yang, Rongxi
Surowy, Harald
Guenel, Pascal
Truong, Therese
Menegaux, Florence
Sanchez, Marie
Bojesen, Stig E.
Nordestgaard, Borge G.
Nielsen, Sune F.
Flyger, Henrik
Gonzalez-Neira, Anna
Benitez, Javier
Pilar Zamora, M.
Arias Perez, Jose Ignacio
Anton-Culver, Hoda
Neuhausen, Susan L.
Brenner, Hermann
Dieffenbach, Aida Karina
Arndt, Volker
Stegmaier, Christa
Meindl, Alfons
Schmutzler, Rita K.
Brauch, Hiltrud
Ko, Yon-Dschun
Bruening, Thomas
Nevanlinna, Heli
Muranen, Taru A.
Aittomaeki, Kristiina
Blomqvist, Carl
Matsuo, Keitaro
Ito, Hidemi
Iwata, Hiroji
Tanaka, Hideo
Doerk, Thilo
Bogdanova, Natalia V.
Helbig, Sonja
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Wu, Anna H.
Tseng, Chiu-chen
Van den Berg, David
Stram, Daniel O.
Lambrechts, Diether
Zhao, Hui
Weltens, Caroline
van Limbergen, Erik
Chang-Claude, Jenny
Flesch-Janys, Dieter
Rudolph, Anja
Seibold, Petra
Radice, Paolo
Peterlongo, Paolo
Barile, Monica
Capra, Fabio
Couch, Fergus J.
Olson, Janet E.
Hallberg, Emily
Vachon, Celine
Giles, Graham G.
Milne, Roger L.
McLean, Catriona
Haiman, Christopher A.
Henderson, Brian E.
Schumacher, Fredrick
Le Marchand, Loic
Simard, Jacques
Goldberg, Mark S.
Labreche, France
Dumont, Martine
Teo, Soo Hwang
Yip, Cheng Har
See, Mee-Hoong
Cornes, Belinda
Cheng, Ching-Yu
Ikram, M. Kamran
Kristensen, Vessela
Zheng, Wei
Halverson, Sandra L.
Shrubsole, Martha
Long, Jirong
Winqvist, Robert
Pylkaes, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Andrulis, Irene L.
Knight, Julia A.
Glendon, Gord
Tchatchou, Sandrine
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline
Van Asperen, Christi J.
Garcia-Closas, Montserrat
Figueroa, Jonine
Chanock, Stephen J.
Lissowska, Jolanta
Czene, Kamila
Klevebring, Daniel
Darabi, Hatef
Eriksson, Mikael
Hooning, Maartje J.
Hollestelle, Antoinette
Martens, John W. M.
Collee, J. Margriet
Hall, Per
Li, Jingmei
Humphreys, Keith
Shu, Xiao-Ou
Lu, Wei
Gao, Yu-Tang
Cai, Hui
Cox, Angela
Cross, Simon S.
Reed, Malcolm W. R.
Blot, William
Signorello, Lisa B.
Cai, Qiuyin
Shah, Mitul
Ghoussaini, Maya
Kang, Daehee
Choi, Ji-Yeob
Park, Sue K.
Noh, Dong-Young
Hartman, Mikael
Miao, Hui
Lim, Wei Yen
Tang, Anthony
Hamann, Ute
Torres, Diana
Jakubowska, Anna
Lubinski, Jan
Jaworska, Katarzyna
Durda, Katarzyna
Sangrajrang, Suleeporn
Gaborieau, Valerie
Brennan, Paul
McKay, James
Olswold, Curtis
Slager, Susan
Toland, Amanda E.
Yannoukakos, Drakoulis
Shen, Chen-Yang
Wu, Pei-Ei
Yu, Jyh-Cherng
Hou, Ming-Feng
Swerdlow, Anthony
Ashworth, Alan
Orr, Nick
Jones, Michael
Pita, Guillermo
Rosario Alonso, M.
Alvarez, Nuria
Herrero, Daniel
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Luccarini, Craig
Baynes, Caroline
Ahmed, Shahana
Healey, Catherine S.
Brown, Melissa A.
Ponder, Bruce A. J.
Chenevix-Trench, Georgia
Thompson, Deborah J.
Edwards, Stacey L.
Easton, Douglas F.
Dunning, Alison M.
French, Juliet D.
CA GENICA Network
KConFab Investigators
Norwegian Breast Canc Study
TI Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least
Three Independent Risk Variants Regulating MAP3K1
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CYCLIN D1 EXPRESSION; FUNCTIONAL VARIANTS;
SUSCEPTIBILITY LOCI; GENES; PROMOTER; ACTIVATION; APOPTOSIS; SUBTYPES;
TUMORS
AB Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER-: odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, p(trend) = 5.7 3 10(-44)) and estrogen-receptor-negative (ER-: OR = 1.10, 95% CI = 1.05-1.15, p(trend) = 3.0 x 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [p(cond) = 1.61 x 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER-: OR = 0.90, 95% CI = 0.87-0.93, p(cond) = 1.4 x 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.
C1 [Glubb, Dylan M.; Betts, Joshua A.; Hillman, Kristine M.; Kaufmann, Susanne; Beesley, Jonathan; Chenevix-Trench, Georgia; Edwards, Stacey L.; French, Juliet D.] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4029, Australia.
[Maranian, Mel J.; Pooley, Karen A.; Pharoah, Paul D. P.; Shah, Mitul; Ghoussaini, Maya; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Easton, Douglas F.; Dunning, Alison M.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England.
[Michailidou, Kyriaki; Kar, Siddhartha; Pharoah, Paul D. P.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Thompson, Deborah J.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Meyer, Kerstin B.; Carlebur, Saskia; O'Reilly, Martin; Ponder, Bruce A. J.] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
[Meyer, Kerstin B.; Carlebur, Saskia; O'Reilly, Martin; Ponder, Bruce A. J.] Univ Cambridge, Dept Oncol, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
[Betts, Joshua A.; Brown, Melissa A.; Edwards, Stacey L.; French, Juliet D.] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia.
[Canisius, Sander; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; Giles, Graham G.; Milne, Roger L.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
[Hopper, John L.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
[Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[van der Schoot, C. Ellen] Sanquin Res, NL-1066 CX Amsterdam, Netherlands.
[Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England.
[Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester M13 9PL, Lancs, England.
[Siriwanarangsan, Pornthep] Minist Publ Hlth, Nonthaburi 11000, Thailand.
[Fasching, Peter A.; Ruebner, Matthias; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Univ Hosp Erlangen,Comprehens Canc Ctr Erlangen E, D-91054 Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, D-91054 Erlangen, Germany.
[Peto, Julian; Dos-Santos-Silva, Isabel] Univ London London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England.
[Fletcher, Olivia; Johnson, Nichola; Garcia-Closas, Montserrat; Ashworth, Alan; Orr, Nick] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Div Canc Studies, London SE1 9RT, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England.
[Kerin, Michael J.; Miller, Nicola] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland.
[Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald] Heidelberg Univ, Dept Obstet & Gynecol, D-69115 Heidelberg, Germany.
[Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.
[Yang, Rongxi; Surowy, Harald; Hamann, Ute; Torres, Diana] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Guenel, Pascal; Truong, Therese; Menegaux, Florence; Sanchez, Marie] INSERM, U1018, Ctr Rech Epidemiol & Sante Populat, F-94807 Villejuif, France.
[Guenel, Pascal; Truong, Therese; Menegaux, Florence; Sanchez, Marie] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark.
[Gonzalez-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Alvarez, Nuria; Herrero, Daniel] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Ctr Nacl Genotipado, Human Genotyping Unit, Madrid 28029, Spain.
[Benitez, Javier] Ctr Invest Red Enfermedades Raras, Valencia 46010, Spain.
[Benitez, Javier] Spanish Natl Canc Ctr, Human Genet Grp, Madrid 28029, Spain.
[Benitez, Javier] Biomed Network Rare Dis, Madrid 28029, Spain.
[Pilar Zamora, M.] Hosp Univ La Paz, Med Oncol Serv, Madrid 28029, Spain.
[Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 33012, Spain.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA.
[Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.
[Brenner, Hermann; Dieffenbach, Aida Karina] German Canc Consortium, D-69120 Heidelberg, Germany.
[Stegmaier, Christa] Saarland Canc Registry, D-66024 Saarbrucken, Germany.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-81675 Munich, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, D-50931 Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, D-50937 Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Integrated Oncol, Ctr Mol Med, D-50937 Cologne, Germany.
[Schmutzler, Rita K.] Univ Cologne, Ctr Mol Med Cologne, D-50923 Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Fac Med, Ctr Integrated Oncol, D-50937 Cologne, Germany.
[Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
[Ko, Yon-Dschun] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, D-53113 Bonn, Germany.
[Bruening, Thomas] German Social Accid Insurance, Inst Prevent & Occupat Med, Inst Ruhr Univ Bochum, D-44789 Bochum, Germany.
[GENICA Network] Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, D-20246 Hamburg, Germany.
[Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Finland.
[Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Cent Hosp, Hosp Dist Helsinki & Uusimaa, Helsinki 00029, Finland.
[Aittomaeki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki 00029, Finland.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki 00029, Finland.
[Blomqvist, Carl] Univ Helsinki, Cent Hosp, Helsinki 00029, Finland.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 8128582, Japan.
[Ito, Hidemi; Tanaka, Hideo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4648681, Japan.
[Iwata, Hiroji] Aichi Canc Ctr Hosp, Dept Breast Oncol, Nagoya, Aichi 4648681, Japan.
[Doerk, Thilo; Helbig, Sonja] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, S-17177 Stockholm, Sweden.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio 70211, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio 70211, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio 70211, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Ctr Canc, Kuopio 70211, Finland.
[KConFab Investigators] Peter MacCallum Canc Inst, East Melbourne, Vic 3002, Australia.
[Wu, Anna H.; Tseng, Chiu-chen; Van den Berg, David; Stram, Daniel O.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
[Lambrechts, Diether; Zhao, Hui] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium.
[Lambrechts, Diether; Zhao, Hui] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium.
[Weltens, Caroline; van Limbergen, Erik] Univ Hosp Gashuisberg, B-3000 Leuven, Belgium.
[Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, D-20246 Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany.
[Radice, Paolo] Ist Nazl Tumori, Fdn Ist Neurologico Carlo Besta, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy.
[Peterlongo, Paolo; Capra, Fabio] Ist Fdn Italiana Ric Canc Oncol Mol, I-20139 Milan, Italy.
[Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy.
[Capra, Fabio] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Olswold, Curtis; Slager, Susan] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia.
[McLean, Catriona] The Alfred, Anat Pathol, Melbourne, Vic 3004, Australia.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
[Simard, Jacques; Dumont, Martine] Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ G1V 4G2, Canada.
[Simard, Jacques; Dumont, Martine] Univ Laval, Quebec City, PQ G1V 4G2, Canada.
[Goldberg, Mark S.] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada.
[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada.
[Labreche, France] Univ Montreal, Dept Sante Environm & Sante Travail, Dept Med Sociale & Prevent, Montreal, PQ H3A 3C2, Canada.
[Teo, Soo Hwang] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya 47500, Malaysia.
[Teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong] Univ Malaya, Breast Canc Res Unit, Canc Res Inst, Med Ctr, Kuala Lumpur 50603, Malaysia.
[Cornes, Belinda; Cheng, Ching-Yu; Ikram, M. Kamran] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 168751, Singapore.
[Kristensen, Vessela] Univ Oslo, Inst Clin Med, N-0450 Oslo, Norway.
[Kristensen, Vessela] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway.
[Kristensen, Vessela] Univ Oslo, Dept Clin Mol Biol, N-0450 Oslo, Norway.
Univ Bergen, Inst Med, Sect Oncol, N-5020 Bergen, Norway.
Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemedicine, N-9038 Tromso, Norway.
Radiumhospitalet, Rikshosp, Natl Resource Ctr Long Term Studies Canc, Canc Clin, N-0310 Oslo, Norway.
Radiumhospitalet, Oslo Univ Hosp, Div Canc Med & Radiotherapy, N-0310 Oslo, Norway.
Akershus Univ Hosp, Dept Surg, N-1478 Lorenskog, Norway.
Radiumhospitalet, Oslo Univ Hosp, Dept Radiol, N-0310 Oslo, Norway.
Akershus Univ Hosp, Dept Pathol, N-1478 Lorenskog, Norway.
Radiumhospitalet, Oslo Univ Hosp, Dept Oncol, N-0310 Oslo, Norway.
Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway.
Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway.
Univ Oslo, Akershus Univ Hosp, Inst Clin Med, Dept Clin Mol Biol, N-1478 Lorenskog, Norway.
[Norwegian Breast Canc Study] Oslo Univ Hosp, Ullevaal Univ Hosp, Inst Clin Med, Dept Breast & Endocrine Surg, N-0450 Oslo, Norway.
[Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Shu, Xiao-Ou; Cai, Hui; Blot, William; Signorello, Lisa B.; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.
[Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Shu, Xiao-Ou; Cai, Hui; Blot, William; Signorello, Lisa B.; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA.
[Winqvist, Robert; Pylkaes, Katri] Univ Oulu, Lab Canc Genet & Tumor Biol, Dept Clin Chem, NordLab Oulu,Oulu Univ Hosp, Oulu 90210, Finland.
[Winqvist, Robert; Pylkaes, Katri] Univ Oulu, Bioctr Oulu, NordLab Oulu, Oulu Univ Hosp, Oulu 90210, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu Univ Hosp, Oulu 90014, Finland.
[Kauppila, Saila] Univ Oulu, Dept Pathol, Oulu Univ Hosp, Oulu 90014, Finland.
[Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada.
[Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada.
[Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
[Glendon, Gord; Tchatchou, Sandrine] Mt Sinai Hosp, Ontario Canc Genet Network, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Devilee, Peter; Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands.
[Devilee, Peter; Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands.
[Seynaeve, Caroline] Netherlands Canc Inst, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands.
[Van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands.
[Garcia-Closas, Montserrat; Swerdlow, Anthony; Jones, Michael] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
[Figueroa, Jonine; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland.
[Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Humphreys, Keith] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.] Erasmus Univ, Med Ctr, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands.
[Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3008 AE Rotterdam, Netherlands.
[Li, Jingmei] Genome Inst Singapore, Div Human Genet, Singapore 138672, Singapore.
[Lu, Wei] Shanghai Ctr Dis Control & Prevent, Shanghai 200336, Peoples R China.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai 200032, Peoples R China.
[Cox, Angela; Reed, Malcolm W. R.] Univ Sheffield, Dept Oncol, Sheffield Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield S10 2RX, S Yorkshire, England.
[Blot, William; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD 20850 USA.
[Kang, Daehee; Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea.
[Kang, Daehee; Park, Sue K.] Seoul Natl Univ, Canc Res Inst, Seoul 110799, South Korea.
[Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 151742, South Korea.
[Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South Korea.
[Noh, Dong-Young] Seoul Natl Univ, Bundang Hosp, Dept Surg, Songnam 110744, South Korea.
[Hartman, Mikael; Miao, Hui; Lim, Wei Yen] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.
[Hartman, Mikael; Miao, Hui; Lim, Wei Yen] Natl Univ Hlth Syst, Singapore 117597, Singapore.
[Hartman, Mikael] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 119228, Singapore.
[Hartman, Mikael] Natl Univ Hlth Syst, Singapore 119228, Singapore.
[Tang, Anthony] Natl Univ Hlth Syst, Div Gen Surg, Singapore 119228, Singapore.
[Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota 11001000, Colombia.
[Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland.
[Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok 10400, Thailand.
[Gaborieau, Valerie; Brennan, Paul; McKay, James] Int Agcy Res Canc, F-69372 Lyon, France.
[Toland, Amanda E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, Inst Radioisotopes & Radiodiagnost Prod, Athens 15310, Greece.
[Shen, Chen-Yang; Wu, Pei-Ei] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan.
[Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung 40402, Taiwan.
[Shen, Chen-Yang; Wu, Pei-Ei] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei 115, Taiwan.
[Yu, Jyh-Cherng] Tri Serv Gen Hosp, Dept Surg, Taipei 114, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Ctr Canc, Chung Ho Mem Hosp, Kaohsiung 807, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Dept Surg, Chung Ho Mem Hosp, Kaohsiung 807, Taiwan.
[Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, Sutton SM2 5NG, Surrey, England.
[Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois] McGill Univ, Montreal, PQ H3A 0G1, Canada.
[Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.
RP Dunning, AM (reprint author), Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England.
EM amd24@medschl.cam.ac.uk; juliet.french@qimrberghofer.edu.au
RI Gonzalez-Neira, Anna/C-5791-2015; Hartman, Mikael/B-4324-2011; Yip,
Cheng-Har/B-1909-2010; Teo, Soo-hwang/H-2353-2014; Hartikainen,
Jaana/E-6256-2015; Li, Jingmei/I-2904-2012; Garcia-Closas, Montserrat
/F-3871-2015; Knight, Julia/A-6843-2012; Shrubsole, Martha/K-5052-2015;
Dork, Thilo/J-8620-2012; U-ID, Kyushu/C-5291-2016; See, Mee-Hoong,
See/P-8440-2014; Bruning, Thomas/G-8120-2015; Andrulis,
Irene/E-7267-2013; Edwards, Stacey/A-4980-2011; Tanaka,
Hideo/A-8145-2016; Glubb, Dylan/M-7514-2016; Brown, Melissa/F-1451-2010;
Brenner, Hermann/B-4627-2017;
OI Dunning, Alison Margaret/0000-0001-6651-7166; Ikram, Mohammad
Kamran/0000-0003-0173-9571; Giles, Graham/0000-0003-4946-9099; Muranen,
Taru/0000-0002-5895-1808; Matsuo, Keitaro/0000-0003-1761-6314; Arndt,
Volker/0000-0001-9320-8684; Li, Jingmei/0000-0001-8587-7511;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Shrubsole,
Martha/0000-0002-5591-7575; See, Mee-Hoong, See/0000-0002-7197-5759;
Bruning, Thomas/0000-0001-9560-5464; Glubb, Dylan/0000-0002-2184-7708;
Brenner, Hermann/0000-0002-6129-1572; Brown,
Melissa/0000-0002-2830-9259; Czene, Kamila/0000-0002-3233-5695; Cross,
Simon/0000-0003-2044-1754; Cox, Angela/0000-0002-5138-1099; Yannoukakos,
Drakoulis/0000-0001-7509-3510
FU Canadian Institutes of Health Research [CRN-87521]; Cancer Research UK
[10124, C1287/A10118, C1287/A10710, C1287/A12014, C490/A10124,
C8197/A16565]; Intramural NIH HHS; NCI NIH HHS [R01 CA176785, CA098758,
CA116167, CA116201, CA128978, CA132839, CA176785, CA54281, CA63464,
N01CN25403, P30 CA015083, P30 CA68485, R01 CA092447, R01 CA77398,
R01CA148667, R01CA64277, R37CA70867, U01 CA116167, U19 CA148065, UM1
CA164920]
NR 38
TC 16
Z9 16
U1 7
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JAN 8
PY 2015
VL 96
IS 1
BP 5
EP 20
DI 10.1016/j.ajhg.2014.11.009
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA AY6YE
UT WOS:000347707800001
PM 25529635
ER
PT J
AU Zhu, XF
Feng, T
Tayo, BO
Liang, JJ
Young, JH
Franceschini, N
Smith, JA
Yanek, LR
Sun, YV
Edwards, TL
Chen, W
Nalls, M
Fox, E
Sale, M
Bottinger, E
Rotimi, C
Liu, YM
McKnight, B
Liu, K
Arnett, DK
Chakravati, A
Cooper, RS
Redline, S
AF Zhu, Xiaofeng
Feng, Tao
Tayo, Bamidele O.
Liang, Jingjing
Young, J. Hunter
Franceschini, Nora
Smith, Jennifer A.
Yanek, Lisa R.
Sun, Yan V.
Edwards, Todd L.
Chen, Wei
Nalls, Mike
Fox, Ervin
Sale, Michele
Bottinger, Erwin
Rotimi, Charles
Liu, Yongmei
McKnight, Barbara
Liu, Kiang
Arnett, Donna K.
Chakravati, Aravinda
Cooper, Richard S.
Redline, Susan
CA COGENT BP Consortium
TI Meta-analysis of Correlated Traits via Summary Statistics from GWASs
with an Application in Hypertension
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMBINING DEPENDENT TESTS; BLOOD-PRESSURE
TRAITS; PRINCIPAL-COMPONENTS; SUSCEPTIBILITY LOCI; GENETIC ASSOCIATION;
PHENOTYPES; VARIANTS; DISEASE; LINKAGE
AB Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 x 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 x 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes.
C1 [Zhu, Xiaofeng; Feng, Tao; Liang, Jingjing] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Feng, Tao] Heilongjiang Univ, Coll Math Sci, Harbin 150080, Peoples R China.
[Tayo, Bamidele O.; Cooper, Richard S.] Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL 60153 USA.
[Young, J. Hunter; Yanek, Lisa R.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Smith, Jennifer A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Sun, Yan V.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Edwards, Todd L.] Vanderbilt Univ, Dept Med, Div Epidemiol, Ctr Human Genet Res, Nashville, TN 37212 USA.
[Chen, Wei] Tulane Univ, Tulane Ctr Cardiovasc Hlth, New Orleans, LA 70112 USA.
[Nalls, Mike] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Fox, Ervin] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39126 USA.
[Sale, Michele] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Bottinger, Erwin] Mt Sinai Sch Med, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Rotimi, Charles] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27157 USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA.
[Chakravati, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA.
[Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Redline, Susan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Zhu, XF (reprint author), Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
EM xiaofeng.zhu@case.edu
RI Singleton, Andrew/C-3010-2009; Bovet, Pascal/F-4477-2011; Bochud,
Murielle/A-3981-2010;
OI Bovet, Pascal/0000-0002-0242-4259; Bochud, Murielle/0000-0002-5727-0218;
Adeyemo, Adebowale/0000-0002-3105-3231; Smith,
Jennifer/0000-0002-3575-5468
FU NIH from the National Human Genome Research Institute [HG003054];
National Heart, Lung, and Blood Institute [HL086718, HL053353, HL113338,
HL123677]
FX We are gratefully indebted to Robert C. Elston for his valuable
discussions and suggestions that greatly improved the manuscript. The
work was supported by the NIH grants HG003054 from the National Human
Genome Research Institute and HL086718, HL053353, HL113338, and HL123677
from the National Heart, Lung, and Blood Institute. Funding information
for the COGENT BP Consortium is provided in the Supplemental Data.
NR 42
TC 22
Z9 23
U1 2
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JAN 8
PY 2015
VL 96
IS 1
BP 21
EP 36
DI 10.1016/j.ajhg.2014.11.011
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA AY6YE
UT WOS:000347707800002
PM 25500260
ER
PT J
AU Schueler, M
Braun, DA
Chandrasekar, G
Gee, HY
Klasson, TD
Halbritter, J
Bieder, A
Porath, JD
Airik, R
Zhou, WB
LoTurco, JJ
Che, A
Otto, EA
Bockenhauer, D
Sebire, NJ
Honzik, T
Harris, PC
Koon, SJ
Gunay-Aygun, M
Saunier, S
Zerres, K
Bruechle, NO
Drenth, JPH
Pelletier, L
Tapia-Paez, I
Lifton, RP
Giles, RH
Kere, J
Hildebrandt, F
AF Schueler, Markus
Braun, Daniela A.
Chandrasekar, Gayathri
Gee, Heon Yung
Klasson, Timothy D.
Halbritter, Jan
Bieder, Andrea
Porath, Jonathan D.
Airik, Rannar
Zhou, Weibin
LoTurco, Joseph J.
Che, Alicia
Otto, Edgar A.
Boeckenhauer, Detlef
Sebire, Neil J.
Honzik, Tomas
Harris, Peter C.
Koon, Sarah J.
Gunay-Aygun, Meral
Saunier, Sophie
Zerres, Klaus
Bruechle, Nadina Ortiz
Drenth, Joost P. H.
Pelletier, Laurence
Tapia-Paez, Isabel
Lifton, Richard P.
Giles, Rachel H.
Kere, Juha
Hildebrandt, Friedhelm
TI DCDC2 Mutations Cause a Renal-Hepatic Ciliopathy by Disrupting Wnt
Signaling
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID MULTIPOINT LINKAGE ANALYSIS; JOUBERT-SYNDROME; CAUSE NEPHRONOPHTHISIS;
CENTROSOMAL PROTEIN; DOMAIN PROTEIN; GENE; CILIARY; DISEASE; INTERACTS;
ZEBRAFISH
AB Nephronophthisis-related ciliopathies (NPHP-RC) are recessive diseases characterized by renal dysplasia or degeneration. We here identify mutations of DCDC2 as causing a renal-hepatic ciliopathy. DCDC2 localizes to the ciliary axoneme and to mitotic spindle fibers in a cell-cycle-dependent manner. Knockdown of Dcdc2 in IMCD3 cells disrupts ciliogenesis, which is rescued by wild-type (WT) human DCDC2, but not by constructs that reflect human mutations. We show that DCDC2 interacts with DVL and DCDC2 overexpression inhibits beta-catenin-dependent Wnt signaling in an effect additive to Wnt inhibitors. Mutations detected in human NPHP-RC lack these effects. A Wnt inhibitor likewise restores ciliogenesis in 3D IMCD3 cultures, emphasizing the importance of Wnt signaling for renal tubulogenesis. Knockdown of dcdc2 in zebrafish recapitulates NPHP-RC phenotypes, including renal cysts and hydrocephalus, which is rescued by a Wnt inhibitor and by WT, but not by mutant, DCDC2. We thus demonstrate a central role of Wnt signaling in the pathogenesis of NPHP-RC, suggesting an avenue for potential treatment of NPHP-RC.
C1 [Schueler, Markus; Braun, Daniela A.; Gee, Heon Yung; Halbritter, Jan; Porath, Jonathan D.; Airik, Rannar; Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Chandrasekar, Gayathri; Bieder, Andrea; Tapia-Paez, Isabel; Kere, Juha] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
[Klasson, Timothy D.; Giles, Rachel H.] Univ Med Ctr Utrecht, Dept Hypertens & Nephrol, NL-3584 CX Utrecht, Netherlands.
[Zhou, Weibin; Otto, Edgar A.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[LoTurco, Joseph J.; Che, Alicia] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 USA.
[Boeckenhauer, Detlef] UCL, Inst Child Hlth & Pediat Nephrol, Great Ormond St Hosp, London WC1N 3JH, England.
[Sebire, Neil J.; Hildebrandt, Friedhelm] Great Ormond St Hosp Sick Children, Dept Histopathol, London WC1N 3JH, England.
[Honzik, Tomas] Charles Univ Prague, Fac Med 1, Dept Pediat & Adolescent Med, Prague 12808 2, Czech Republic.
[Honzik, Tomas] Gen Univ Hosp, Prague 12808 2, Czech Republic.
[Harris, Peter C.; Koon, Sarah J.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA.
[Gunay-Aygun, Meral] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Saunier, Sophie] Univ Paris 05, Necker Hosp, Inserm U574, F-75015 Paris, France.
[Saunier, Sophie] Univ Paris 05, Necker Hosp, Dept Genet, F-75015 Paris, France.
[Zerres, Klaus; Bruechle, Nadina Ortiz] Rhein Westfal TH Aachen, Univ Hosp, Inst Human Genet, D-52074 Aachen, Germany.
[Drenth, Joost P. H.] Radboud UMC, Dept Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands.
[Pelletier, Laurence] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Pelletier, Laurence] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Lifton, Richard P.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Kere, Juha] Univ Helsinki, Mol Neurol Res Program, Helsinki 00014, Finland.
[Kere, Juha] Folkhalsan Inst Genet, Helsinki 00014, Finland.
[Kere, Juha] Karolinska Inst, Sci Life Lab, S-17121 Solna, Sweden.
RP Kere, J (reprint author), Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
EM juha.kere@ki.se; friedhelm.hildebrandt@childrens.harvard.edu
RI Kere, Juha/A-9179-2008; Drenth, J.P.H./H-8025-2014;
OI Kere, Juha/0000-0003-1974-0271; Otto, Edgar/0000-0002-2387-9973; Bieder,
Andrea/0000-0002-4566-050X
FU Live Cell Imaging unit/Nikon Center of Excellence; Department of
Biosciences and Nutrition, Karolinska Institutet; National Institutes of
Health [DK1069274, DK1068306, DK064614, DK090728, DK059597, DK099434];
CIHR [MOP130507]; NephCure Foundation; ASN Foundation for Kidney
Research; General University Hospital [RVO-VFN 64165/2012]; Knut and
Alice Wallenberg Foundation; Swedish Research Council; Centre for
Biosciences; Centre for Innovative Medicine; Kungliga Tekniska
Hogskolan; Swedish Brain Foundation (Hjarnfonden); Swedish Brain
Foundation; European Union [241955, 305608]; Dutch Kidney Foundation
[CP11.18 "KOUNCIL"/13A3D103]; Deutsche Forschungs-gemeinschaft [ZE
205/14-1]; Jonasson
FX We are grateful to families and study individuals for their
contribution. We would like to thank Milan Elleder and Helena Hulkova
(Institute for Inherited Metabolic Disorders) for histological
preparation of liver biopsy specimen. We thank the zebrafish core
facility, Karolinska Institutet for providing zebrafish embryos. We
thank Kjell Hultenby, Eva Blomen, and Sally Cheung for technical
support. We thank the Live Cell Imaging unit/Nikon Center of Excellence,
Department of Biosciences and Nutrition, Karolinska Institutet for their
support. This research was supported by grants from the National
Institutes of Health to F.H. (DK1069274, DK1068306, DK064614), to P.C.H.
(DK090728, DK059597), to R.A. (DK099434), and by the CIHR to L.P.
(MOP130507). H.Y.G. is supported by the NephCure Foundation and by the
ASN Foundation for Kidney Research. T.H. was supported by General
University Hospital program RVO-VFN 64165/2012. This work was in part
supported by grants to J.K. from Knut and Alice Wallenberg Foundation,
the Swedish Research Council, the Centre for Biosciences, the Centre for
Innovative Medicine, and Jonasson donation to the School of Technology
and Health, Kungliga Tekniska Hogskolan, Swedish Brain Foundation
(Hjarnfonden) and Swedish Brain Foundations postdoc fellowship award to
G.C., from the European Union Framework Programmes 241955 "SYSCILIA" and
305608 "EURenOmics" as well as the Dutch Kidney Foundation grants
CP11.18 "KOUNCIL"/13A3D103 to R.H.G., and from the Deutsche
Forschungs-gemeinschaft to K.Z. (ZE 205/14-1). F.H. is an Investigator
of the Howard Hughes Medical Institute, a Doris Duke Distinguished
Clinical Scientist, and the Warren E. Grupe Professor.
NR 41
TC 14
Z9 19
U1 3
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JAN 8
PY 2015
VL 96
IS 1
BP 81
EP 92
DI 10.1016/j.ajhg.2014.12.002
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AY6YE
UT WOS:000347707800006
PM 25557784
ER
PT J
AU Neta, G
Sanchez, MA
Chambers, DA
Phillips, SM
Leyva, B
Cynkin, L
Farrell, MM
Heurtin-Roberts, S
Vinson, C
AF Neta, Gila
Sanchez, Michael A.
Chambers, David A.
Phillips, Siobhan M.
Leyva, Bryan
Cynkin, Laurie
Farrell, Margaret M.
Heurtin-Roberts, Suzanne
Vinson, Cynthia
TI Implementation science in cancer prevention and control: a decade of
grant funding by the National Cancer Institute and future directions
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Grants; Review; Implementation science; Study characteristics
ID DISSEMINATION; HEALTH; TRANSLATION
AB Background: The National Cancer Institute (NCI) has supported implementation science for over a decade. We explore the application of implementation science across the cancer control continuum, including prevention, screening, treatment, and survivorship.
Methods: We reviewed funding trends of implementation science grants funded by the NCI between 2000 and 2012. We assessed study characteristics including cancer topic, position on the T2-T4 translational continuum, intended use of frameworks, study design, settings, methods, and replication and cost considerations.
Results: We identified 67 NCI grant awards having an implementation science focus. R01 was the most common mechanism, and the total number of all awards increased from four in 2003 to 15 in 2012. Prevention grants were most frequent (49.3%) and cancer treatment least common (4.5%). Diffusion of Innovations and Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) were the most widely reported frameworks, but it is unclear how implementation science models informed planned study measures. Most grants (69%) included mixed methods, and half reported replication and cost considerations (49.3%).
Conclusions: Implementation science in cancer research is active and diverse but could be enhanced by greater focus on measures development, assessment of how conceptual frameworks and their constructs lead to improved dissemination and implementation outcomes, and harmonization of measures that are valid, reliable, and practical across multiple settings.
C1 [Neta, Gila; Sanchez, Michael A.; Chambers, David A.; Phillips, Siobhan M.; Leyva, Bryan; Cynkin, Laurie; Farrell, Margaret M.; Heurtin-Roberts, Suzanne; Vinson, Cynthia] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
RP Neta, G (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E442, Rockville, MD 20852 USA.
EM netagil@mail.nih.gov
NR 24
TC 9
Z9 9
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD JAN 8
PY 2015
VL 10
AR 4
DI 10.1186/s13012-014-0200-2
PG 10
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA CA8PT
UT WOS:000349184100001
PM 25567702
ER
PT J
AU Ahn, M
Han, YH
Park, JE
Kim, S
Lee, WC
Lee, SJ
Gunasekaran, P
Cheong, C
Shin, SY
Kim, HY
Ryu, EK
Murugan, RN
Kim, NH
Bang, JK
AF Ahn, Mija
Han, Young-Hyun
Park, Jung-Eun
Kim, Sungmin
Lee, Woo Cheol
Lee, Soo Jae
Gunasekaran, Pethaiah
Cheong, Chaejoon
Shin, Song Yub, Sr.
Kim, Hye-Yeon
Ryu, Eun Kyung
Murugan, Ravichandran N.
Kim, Nam-Hyung
Bang, Jeong Kyu
TI A New Class of Peptidomimetics Targeting the Polo-Box Domain of
Polo-Like Kinase 1
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID INHIBITORS; BINDING; DESIGN
AB Recent progress in the development of peptide-derived Polo-like kinase (Plk1) polo-box domain (PBD) inhibitors has led to the synthesis of multiple peptide ligands with high binding affinity and selectivity. However, few systematic analyses have been conducted to identify key Plk1 residues and characterize their interactions with potent Plk1 peptide inhibitors. We performed systematic deletion analysis using the most potent 4j peptide and studied N-terminal capping of the minimal peptide with diverse organic moieties, leading to the identification of the peptidomimetic 8 (AB-103) series with high binding affinity and selectivity. To evaluate the bioavailability of short peptidomimetic ligands, PEGylated 8 series were synthesized and incubated with HeLa cells to test for cellular uptake, antiproliferative activity, and Plk1 kinase inhibition. Finally, crystallographic studies of the Plk1 PBD in complex with peptidomimetics 8 and 22 (AB-103-5) revealed the presence of two hydrogen bond interactions responsible for their high binding affinity and selectivity.
C1 [Ahn, Mija; Kim, Sungmin; Lee, Woo Cheol; Cheong, Chaejoon; Kim, Hye-Yeon; Ryu, Eun Kyung; Murugan, Ravichandran N.; Bang, Jeong Kyu] Korea Basic Sci Inst, Div Magnet Resonance, Chungbuk 363883, Cheongwon, South Korea.
[Han, Young-Hyun; Gunasekaran, Pethaiah; Kim, Nam-Hyung] Chungbuk Natl Univ, Dept Anim Sci, Mol Embryol Lab, Cheongju 361763, Chungbuk, South Korea.
[Park, Jung-Eun] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lee, Soo Jae] Chungbuk Natl Univ, Coll Pharm, Cheongju 361763, Chungbuk, South Korea.
[Shin, Song Yub, Sr.] Chosun Univ, Grad Sch, Dept Biomat, Kwangju 501759, South Korea.
[Shin, Song Yub, Sr.] Chosun Univ, Sch Med, Dept Cellular & Mol Med, Kwangju 501759, South Korea.
RP Bang, JK (reprint author), Korea Basic Sci Inst, Div Magnet Resonance, 804-1 Yangcheong Ri, Chungbuk 363883, Cheongwon, South Korea.
EM bangjk@kbsi.re.kr
FU Korea Basic Science Institute's Research Program [T34418];
Next-Generation BioGreen 21 Program, Rural Development Administration
[PJ009594]
FX This work was supported by the Korea Basic Science Institute's Research
Program grant T34418 (J.K.B.) and the Next-Generation BioGreen 21
Program (no. PJ009594), Rural Development Administration (NHK).
NR 20
TC 12
Z9 13
U1 0
U2 16
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 JAN 8
PY 2015
VL 58
IS 1
SI SI
BP 294
EP 304
DI 10.1021/jm501147g
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AY7MH
UT WOS:000347743700019
PM 25347203
ER
PT J
AU Marchetti, F
Bishop, J
Gingerich, J
Wyrobek, AJ
AF Marchetti, Francesco
Bishop, Jack
Gingerich, John
Wyrobek, Andrew J.
TI Meiotic interstrand DNA damage escapes paternal repair and causes
chromosomal aberrations in the zygote by maternal misrepair
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CROSS-LINK REPAIR; NITROGEN MUSTARDS; TOPOISOMERASE-II; MOUSE ZYGOTES;
MUTATIONS; MELPHALAN; ABNORMALITIES; CHROMATIN; CANCER; SPERM
AB De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction. We report that treatment of male mice with melphalan (MLP), a bifunctional alkylating agent widely used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development. After fertilization, unrepaired sperm DNA lesions are mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally abnormal offspring. These findings highlight the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus.
C1 [Marchetti, Francesco; Gingerich, John] Hlth Canada, Environm Hlth Sci Res Bur, Ottawa, ON K1A 0K9, Canada.
[Marchetti, Francesco; Wyrobek, Andrew J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Marchetti, Francesco; Wyrobek, Andrew J.] Lawrence Livermore Natl Lab, Dept Biosci, Livermore, CA 94550 USA.
[Bishop, Jack] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Marchetti, F (reprint author), Hlth Canada, Environm Hlth Sci Res Bur, Ottawa, ON K1A 0K9, Canada.
EM Francesco.marchetti@hc-sc.gc.ca
OI Marchetti, Francesco/0000-0002-9435-4867
FU National Institute of Environmental Health Sciences through a National
Institute of Environmental Health Sciences/Department of Energy
Interagency Agreement [Y01-ES-102-00]; Canadian Regulatory System for
Biotechnology; US Department of Energy by the Lawrence Livermore
National Laboratory [W-7405-END-48]; Lawrence Berkeley National
Laboratory [DE-AC02-05CH11231]
FX This work was funded by the National Institute of Environmental Health
Sciences through a National Institute of Environmental Health
Sciences/Department of Energy Interagency Agreement (Y01-ES-102-00) and
the Canadian Regulatory System for Biotechnology. Work conducted in part
under the auspices of the US Department of Energy by the Lawrence
Livermore National Laboratory through contract W-7405-END-48 and by the
Lawrence Berkeley National Laboratory under contract DE-AC02-05CH11231.
We thank Debbie Cabreros for help with the CT8 assay.
NR 51
TC 7
Z9 8
U1 2
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 JAN 8
PY 2015
VL 5
AR 7689
DI 10.1038/srep07689
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY8LF
UT WOS:000347804300022
PM 25567288
ER
PT J
AU Zarin, DA
Tse, T
Sheehan, J
AF Zarin, Deborah A.
Tse, Tony
Sheehan, Jerry
TI The Proposed Rule for US Clinical Trial Registration and Results
Submission
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PUBLICATION
C1 [Zarin, Deborah A.; Tse, Tony; Sheehan, Jerry] NIH, Natl Lib Med, US Dept HHS, Bethesda, MD 20892 USA.
RP Zarin, DA (reprint author), NIH, Natl Lib Med, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural Research Program of the National Library of Medicine,
National Institutes of Health
FX Supported in part by the Intramural Research Program of the National
Library of Medicine, National Institutes of Health.
NR 22
TC 23
Z9 24
U1 1
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 JAN 8
PY 2015
VL 372
IS 2
BP 174
EP 180
DI 10.1056/NEJMsr1414226
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AY2UA
UT WOS:000347443300014
PM 25539444
ER
PT J
AU Cunningham, LL
Tucci, DL
AF Cunningham, Lisa L.
Tucci, Debara L.
TI Restoring Synaptic Connections in the Inner Ear after Noise Damage
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Cunningham, Lisa L.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA.
[Tucci, Debara L.] Duke Univ Med Ctr, Dept Otolaryngol Head & Neck Surg, Durham, NC USA.
RP Cunningham, LL (reprint author), Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA.
NR 4
TC 4
Z9 4
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 JAN 8
PY 2015
VL 372
IS 2
BP 181
EP 182
DI 10.1056/NEJMcibr1413201
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AY2UA
UT WOS:000347443300015
PM 25564901
ER
PT J
AU Pepper, DJ
AF Pepper, Dominique J.
TI Goal-Directed Resuscitation in Septic Shock
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 NIH, Bethesda, MD 20892 USA.
RP Pepper, DJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dominiquepepper@gmail.com
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 8
PY 2015
VL 372
IS 2
BP 190
EP 190
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AY2UA
UT WOS:000347443300022
PM 25564909
ER
PT J
AU Lin, A
Clasen, L
Lee, NR
Wallace, GL
Lalonde, F
Blumenthal, J
Giedd, JN
Raznahan, A
AF Lin, Amy
Clasen, Liv
Lee, Nancy Raitano
Wallace, Gregory L.
Lalonde, Francois
Blumenthal, Jonathan
Giedd, Jay N.
Raznahan, Armin
TI Mapping the Stability of Human Brain Asymmetry across Five
Sex-Chromosome Aneuploidies
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE asymmetry; brain; neurodevelopment; sex chromosome
ID CORTICAL THICKNESS; CEREBRAL ASYMMETRY; X-CHROMOSOME; GENE-EXPRESSION;
HANDEDNESS; CHILDREN; CORTEX; LANGUAGE; SCHIZOPHRENIA; ASSOCIATION
AB The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY(n = 26), XXYY(n = 20), and XXXXY(n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.
C1 [Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L.; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N.; Raznahan, Armin] NIMH, Sect Brain Imaging, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Wallace, Gregory L.] George Washington Univ, Dept Speech & Hearing Sci, Washington, DC 20052 USA.
RP Raznahan, A (reprint author), Bldg 10,Room 4C108,10 Ctr Dr, Bethesda, MD 20892 USA.
EM raznahana@mail.nih.gov
RI Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016;
OI Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713; Wallace,
Gregory/0000-0003-0329-5054
FU National Institutes of Health Intramural Research Program
FX This work was funded by the National Institutes of Health Intramural
Research Program. We thank the participants and families who took part
in this study. We are also grateful to Dr Stephen J. Gotts of the NIH
IRP Laboratory of Brain and Cognition for his advice on data modeling
methods.
NR 45
TC 3
Z9 3
U1 5
U2 21
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 7
PY 2015
VL 35
IS 1
BP 140
EP 145
DI 10.1523/JNEUROSCI.3489-14.2015
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA CB1SB
UT WOS:000349407200012
PM 25568109
ER
PT J
AU Scaramuzzino, C
Casci, I
Parodi, S
Lievens, PMJ
Polanco, MJ
Milioto, C
Chivet, M
Monaghan, J
Mishra, A
Badders, N
Aggarwal, T
Grunseich, C
Sambataro, F
Basso, M
Fackelmayer, FO
Taylor, JP
Pandey, UB
Pennuto, M
AF Scaramuzzino, Chiara
Casci, Ian
Parodi, Sara
Lievens, Patricia M. J.
Polanco, Maria J.
Milioto, Carmelo
Chivet, Mathilde
Monaghan, John
Mishra, Ashutosh
Badders, Nisha
Aggarwal, Tanya
Grunseich, Christopher
Sambataro, Fabio
Basso, Manuela
Fackelmayer, Frank O.
Taylor, J. Paul
Pandey, Udai Bhan
Pennuto, Maria
TI Protein Arginine Methyltransferase 6 Enhances Polyglutamine-Expanded
Androgen Receptor Function and Toxicity in Spinal and Bulbar Muscular
Atrophy
SO NEURON
LA English
DT Article
ID TRANSGENIC MOUSE MODEL; IN-VIVO; DROSOPHILA MODEL; NATIVE FUNCTIONS;
INDUCED DISEASE; METHYLATION; NEURODEGENERATION; PRMT6; EXPRESSION;
COACTIVATOR
AB Polyglutamine expansion in androgen receptor (AR) is responsible for spinobulbar muscular atrophy (SBMA) that leads to selective loss of lower motor neurons. Using SBMA as a model, we explored the relationship between protein structure/function and neurodegeneration in polyglutamine diseases. We show here that protein arginine methyltransferase 6 (PRMT6) is a specific co-activator of normal and mutant AR and that the interaction of PRMT6 with AR is significantly enhanced in the AR mutant. AR and PRMT6 interaction occurs through the PRMT6 steroid receptor interaction motif, LXXLL, and the AR activating function 2 surface. AR transactivation requires PRMT6 catalytic activity and involves methylation of arginine residues at Akt consensus site motifs, which is mutually exclusive with serine phosphorylation by Akt. The enhanced interaction of PRMT6 and mutant AR leads to neurodegeneration in cell and fly models of SBMA. These findings demonstrate a direct role of arginine methylation in polyglutamine disease pathogenesis.
C1 [Scaramuzzino, Chiara; Parodi, Sara; Lievens, Patricia M. J.; Polanco, Maria J.; Milioto, Carmelo; Aggarwal, Tanya; Pennuto, Maria] Ist Italiano Tecnologia, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy.
[Casci, Ian; Monaghan, John; Pandey, Udai Bhan] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15261 USA.
[Casci, Ian] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Parodi, Sara; Grunseich, Christopher] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Lievens, Patricia M. J.] Univ Verona, Sect Biol & Genet, Dept Life & Reprod Sci, I-37134 Verona, Italy.
[Polanco, Maria J.; Milioto, Carmelo; Chivet, Mathilde; Pennuto, Maria] Univ Trento, Dulbecco Telethon Inst Lab Neurodegenerat Dis, Ctr Integrat Biol CIBIO, I-38123 Trento, Italy.
[Mishra, Ashutosh] St Jude Childrens Res Hosp, St Jude Prote Facil, Memphis, TN 38105 USA.
[Badders, Nisha; Taylor, J. Paul] St Jude Childrens Res Hosp, Dept Cell & Mol Biol, Memphis, TN 38105 USA.
[Sambataro, Fabio] Ist Italiano Tecnol UniPR, Brain Ctr Motor & Social Cognit, I-43100 Parma, Italy.
[Basso, Manuela] Univ Trento, Ctr Integrat Biol CIBIO, Lab Transcript Neurobiol, I-38123 Trento, Italy.
[Fackelmayer, Frank O.] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Dept Biomed Res, Lab Epigenet & Chromosome Biol, Ioannina 45110, Greece.
RP Pennuto, M (reprint author), Ist Italiano Tecnologia, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy.
EM maria.pennuto@unitn.it
RI Sambataro, Fabio/E-3426-2010;
OI Sambataro, Fabio/0000-0003-2102-416X; Pennuto, Maria/0000-0001-8634-0767
FU Telethon-Italy [GGP10037, TCP12013]; Marie-Curie Reintegration Grants
[FP7-256448, FP7-276981]; Muscular Dystrophy Association [92333];
National Institutes of Health (NIH) [1R01NS081303-01A1]; ALS
Association; Robert Packard Center for ALS at Johns Hopkins; NINDS-NIH;
EU Cost Action [TD0905]; Boehringer Ingelheim; Marie Curie International
Outgoing Fellowships [PIO-GA-2011-300723]
FX We thank Dr. Stephane Richard (McGill University) for scientific
discussion and comments and Dr. Ernesto Guccione (Institute of Molecular
and Cell Biology, Singapore) for providing us with the lentiviral
constructs for shRNA against PRMT6. We thank Drs. Massimo Pizzato and
Serena Ziglio for assistance with lentivirus production. This work was
supported by Telethon-Italy (GGP10037 and TCP12013 to M.P.), Marie-Curie
Reintegration Grants (FP7-256448 to M.P. and FP7-276981 to F.S.),
Muscular Dystrophy Association (92333 to M.P.), National Institutes of
Health (NIH, 1R01NS081303-01A1 to U.B.P.), the ALS Association and the
Robert Packard Center for ALS at Johns Hopkins (to U.B.P.), intramural
funds from NINDS-NIH, and EU Cost Action TD0905 "Epigenetics: From Bench
to Bedside." C.S. was supported by a Boehringer Ingelheim travel grant,
and S.P. by Marie Curie International Outgoing Fellowships
(PIO-GA-2011-300723).
NR 58
TC 20
Z9 20
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JAN 7
PY 2015
VL 85
IS 1
BP 88
EP 100
DI 10.1016/j.neuron.2014.12.031
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AZ5YS
UT WOS:000348295100011
PM 25569348
ER
PT J
AU Del Valle-Pinero, AY
Sherwin, LB
Anderson, EM
Caudle, RM
Henderson, WA
AF Del Valle-Pinero, Arseima Y.
Sherwin, LeeAnne B.
Anderson, Ethan M.
Caudle, Robert M.
Henderson, Wendy A.
TI Altered vasoactive intestinal peptides expression in irritable bowel
syndrome patients and rats with trinitrobenzene sulfonic acid-induced
colitis
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Irritable bowel syndrome; Vasoactive intestinal peptide; Trinitrobenzene
sulfonic acid; Gene expression; PCR arrays
ID CYCLASE-ACTIVATING POLYPEPTIDE; NOXIOUS VISCERAL STIMULUS; TNBS-INDUCED
COLITIS; ULCERATIVE-COLITIS; COLONIC MOTILITY; HYPERSENSITIVITY;
DISEASE; IBS; DISORDERS; PAIN
AB AIM: To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis.
METHODS: The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naive and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array.
RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 +/- 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naive rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naive animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with controls (P = 0.193).
CONCLUSION: Alterations in VIP expression may play a role in IBS. Therefore, a better understanding of the physiology of VIP could lead to new therapeutics.
C1 [Del Valle-Pinero, Arseima Y.; Sherwin, LeeAnne B.; Henderson, Wendy A.] NINR, Digest Disorders Unit, Biobehav Branch, Div Intramural Res,NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Del Valle-Pinero, Arseima Y.; Anderson, Ethan M.; Caudle, Robert M.] Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL 32610 USA.
[Caudle, Robert M.] Univ Florida, Coll Dent, Dept Oral & Maxillofacial Surg, Gainesville, FL 32610 USA.
RP Henderson, WA (reprint author), NINR, Digest Disorders Unit, Biobehav Branch, Div Intramural Res,NIH,US Dept HHS, Bethesda, MD 20892 USA.
EM hendersw@mail.nih.gov
OI Henderson, Wendy/0000-0003-3924-7118
FU National Institutes of Health [NS045614]; National Institute of Diabetes
and Digestive and Kidney Diseases [1F31 DK083165-01A1]; Division of
Intramural Research, National Institute of Nursing Research
[1ZIANR000018-01-05]; Intramural Training Award
FX Supported by National Institutes of Health grant, No. NS045614 and the
Ruth L. Kirschstein National Research Service Award, No. 1F31
DK083165-01A1 from the National Institute of Diabetes and Digestive and
Kidney Diseases; Division of Intramural Research, National Institute of
Nursing Research, No. 1ZIANR000018-01-05 to Henderson WA and Intramural
Training Award to Del Valle-Pinero AY and Sherwin LB
NR 41
TC 2
Z9 2
U1 1
U2 7
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1007-9327
EI 2219-2840
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD JAN 7
PY 2015
VL 21
IS 1
BP 155
EP 163
DI 10.3748/wjg.v21.i1.155
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AY3CG
UT WOS:000347461500014
PM 25574088
ER
PT J
AU Kubinak, JL
Cornwall, DH
Hasenkrug, KJ
Adler, FR
Potts, WK
AF Kubinak, Jason L.
Cornwall, Douglas H.
Hasenkrug, Kim J.
Adler, Frederick R.
Potts, Wayne K.
TI Serial infection of diverse host (Mus) genotypes rapidly impedes
pathogen fitness and virulence
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE virulence evolution; endangered species; livestock;
sex-against-virulence; genetic diversity; experimental evolution
ID EXPERIMENTAL VIRAL EVOLUTION; FOCUS-FORMING VIRUS; GENETIC DIVERSITY;
FRIEND-VIRUS; PARASITE INTERACTIONS; MULTILINE CULTIVARS; LABORATORY
MOUSE; DISEASE SPREAD; TRADE-OFFS; RESISTANCE
AB Reduced genetic variation among hosts may favour the emergence of virulent infectious diseases by enhancing pathogen replication and its associated virulence due to adaptation to a limited set of host genotypes. Here, we test this hypothesis using experimental evolution of a mouse-specific retroviral pathogen, Friend virus (FV) complex. We demonstrate rapid fitness (i.e. viral titre) and virulence increases when FV complex serially infects a series of inbred mice representing the same genotype, but not when infecting a diverse array of inbred mouse strains modelling the diversity in natural host populations. Additionally, a single infection of a different host genotype was sufficient to constrain the emergence of a high fitness/high virulence FV complex phenotype in these experiments. The potent inhibition of viral fitness and virulence was associated with an observed loss of the defective retroviral genome (spleen focus-forming virus), whose presence exacerbates infection and drives disease in susceptible mice. Results from our experiments provide an important first step in understanding how genetic variation among vertebrate hosts influences pathogen evolution and suggests that serial exposure to different genotypes within a single host species may act as a constraint on pathogen adaptation that prohibits the emergence of more virulent infections. From a practical perspective, these results have implications for low-diversity host populations such as endangered species and domestic animals.
C1 [Kubinak, Jason L.] Univ Utah, Sch Med, Div Microbiol & Immunol, Dept Pathol, Salt Lake City, UT 84112 USA.
[Cornwall, Douglas H.; Adler, Frederick R.; Potts, Wayne K.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
[Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Adler, Frederick R.] Univ Utah, Dept Math, Salt Lake City, UT 84112 USA.
RP Kubinak, JL (reprint author), Univ Utah, Sch Med, Div Microbiol & Immunol, Dept Pathol, 15 North Med Dr East, Salt Lake City, UT 84112 USA.
EM jason.kubinak@path.utah.edu
FU National Science Foundation [DEB 0918969]; National Institute of Health
[R01-GM109500]; National Science Foundation Doctoral Dissertation
Improvement grant [DEB 0910052]; National Institute of Allergic and
Infectious Diseases [T32AI055434]; National Science Foundation
Educational Outreach grant [DGE 08-41233]
FX This work was supported by National Science Foundation Grant (DEB
0918969) and a National Institute of Health grant (R01-GM109500) to W.
K. P. and F. R. A. J.L.K. was supported by a National Science Foundation
Doctoral Dissertation Improvement grant (DEB 0910052) and a National
Institute of Allergic and Infectious Diseases training grant
(T32AI055434). J.L.K. was also supported by a National Science
Foundation Educational Outreach grant (DGE 08-41233).
NR 57
TC 0
Z9 0
U1 1
U2 28
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD JAN 7
PY 2015
VL 282
IS 1798
AR 20141568
DI 10.1098/rspb.2014.1568
PG 9
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA AS9YT
UT WOS:000344595000003
PM 25392466
ER
PT J
AU Wilky, BA
Rudek, MA
Ahmed, S
Laheru, DA
Cosgrove, D
Donehower, RC
Nelkin, B
Ball, D
Doyle, LA
Chen, H
Ye, X
Bigley, G
Womack, C
Azad, NS
AF Wilky, B. A.
Rudek, M. A.
Ahmed, S.
Laheru, D. A.
Cosgrove, D.
Donehower, R. C.
Nelkin, B.
Ball, D.
Doyle, L. A.
Chen, H.
Ye, X.
Bigley, G.
Womack, C.
Azad, N. S.
TI A phase I trial of vertical inhibition of IGF signalling using
cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2
inhibitor, in advanced solid tumours
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE IGF-1R; MEK; IGF; BRAF; clinical trial
ID KINASE KINASE-1/2 INHIBITOR; MUTANT LUNG-CANCER; HEMATOPOIETIC-CELLS;
AZD6244 ARRY-142886; OPEN-LABEL; RECEPTOR; GROWTH; RESISTANCE; PATHWAYS;
PHOSPHORYLATION
AB Background: We completed a phase I clinical trial to test the safety and toxicity of combined treatment with cixutumumab (anti-IGF-1R antibody) and selumetinib (MEK 1/2 inhibitor).
Methods: Patients with advanced solid tumours, refractory to standard therapy received selumetinib hydrogen sulphate capsules orally twice daily, and cixutumumab intravenously on days 1 and 15 of each 28-day cycle. The study used a 3+3 design, with a dose-finding cohort followed by an expansion cohort at the maximally tolerated dose that included pharmacokinetic and pharmacodynamic correlative studies.
Results: Thirty patients were enrolled, with 16 in the dose-finding cohort and 14 in the expansion cohort. Grade 3 or greater toxicities included nausea and vomiting, anaemia, CVA, hypertension, hyperglycaemia, and ophthalmic symptoms. The maximally tolerated combination dose was 50 mg twice daily of selumetinib and 12 mg kg(-1) every 2 weeks of cixutumumab. Two patients achieved a partial response (one unconfirmed), including a patient with BRAF wild-type thyroid carcinoma, and a patient with squamous cell carcinoma of the tongue, and six patients achieved time to progression of 46 months, including patients with thyroid carcinoma, colorectal carcinoma, and basal cell carcinoma. Comparison of pre- and on-treatment biopsies showed significant suppression of pERK and pS6 activity with treatment.
Conclusions: Our study of anti-IGF-1R antibody cixutumumab and MEK 1/2 inhibitor selumetinib showed that the combination is safe and well-tolerated at these doses, with preliminary evidence of clinical benefit and pharmacodynamic evidence of target inhibition.
C1 [Wilky, B. A.; Rudek, M. A.; Ahmed, S.; Laheru, D. A.; Cosgrove, D.; Donehower, R. C.; Nelkin, B.; Ball, D.; Ye, X.; Azad, N. S.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA.
[Doyle, L. A.; Chen, H.] NCI, Bethesda, MD 20892 USA.
[Bigley, G.; Womack, C.] AstraZeneca, Oncol iMed, Macclesfield SK10 4TG, Cheshire, England.
RP Azad, NS (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, 1650 Orleans St, Baltimore, MD 21231 USA.
EM nazad2@jhmi.edu
FU NIH [U01 CA070095]; NCI ACTNOW [P30 CA006973]; AstraZeneca
FX This work is supported by NIH grants U01 CA070095, with added support
from NCI ACTNOW, P30 CA006973, and AstraZeneca.
NR 36
TC 14
Z9 15
U1 1
U2 2
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 JAN 6
PY 2015
VL 112
IS 1
BP 24
EP 31
DI 10.1038/bjc.2014.515
PG 8
WC Oncology
SC Oncology
GA AZ5SW
UT WOS:000348280900006
PM 25268371
ER
PT J
AU Hauptmann, M
Fossa, SD
Stovall, M
van Leeuwen, FE
Johannesen, TB
Rajaraman, P
Gilbert, ES
Smith, SA
Weathers, RE
Aleman, BMP
Andersson, M
Curtis, RE
Dores, GM
Fraumeni, JF
Hall, P
Holowaty, EJ
Joensuu, H
Kaijser, M
Kleinerman, RA
Langmark, F
Lynch, CF
Pukkala, E
Storm, HH
Vaalavirta, L
van den Belt-Dusebout, AW
Travis, LB
Morton, LM
AF Hauptmann, M.
Fossa, S. D.
Stovall, M.
van Leeuwen, F. E.
Johannesen, T. B.
Rajaraman, P.
Gilbert, E. S.
Smith, S. A.
Weathers, R. E.
Aleman, B. M. P.
Andersson, M.
Curtis, R. E.
Dores, G. M.
Fraumeni, J. F.
Hall, P.
Holowaty, E. J.
Joensuu, H.
Kaijser, M.
Kleinerman, R. A.
Langmark, F.
Lynch, C. F.
Pukkala, E.
Storm, H. H.
Vaalavirta, L.
van den Belt-Dusebout, A. W.
Travis, L. B.
Morton, L. M.
TI Increased stomach cancer risk following radiotherapy for testicular
cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE stomach cancer; testicular cancer; radiotherapy; chemotherapy
ID LONG-TERM SURVIVORS; 2ND MALIGNANT NEOPLASMS; HODGKINS-DISEASE;
GASTROINTESTINAL CANCER; CARDIOVASCULAR-DISEASE; CHILDHOOD-CANCER;
SEMINOMA; CHEMOTHERAPY; MORTALITY; AGE
AB Background: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse.
Methods: In a cohort of 22 269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression.
Results: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend <0.001), with an OR of 20.5 (3.7-114.3) for >= 50.0 Gy compared with <10 Gy. Radiation-related risks remained elevated >= 20 years after exposure (P<0.001). Risk after any chemotherapy was not elevated (OR = 1.1; 95% CI 0.5-2.5; 14 cases and 23 controls).
Conclusions: Radiotherapy for TC involving parts of the stomach increased gastric cancer risk for several decades, with the highest risks after stomach doses of >= 30 Gy. Clinicians should be aware of these excesses when previously irradiated TC survivors present with gastrointestinal symptoms and when any radiotherapy is considered in newly diagnosed TC patients.
C1 [Hauptmann, M.; van Leeuwen, F. E.; Aleman, B. M. P.; van den Belt-Dusebout, A. W.] Netherlands Canc Inst, Dept Epidemiol & Biostat, NL-1066 CX Amsterdam, Netherlands.
[Fossa, S. D.] Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
[Fossa, S. D.] Univ Oslo, Oslo, Norway.
[Stovall, M.; Smith, S. A.; Weathers, R. E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Johannesen, T. B.; Langmark, F.] Canc Registry Norway, Oslo, Norway.
[Rajaraman, P.; Gilbert, E. S.; Curtis, R. E.; Dores, G. M.; Fraumeni, J. F.; Kleinerman, R. A.; Morton, L. M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Aleman, B. M. P.] Netherlands Canc Inst, Dept Radiat Oncol, Amsterdam, Netherlands.
[Andersson, M.] Copenhagen Univ Hosp, Dept Oncol, Copenhagen, Denmark.
[Dores, G. M.] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA.
[Hall, P.; Kaijser, M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hall, P.] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
[Holowaty, E. J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Joensuu, H.; Vaalavirta, L.] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Lynch, C. F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Pukkala, E.] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland.
[Pukkala, E.] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland.
[Storm, H. H.] Danish Canc Soc, Copenhagen, Denmark.
[Travis, L. B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
RP Hauptmann, M (reprint author), Netherlands Canc Inst, Dept Epidemiol & Biostat, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM m.hauptmann@nki.nl
OI Storm, Hans/0000-0001-7223-8198; Kleinerman, Ruth/0000-0001-7415-2478;
Joensuu, Heikki/0000-0003-0281-2507
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health, Department of Health and Human Services and
National Cancer Institute [N01-CP-31157]; Danish Cancer Society,
Copenhagen, Denmark [N01-CP-31019]; Finnish Cancer Registry, Helsinki,
Finland [N01-CP-31154]; Information Management Services, Inc., Silver
Spring, USA [N01-CP-31003]; Karolinska Institute, Stockholm, Sweden
[N01-CP-31156]; University of Iowa, Iowa City, USA [N01-CP-31155];
University of Texas MD Anderson Cancer Center, Houston, USA
[N02-CP-55503]; Westat, Inc., Rockville, USA [N02-CP-31136]; Lance
Armstrong Foundation; Dutch Cancer Society [NKI 04-3068]; National
Cancer Institute [1R01 CA 157823-01A1]
FX We thank Diane Fuchs, Janet Lawler-Heavner and their staff at Westat,
Inc. (Rockville, MD, USA) for administrative assistance in conducting
the field studies, and Jeremy Miller (Information Management Services,
Silver Spring, MD, USA) for computer programming support. This work was
supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services and National Cancer Institute contracts to Cancer Care Ontario,
Toronto, Canada (N01-CP-31157); Danish Cancer Society, Copenhagen,
Denmark (N01-CP-31019); Finnish Cancer Registry, Helsinki, Finland
(N01-CP-31154); Information Management Services, Inc., Silver Spring,
USA (N01-CP-31003); Karolinska Institute, Stockholm, Sweden
(N01-CP-31156); University of Iowa, Iowa City, USA (N01-CP-31155); The
University of Texas MD Anderson Cancer Center, Houston, USA
(N02-CP-55503); and Westat, Inc., Rockville, USA (N02-CP-31136). The
Dutch study was also supported by the Lance Armstrong Foundation and the
Dutch Cancer Society (Grant No. NKI 04-3068). Dr Travis was supported by
National Cancer Institute 1R01 CA 157823-01A1.
NR 49
TC 10
Z9 10
U1 0
U2 1
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 JAN 6
PY 2015
VL 112
IS 1
BP 44
EP 51
DI 10.1038/bjc.2014.552
PG 8
WC Oncology
SC Oncology
GA AZ5SW
UT WOS:000348280900009
PM 25349972
ER
PT J
AU Agarwal, S
Hanna, J
Sherman, ME
Figueroa, J
Rimm, DL
AF Agarwal, Seema
Hanna, J.
Sherman, M. E.
Figueroa, J.
Rimm, D. L.
TI Quantitative assessment of miR34a as an independent prognostic marker in
breast cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE miR34a; breast cancer; qISH
ID IN-SITU HYBRIDIZATION; TUMOR-SUPPRESSOR; TISSUE MICROARRAYS; PROTEIN
EXPRESSION; FIXED TISSUES; MICRORNAS; MIR-34A; CELLS; METASTASIS;
INVASION
AB Background: Aberrant expression of microRNAs (miRNAs) is associated with cancer progression, initiation and metastasis. MiR34a is a miRNA that has been previously described as a tumour suppressor. Herein, we assess the expression of miR34a in three independent breast cancer cohorts using a quantitative in situ hybridisation assay (qISH) and determined its association with disease-specific death in breast cancer.
Methods: The qISH method was applied to three independent primary breast cancer cohorts (Cohort 1 with 461, Cohort 2 with 279 and Cohort 3 with 795 patients) using 50 and 30 double DIG-labelled LNA-modified probe against miR34a using the protocol described previously. Level of expression measured as automated quantitative analysis (AQUA) score for miR34a was determined for each patient and assessed for association with risk of disease-specific death. An optimal cutpoint was determined using the X-tile software for disease-specific survival in Cohort 1 and this cutpoint was then applied to the other two cohorts after median normalisation of AQUA scores.
Results: Loss of miR34a is associated with poor outcome in three independent breast cancer cohorts (uncorrected log- rank P = 0.0188 for Cohort 1, log-rank P = 0.0024 for Cohort 2 and log-rank P = 0.0455 for Cohort 3). In all three cohorts, loss of miR34a is able to stratify patients with poor disease-specific survival among node-negative patients, but not in node-positive population. Multivariate Cox proportional hazards analysis in Cohort 1 (P = 0.0381) and Cohort 2 (P = 0.0468) revealed that loss of miR34a is associated with poor outcome, independent of age, node status, receptor status and tumour size.
Conclusion: Loss of the tumour suppressor, miR34a, identifies a subgroup of breast cancer patients with poor disease-specific survival. This study is consistent with the well-established preclinical observations for miR34a as a tumour suppressor and suggests that miR34a may have future value as a biomarker in breast cancer.
C1 [Agarwal, Seema; Hanna, J.; Rimm, D. L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Sherman, M. E.; Figueroa, J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Agarwal, S (reprint author), Georgetown Univ, Dept Pathol, Med Ctr, Washington, DC 20057 USA.
EM sa1137@georgetown.edu; david.rimm@yale.edu
OI Hanna, Jason/0000-0001-7253-7964
FU Cure Investigator Initiated Research
FX This work was supported in part by a Susan G Komen for the Cure
Investigator Initiated Research Grant to DLR. We thank Pei Chao and
Michael Stagner from Information Management Services (Silver Spring, MD)
for data management support; the participants, physicians, pathologists,
nurses and interviewers from participating centres in Poland for their
efforts during field work; and Drs Montserrat Garcia-Closas, Louise
Brinton, Jolanta Lissowska, B Peplonska for their contributions to the
PBCS study design. We also thank Stephen Hewitt for TMA construction.
NR 43
TC 4
Z9 5
U1 1
U2 2
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 JAN 6
PY 2015
VL 112
IS 1
BP 61
EP 68
DI 10.1038/bjc.2014.573
PG 8
WC Oncology
SC Oncology
GA AZ5SW
UT WOS:000348280900011
PM 25474246
ER
PT J
AU Journy, N
Rehel, JL
Le Pointe, HD
Lee, C
Brisse, H
Chateil, JF
Caer-Lorho, S
Laurier, D
Bernier, MO
AF Journy, N.
Rehel, J-L
Le Pointe, H. Ducou
Lee, C.
Brisse, H.
Chateil, J-F
Caer-Lorho, S.
Laurier, D.
Bernier, M-O
TI Are the studies on cancer risk from CT scans biased by indication?
Elements of answer from a large-scale cohort study in France
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE cancer risk; computed tomography; radiation protection; radiology;
paediatrics; indication bias; cohort study
ID ATOMIC-BOMB SURVIVORS; RADIATION-EXPOSURE; COMPUTED-TOMOGRAPHY;
IONIZING-RADIATION; CHILDHOOD-CANCER; SUBSEQUENT RISK; PEDIATRIC CT;
BRAIN-TUMORS; CHILDREN; LEUKEMIA
AB Background: Recent epidemiological results suggested an increase of cancer risk after receiving computed tomography (CT) scans in childhood or adolescence. Their interpretation is questioned due to the lack of information about the reasons for examination. Our objective was to estimate the cancer risk related to childhood CT scans, and examine how cancer-predisposing factors (PFs) affect assessment of the radiation-related risk.
Methods: The cohort included 67 274 children who had a first scan before the age of 10 years from 2000 to 2010 in 23 French departments. Cumulative X-rays doses were estimated from radiology protocols. Cancer incidence was retrieved through the national registry of childhood cancers; PF from discharge diagnoses.
Results: During a mean follow-up of 4 years, 27 cases of tumours of the central nervous system, 25 of leukaemia and 21 of lymphoma were diagnosed; 32% of them among children with PF. Specific patterns of CT exposures were observed according to PFs. Adjustment for PF reduced the excess risk estimates related to cumulative doses from CT scans. No significant excess risk was observed in relation to CT exposures.
Conclusions: This study suggests that the indication for examinations, whether suspected cancer or PF management, should be considered to avoid overestimation of the cancer risks associated with CT scans.
C1 [Journy, N.; Caer-Lorho, S.; Laurier, D.; Bernier, M-O] Inst Radiol Protect & Nucl Safety, Lab Epidemiol, F-92262 Fontenay Aux Roses, France.
[Rehel, J-L] Inst Radiol Protect & Nucl Safety, Med Radiat Protect Expertise Unit, F-92262 Fontenay Aux Roses, France.
[Le Pointe, H. Ducou] Trousseau Univ Hosp, Dept Paediat Radiol, F-75012 Paris, France.
[Lee, C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Brisse, H.] Inst Curie, Dept Radiol, F-75005 Paris, France.
[Chateil, J-F] Pellegrin Univ Hosp, Dept Paediat Radiol, F-33000 Bordeaux, France.
RP Bernier, MO (reprint author), Inst Radiol Protect & Nucl Safety, Lab Epidemiol, BP 17, F-92262 Fontenay Aux Roses, France.
EM marie-odile.bernier@irsn.fr
RI Lee, Choonsik/C-9023-2015
OI BRISSE, Herve J./0000-0003-2794-5875; Lee, Choonsik/0000-0003-4289-9870
FU La Ligue contre le cancer [PRE09/MOB]; French National Cancer Institute
(INCa) [2011-1-PL-SHS-01-IRSN-1]; European Union's Seventh Programme
[269912-EPI-CT]
FX We are grateful to the radiologists, clinicians, physicists and
administrators working in the participating hospitals who took so much
of their time to provide us with the necessary radiology and clinical
data: N Andreu, F Clemenceau, D Loisel, B Ory, D Weil (CHU Angers), J-M
Garcier, J Guersen, S Mangin (CHU Clermont-Ferrand), S Baron, J
Charbonnier, C Gaborit, D Sirinelli (CHU Tours), J-M Chave, E Chirpaz, O
Fels, JF Rouanet (CHU La Reunion), N Boutry, A Bruandet, G Potier (CHU
Lille), D Defez, Perrot, M Teisseire (CHU Lyon), B Bourliere, P Petit, C
Seyler (CHU Marseille), M Saguintaah (CHU Montpellier), M Balde, F
Collignon, M-A Galloy, E Pozza, E Schmitt (CHU Nancy), B Dupas, T
Lefrancois, M Salaud, N Surer (CHU Nantes), C Barat, C Bertini, M Hajjar
(CHU Bordeaux), N Baray, M-A Perrier, H Daubert, L Froment (CHU Rouen),
S Dupont, B Giachetto, L Molinier, J Vial (CHU Toulouse), A Bouette, P
Chambert (CHU Armand Trousseau-Paris), F Brunelle (CHU
Necker-Enfants-Malades-Paris), E Dion (CHU Louis Mourier-Colombes), J
Costa, G Sebag (CHU Robert Debre - Paris), G Khalifa (CHU Saint-Vincent
de Paul-Paris), J Betout, E Maupu (APHP Siege), D Musset (CHU Antoine
Beclere-Clamart), C Adamsbaum, S Franchi, D Pariente (CHU Bicetre), N
Sellier (CHU Jean Verdier-Bondy). We also warmly thank E N'Guyen, N
Simon, B Lacour and J Clavel (Registre National des Cancers de l'Enfant)
for their valuable help in providing data about cancer diagnoses. The
research leading to these results has received funding from La Ligue
contre le cancer (PRE09/MOB), the French National Cancer Institute
(INCa) (2011-1-PL-SHS-01-IRSN-1), and the European Union's Seventh
Programme for research, technological development and demonstration
under Grant Agreement No 269912-EPI-CT: epidemiological study to
quantify risks for paediatric-computerised tomography and to optimise
doses. As the methodology for dose assessment applied for the present
study differs to this one defined within the Epi-CT project
(http://epi-ct.iarc.fr/), this paper does not necessarily reflect the
results that will be obtained in the collaborative project from the use
of French exposure data. The use of the personal data for this study was
approved by the Commission Nationale Informatique et Libertes,
responsible for enforcement of data privacy laws in France (approval ID
908354).
NR 35
TC 36
Z9 37
U1 1
U2 14
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 JAN 6
PY 2015
VL 112
IS 1
BP 185
EP 193
DI 10.1038/bjc.2014.526
PG 9
WC Oncology
SC Oncology
GA AZ5SW
UT WOS:000348280900028
PM 25314057
ER
PT J
AU Bergeron, JRC
Worrall, LJ
De, S
Sgourakis, NG
Cheung, AH
Lameignere, E
Okon, M
Wasney, GA
Baker, D
McIntosh, LP
Strynadka, NCJ
AF Bergeron, Julien R. C.
Worrall, Liam J.
De, Soumya
Sgourakis, Nikolaos G.
Cheung, Adrienne H.
Lameignere, Emilie
Okon, Mark
Wasney, Gregory A.
Baker, David
McIntosh, Lawrence P.
Strynadka, Natalie C. J.
TI The Modular Structure of the Inner-Membrane Ring Component PrgK
Facilitates Assembly of the Type III Secretion System Basal Body
SO STRUCTURE
LA English
DT Article
ID GRAM-NEGATIVE BACTERIA; NEEDLE COMPLEX; SALMONELLA; LIPOPROTEIN;
PROTEINS; DISEASE; EXPORT; HOST
AB The type III secretion system (T3SS) is a large macromolecular assembly found at the surface of many pathogenic Gram-negative bacteria. Its role is to inject toxic "effector'' proteins into the cells of infected organisms. The molecular details of the assembly of this large, multimembrane-spanning complex remain poorly understood. Here, we report structural, biochemical, and functional analyses of PrgK, an inner-membrane component of the prototypical Salmonella typhimurium T3SS. We have obtained the atomic structures of the two ring building globular domains and show that the C-terminal transmembrane helix is not essential for assembly and secretion. We also demonstrate that structural rearrangement of the two PrgK globular domains, driven by an interconnecting linker region, may promote oligomerization into ring structures. Finally, we used electron microscopy-guided symmetry modeling to propose a structural model for the intimately associated PrgH-PrgK ring interaction within the assembled basal body.
C1 [Bergeron, Julien R. C.; Worrall, Liam J.; De, Soumya; Cheung, Adrienne H.; Lameignere, Emilie; Okon, Mark; Wasney, Gregory A.; McIntosh, Lawrence P.; Strynadka, Natalie C. J.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
[Bergeron, Julien R. C.; Worrall, Liam J.; Lameignere, Emilie; Wasney, Gregory A.; Strynadka, Natalie C. J.] Univ British Columbia, Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada.
[Sgourakis, Nikolaos G.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Baker, David] Univ Washington, Dept Genome Sci, Dept Biochem, Seattle, WA 98195 USA.
[Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
[McIntosh, Lawrence P.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z3, Canada.
RP Strynadka, NCJ (reprint author), Univ British Columbia, Dept Biochem & Mol Biol, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada.
EM ncjs@mail.ubc.ca
RI Baker, David/K-8941-2012
OI Baker, David/0000-0001-7896-6217
FU Natural Sciences and Engineering Research Council of Canada; National
Research Council Canada; Canadian Institutes of Health Research;
Province of Saskatchewan; Western Economic Diversification Canada;
University of Saskatchewan; Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, NIH; Canadian
Institute of Health Research; HHMI International Scholar Program
FX We thank Samuel Miller for providing the S. typhimurium prgK- and
fliC/prgK-deletion strains. We are also grateful to Kelvin Lau, Bradford
Ross, Gerd Prenha, Matthew Solomonson, and Fred Rosell for technical
advice. X-ray diffraction data were collected at beamline 08B1-1 at the
Canadian Light Source, which is supported by the Natural Sciences and
Engineering Research Council of Canada, the National Research Council
Canada, the Canadian Institutes of Health Research, the Province of
Saskatchewan, Western Economic Diversification Canada, and the
University of Saskatchewan. Instrument support was provided by the
Canada Foundation for Innovation, the British Columbia Knowledge
Development Fund, the UBC Blusson Fund, and the Michael Smith Foundation
for Health Research. N.G.S. acknowledges funding by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases, NIH. J.R.C.B. is a MSFHR postdoctoral fellow. N.C.J.S.
is a Canada Research Chair Tier 1 in Antibiotic Discovery. This work was
supported by operating grants from the Canadian Institute of Health
Research and HHMI International Scholar Program (to N.C.J.S.).
NR 37
TC 11
Z9 11
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD JAN 6
PY 2015
VL 23
IS 1
BP 161
EP 172
DI 10.1016/j.str.2014.10.021
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AY3FI
UT WOS:000347469500020
PM 25533490
ER
PT J
AU Sgourakis, NG
Yau, WM
Qiang, W
AF Sgourakis, Nikolaos G.
Yau, Wai-Ming
Qiang, Wei
TI Modeling an In-Register, Parallel "Iowa'' A beta Fibril Structure Using
Solid-State NMR Data from Labeled Samples with Rosetta
SO STRUCTURE
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; AMYLOID PRECURSOR PROTEIN; ASP23-LYS28
SALT-BRIDGE; STRUCTURE-BASED DESIGN; X-RAY-DIFFRACTION;
ALZHEIMERS-DISEASE; EXPERIMENTAL CONSTRAINTS; ELECTRON-MICROSCOPY;
CHEMICAL-SHIFTS; CORE STRUCTURE
AB Determining the structures of amyloid fibrils is an important first step toward understanding the molecular basis of neurodegenerative diseases. For beta-amyloid (A beta) fibrils, conventional solid-state NMR structure determination using uniform labeling is limited by extensive peak overlap. We describe the characterization of a distinct structural polymorph of Ab using solid-state NMR, transmission electron microscopy (TEM), and Rosetta model building. First, the overall fibril arrangement is established using mass-per-length measurements from TEM. Then, the fibril backbone arrangement, stacking registry, and "steric zipper'' core interactions are determined using a number of solid-state NMR techniques on sparsely C-13-labeled samples. Finally, we perform Rosetta structure calculations with an explicitly symmetric representation of the system. We demonstrate the power of the hybrid Rosetta/NMR approach by modeling the in-register, parallel "Iowa'' mutant (D23N) at high resolution (1.2 angstrom backbone rmsd). The final models are validated using an independent set of NMR experiments that confirm key features.
C1 [Sgourakis, Nikolaos G.; Yau, Wai-Ming; Qiang, Wei] NIDDK, Lab Chem Phys, NIH, Bethesda, MD 20892 USA.
[Qiang, Wei] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
RP Qiang, W (reprint author), NIDDK, Lab Chem Phys, NIH, Bethesda, MD 20892 USA.
EM wqiang@binghamton.edu
FU National Institute of Diabetes, Digestive, and Kidney Disease; National
Institute of Allergy and Infectious Diseases; Intramural AIDS-Targeted
Antiviral Program of the Office of the Director; NIH; Research
Foundation at the State University of New York; National Science
Foundation [NSF 0922815]
FX This work is supported by the National Institute of Diabetes, Digestive,
and Kidney Disease and the National Institute of Allergy and Infectious
Diseases Intramural Research Programs; the Intramural AIDS-Targeted
Antiviral Program of the Office of the Director; the NIH; and the
Research Foundation at the State University of New York. Part of the
solid-state NMR measurements was supported by the National Science
Foundation Major Instrumentation Program (NSF 0922815). We greatly
appreciate the support from Dr. Robert Tycko and Dr. David Baker on
materials, instrumentation and computation time, and helpful discussion.
We thank Dr. Frank DiMaio for useful discussions.
NR 54
TC 13
Z9 13
U1 3
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD JAN 6
PY 2015
VL 23
IS 1
BP 216
EP 227
DI 10.1016/j.str.2014.10.022
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AY3FI
UT WOS:000347469500026
PM 25543257
ER
PT J
AU Nishiura, H
Chowell, G
AF Nishiura, Hiroshi
Chowell, Gerardo
TI Theoretical perspectives on the infectiousness of Ebola virus disease
SO THEORETICAL BIOLOGY AND MEDICAL MODELLING
LA English
DT Review
ID REPRODUCTION NUMBER; WEST-AFRICA; TRANSMISSION; EPIDEMIC; OUTBREAK;
MODEL
AB Background: Ebola virus disease (EVD) has generated a large epidemic in West Africa since December 2013. This mini-review is aimed to clarify and illustrate different theoretical concepts of infectiousness in order to compare the infectiousness across different communicable diseases including EVD.
Methods: We employed a transmission model that rests on the renewal process in order to clarify theoretical concepts on infectiousness, namely the basic reproduction number, R-0, which measures the infectiousness per generation of cases, the force of infection (i.e. the hazard rate of infection), the intrinsic growth rate (i.e. infectiousness per unit time) and the per-contact probability of infection (i.e. infectiousness per effective contact).
Results: Whereas R-0 of EVD is similar to that of influenza, the growth rate (i.e. the measure of infectiousness per unit time) for EVD was shown to be comparatively lower than that for influenza. Moreover, EVD and influenza differ in mode of transmission whereby the probability of transmission per contact is lower for EVD compared to that of influenza.
Conclusions: The slow spread of EVD associated with the need for physical contact with body fluids supports social distancing measures including contact tracing and case isolation. Descriptions and interpretations of different variables quantifying infectiousness need to be used clearly and objectively in the scientific community and for risk communication.
C1 [Nishiura, Hiroshi] Univ Tokyo, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan.
[Nishiura, Hiroshi] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
[Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Chowell, Gerardo] Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, NIH, Bethesda, MD 20892 USA.
[Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85282 USA.
RP Nishiura, H (reprint author), Univ Tokyo, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM nishiurah@m.u-tokyo.ac.jp
OI Nishiura, Hiroshi/0000-0003-0941-8537
FU Japan Science and Technology Agency (JST) CREST program; RISTEX program
for Science of Science, Technology and Innovation Policy; St Luke's Life
Science Institute Research Grant for Clinical Epidemiology Research;
NSF, joint NSF-NIH-USDA Ecology and Evolution of Infectious Diseases
program [1414374]; UK Biotechnology and Biological Sciences Research
Council [BB/M008894/1]; Division of International Epidemiology and
Population Studies, The Fogarty International Center, US National
Institutes of Health
FX HN received funding support from the Japan Science and Technology Agency
(JST) CREST program, RISTEX program for Science of Science, Technology
and Innovation Policy, and St Luke's Life Science Institute Research
Grant for Clinical Epidemiology Research 2014. GC acknowledges financial
support from the NSF grant 1414374 as part of the joint NSF-NIH-USDA
Ecology and Evolution of Infectious Diseases program, UK Biotechnology
and Biological Sciences Research Council grant BB/M008894/1, and the
Division of International Epidemiology and Population Studies, The
Fogarty International Center, US National Institutes of Health.
NR 27
TC 1
Z9 1
U1 4
U2 31
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4682
J9 THEOR BIOL MED MODEL
JI Theor. Biol. Med. Model.
PD JAN 6
PY 2015
VL 12
AR UNSP 1
DI 10.1186/1742-4682-12-1
PG 8
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA CA3QJ
UT WOS:000348821100001
PM 25566687
ER
PT J
AU Gopal, T
Nagarajan, V
Elasri, MO
AF Gopal, Tamilselvi
Nagarajan, Vijayaraj
Elasri, Mohamed O.
TI SATRAT: Staphylococcus aureus transcript regulatory network analysis
tool
SO PEERJ
LA English
DT Article
DE Transcriptome; RNA sequencing; Staphylococcus aureus transcriptome
meta-database (SATMD); RNA-Seq; Staphylococcus aureus microarray
meta-database (SAMMD); Staphylococcus aureus; Transcript regulatory
network; Infectious disease
ID COMMUNITY-ONSET PNEUMONIA
AB Staphylococcus aureus is a commensal organism that primarily colonizes the nose of healthy individuals. S. aureus causes a spectrum of infections that range from skin and soft-tissue infections to fatal invasive diseases. S. aureus uses a large number of virulence factors that are regulated in a coordinated fashion. The complex regulatory mechanisms have been investigated in numerous high-throughput experiments. Access to this data is critical to studying this pathogen. Previously, we developed a compilation of microarray experimental data to enable researchers to search, browse, compare, and contrast transcript profiles. We have substantially updated this database and have built a novel exploratory tool-SATRAT-the S. aureus transcript regulatory network analysis tool, based on the updated database. This tool is capable of performing deep searches using a query and generating an interactive regulatory network based on associations among the regulators of any query gene. We believe this integrated regulatory network analysis tool would help researchers explore the missing links and identify novel pathways that regulate virulence in S. aureus. Also, the data model and the network generation code used to build this resource is open sourced, enabling researchers to build similar resources for other bacterial systems.
C1 [Gopal, Tamilselvi] Informat LLC, Silver Spring, MD 20910 USA.
[Nagarajan, Vijayaraj] NIAID, BCBB, OCICB, NIH, Bethesda, MD 20892 USA.
[Elasri, Mohamed O.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA.
RP Gopal, T (reprint author), Informat LLC, Silver Spring, MD 20910 USA.
EM informaticsllcmd@gmail.com
FU National Institute of Allergy and Infectious Diseases (NIAID/NIH)
[1R15AI099922]; Mississippi INBRE; National Institute of General Medical
Sciences [P20GM103476]
FX This work was funded by the National Institute of Allergy and Infectious
Diseases (NIAID/NIH) grant number 1R15AI099922 (to MOE) and by the
Mississippi INBRE, an Institutional Development Award from the National
Institute of General Medical Sciences under grant number P20GM103476.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 12
TC 0
Z9 0
U1 1
U2 1
PU PEERJ INC
PI LONDON
PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND
SN 2167-8359
J9 PEERJ
JI PeerJ
PD JAN 6
PY 2015
VL 3
AR UNSP e717
DI 10.7717/peerj.717
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY5SK
UT WOS:000347631700001
PM 25653902
ER
PT J
AU Liu, J
AF Liu, Jian
TI The Ghost in the Machine: Is the Bacterial Chromosome a Phantom Chain?
SO BIOPHYSICAL JOURNAL
LA English
DT News Item
ID ESCHERICHIA-COLI; SEGREGATION
C1 NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Liu, J (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM liuj7@nhlbi.nih.gov
NR 10
TC 1
Z9 1
U1 2
U2 5
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 JAN 6
PY 2015
VL 108
IS 1
BP 20
EP 21
DI 10.1016/j.bpj.2014.11.3451
PG 2
WC Biophysics
SC Biophysics
GA AY3FC
UT WOS:000347468900006
PM 25564847
ER
PT J
AU Khrenova, M
Topol, I
Collins, J
Nemukhin, A
AF Khrenova, Maria
Topol, Igor
Collins, Jack
Nemukhin, Alexander
TI Estimating Orientation Factors in the FRET Theory of Fluorescent
Proteins: The TagRFP-KFP Pair and Beyond
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID TRANSITION DIPOLE-MOMENT; ENERGY-TRANSFER; ABSORPTION; LIFETIME;
SPECTRA; SYSTEM; GFP
AB The orientation factor kappa(2), one of the key parameters defining Forster resonance energy transfer efficiency, is determined by the transition dipole moment orientations of the donor and acceptor species. Using the results of quantum chemical and quantum mechanical/molecular mechanical calculations for the chromophore-containing pockets in selected colored proteins of the green fluorescent protein family, we derived transition dipole moments corresponding to the S-0,S-min -> S-1 excitation for green fluorescent protein, red fluorescent protein (TagRFP), and kindling fluorescent protein, and the S-1,S-min -> S-0 emission for TagRFP. These data allowed us to estimate kappa(2) values for the TagRFP-linker-kindling fluorescent protein tetrameric complex required for constructing novel sensors.
C1 [Khrenova, Maria; Nemukhin, Alexander] Moscow MV Lomonosov State Univ, Dept Chem, Moscow, Russia.
[Topol, Igor; Collins, Jack] Leidos Biomed Res Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Informat Syst Program, Frederick, MD 21702 USA.
[Nemukhin, Alexander] Emanuel Inst Biochem Phys, Moscow, Russia.
RP Topol, I (reprint author), Leidos Biomed Res Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Informat Syst Program, Frederick, MD 21702 USA.
EM igor.topol@fnlcr.nih.gov
RI Khrenova, Maria/I-4829-2014; Nemukhin, Alexander/P-9662-2015;
OI Khrenova, Maria/0000-0001-7117-3089
FU Program on Molecular and Cell Biology from the Russian Academy of
Sciences; Russian Foundation for Basic Research [13-03-00207]; Dynasty
Foundation fellowship; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This work was supported by the Program on Molecular and Cell Biology
from the Russian Academy of Sciences and by the Russian Foundation for
Basic Research (project 13-03-00207). M.K. acknowledges support from the
Dynasty Foundation fellowship. We acknowledge the use of supercomputer
resources of the M.V. Lomonosov Moscow State University and of the Joint
Supercomputer Center of the Russian Academy of Sciences. We thank the
staff and administration of the Advanced Biomedical Computing Center for
their support of this project. 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 organization imply endorsement by
the U.S. government.
NR 38
TC 2
Z9 3
U1 2
U2 18
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 JAN 6
PY 2015
VL 108
IS 1
BP 126
EP 132
DI 10.1016/j.bpj.2014.11.1859
PG 7
WC Biophysics
SC Biophysics
GA AY3FC
UT WOS:000347468900018
PM 25564859
ER
PT J
AU Greathouse, KL
Harris, CC
Bultman, SJ
AF Greathouse, K. Leigh
Harris, Curtis C.
Bultman, Scott J.
TI Dysfunctional Families: Clostridium scindens and Secondary Bile Acids
Inhibit the Growth of Clostridium difficile
SO CELL METABOLISM
LA English
DT Editorial Material
C1 [Greathouse, K. Leigh; Harris, Curtis C.] NCI, Lab Human Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bultman, Scott J.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27516 USA.
RP Bultman, SJ (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27516 USA.
EM scott_bultman@med.unc.edu
NR 10
TC 1
Z9 1
U1 1
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD JAN 6
PY 2015
VL 21
IS 1
BP 9
EP 10
DI 10.1016/j.cmet.2014.12.016
PG 2
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AY3ER
UT WOS:000347467900003
PM 25565200
ER
PT J
AU Palsson-McDermott, EM
Curtis, AM
Goel, G
Lauterbach, MAR
Sheedy, FJ
Gleeson, LE
van den Bosch, MWM
Quinn, SR
Domingo-Fernandez, R
Johnson, DGW
Jiang, JK
Israelsen, WJ
Keane, J
Thomas, C
Clish, C
Vanden Heiden, M
Xavier, RJ
O'Neill, LAJ
AF Palsson-McDermott, Eva M.
Curtis, Anne M.
Goel, Gautam
Lauterbach, Mario A. R.
Sheedy, Frederick J.
Gleeson, Laura E.
van den Bosch, Mirjam W. M.
Quinn, Susan R.
Domingo-Fernandez, Raquel
Johnson, Daniel G. W.
Jiang, Jain-kang
Israelsen, William J.
Keane, Joseph
Thomas, Craig
Clish, Clary
Vanden Heiden, Matthew
Xavier, Ramnik J.
O'Neill, Luke A. J.
TI Pyruvate Kinase M2 Regulates Hif-1 alpha Activity and IL-1 beta
Induction and Is a Critical Determinant of the Warburg Effect in
LPS-Activated Macrophages
SO CELL METABOLISM
LA English
DT Article
ID TUMOR-GROWTH; MYCOBACTERIUM-TUBERCULOSIS; NUCLEAR TRANSLOCATION; CANCER
METABOLISM; PKM2; ISOFORM; PROMOTES; GLUCOSE; GENE;
FRUCTOSE-1,6-BISPHOSPHATE
AB Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their metabolic activity. We here show that LPS induces expression of the key metabolic regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using two well-characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif-1 alpha and IL-1 beta, as well as the expression of a range of other Hif-1 alpha-dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1 macrophage phenotype while promoting traits typical of an M2 macrophage. We show that LPS-induced PKM2 enters into a complex with Hif-1 alpha, which can directly bind to the IL-1b promoter, an event that is inhibited by activation of PKM2. Both compounds inhibited LPS-induced glycolytic reprogramming and succinate production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and Salmonella typhimurium-induced IL-1 beta production, while boosting production of IL-10. PKM2 is therefore a critical determinant of macrophage activation by LPS, promoting the inflammatory response.
C1 [Palsson-McDermott, Eva M.; Curtis, Anne M.; Lauterbach, Mario A. R.; van den Bosch, Mirjam W. M.; Quinn, Susan R.; Domingo-Fernandez, Raquel; Johnson, Daniel G. W.; O'Neill, Luke A. J.] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland.
[Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Goel, Gautam; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Goel, Gautam; Clish, Clary; Xavier, Ramnik J.] Broad Inst Harvard Univ & Massachusetts Inst Tec, Cambridge, MA 02142 USA.
[Sheedy, Frederick J.; Gleeson, Laura E.; Keane, Joseph] Univ Dublin Trinity Coll, Dept Clin Med, Sch Med, Dublin 2, Ireland.
[Israelsen, William J.; Vanden Heiden, Matthew] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
[Jiang, Jain-kang; Thomas, Craig] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Vanden Heiden, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
RP O'Neill, LAJ (reprint author), Univ Dublin Trinity Coll, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland.
EM laoneill@tcd.ie
OI Keane, Joseph/0000-0001-5313-385X
FU Science Foundation Ireland; European Research Council; Health Research
Board; European Community [HEALTH-14-2011-281608]; Wellcome Trust;
Baggot St Hospital Trust; National Institutes of Health
FX We thank Science Foundation Ireland, the European Research Council, the
Health Research Board, European Community Seventh Framework Programme
(FP7-2007-2013) under grant agreement No. HEALTH-14-2011-281608 'TIMER',
Wellcome Trust, Baggot St Hospital Trust, and National Institutes of
Health for funding.
NR 36
TC 70
Z9 71
U1 12
U2 40
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD JAN 6
PY 2015
VL 21
IS 1
BP 65
EP 80
DI 10.1016/j.cmet.2014.12.005
PG 16
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AY3ER
UT WOS:000347467900011
PM 25565206
ER
PT J
AU Sorlie, PD
Sholinsky, PD
Lauer, MS
AF Sorlie, Paul D.
Sholinsky, Phyliss D.
Lauer, Michael S.
TI Reinvestment in Government-Funded Research A Great Way to Share
SO CIRCULATION
LA English
DT Editorial Material
ID BIOMEDICAL-RESEARCH
C1 [Sorlie, Paul D.; Sholinsky, Phyliss D.; Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
NR 11
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 6
PY 2015
VL 131
IS 1
BP 17
EP 18
DI 10.1161/CIRCULATIONAHA.114.014204
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AY0PW
UT WOS:000347299900012
PM 25411156
ER
PT J
AU Pfeffer, MA
Claggett, B
Assmann, SF
Boineau, R
Anand, IS
Clausell, N
Desai, AS
Diaz, R
Fleg, JL
Gordeev, I
Heitner, JF
Lewis, EF
O'Meara, E
Rouleau, JL
Probstfield, JL
Shaburishvili, T
Shah, SJ
Solomon, SD
Sweitzer, NK
McKinlay, SM
Pitt, B
AF Pfeffer, Marc A.
Claggett, Brian
Assmann, Susan F.
Boineau, Robin
Anand, Inder S.
Clausell, Nadine
Desai, Akshay S.
Diaz, Rafael
Fleg, Jerome L.
Gordeev, Ivan
Heitner, John F.
Lewis, Eldrin F.
O'Meara, Eileen
Rouleau, Jean-Lucien
Probstfield, Jeffrey L.
Shaburishvili, Tamaz
Shah, Sanjiv J.
Solomon, Scott D.
Sweitzer, Nancy K.
McKinlay, Sonja M.
Pitt, Bertram
TI Regional Variation in Patients and Outcomes in the Treatment of
Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist
(TOPCAT) Trial
SO CIRCULATION
LA English
DT Article
DE heart failure; randomized controlled trials; spironolactone
ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR EJECTION FRACTION;
CLINICAL-TRIALS; SUBGROUP ANALYSES; INTERNATIONAL DIFFERENCES;
SUBSEQUENT MORTALITY; TASK-FORCE; HOSPITALIZATION; HYPERKALEMIA;
PREVALENCE
AB Background-Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an approximate to 4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas).
Methods and Results-To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone.
Conclusions-This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas.
C1 [Pfeffer, Marc A.; Claggett, Brian; Desai, Akshay S.; Lewis, Eldrin F.; Solomon, Scott D.] Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA.
[Assmann, Susan F.; McKinlay, Sonja M.] New England Res Inst Inc, Watertown, MA USA.
[Boineau, Robin; Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Anand, Inder S.] VA Med Ctr, Minneapolis, MN USA.
[Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA.
[Clausell, Nadine] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Diaz, Rafael] Estudios Clin Latinoamer, Rosario, Santa Fe, Argentina.
[Gordeev, Ivan] Pirogov Russian Natl Res Med Univ, Moscow, Russia.
[Heitner, John F.] New York Methodist Hosp, Brooklyn, NY USA.
[O'Meara, Eileen; Rouleau, Jean-Lucien] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Probstfield, Jeffrey L.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Shaburishvili, Tamaz] Diagnost Serv Clin, Tbilisi, Rep of Georgia.
[Shah, Sanjiv J.] Northwestern Univ, Chicago, IL 60611 USA.
[Sweitzer, Nancy K.] Univ Wisconsin, Madison, WI 53706 USA.
[Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA.
RP Pfeffer, MA (reprint author), Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
EM mpfeffer@rics.bwh.harvard.edu
RI Clausell, Nadine /C-7813-2016
OI Clausell, Nadine /0000-0003-4207-3809
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[HHSN268200425207C]
FX This work was funded by the National Heart, Lung, and Blood Institute,
National Institutes of Health, contract HHSN268200425207C. The content
of this article does not necessarily represent the views of the National
Heart, Lung, and Blood Institute or of the Department of Health and
Human Services.
NR 48
TC 82
Z9 82
U1 3
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 6
PY 2015
VL 131
IS 1
BP 34
EP +
DI 10.1161/CIRCULATIONAHA.114.013255
PG 23
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AY0PW
UT WOS:000347299900015
PM 25406305
ER
PT J
AU Greco, G
Shi, W
Michler, RE
Meltzer, DO
Ailawadi, G
Hohmann, SF
Thourani, VH
Argenziano, M
Alexander, JH
Sankovic, K
Gupta, L
Blackstone, EH
Acker, MA
Russo, MJ
Lee, A
Burks, SG
Gelijns, AC
Bagiella, E
Moskowitz, AJ
Gardner, TJ
AF Greco, Giampaolo
Shi, Wei
Michler, Robert E.
Meltzer, David O.
Ailawadi, Gorav
Hohmann, Samuel F.
Thourani, Vinod H.
Argenziano, Michael
Alexander, John H.
Sankovic, Kathy
Gupta, Lopa
Blackstone, Eugene H.
Acker, Michael A.
Russo, Mark J.
Lee, Albert
Burks, Sandra G.
Gelijns, Annetine C.
Bagiella, Emilia
Moskowitz, Alan J.
Gardner, Timothy J.
TI Costs Associated With Health Care-Associated Infections in Cardiac
Surgery
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE health care-associated infection; hospital costs; length of stay
ID SURGICAL-SITE INFECTIONS; VENTILATOR-ASSOCIATED PNEUMONIA; BLOOD-STREAM
INFECTIONS; BYPASS GRAFT-SURGERY; LENGTH-OF-STAY; QUALITY IMPROVEMENT;
ACQUIRED INFECTION; IMPACT; COMPLICATIONS; READMISSION
AB BACKGROUND Health care-associated infections (HAIs) are the most common noncardiac complications after cardiac surgery and are associated with increased morbidity and mortality. Current information about their economic burden is limited.
OBJECTIVES This research was designed to determine the cost associated with major types of HAIs during the first 2 months after cardiac surgery.
METHODS Prospectively collected data from a multicenter, observational study of the Cardiothoracic Surgery Clinical Trials Network, in which patients were monitored for infections for 65 days after surgery, were merged with related financial data routinely collected by the University HealthSystem Consortium. Incremental length of stay (LOS) and cost associated with HAIs were estimated using generalized linear models, with adjustments for patient demographics, clinical history, baseline laboratory values, and surgery type.
RESULTS Among 4,320 cardiac surgery patients (mean age: 64 +/- 13 years), 119 (2.8%) experienced a major HAI during the index hospitalization. The most common HAIs were pneumonia (48%), sepsis (20%), and Clostridium difficile colitis (18%). On average, the estimated incremental cost associated with a major HAI was nearly $38,000, of which 47% was related to intensive care unit services. The incremental LOS was 14 days. Overall, there were 849 readmissions; among these, 8.7% were attributed to major HAIs. The cost of readmissions due to major HAIs was, on average, nearly threefold that of readmissions not related to HAIs.
CONCLUSIONS Hospital cost, LOS, and readmissions are strongly associated with HAIs. These associations suggest the potential for large reductions in costs if HAIs following cardiac surgery can be reduced. (Management Practices and the Risk of Infections Following Cardiac Surgery; NCT01089712) (C) 2015 by the American College of Cardiology Foundation.
C1 [Greco, Giampaolo; Shi, Wei; Gelijns, Annetine C.; Bagiella, Emilia; Moskowitz, Alan J.] Icahn Sch Med Mt Sinai, Icahn Sch Med, Dept Populat Sci & Policy, InCHOIR, New York, NY 10029 USA.
[Michler, Robert E.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Cardiothorac Surg, New York, NY USA.
[Meltzer, David O.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Ailawadi, Gorav] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA.
[Hohmann, Samuel F.] Univ HealthSyst Consortium, Chicago, IL USA.
[Thourani, Vinod H.] Emory Univ, Sch Med, Div Cardiothorac Surg, Clin Res Unit, Atlanta, GA 30322 USA.
[Argenziano, Michael] Columbia Univ, Coll Phys & Surg, Dept Surg, Div Cardiothorac Surg, New York, NY USA.
[Alexander, John H.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA.
[Sankovic, Kathy] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA.
[Acker, Michael A.] Univ Penn, Sch Med, Div Cardiovasc Surg, Dept Surg, Philadelphia, PA 19104 USA.
[Russo, Mark J.] Barnabas Heart Hosp, Newark, NJ USA.
[Lee, Albert] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Gardner, Timothy J.] Christiana Care Hlth Syst, Ctr Heart & Vasc Hlth, Newark, DE USA.
RP Greco, G (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1077, New York, NY 10029 USA.
EM giampaolo.greco@mountsinai.org
RI Meltzer, David/C-2926-2009;
OI Meltzer, David/0000-0003-2790-7393; Moskowitz, Alan/0000-0002-4412-9450
FU Canadian Institutes of Health Research; NCATS NIH HHS [UL1 TR000430];
NHLBI NIH HHS [7U01 HL088942, U01 HL088942]
NR 47
TC 12
Z9 12
U1 2
U2 7
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 JAN 6
PY 2015
VL 65
IS 1
BP 15
EP 23
DI 10.1016/j.jacc.2014.09.079
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AY2GI
UT WOS:000347406400003
PM 25572505
ER
PT J
AU Mock, JY
Chartron, JW
Zaslaver, M
Xu, Y
Ye, YH
Clemons, WM
AF Mock, Jee-Young
Chartron, Justin William
Zaslaver, Ma'ayan
Xu, Yue
Ye, Yihong
Clemons, William Melvon, Jr.
TI Bag6 complex contains a minimal tail-anchor-targeting module and a mock
BAG domain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE GET pathway; Scythe; Bat3; X-ray crystallography; tail-anchored proteins
ID UBIQUITIN-LIKE DOMAIN; RETICULUM-ASSOCIATED DEGRADATION;
MEMBRANE-PROTEIN INSERTION; ENDOPLASMIC-RETICULUM; INDUCED APOPTOSIS;
CHAPERONE ACTIVITY; GET4/GET5 COMPLEX; CRYSTAL-STRUCTURE;
MAMMALIAN-CELLS; BCL-2 FAMILY
AB BCL2-associated athanogene cochaperone 6 (Bag6) plays a central role in cellular homeostasis in a diverse array of processes and is part of the heterotrimeric Bag6 complex, which also includes ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This complex recently has been shown to be important in the TRC pathway, the mislocalized protein degradation pathway, and the endoplasmic reticulum-associated degradation pathway. Here we define the architecture of the Bag6 complex, demonstrating that both TRC35 and Ubl4A have distinct C-terminal binding sites on Bag6 defining a minimal Bag6 complex. A crystal structure of the Bag6-Ubl4A dimer demonstrates that Bag6-BAG is not a canonical BAG domain, and this finding is substantiated biochemically. Remarkably, the minimal Bag6 complex defined here facilitates tail-anchored substrate transfer from small glutamine-rich tetratricopeptide repeat-containing protein a to TRC40. These findings provide structural insight into the complex network of proteins coordinated by Bag6.
C1 [Mock, Jee-Young; Chartron, Justin William; Zaslaver, Ma'ayan; Clemons, William Melvon, Jr.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
[Xu, Yue; Ye, Yihong] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Clemons, WM (reprint author), CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
EM clemons@caltech.edu
RI Xu, Yue/F-8188-2015;
OI Mock, Jee-Young/0000-0002-4656-3357; Clemons,
William/0000-0002-0021-889X
FU National Institutes of Health [R01GM097572]
FX We thank Daniel Lin and Jens Kaiser for help with data processing; Yoko
Shibata and Richard Morimoto (Northwestern University) for plasmids;
Michael Rome and Meera Rao for critical reading of the manuscript;
members of the W.M.C. laboratory for support and useful discussions; the
staff at the Advanced Light Source for assistance with synchrotron data
collection; and Gordon and Betty Moore for support of the Molecular
Observatory at California Institute of Technology. W.M.C. is supported
by National Institutes of Health Grant R01GM097572.
NR 54
TC 12
Z9 12
U1 0
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 6
PY 2015
VL 112
IS 1
BP 106
EP 111
DI 10.1073/pnas.1402745112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY2WN
UT WOS:000347447100037
PM 25535373
ER
PT J
AU Tian, HY
Zhou, S
Dong, L
Van Boeckel, TP
Cui, YJ
Wu, YR
Cazelles, B
Huang, SQ
Yang, RF
Grenfell, BT
Xu, B
AF Tian, Huaiyu
Zhou, Sen
Dong, Lu
Van Boeckel, Thomas P.
Cui, Yujun
Wu, Yarong
Cazelles, Bernard
Huang, Shanqian
Yang, Ruifu
Grenfell, Bryan T.
Xu, Bing
TI Avian influenza H5N1 viral and bird migration networks in Asia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE bird migration; HPAI H5N1; viral migration; network; satellite tracking
ID WILD BIRDS; A VIRUS; SPREAD; EVOLUTION; DYNAMICS; IDENTIFICATION;
SURVEILLANCE; WATERFOWL; DISTANCE; AFRICA
AB The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.
C1 [Tian, Huaiyu; Huang, Shanqian; Xu, Bing] Beijing Normal Univ, Coll Global Change & Earth Syst Sci, State Key Lab Remote Sensing Sci, Beijing 100875, Peoples R China.
[Zhou, Sen; Xu, Bing] Tsinghua Univ, Ctr Earth Syst Sci, Key Lab Earth Syst Modelling, Minist Educ, Beijing 100084, Peoples R China.
[Zhou, Sen; Xu, Bing] Tsinghua Univ, Sch Environm, Beijing 100084, Peoples R China.
[Dong, Lu] Beijing Normal Univ, Coll Life Sci, Key Lab Biodivers & Ecol Engn, Minist Educ, Beijing 100875, Peoples R China.
[Van Boeckel, Thomas P.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
[Cui, Yujun; Wu, Yarong; Yang, Ruifu] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100071, Peoples R China.
[Cazelles, Bernard] Univ Paris 06, CNRS, UMR 7625, F-75230 Paris 05, France.
[Cazelles, Bernard] Ecole Normale Super, F-75230 Paris 05, France.
[Cazelles, Bernard] Inst Rech Dev, Unite Modelisat Mathemat & Informat Syst Complexe, Unite Mixte Int 209, F-93142 Bondy, France.
[Cazelles, Bernard] Univ Paris 06, F-93142 Bondy, France.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Xu, Bing] Univ Utah, Dept Geog, Salt Lake City, UT 84112 USA.
RP Grenfell, BT (reprint author), Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
EM grenfell@princeton.edu; bingxu@tsinghua.edu.cn
RI Xu, Bing/C-5769-2015; Xu, Bing/C-7732-2015; Cazelles,
Bernard/B-1572-2013; Tian, Huaiyu/G-1934-2016
OI Cazelles, Bernard/0000-0002-7972-361X;
FU Ministry of Science and Technology, China, National Research Program
[2010CB530300, 2012CB955501, 2012AA12A407]; National Natural Science
Foundation of China [41271099]; Science and Technology Directorate, US
Department of Homeland Security [HSHQDC-12-C-00058]; Bill and Melinda
Gates Foundation; Fogarty International Center, National Institutes of
Health
FX We thank the US Geological Survey, Western Ecological Research Center,
Patuxent Wildlife Research Center, and Avian Influenza Program. This
research was supported by the Ministry of Science and Technology, China,
National Research Program (2010CB530300, 2012CB955501, and
2012AA12A407), and the National Natural Science Foundation of China
(41271099). B.T.G. was supported by the Science and Technology
Directorate, US Department of Homeland Security (Contract
HSHQDC-12-C-00058 and the Research and Policy for Infectious Disease
Dynamics program), the Bill and Melinda Gates Foundation, and the
Fogarty International Center, National Institutes of Health.
NR 53
TC 29
Z9 32
U1 6
U2 76
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 6
PY 2015
VL 112
IS 1
BP 172
EP 177
DI 10.1073/pnas.1405216112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY2WN
UT WOS:000347447100048
PM 25535385
ER
PT J
AU Wang, Y
Lang, LX
Huang, P
Wang, Z
Jacobson, O
Kiesewetter, DO
Ali, IU
Teng, GJ
Niu, G
Chen, XY
AF Wang, Yu
Lang, Lixin
Huang, Peng
Wang, Zhe
Jacobson, Orit
Kiesewetter, Dale O.
Ali, Iqbal U.
Teng, Gaojun
Niu, Gang
Chen, Xiaoyuan
TI In vivo albumin labeling and lymphatic imaging
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE PET; lymph node; optical imaging; albumin; Evans blue
ID BREAST-CANCER PATIENTS; SENTINEL-NODE BIOPSY; BLUE-DYE;
MOLECULAR-MECHANISMS; SERUM-ALBUMIN; SURGERY; PET; DIFFERENTIATION;
METASTASIS; NAVIGATION
AB The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N, N',N''-triaceticacid)-conjugated truncated Evans blue (F-18-AlF-NEB) and Evans blue (EB) dye. After local injection, both 18F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from F-18-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of F-18-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance.
C1 [Wang, Yu; Teng, Gaojun] Southeast Univ, Sch Med, Zhongda Hosp, Dept Radiol,Jiangsu Key Lab Mol Imaging & Funct I, Nanjing 210009, Jiangsu, Peoples R China.
[Wang, Yu; Lang, Lixin; Huang, Peng; Wang, Zhe; Jacobson, Orit; Kiesewetter, Dale O.; Ali, Iqbal U.; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM gjteng@vip.sina.com; niug@mail.nih.gov; shawn.chen@nih.gov
RI Huang, Peng/H-9985-2013; Ali, Imran/F-7710-2010; Huang, Peng/R-2480-2016
OI Ali, Imran/0000-0001-6511-8374; Huang, Peng/0000-0003-3651-7813
FU Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering, NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering, NIH.
NR 36
TC 10
Z9 10
U1 10
U2 36
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 6
PY 2015
VL 112
IS 1
BP 208
EP 213
DI 10.1073/pnas.1414821112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY2WN
UT WOS:000347447100054
PM 25535368
ER
PT J
AU Bowles, NP
Karatsoreos, IN
Li, XS
Vemuri, VK
Wood, JA
Li, ZY
Tamashiro, KLK
Schwartz, GJ
Makriyannis, AM
Kunos, G
Hillard, CJ
McEwen, BS
Hill, MN
AF Bowles, Nicole P.
Karatsoreos, Ilia N.
Li, Xiaosong
Vemuri, V. Kiran
Wood, Jodi-Anne
Li, Zhiying
Tamashiro, Kellie L. K.
Schwartz, Gary J.
Makriyannis, Alexandros M.
Kunos, George
Hillard, Cecilia J.
McEwen, Bruce S.
Hill, Matthew N.
TI A peripheral endocannabinoid mechanism contributes to
glucocorticoid-mediated metabolic syndrome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE corticosterone; 2-AG; anandamide; obesity; liver
ID DIET-INDUCED OBESITY; INDUCED INSULIN-RESISTANCE; STRESS-INDUCED
OBESITY; ADIPOSE-TISSUE; FOOD-INTAKE; CARDIOMETABOLIC RISK;
ENERGY-BALANCE; CB1 RECEPTOR; LEPTIN; MICE
AB Glucocorticoids are known to promote the development of metabolic syndrome through the modulation of both feeding pathways and metabolic processes; however, the precise mechanisms of these effects are not well-understood. Recent evidence shows that glucocorticoids possess the ability to increase endocannabinoid signaling, which is known to regulate appetite, energy balance, and metabolic processes through both central and peripheral pathways. The aim of this study was to determine the role of endocannabinoid signaling in glucocorticoid-mediated obesity and metabolic syndrome. Using a mouse model of excess corticosterone exposure, we found that the ability of glucocorticoids to increase adiposity, weight gain, hormonal dysregulation, hepatic steatosis, and dyslipidemia was reduced or reversed in mice lacking the cannabinoid CB1 receptor as well as mice treated with the global CB1 receptor antagonist AM251. Similarly, a neutral, peripherally restricted CB1 receptor antagonist (AM6545) was able to attenuate the metabolic phenotype caused by chronic corticosterone, suggesting a peripheral mechanism for these effects. Biochemical analyses showed that chronic excess glucocorticoid exposure produced a significant increase in hepatic and circulating levels of the endocannabinoid anandamide, whereas no effect was observed in the hypothalamus. To test the role of the liver, specific and exclusive deletion of hepatic CB1 receptor resulted in a rescue of the dyslipidemic effects of glucocorticoid exposure, while not affecting the obesity phenotype or the elevations in insulin and leptin. Together, these data indicate that glucocorticoids recruit peripheral endocannabinoid signaling to promote metabolic dysregulation, with hepatic endocannabinoid signaling being especially important for changes in lipid metabolism.
C1 [Bowles, Nicole P.; Karatsoreos, Ilia N.; McEwen, Bruce S.; Hill, Matthew N.] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10065 USA.
[Li, Zhiying] Rockefeller Univ, Mol Genet Lab, New York, NY 10065 USA.
[Karatsoreos, Ilia N.] Washington State Univ, Dept Integrat Physiol & Neurosci, Pullman, WA 99164 USA.
[Li, Xiaosong; Schwartz, Gary J.] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA.
[Li, Xiaosong; Schwartz, Gary J.] Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA.
[Vemuri, V. Kiran; Wood, Jodi-Anne; Makriyannis, Alexandros M.] Northeastern Univ, Dept Pharmaceut Sci, Ctr Drug Discovery, Boston, MA 02115 USA.
[Vemuri, V. Kiran; Wood, Jodi-Anne; Makriyannis, Alexandros M.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
[Tamashiro, Kellie L. K.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Kunos, George] NIAAA, NIH, Bethesda, MD 20892 USA.
[Hillard, Cecilia J.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA.
[Hillard, Cecilia J.] Med Coll Wisconsin, Neurosci Res Ctr, Milwaukee, WI 53226 USA.
[Hill, Matthew N.] Univ Calgary, Hotchkiss Brain Inst, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada.
[Hill, Matthew N.] Univ Calgary, Hotchkiss Brain Inst, Dept Psychiat, Calgary, AB T2N 4N1, Canada.
RP Bowles, NP (reprint author), Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10065 USA.
EM nbowles@mail.rockefeller.edu; mcewen@mail.rockefeller.edu;
mnhill@ucalgary.ca
FU Hope for Depression Research Foundation; Johnson and Johnson
Pharmaceuticals; NIH Einstein DRTC Animal Physiology Core [DK 020541,
DA9158, DA23142, DA026996]; Research and Education Component of the
Advancing a Healthier Wisconsin Endowment; National Institute on Alcohol
Abuse and Alcoholism, NIH; Ford Foundation Fellowship; Tier II Canada
Research Chair; Natural Sciences and Engineering Research Council of
Canada
FX We thank Sarah Bhagat for her technical assistance at the early stage of
this study. This research was supported, in part, by an operating grant
from the Hope for Depression Research Foundation and an unrestricted
operating grant from Johnson and Johnson Pharmaceuticals (to B.S.M.).
NIH Grants DK 020541 Einstein DRTC Animal Physiology Core (to G.J.S.),
DA9158 (to A.M.M.), DA23142 (to A.M.M.), and DA026996 (to C.J.H.); the
Research and Education Component of the Advancing a Healthier Wisconsin
Endowment to the Medical College of Wisconsin; and intramural funds from
the National Institute on Alcohol Abuse and Alcoholism, NIH (G.K.) also
supported this research. N.P.B. was a recipient of a predoctoral Ford
Foundation Fellowship. M.N.H. is the recipient of a Tier II Canada
Research Chair, and this research was supported by an operating grant
from the Natural Sciences and Engineering Research Council of Canada.
NR 61
TC 14
Z9 14
U1 2
U2 14
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 6
PY 2015
VL 112
IS 1
BP 285
EP 290
DI 10.1073/pnas.1421420112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AY2WN
UT WOS:000347447100067
PM 25535367
ER
PT J
AU Stringer, TP
Guerrieri, D
Vivar, C
van Praag, H
AF Stringer, T. P.
Guerrieri, D.
Vivar, C.
van Praag, H.
TI Plant-derived flavanol (-)epicatechin mitigates anxiety in association
with elevated hippocampal monoamine and BDNF levels, but does not
influence pattern separation in mice
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; SPATIAL MEMORY; OXIDATIVE STRESS; TEA POLYPHENOL;
ELECTROCONVULSIVE SEIZURE; VAL66MET POLYMORPHISM; PARKINSONS-DISEASE;
SIGNALING PATHWAYS; ADULT HIPPOCAMPUS; DENTATE GYRUS
AB Flavanols found in natural products such as cocoa and green tea elicit structural and biochemical changes in the hippocampus, a brain area important for mood and cognition. Here, we evaluated the outcome of daily consumption of the flavanol (-)epicatechin (4 mg per day in water) by adult male C57BL/6 mice on measures of anxiety in the elevated plus maze (EPM) and open field (OF). Furthermore, pattern separation, the ability to distinguish between closely spaced identical stimuli, considered to be mediated by the hippocampal dentate gyrus (DG), was tested using the touchscreen. To investigate mechanisms through which (-)epicatechin may exert its effects, mice were injected with bromodeoxyuridine (50 mg kg(-1)) to evaluate adult hippocampal neurogenesis. In addition, monoaminergic and neurotrophin signaling pathway proteins were measured in tissue derived from subject cortices and hippocampi. Flavanol consumption reduced anxiety in the OF and EPM. Elevated hippocampal and cortical tyrosine hydroxylase, downregulated cortical monoamine oxidase-A levels, as well as increased hippocampal brain-derived neurotrophic factor (BDNF) and pro-BDNF support the flavanol's anxiolytic effects. In addition, elevated pAkt in hippocampus and cortex was observed. (-)Epicatechin ingestion did not facilitate touchscreen performance or DG neurogenesis, suggesting a non-neurogenic mechanism. The concurrent modulation of complementary neurotrophic and monoaminergic signaling pathways may contribute to beneficial mood-modulating effects of this flavanol.
C1 [Stringer, T. P.; Guerrieri, D.; Vivar, C.; van Praag, H.] NIA, Neuroplast & Behav Unit, Lab Neurosci, Intramural Res Program,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
RP van Praag, H (reprint author), NIA, Neuroplast & Behav Unit, Lab Neurosci, Intramural Res Program,NIH,Biomed Res Ctr, Suite 100,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vanpraagh@mail.nih.gov
RI van Praag, Henriette/F-3939-2015
OI van Praag, Henriette/0000-0002-5727-434X
FU Intramural Research Program of the National Institute on Aging
FX This work was supported by the Intramural Research Program of the
National Institute on Aging. We thank Sarah Collica for technical
assistance and Linda Kitabayashi for preparation of the photomicrograph.
NR 85
TC 10
Z9 11
U1 8
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JAN 6
PY 2015
VL 5
AR e493
DI 10.1038/tp.2014.135
PG 9
WC Psychiatry
SC Psychiatry
GA DA2TU
UT WOS:000367650100003
PM 25562843
ER
PT J
AU Caudron, Q
Mahmud, AS
Metcalf, CJE
Gottfredsson, M
Viboud, C
Cliff, AD
Grenfell, BT
AF Caudron, Q.
Mahmud, A. S.
Metcalf, C. J. E.
Gottfredsson, M.
Viboud, C.
Cliff, A. D.
Grenfell, B. T.
TI Predictability in a highly stochastic system: final size of measles
epidemics in small populations
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Article
DE measles; dynamics; epidemiology; small populations
ID COMMUNITY SIZE; DYNAMICS; PERSISTENCE; DISEASES; RATES; MODEL
AB A standard assumption in the modelling of epidemic dynamics is that the population of interest is well mixed, and that no clusters of metapopulations exist. The well-known and oft-used SIR model, arguably the most important compartmental model in theoretical epidemiology, assumes that the disease being modelled is strongly immunizing, directly transmitted and has a well-defined period of infection, in addition to these population mixing assumptions. Childhood infections, such as measles, are prime examples of diseases that fit the SIR-like mechanism. These infections have been well studied for many systems with large, well-mixed populations with endemic infection. Here, we consider a setting where populations are small and isolated. The dynamics of infection are driven by stochastic extinction-recolonization events, producing large, sudden and short-lived epidemics before rapidly dying out from a lack of susceptible hosts. Using a TSIR model, we fit prevaccination measles incidence and demographic data in Bornholm, the Faroe Islands and four districts of Iceland, between 1901 and 1965. The datasets for each of these countries suffer from different levels of data heterogeneity and sparsity. We explore the potential for prediction of this model: given historical incidence data and up-to-date demographic information, and knowing that a new epidemic has just begun, can we predict how large it will be? We show that, despite a lack of significant seasonality in the incidence of measles cases, and potentially severe heterogeneity at the population level, we are able to estimate the size of upcoming epidemics, conditioned on the first time step, to within reasonable confidence. Our results have potential implications for possible control measures for the early stages of new epidemics in small populations.
C1 [Caudron, Q.; Metcalf, C. J. E.; Grenfell, B. T.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Mahmud, A. S.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Off Populat Res, Princeton, NJ 08544 USA.
[Metcalf, C. J. E.; Gottfredsson, M.; Viboud, C.; Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Gottfredsson, M.] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
[Gottfredsson, M.] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
[Cliff, A. D.] Univ Cambridge, Dept Geog, Cambridge CB2 3EN, England.
RP Caudron, Q (reprint author), Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM qcaudron@princeton.edu
OI CAUDRON, Quentin/0000-0002-0132-5005; Gottfredsson,
Magnus/0000-0003-2465-0422
FU US Department of Homeland Security [HSHQDC-12-C-00058]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development
[5R24HD047879]; National Institutes of Health [5T32HD007163]; Bill and
Melinda Gates Foundation; RAPIDD program of the Science and Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX Q.C., C.J.E.M. and B.T.G. were supported by funding from the US
Department of Homeland Security contract HSHQDC-12-C-00058. A.S.M.
acknowledges funding from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (grant no. 5R24HD047879) and from
the National Institutes of Health (training grant no. 5T32HD007163).
B.T.G. acknowledges support from the Bill and Melinda Gates Foundation.
C.J.E.M. and B.T.G. were funded by the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health.
NR 21
TC 2
Z9 2
U1 1
U2 21
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
EI 1742-5662
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD JAN 6
PY 2015
VL 12
IS 102
AR 20141125
DI 10.1098/rsif.2014.1125
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU3GI
UT WOS:000345500000031
PM 25411411
ER
PT J
AU Harly, C
Peigne, CM
Scotet, E
AF Harly, Christelle
Peigne, Cassie-Marie
Scotet, Emmanuel
TI Molecules and mechanisms implicated in the peculiar antigenic activation
process of human V gamma 9V delta 2T cells
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE human gamma delta T lymphocytes; functions; antigenic activation;
phosphoantigens; butyrophilin
ID DELTA-T-CELLS; NONPEPTIDIC MYCOBACTERIAL LIGANDS; PRENYL PYROPHOSPHATE
ANTIGENS; BURKITTS-LYMPHOMA CELLS; TCR-GAMMA-DELTA; DENDRITIC-CELLS;
ISOPRENOID BIOSYNTHESIS; TUMOR-CELLS; PHOSPHORYLATED ANTIGENS;
V-GAMMA-2V-DELTA-2 TCR
AB In human beings, as well as in most non-human primates, the major peripheral gamma delta T cell subset, which accounts several percent of the whole lymphoid cells pool in adults, carries an heterodimeric TCR composed of V gamma 9 and V delta 2 chains. V gamma 9V delta 2 T cells are specifically and strongly activated by small organic pyrophosphate molecules termed phosphoantigens (phosphoAg). These low molecular weight compounds are metabolites that are produced by either microbes or endogenously, as intermediates of the mammalian mevalonate pathway, and can accumulate intracellularly during cell stress like transformation or infection. Despite the characterization of numerous natural and synthetic phosphoAg, the mechanism(s) underlying the unique and specific antigenic activation process induced by these compounds remains poorly understood. Activation is both TCR-and cell-to-cell contact-dependent, and results of previous studies have also strongly suggested a key contribution of membrane-associated molecules of primate origin expressed on target cells. The recent identification of B7-related butyrophilin (BIN) molecules CD277/BTN3A, and more precisely their BTN3A1 isoforms, as mandatory molecules in the phosphoAginduced recognition of target cells by V gamma 9V delta 2 T cells opens important opportunities for research and applications in this field. Here, we review the unusual and complex antigenic reactivity of human V gamma 9V delta 2 T cells. We highlight the recent advances in our understanding of this process, and propose a model that integrates the type I glycoprotein BTN3A1 and its intracellular B30.2 domain as a physical intermediate implicated in the detection of dysregulated intracellular levels of phosphoAg and the sensing of cell stress by V gamma 9V delta 2T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that utilize the unique functional potential of this major gamma delta T cell subset.
C1 [Harly, Christelle] NCI, Lab Genome Integr, Ctr Canc Res, Bethesda, MD 20892 USA.
[Harly, Christelle] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA.
[Peigne, Cassie-Marie; Scotet, Emmanuel] Ctr Rech Cancerol Nantes Angers, INSERM, Unite Mixte Rech 892, Nantes, France.
[Peigne, Cassie-Marie; Scotet, Emmanuel] Univ Nantes, Nantes, France.
[Peigne, Cassie-Marie; Scotet, Emmanuel] CNRS, Unite Mixte Rech 6299, Nantes, France.
RP Scotet, E (reprint author), IRS UN, Ctr Rech Cancerol Nantes Angers, INSERM UMR 892, 8 Quai Moncousu, F-44007 Nantes, France.
EM emmanuel.scotet@inserm.fr
RI SCOTET, Emmanuel/L-2576-2015
FU INSERM; Universite de Nantes; Association pour la Recherche contre le
Cancer; Institut National du Cancer; Agence Nationale de la Recherche;
Ligue Nationale contre le Cancer; Investissements d'Avenir; US National
Institute of Health [AI059621]
FX The authors thank Ulrich tarry for help preparing this manuscript. This
work was supported by INSERM, Universite de Nantes, Association pour la
Recherche contre le Cancer, Institut National du Cancer, Agence
Nationale de la Recherche (#GDSTRESS), Ligue Nationale contre le Cancer
and Investissements d'Avenir (Agence Nationale de la Recherche-Programme
Laboratoires d'Excellence Immunotherapy Graft Oncology), and the US
National Institute of Health (AI059621).
NR 97
TC 4
Z9 4
U1 2
U2 7
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD JAN 5
PY 2015
VL 5
AR 657
DI 10.3389/fimmu.2014.00657
PG 13
WC Immunology
SC Immunology
GA CI2SS
UT WOS:000354597900001
ER
PT J
AU Liu, MT
Wang, J
Wu, XG
Wang, E
Abergel, RJ
Shuh, DK
Raymond, KN
Liu, P
AF Liu, Mingtao
Wang, Jennie
Wu, Xiaogang
Wang, Euphemia
Abergel, Rebecca J.
Shuh, David K.
Raymond, Kenneth N.
Liu, Paul
TI Characterization, HPLC method development and impurity identification
for 3,4,3-LI(1,2-HOPO), a potent actinide chelator for radionuclide
decorporation
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE 3,4,3-LI(1,2-HOPO); NSC 749716; HPLC method development and validation;
Metal chelation; Speciation; Impurity and degradation product
characterization
ID LIQUID-CHROMATOGRAPHY; AGENTS; 5-LIO(ME-3,2-HOPO); COMPLEXES; EFFICACY;
EDTA
AB 3,4,3-LI(1,2-HOPO), 1,5,10,14-tetra(1-hydroxy-2-pyridon-6-oyl)-1,5,10,14-tetraazatetradecane), is a potent octadentate chelator of actinides. It is being developed as a decorporation treatment for internal contamination with radionuclides. Conventional HPLC methods exhibited speciation peaks and bridging, likely attributable to the agent's complexation with residual metallic ions in the HPLC system. Derivatization of the target ligand in situ with Fe(III) chloride, however, provided a single homogeneous iron-complex that can readily be detected and analyzed by HPLC. The HPLC method used an Agilent Eclipse XDB-C18 column (150 mm x 4.6 mm, 5 mu m) at 25 degrees C with UV detection at 280 nm. A gradient elution, with acetonitrile (11% to 100%)/buffer mobile phase, was developed for impurity profiling. The buffer consisted of 0.02% formic acid and 10 mM ammonium formate at pH 4.6. An Agilent 1200 LC-6530 Q-TOF/MS system was employed to characterize the [Fe(III)-3,4,3-LI(1,2-HOPO)] derivative and impurities. The proposed HPLC method was validated for specificity, linearity (concentration range 0.13-0.35 mg/mL, r = 0.9999), accuracy (recovery 98.3-103.3%), precision (RSD <= 1.6%) and sensitivity (LOD 0.08 mu g/mL). The LC/HRMS revealed that the derivative was a complex consisting of one 3,4,3-LI(1,2-HOPO) molecule, one hydroxide ligand, and two iron atoms. Impurities were also identified with LC/HRMS. The validated HPLC method was used in shelf-life evaluation studies which showed that the API remained unchanged for one year at 25 degrees C/60% RH. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Liu, Mingtao; Wang, Jennie; Wu, Xiaogang; Wang, Euphemia] SRI Int, Pharmaceut Dev Dept, Biosci Div, Menlo Pk, CA 94025 USA.
[Abergel, Rebecca J.; Shuh, David K.; Raymond, Kenneth N.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Chem Sci, Berkeley, CA 94720 USA.
[Raymond, Kenneth N.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Liu, Paul] NCI, Pharmaceut Resources Branch, DCTD, NIH, Bethesda, MD 20892 USA.
RP Wang, J (reprint author), SRI Int, Pharmaceut Dev Dept, Biosci Div, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.
EM jennie.wang@sri.com
FU NIH Common Fund; NIAID through Developmental Therapeutics Program,
Division of Cancer Treatment and Diagnosis, National Cancer Institute,
U.S. National Institutes of Health [HHSN261200722003C,
HHSN261201200028C]
FX This work was supported by the NIH Common Fund and NIAID through
Developmental Therapeutics Program, Division of Cancer Treatment and
Diagnosis, National Cancer Institute, U.S. National Institutes of Health
under Contract No. HHSN261200722003C and Contract No. HHSN261201200028C.
NR 15
TC 3
Z9 3
U1 3
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JAN 5
PY 2015
VL 102
BP 443
EP 449
DI 10.1016/j.jpba.2014.10.015
PG 7
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA AY0HH
UT WOS:000347277500054
PM 25459944
ER
PT J
AU Weidlich, IE
Pevzner, Y
Miller, BT
Filippov, IV
Woodcock, HL
Brooks, BR
AF Weidlich, Iwona E.
Pevzner, Yuri
Miller, Benjamin T.
Filippov, Igor V.
Woodcock, H. Lee
Brooks, Bernard R.
TI Development and Implementation of (Q)SAR Modeling Within the CHARMMing
Web-User Interface
SO JOURNAL OF COMPUTATIONAL CHEMISTRY
LA English
DT Article
DE CHARMMing; SAR; QSAR; machine learning; random forest
ID DRUG DISCOVERY; NEAREST-NEIGHBOR; CHEMICAL SPACE; PUBCHEM; QSAR;
VALIDATION; GENERATION; SAR
AB Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a web-based tool for structure activity relationship and quantitative structure activity relationship modeling to add to the services provided by CHARMMing (). This new module implements some of the most recent advances in modern machine learning algorithmsRandom Forest, Support Vector Machine, Stochastic Gradient Descent, Gradient Tree Boosting, so forth. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity. (c) 2014 Wiley Periodicals, Inc.
C1 [Weidlich, Iwona E.] Computat Drug Design Syst CODDES LLC, Rockville, MD 20852 USA.
[Weidlich, Iwona E.; Miller, Benjamin T.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20852 USA.
[Pevzner, Yuri; Woodcock, H. Lee] Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
[Filippov, Igor V.] VIF Innovat LLC, Rockville, MD 20852 USA.
RP Weidlich, IE (reprint author), Computat Drug Design Syst CODDES LLC, Rockville, MD 20852 USA.
EM iweidlic@coddes.com
OI Miller, Benjamin/0000-0003-1647-0122
FU Intramural Research Program of the National Heart, Lung and Blood
Institute of the National Institutes of Health; NIH [1K22HL088341-01A1];
University of South Florida
FX Contract grant sponsor: Intramural Research Program of the National
Heart, Lung and Blood Institute of the National Institutes of Health;
Contract grant sponsor: NIH; Contract grant number: 1K22HL088341-01A1;
Contract grant sponsor: University of South Florida
NR 52
TC 3
Z9 3
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0192-8651
EI 1096-987X
J9 J COMPUT CHEM
JI J. Comput. Chem.
PD JAN 5
PY 2015
VL 36
IS 1
BP 62
EP 67
DI 10.1002/jcc.23765
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA AU3KC
UT WOS:000345510800007
PM 25362883
ER
PT J
AU Bogoch, II
Creatore, MI
Cetron, MS
Brownstein, JS
Pesik, N
Miniota, J
Tam, T
Hu, W
Nicolucci, A
Ahmed, S
Yoon, JW
Berry, I
Hay, SI
Anema, A
Tatem, AJ
MacFadden, D
German, M
Khan, K
AF Bogoch, Isaac I.
Creatore, Maria I.
Cetron, Martin S.
Brownstein, John S.
Pesik, Nicki
Miniota, Jennifer
Tam, Theresa
Hu, Wei
Nicolucci, Adriano
Ahmed, Saad
Yoon, James W.
Berry, Isha
Hay, Simon I.
Anema, Aranka
Tatem, Andrew J.
MacFadden, Derek
German, Matthew
Khan, Kamran
TI Assessment of the potential for international dissemination of Ebola
virus via commercial air travel during the 2014 west African outbreak
SO LANCET
LA English
DT Article
ID HEALTH REGULATIONS
AB Background The WHO declared the 2014 west African Ebola epidemic a public health emergency of international concern in view of its potential for further international spread. Decision makers worldwide are in need of empirical data to inform and implement emergency response measures. Our aim was to assess the potential for Ebola virus to spread across international borders via commercial air travel and assess the relative efficiency of exit versus entry screening of travellers at commercial airports.
Methods We analysed International Air Transport Association data for worldwide flight schedules between Sept 1, 2014, and Dec 31, 2014, and historic traveller flight itinerary data from 2013 to describe expected global population movements via commercial air travel out of Guinea, Liberia, and Sierra Leone. Coupled with Ebola virus surveillance data, we modelled the expected number of internationally exported Ebola virus infections, the potential effect of air travel restrictions, and the efficiency of airport-based traveller screening at international ports of entry and exit. We deemed individuals initiating travel from any domestic or international airport within these three countries to have possible exposure to Ebola virus. We deemed all other travellers to have no significant risk of exposure to Ebola virus.
Findings Based on epidemic conditions and international flight restrictions to and from Guinea, Liberia, and Sierra Leone as of Sept 1, 2014 (reductions in passenger seats by 51% for Liberia, 66% for Guinea, and 85% for Sierra Leone), our model projects 2.8 travellers infected with Ebola virus departing the above three countries via commercial flights, on average, every month. 91 547 (64%) of all air travellers departing Guinea, Liberia, and Sierra Leone had expected destinations in low-income and lower-middle-income countries. Screening international travellers departing three airports would enable health assessments of all travellers at highest risk of exposure to Ebola virus infection.
C1 [Bogoch, Isaac I.; MacFadden, Derek; Khan, Kamran] Univ Toronto, Dept Med, Div Infect Dis, Toronto, ON, Canada.
[Bogoch, Isaac I.] Univ Hlth Network, Div Internal Med, Toronto, ON, Canada.
[Bogoch, Isaac I.] Univ Hlth Network, Div Infect Dis, Toronto, ON, Canada.
[Creatore, Maria I.; Miniota, Jennifer; Hu, Wei; Nicolucci, Adriano; Yoon, James W.; Berry, Isha; German, Matthew; Khan, Kamran] St Michaels Hosp, Li Ka Shing Knowledge Inst, Ctr Res Inner City Hlth, Toronto, ON M5B 1W8, Canada.
[Cetron, Martin S.] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA USA.
[Brownstein, John S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA.
[Brownstein, John S.; Anema, Aranka] Boston Childrens Hosp, Childrens Hosp Informat Program, Boston, MA USA.
[Pesik, Nicki] Ctr Dis Control & Prevent, Quarantine & Border Hlth Serv Branch, Div Global Migrat & Quarantine, Atlanta, GA USA.
[Tam, Theresa] Publ Hlth Agcy Canada, Hlth Secur Infrastruct Branch, Ottawa, ON, Canada.
[Ahmed, Saad] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada.
[Hay, Simon I.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Anema, Aranka] Univ British Columbia, Fac Med, Dept Med, Vancouver, BC, Canada.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
RP Khan, K (reprint author), St Michaels Hosp, 30 Bond St, Toronto, ON M5B 1W8, Canada.
EM khank@smh.ca
RI Hay, Simon/F-8967-2015
OI Hay, Simon/0000-0002-0611-7272
FU Canadian Institutes of Health Research
FX Canadian Institutes of Health Research.
NR 18
TC 40
Z9 41
U1 3
U2 75
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JAN 3
PY 2015
VL 385
IS 9962
BP 29
EP 35
DI 10.1016/S0140-6736(14)61828-6
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AX8IW
UT WOS:000347154200025
PM 25458732
ER
PT J
AU Malinovsky, Y
Albert, PS
AF Malinovsky, Yaakov
Albert, Paul S.
TI A Note on the Minimax Solution for the Two-Stage Group Testing Problem
SO AMERICAN STATISTICIAN
LA English
DT Article
DE Loss function; Optimal design; Optimization problem
ID COST; PRIORS; HIV; DISTRIBUTIONS; INFECTIONS; DEFECTIVES
AB Group testing is an active area of current research and has important applications in medicine, biotechnology, genetics, and product testing. There have been recent advances in design and estimation, but the simple Dorfman procedure introduced by R. Dorfman in 1943 is widely used in practice. In many practical situations, the exact value of the probability p of being affected is unknown. We present both minimax and Bayesian solutions for the group size problem when p is unknown. For unbounded p, we show that the minimax solution for group size is 8, while using a Bayesian strategy with Jeffreys' prior results in a group size of 13. We also present solutions when p is bounded from above. For the practitioner, we propose strong justification for using a group size of between 8 and 13 when a constraint on p is not incorporated and provide useable code for computing the minimax group size under a constrained p.
C1 [Malinovsky, Yaakov] Univ Maryland, Dept Math & Stat, Baltimore, MD 21250 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
RP Malinovsky, Y (reprint author), Univ Maryland, Dept Math & Stat, Baltimore, MD 21250 USA.
EM yaakovm@umbc.edu; albertp@mail.nih.gov
FU UMBC Summer Faculty Fellowship; Eunice Kennedy Shriver National
Institute of Child Health and Human Development intramural program
FX The work was partially supported by a 2013 UMBC Summer Faculty
Fellowship grant and the Eunice Kennedy Shriver National Institute of
Child Health and Human Development intramural program. The authors thank
an editor, associate editor, and two referees for their thoughtful and
constructive comments and suggestions that resulted in very significant
improvements in the article. The authors also thank Sara Joslyn for
editing the article and Abram Kagan and Yosef Rinott for discussions on
the topic and comments on the article.
NR 32
TC 1
Z9 1
U1 0
U2 1
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0003-1305
EI 1537-2731
J9 AM STAT
JI Am. Stat.
PD JAN 2
PY 2015
VL 69
IS 1
BP 45
EP 52
DI 10.1080/00031305.2014.983545
PG 8
WC Statistics & Probability
SC Mathematics
GA CE3ZC
UT WOS:000351767700009
PM 28042146
ER
PT J
AU Hobson, JA
AF Hobson, J. Allan
TI Dreams and Consciousness: Response to Colace and Boag
SO CONTEMPORARY PSYCHOANALYSIS
LA English
DT Article
C1 [Hobson, J. Allan] Harvard Univ, Sch Med, Psychiat, Boston, MA USA.
[Hobson, J. Allan] Bellevue Hosp, Med, New York, NY USA.
[Hobson, J. Allan] Massachusetts Mental Hlth Ctr, Psychiat, Boston, MA 02115 USA.
[Hobson, J. Allan] NIMH, New York, NY USA.
[Hobson, J. Allan] Univ Lyon, Natl Inst Mental Hlth, Dept Physiol, Lyon, France.
RP Hobson, JA (reprint author), 322 Shore Dr, Salem, NH 03079 USA.
EM allan_hobson@hms.harvard.edu
NR 11
TC 1
Z9 1
U1 0
U2 3
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0010-7530
EI 2330-9091
J9 CONTEMP PSYCHOANAL
JI Contemp. Psychoanal.
PD JAN 2
PY 2015
VL 51
IS 1
BP 126
EP 131
DI 10.1080/00107530.2014.958048
PG 6
WC Psychiatry; Psychology, Psychoanalysis
SC Psychiatry; Psychology
GA CD5WQ
UT WOS:000351159800006
ER
PT J
AU Colon-Ramos, U
Rutten, LJF
Moser, RP
Colon-Lopez, V
Ortiz, AP
Yaroch, AL
AF Colon-Ramos, Uriyoan
Rutten, Lila J. Finney
Moser, Richard P.
Colon-Lopez, Vivian
Ortiz, Ana P.
Yaroch, Amy Lazarus
TI The Association Between Fruit and Vegetable Intake, Knowledge of the
Recommendations, and Health Information Seeking Within Adults in the
U.S. Mainland and in Puerto Rico
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID FACTOR SURVEILLANCE SYSTEM; NATIONAL TRENDS SURVEY; INTERVIEW SURVEY;
MEDICAL ENCOUNTER; CONSUMPTION; DISPARITIES; SUBGROUPS; LITERACY
AB Health information correlates of fruit and vegetable intake and of knowledge of the fruit and vegetable recommendations were examined using bivariate and multivariate regressions with data from the 2007-2008 U.S. National Cancer Institute's Health Information National Trends Survey in the United States and in Puerto Rico. Residents from Puerto Rico had the lowest reported fruit and vegetable intake and the lowest knowledge of the recommended servings of fruits and vegetables to maintain good health, compared with U.S. Hispanics, non-Hispanic Whites, and Blacks. Sixty-seven percent of Puerto Rican residents and 62% of U.S. Hispanics reported never seeking information on health or medical topics. In multivariate analysis, those who never sought information on health or medical topics reported significantly lower fruit and vegetable intake (coefficient=-0.24; 95% CI [-0.38, -0.09]), and were less likely to know the fruit and vegetable recommendations (OR=0.32; 95% CI [0.20, 0.52]), compared with those who obtained information from their health care providers. Health promotion initiatives in the United States and Puerto Rico have invested in mass media campaigns to increase consumption of and knowledge about fruit and vegetables, but populations with the lowest intake are less likely to seek information. Strategies must be multipronged to address institutional, economic, and behavioral constraints of populations who do not seek out health information from any sources.
C1 [Colon-Ramos, Uriyoan] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC 20052 USA.
[Rutten, Lila J. Finney] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Rutten, Lila J. Finney] Mayo Clin, Populat Hlth Sci Program, Ctr Sci Hlth Care Delivery, Rochester, MN USA.
[Moser, Richard P.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
[Colon-Lopez, Vivian] Univ Puerto Rico, Grad Sch Publ Hlth, Dept Hlth Serv Adm, San Juan, PR 00936 USA.
[Ortiz, Ana P.] Univ Puerto Rico, Grad Sch Publ Hlth, Dept Biostat & Epidemiol, San Juan, PR 00936 USA.
[Yaroch, Amy Lazarus] Gretchen Swanson Ctr Nutr, Omaha, NE USA.
RP Colon-Ramos, U (reprint author), George Washington Univ, Dept Global Hlth, Milken Inst Sch Publ Hlth, 950 New Hampshire Ave 410, Washington, DC 20052 USA.
EM uriyoan@gwu.edu
NR 35
TC 1
Z9 1
U1 1
U2 10
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD JAN 2
PY 2015
VL 20
IS 1
BP 105
EP 111
DI 10.1080/10810730.2014.914607
PG 7
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA CB0LD
UT WOS:000349316500011
PM 25204843
ER
PT J
AU Schutt, RC
Trachtenberg, BH
Cooke, JP
Traverse, JH
Henry, TD
Pepine, CJ
Willerson, JT
Perin, EC
Ellis, SG
Zhao, DXM
Bhatnagar, A
Johnstone, BH
Lai, DJ
Resende, M
Ebert, RF
Wu, JC
Sayre, SL
Orozco, A
Zierold, C
Simari, RD
Moye, L
Cogle, CR
Taylor, DA
AF Schutt, Robert C.
Trachtenberg, Barry H.
Cooke, John P.
Traverse, Jay H.
Henry, Timothy D.
Pepine, Carl J.
Willerson, James T.
Perin, Emerson C.
Ellis, Stephen G.
Zhao, David X. M.
Bhatnagar, Aruni
Johnstone, Brian H.
Lai, Dejian
Resende, Micheline
Ebert, Ray F.
Wu, Joseph C.
Sayre, Shelly L.
Orozco, Aaron
Zierold, Claudia
Simari, Robert D.
Moye, Lem
Cogle, Christopher R.
Taylor, Doris A.
CA CCTRN
TI Bone Marrow Characteristics Associated With Changes in Infarct Size
After STEMI A Biorepository Evaluation From the CCTRN TIME Trial
SO CIRCULATION RESEARCH
LA English
DT Article
DE acute myocardial infarction; adult stem cell; coronary circulation;
regeneration
ID ENDOTHELIAL PROGENITOR CELLS; ACUTE MYOCARDIAL-INFARCTION;
CARDIOVASCULAR RISK; RANDOMIZED-TRIAL; THERAPY; NEOVASCULARIZATION;
TRANSPLANTATION; ANGIOGENESIS; POPULATION; COLONIES
AB Rationale: Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear.
Objective: The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction.
Methods and Results: This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0+/-17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively).
Conclusions: This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation.
C1 [Schutt, Robert C.; Trachtenberg, Barry H.; Cooke, John P.] Houston Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA.
[Schutt, Robert C.; Trachtenberg, Barry H.; Cooke, John P.] Houston Methodist Res Inst, Houston, TX USA.
[Traverse, Jay H.] Minneapolis Heart Inst Fdn, Abbott Northwestern Hosp, Minneapolis, MN USA.
[Henry, Timothy D.] Cedars Sinai Heart Inst, Los Angeles, CA USA.
[Pepine, Carl J.; Cogle, Christopher R.] Univ Florida, Coll Med, Gainesville, FL USA.
[Willerson, James T.; Perin, Emerson C.; Resende, Micheline; Orozco, Aaron; Taylor, Doris A.] CHI St Lukes Hlth, Texas Heart Inst, Houston, TX USA.
[Zierold, Claudia] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Ellis, Stephen G.] Cleveland Clin Fdn, Cleveland, OH USA.
[Zhao, David X. M.] Sch Med, Winston Salem, NC USA.
[Bhatnagar, Aruni] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
[Johnstone, Brian H.] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Lai, Dejian; Sayre, Shelly L.; Moye, Lem] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA.
[Ebert, Ray F.] NHLBI, Bethesda, MD 20892 USA.
[Wu, Joseph C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Simari, Robert D.] Univ Kansas, Med Ctr, Sch Med, Lawrence, KS 66045 USA.
RP Moye, L (reprint author), 1200 Pressler St E1009, Houston, TX 77030 USA.
EM Lemmoye@msn.com
RI Cogle, Christopher/H-1746-2016;
OI Cogle, Christopher/0000-0001-5422-6863; Cooke, John/0000-0003-0033-9138
FU University of Florida [R01 HL091005, UM1 HL087318]
FX This study was funded by UM1 HL087318 (Cardiovascular Cell Therapy
Research Network) and R01 HL091005 (Ancillary Studies), University of
Florida.
NR 42
TC 13
Z9 13
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JAN 2
PY 2015
VL 116
IS 1
BP 99
EP U240
DI 10.1161/CIRCRESAHA.116.304710
PG 17
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AX6TA
UT WOS:000347052800017
PM 25406300
ER
PT J
AU Gupta, SD
Gable, K
Alexaki, A
Chandris, P
Proia, RL
Dunn, TM
Harmon, JM
AF Gupta, Sita D.
Gable, Kenneth
Alexaki, Aikaterini
Chandris, Panagiotis
Proia, Richard L.
Dunn, Teresa M.
Harmon, Jeffrey M.
TI Expression of the ORMDLS, Modulators of Serine Palmitoyltransferase, Is
Regulated by Sphingolipids in Mammalian Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Enzyme; Lipid Metabolism; Metabolic Regulation; Serine
Palmitoyltransferase; Sphingolipid
ID PROTEINS MEDIATE; HOMEOSTASIS; ASTHMA; BIOSYNTHESIS; GENE; ORM2;
ACCUMULATION; INHIBITION; SUBUNITS; STRESS
AB Background: In contrast to their yeast orthologues, the mechanism by which mammalian ORMDLs regulate serine palmitoyltransferase is not understood. Results: Overexpression of serine palmitoyltransferase in HEK293 cells results in increased long-chain base synthesis and an activity-dependent increase in ORMDL expression. Conclusion: A product of ceramide synthase mediates regulation of ORMDL expression and inhibition of serine palmitoyltransferase. Significance: Serine palmitoyltransferase activity indirectly regulates ORMDL expression.
The relationship between serine palmitoyltransferase (SPT) activity and ORMDL regulation of sphingolipid biosynthesis was investigated in mammalian HEK293 cells. Each of the three human ORMDLs reduced the increase in long-chain base synthesis seen after overexpression of wild-type SPT or SPT containing the C133W mutation in hLCB1, which produces the non-catabolizable sphingoid base, 1-deoxySa. ORMDL-dependent repression of sphingoid base synthesis occurred whether SPT was expressed as individual subunits or as a heterotrimeric single-chain SPT fusion protein. Overexpression of the single-chain SPT fusion protein under the control of a tetracycline-inducible promoter in stably transfected cells resulted in increased endogenous ORMDL expression. This increase was not transcriptional; there was no significant increase in any of the ORMDL mRNAs. Increased ORMDL protein expression required SPT activity since overexpression of a catalytically inactive SPT with a mutation in hLCB2a had little effect. Significantly, increased ORMDL expression was also blocked by myriocin inhibition of SPT as well as fumonisin inhibition of the ceramide synthases, suggesting that increased expression is a response to a metabolic signal. Moreover, blocking ORMDL induction with fumonisin treatment resulted in significantly greater increases in in vivo SPT activity than was seen when ORMDLs were allowed to increase, demonstrating the physiological significance of this response.
C1 [Gupta, Sita D.; Gable, Kenneth; Dunn, Teresa M.] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
[Harmon, Jeffrey M.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
[Alexaki, Aikaterini; Chandris, Panagiotis; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Harmon, JM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM jeffrey.harmon@usuhs.edu
OI Harmon, Jeffrey/0000-0001-7833-931X
FU Uniformed Services University [R071KD, CO75PI]; National Institutes of
Health [R01NS072446, R21HD080181]; Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by Uniformed Services University Grants R071KD
and CO75PI, by National Institutes of Health Grants R01NS072446 and
R21HD080181, and by the Intramural Research Program of the National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 29
TC 9
Z9 9
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 2
PY 2015
VL 290
IS 1
BP 90
EP 98
DI 10.1074/jbc.M114.588236
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AX9OG
UT WOS:000347231200009
PM 25395622
ER
PT J
AU Neafsey, DE
Waterhouse, RM
Abai, MR
Aganezov, SS
Alekseyev, MA
Allen, JE
Amon, J
Arca, B
Arensburger, P
Artemov, G
Assour, LA
Basseri, H
Berlin, A
Birren, BW
Blandin, SA
Brockman, AI
Burkot, TR
Burt, A
Chan, CS
Chauve, C
Chiu, JC
Christensen, M
Costantini, C
Davidson, VLM
Deligianni, E
Dottorini, T
Dritsou, V
Gabriel, SB
Guelbeogo, WM
Hall, AB
Han, MV
Hlaing, T
Hughes, DST
Jenkins, AM
Jiang, XF
Jungreis, I
Kakani, EG
Kamali, M
Kemppainen, P
Kennedy, RC
Kirmitzoglou, IK
Koekemoer, LL
Laban, N
Langridge, N
Lawniczak, MKN
Lirakis, M
Lobo, NF
Lowy, E
MacCallum, RM
Mao, CH
Maslen, G
Mbogo, C
McCarthy, J
Michel, K
Mitchell, SN
Moore, W
Murphy, KA
Naumenko, AN
Nolan, T
Novoa, EM
O'Loughlin, S
Oringanje, C
Oshaghi, MA
Pakpour, N
Papathanos, PA
Peery, AN
Povelones, M
Prakash, A
Price, DP
Rajaraman, A
Reimer, LJ
Rinker, DC
Rokas, A
Russell, TL
Sagnon, N
Sharakhova, MV
Shea, T
Simao, FA
Simard, F
Slotman, MA
Somboon, P
Stegniy, V
Struchiner, CJ
Thomas, GWC
Tojo, M
Topalis, P
Tubio, JMC
Unger, MF
Vontas, J
Walton, C
Wilding, CS
Willis, JH
Wu, YC
Yan, GY
Zdobnov, EM
Zhou, XF
Catteruccia, F
Christophides, GK
Collins, FH
Cornman, RS
Crisanti, A
Donnelly, MJ
Emrich, SJ
Fontaine, MC
Gelbart, W
Hahn, MW
Hansen, IA
Howell, PI
Kafatos, FC
Kellis, M
Lawson, D
Louis, C
Luckhart, S
Muskavitch, MAT
Ribeiro, JM
Riehle, MA
Sharakhov, IV
Tu, ZJ
Zwiebel, LJ
Besansky, NJ
AF Neafsey, Daniel E.
Waterhouse, Robert M.
Abai, Mohammad R.
Aganezov, Sergey S.
Alekseyev, Max A.
Allen, James E.
Amon, James
Arca, Bruno
Arensburger, Peter
Artemov, Gleb
Assour, Lauren A.
Basseri, Hamidreza
Berlin, Aaron
Birren, Bruce W.
Blandin, Stephanie A.
Brockman, Andrew I.
Burkot, Thomas R.
Burt, Austin
Chan, Clara S.
Chauve, Cedric
Chiu, Joanna C.
Christensen, Mikkel
Costantini, Carlo
Davidson, Victoria L. M.
Deligianni, Elena
Dottorini, Tania
Dritsou, Vicky
Gabriel, Stacey B.
Guelbeogo, Wamdaogo M.
Hall, Andrew B.
Han, Mira V.
Hlaing, Thaung
Hughes, Daniel S. T.
Jenkins, Adam M.
Jiang, Xiaofang
Jungreis, Irwin
Kakani, Evdoxia G.
Kamali, Maryam
Kemppainen, Petri
Kennedy, Ryan C.
Kirmitzoglou, Ioannis K.
Koekemoer, Lizette L.
Laban, Njoroge
Langridge, Nicholas
Lawniczak, Mara K. N.
Lirakis, Manolis
Lobo, Neil F.
Lowy, Ernesto
MacCallum, Robert M.
Mao, Chunhong
Maslen, Gareth
Mbogo, Charles
McCarthy, Jenny
Michel, Kristin
Mitchell, Sara N.
Moore, Wendy
Murphy, Katherine A.
Naumenko, Anastasia N.
Nolan, Tony
Novoa, Eva M.
O'Loughlin, Samantha
Oringanje, Chioma
Oshaghi, Mohammad A.
Pakpour, Nazzy
Papathanos, Philippos A.
Peery, Ashley N.
Povelones, Michael
Prakash, Anil
Price, David P.
Rajaraman, Ashok
Reimer, Lisa J.
Rinker, David C.
Rokas, Antonis
Russell, Tanya L.
Sagnon, N'Fale
Sharakhova, Maria V.
Shea, Terrance
Simao, Felipe A.
Simard, Frederic
Slotman, Michel A.
Somboon, Pradya
Stegniy, Vladimir
Struchiner, Claudio J.
Thomas, Gregg W. C.
Tojo, Marta
Topalis, Pantelis
Tubio, Jose M. C.
Unger, Maria F.
Vontas, John
Walton, Catherine
Wilding, Craig S.
Willis, Judith H.
Wu, Yi-Chieh
Yan, Guiyun
Zdobnov, Evgeny M.
Zhou, Xiaofan
Catteruccia, Flaminia
Christophides, George K.
Collins, Frank H.
Cornman, Robert S.
Crisanti, Andrea
Donnelly, Martin J.
Emrich, Scott J.
Fontaine, Michael C.
Gelbart, William
Hahn, Matthew W.
Hansen, Immo A.
Howell, Paul I.
Kafatos, Fotis C.
Kellis, Manolis
Lawson, Daniel
Louis, Christos
Luckhart, Shirley
Muskavitch, Marc A. T.
Ribeiro, Jose M.
Riehle, Michael A.
Sharakhov, Igor V.
Tu, Zhijian
Zwiebel, Laurence J.
Besansky, Nora J.
TI Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes
SO SCIENCE
LA English
DT Article
ID ANTENNAL TRANSCRIPTOME PROFILES; SEX-CHROMOSOME EVOLUTION; CUTICULAR
PROTEIN GENES; AEDES-AEGYPTI; R CONSENSUS; GAMBIAE; DROSOPHILA;
EXPRESSION; ANNOTATION; FAMILY
AB Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning similar to 100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.
C1 [Neafsey, Daniel E.; Berlin, Aaron; Birren, Bruce W.; Shea, Terrance] Broad Inst, Genome Sequencing & Anal Program, Cambridge, MA 02142 USA.
[Waterhouse, Robert M.; Chan, Clara S.; Jungreis, Irwin; Novoa, Eva M.; Wu, Yi-Chieh; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Waterhouse, Robert M.; Chan, Clara S.; Jungreis, Irwin; Novoa, Eva M.; Wu, Yi-Chieh; Kellis, Manolis] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA.
[Waterhouse, Robert M.; Simao, Felipe A.; Zdobnov, Evgeny M.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
[Waterhouse, Robert M.; Simao, Felipe A.; Zdobnov, Evgeny M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland.
[Abai, Mohammad R.; Basseri, Hamidreza; Oshaghi, Mohammad A.] Univ Tehran Med Sci, Dept Med Entomol & Vector Control, Sch Publ Hlth, Tehran, Iran.
[Abai, Mohammad R.; Basseri, Hamidreza; Oshaghi, Mohammad A.] Univ Tehran Med Sci, Inst Hlth Res, Tehran, Iran.
[Aganezov, Sergey S.; Alekseyev, Max A.] George Washington Univ, Dept Math, Ashburn, VA 20147 USA.
[Aganezov, Sergey S.; Alekseyev, Max A.] George Washington Univ, Computat Biol Inst, Ashburn, VA 20147 USA.
[Allen, James E.; Christensen, Mikkel; Hughes, Daniel S. T.; Langridge, Nicholas; Lowy, Ernesto; Maslen, Gareth; Lawson, Daniel] EMBL EBI, Cambridge CB10 1SD, England.
[Amon, James] Minist Hlth, Natl Vector Borne Dis Control Programme, Port Vila, Tafea Province, Vanuatu.
[Arca, Bruno] Univ Roma La Sapienza, Div Parasitol, Dept Publ Hlth & Infect Dis, I-00185 Rome, Italy.
[Arensburger, Peter; McCarthy, Jenny] Calif State Polytech Pomona, Dept Biol Sci, Pomona, CA 91768 USA.
[Artemov, Gleb; Stegniy, Vladimir] Tomsk State Univ, Tomsk 634050, Russia.
[Assour, Lauren A.; Emrich, Scott J.] Univ Notre Dame, Eck Inst Global Hlth, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA.
[Blandin, Stephanie A.] INSERM, U963, F-67084 Strasbourg, France.
[Blandin, Stephanie A.] CNRS, UPR9022, IBMC, F-67084 Strasbourg, France.
[Brockman, Andrew I.; Dottorini, Tania; Kirmitzoglou, Ioannis K.; Lawniczak, Mara K. N.; MacCallum, Robert M.; Nolan, Tony; Papathanos, Philippos A.; Christophides, George K.; Crisanti, Andrea; Kafatos, Fotis C.] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England.
[Burkot, Thomas R.; Russell, Tanya L.] James Cook Univ, Australian Inst Trop Hlth Med, Fac Med Hlth & Mol Sci, Cairns 4870, Australia.
[Burt, Austin; O'Loughlin, Samantha] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, Ascot SL5 7PY, Berks, England.
[Chauve, Cedric; Rajaraman, Ashok] Simon Fraser Univ, Dept Math, Burnaby, BC V5A 1S6, Canada.
[Chiu, Joanna C.; Murphy, Katherine A.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Costantini, Carlo; Simard, Frederic] Inst Rech Dev, Unites Mixtes Rech Malad Infect & Vecteurs Ecol G, F-64501 Montpellier, France.
[Davidson, Victoria L. M.; Michel, Kristin] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
[Deligianni, Elena; Topalis, Pantelis; Louis, Christos] Fdn Res & Technol, Inst Mol Biol & Biotechnol, GR-70013 Iraklion, Crete, Greece.
[Dritsou, Vicky; Papathanos, Philippos A.; Crisanti, Andrea; Louis, Christos] Univ Perugia, Ctr Funct Genom, I-06100 Perugia, Italy.
[Gabriel, Stacey B.] Broad Inst, Cambridge, MA 02142 USA.
[Guelbeogo, Wamdaogo M.; Sagnon, N'Fale] Ctr Natl Rech & Format Paludisme, Ouagadougou, Burkina Faso.
[Hall, Andrew B.; Jiang, Xiaofang; Sharakhov, Igor V.; Tu, Zhijian] Virginia Polytech Inst & State Univ, Program Genet Bioinformat & Computat Biol, Blacksburg, VA 24061 USA.
[Han, Mira V.] Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA.
[Hlaing, Thaung] Dept Med Res, Dagon Township 11191, Yangon, Myanmar.
[Hughes, Daniel S. T.] Baylor Coll Med, Houston, TX 77030 USA.
[Jenkins, Adam M.; Muskavitch, Marc A. T.] Boston Coll, Chestnut Hill, MA 02467 USA.
[Jiang, Xiaofang; Tu, Zhijian] Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA.
[Kakani, Evdoxia G.; Mitchell, Sara N.; Catteruccia, Flaminia] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Kakani, Evdoxia G.; Catteruccia, Flaminia] Univ Perugia, Dipartimento Med Sperimentale & Sci Biochim, Perugia, Italy.
[Kamali, Maryam; Naumenko, Anastasia N.; Peery, Ashley N.; Sharakhova, Maria V.; Sharakhov, Igor V.] Virginia Polytech Inst & State Univ, Dept Entomol, Blacksburg, VA 24061 USA.
[Kemppainen, Petri; Walton, Catherine] Univ Manchester, Fac Life Sci, Computat Evolutionary Biol Grp, Oxford M13 9PT, England.
[Kennedy, Ryan C.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Kirmitzoglou, Ioannis K.] Univ Cyprus, Dept Biol Sci, Bioinformat Res Lab, CY-1678 Nicosia, Cyprus.
[Koekemoer, Lizette L.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Wits Res Inst Malaria, Fac Hlth Sci, ZA-2131 Johannesburg, South Africa.
[Koekemoer, Lizette L.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Vector Control Reference Unit, ZA-2131 Johannesburg, South Africa.
[Laban, Njoroge] Natl Museums Kenya, Nairobi, Kenya.
[Lirakis, Manolis; Vontas, John; Louis, Christos] Univ Crete, Dept Biol, GR-70013 Iraklion, Greece.
[Lobo, Neil F.; Unger, Maria F.; Collins, Frank H.; Fontaine, Michael C.; Besansky, Nora J.] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Lobo, Neil F.; Unger, Maria F.; Collins, Frank H.; Fontaine, Michael C.; Besansky, Nora J.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Mao, Chunhong] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA.
[Mbogo, Charles] Ctr Geog Med Res, Kenya Med Res Inst, Wellcome Trust Res Programme, Kilifi, Kenya.
[Moore, Wendy; Oringanje, Chioma; Riehle, Michael A.] Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA.
[Pakpour, Nazzy; Luckhart, Shirley] Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
[Povelones, Michael] Univ Penn, Sch Vet Med, Dept Pathol, Philadelphia, PA 19104 USA.
[Prakash, Anil] Indian Council Med Res, Reg Med Res Ctr NE, Dibrugarh 786001, Assam, India.
[Price, David P.; Hansen, Immo A.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA.
[Price, David P.; Hansen, Immo A.] New Mexico State Univ, Mol Biol Program, Las Cruces, NM 88003 USA.
[Reimer, Lisa J.; Donnelly, Martin J.] Univ Liverpool Liverpool Sch Trop Med, Dept Vector Biol, Liverpool L3 5QA, Merseyside, England.
[Rinker, David C.; Rokas, Antonis] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Rokas, Antonis; Zhou, Xiaofan] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
[Slotman, Michel A.] Texas A&M Univ, Dept Entomol, College Stn, TX 77807 USA.
[Somboon, Pradya] Chiang Mai Univ, Fac Med, Dept Parasitol, Chiang Mai 50200, Thailand.
[Struchiner, Claudio J.] Fundacao Oswaldo Cruz, Rio De Janeiro, RJ, Brazil.
[Struchiner, Claudio J.] Univ Estado Rio de Janeiro, Inst Social Med, BR-20550011 Rio De Janeiro, Brazil.
[Thomas, Gregg W. C.; Hahn, Matthew W.] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA.
[Tojo, Marta] Univ Santiago de Compostela, Inst Invest Sanitarias, Ctr Res Mol Med & Chron Dis, Sch Med,Dept Physiol, La Coruna, Spain.
[Tubio, Jose M. C.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
[Wilding, Craig S.] Liverpool John Moores Univ, Sch Nat Sci & Psychol, Liverpool L3 3AF, Merseyside, England.
[Willis, Judith H.; Cornman, Robert S.] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA.
[Wu, Yi-Chieh] Harvey Mudd Coll, Dept Comp Sci, Claremont, CA 91711 USA.
[Yan, Guiyun] Univ Calif Irvine, Coll Hlth Sci, Program Publ Hlth, Irvine, CA 92697 USA.
[Donnelly, Martin J.] Wellcome Trust Sanger Inst, Malaria Programme, Cambridge CB10 1SJ, England.
[Fontaine, Michael C.] Univ Groningen, Ctr Evolutionary & Ecol Studies, Marine Evolut & Conservat Grp, NL-9747 AG Groningen, Netherlands.
[Gelbart, William] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Hahn, Matthew W.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Howell, Paul I.] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA.
[Muskavitch, Marc A. T.] Biogen Idec Inc, Cambridge, MA 02142 USA.
[Ribeiro, Jose M.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Zwiebel, Laurence J.] Vanderbilt Univ & Med Ctr, Dept Biol Sci, Inst Chem Biol, Nashville, TN 37235 USA.
[Zwiebel, Laurence J.] Vanderbilt Univ & Med Ctr, Dept Pharmacol, Inst Genet & Global Hlth, Nashville, TN 37235 USA.
RP Neafsey, DE (reprint author), Broad Inst, Genome Sequencing & Anal Program, 415 Main St, Cambridge, MA 02142 USA.
EM neafsey@broadinstitute.org; nbesansk@nd.edu
RI Novoa, Eva Maria/B-1004-2015; Stegniy, Vladimir/N-7656-2014; Tubio,
Jose/H-5076-2015; Ribeiro, Jose/J-7011-2015; Wilding, Craig/C-5500-2012;
Rokas, Antonis/A-9775-2008; Alekseyev, Max/D-9362-2016; Waterhouse,
Robert/A-1858-2010; Artemov, Gleb/N-7651-2014; Blandin,
Stephanie/I-2786-2016; SIMARD, Frederic/J-9489-2016; Zdobnov,
Evgeny/K-1133-2012
OI Hahn, Matthew/0000-0002-5731-8808; Ribeiro, Jose/0000-0002-9107-0818;
Arca, Bruno/0000-0002-4029-0984; Novoa, Eva Maria/0000-0001-5567-1299;
Tubio, Jose/0000-0003-3540-2459; Wilding, Craig/0000-0001-5818-2706;
Rokas, Antonis/0000-0002-7248-6551; Alekseyev, Max/0000-0002-5140-8095;
Waterhouse, Robert/0000-0003-4199-9052; SIMARD,
Frederic/0000-0002-2871-5329;
FU National Center for Biotechnology Information [PRJNA67511]
FX All sequencing reads and genome assemblies have been submitted to the
National Center for Biotechnology Information (umbrella BioProject ID,
PRJNA67511). Genome and transcriptome assemblies are also available from
VectorBase (https://vectorbase.org) and the Broad Institute
(https://olive.broadinstitute.org/collections/anopheles.4). The authors
acknowledge the NIH Eukaryotic Pathogen and Disease Vector Sequencing
Project Working Group for guidance and development of this project.
Sequence data generation was supported at the Broad Institute by the
National Human Genome Research Institute (U54 HG003067). We thank the
many members of the Broad Institute Genomics Platform and Genome
Sequencing and Analysis Program who contributed to sequencing data
generation and analysis.
NR 53
TC 92
Z9 97
U1 30
U2 171
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JAN 2
PY 2015
VL 347
IS 6217
AR UNSP 1258522
DI 10.1126/science.1258522
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AX7NK
UT WOS:000347102300042
PM 25554792
ER
PT J
AU Li, KG
Seo, DC
Torabi, MR
AF Li, Kaigang
Seo, Dong-Chul
Torabi, Mohammad R.
TI Measuring Outcome Expectancy Value of Leisure-Time Physical Activity for
African Americans
SO BEHAVIORAL MEDICINE
LA English
DT Article
DE cross-validation; African Americans; leisure-time physical activity;
confirmatory factor analysis; outcome expectancy value
ID SOCIAL-COGNITIVE THEORY; SELF-EFFICACY; HEALTH-PROMOTION; ADOLESCENT
GIRLS; US ADULTS; DETERMINANTS; PREVENTION; BARRIERS; DISEASE; OBESITY
AB A scale was adapted from existing scales to measure the outcome expectancy value (EV) as one of contributory factors to leisure-time physical activity (LTPA) and was administered to 649 African American adults. The eligible participants (N = 569) for the analysis were split into three subsamples (rate = 0.5 : 0.25 : 0.25) respectively for Exploratory Factor Analysis (N = 285) and cross-validation (N = 142 for the calibration group and N = 142 for the validation group) to evaluate the psychometric properties of the scale. Item analysis of the scale provided adequate psychometric properties. The 2-factor solution with positive and negative outcome EV subscales was supported based on the exploratory factor analysis and the multiple-group confirmatory factor analysis for both the calibration and validation samples. The results support the factorial construct validity and criterion validity of the outcome EV scale applied to assess LTPA in a sample of church-going African Americans.
C1 [Li, Kaigang] NICHHD, Bethesda, MD 20852 USA.
[Seo, Dong-Chul] Ewha Womans Univ, Coll Hlth Sci, Seoul, South Korea.
[Torabi, Mohammad R.] Indiana Univ Sch Publ Hlth Bloomington, Bloomington, IN USA.
RP Li, KG (reprint author), NICHHD, Hlth Behav Branch, 6100 Execut Blvd 7B13B, Bethesda, MD 20852 USA.
EM likaigang@gmail.com
RI Seo, Dong-Chul/A-6935-2009
OI Seo, Dong-Chul/0000-0002-1972-6237
NR 46
TC 0
Z9 0
U1 3
U2 14
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0896-4289
EI 1940-4026
J9 BEHAV MED
JI Behav. Med.
PD JAN 2
PY 2015
VL 41
IS 1
BP 33
EP 39
DI 10.1080/08964289.2014.881775
PG 7
WC Behavioral Sciences; Psychiatry
SC Behavioral Sciences; Psychiatry
GA AW6BB
UT WOS:000346353400005
PM 24438219
ER
PT J
AU Somsouk, M
Estes, JD
Deleage, C
Dunham, RM
Albright, R
Inadomi, JM
Martin, JN
Deeks, SG
McCune, JM
Hunt, PW
AF Somsouk, Ma
Estes, Jacob D.
Deleage, Claire
Dunham, Richard M.
Albright, Rebecca
Inadomi, John M.
Martin, Jeffrey N.
Deeks, Steven G.
McCune, Joseph M.
Hunt, Peter W.
TI Gut epithelial barrier and systemic inflammation during chronic HIV
infection
SO AIDS
LA English
DT Article
DE epithelial proliferation; HIV; immune activation; inflammation;
microbial translocation
ID IMMUNODEFICIENCY-VIRUS-INFECTION; COMBINATION ANTIRETROVIRAL THERAPY;
T-CELL-ACTIVATION; IMMUNE ACTIVATION; MICROBIAL TRANSLOCATION; MUCOSAL;
MORTALITY; APOPTOSIS; DYSFUNCTION; DEPLETION
AB Objective: Microbial translocation and innate immune action characterize HIV infection. Continued gut mucosal dysfunction during treatment and its relationship to CD4(+) T-cell recovery has not been well described.
Design: A cross-sectional study was performed of antiretroviral therapy (ART)-suppressed (immunologic responders with CD4(+) > 500 cells/mu l and immunologic nonresponders with CD4(+) < 350 cells/mu l), untreated HIV-infected, and seronegative participants consenting to gut biopsies and a blood draw.
Methods: Neutrophil infiltration as a surrogate response to epithelial breach, colorectal epithelial proliferation as a measure of repair, and mucosal apoptosis by immunohistochemistry were determined in gut biopsies. Plasma markers of monocyte activation (sCD14), immune activation (interleukin-6), and indoleamine 2,3-dioxygenase-1 activity (plasma kynurenine/tryptophanratio) were concurrently measured.
Results: Each HIV-infected group had greater neutrophil infiltration than controls. Similarly, untreated HIV-infected participants and ART-suppressed immunologic responders had increased epithelial proliferation compared with controls, but immunologic nonresponders had no appreciable increase in epithelial proliferation despite elevated neutrophil infiltration. The CD4(+) T-cell count was positively correlated with epithelial proliferation and was modestly negatively correlated with neutrophil infiltration in ART-suppressed patients. Epithelial proliferation was inversely correlated with mucosal apoptosis, and apoptosis was linked to plasma sCD14 and modestly to kynurenine/tryptophan ratio.
Conclusions: Neutrophil infiltration and mucosal apoptosis remain abnormally high despite ART. Epithelial proliferation increases in HIV, but may be impaired in immunologic nonresponders. Whether mucosal apoptosis is a cause or consequence of epithelial proliferative defects is unclear, but appears to be associated with systemic inflammation. The impact of ART and interventions targeting the gut epithelial barrier in treated HIV infection warrant further investigation. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Somsouk, Ma] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA.
[Estes, Jacob D.; Deleage, Claire] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Dunham, Richard M.; Albright, Rebecca; McCune, Joseph M.] Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA USA.
[Inadomi, John M.] Univ Washington, Dept Med, Div Gastroenterol, Washington, DC USA.
[Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Deeks, Steven G.; Hunt, Peter W.] Univ Calif San Francisco, Dept Med, Div HIV AIDS, San Francisco, CA USA.
RP Somsouk, M (reprint author), 1001 Potrero Ave, San Francisco, CA 94110 USA.
EM somsoukma@medsfgh.ucsf.edu
FU National Cancer Institute [K23 CA157929]; National Institute of Allergy
and Infectious Disease [P30 AI27763]; NIH [R24 AI067039]; federal funds
from the National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX Funding: This work was supported by the National Cancer Institute (K23
CA157929 to M.S.), the National Institute of Allergy and Infectious
Disease (P30 AI27763), NIH grant number: R24 AI067039 and in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under Contract No. HHSN261200800001E. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 42
TC 29
Z9 30
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 2
PY 2015
VL 29
IS 1
BP 43
EP 51
DI 10.1097/QAD.0000000000000511
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AU4NB
UT WOS:000345586900006
PM 25387317
ER
PT J
AU Lipshultz, SE
Williams, PL
Zeldow, B
Wilkinson, JD
Rich, KC
van Dyke, RB
Seage, GR
Dooley, LB
Kaltman, JR
Siberry, GK
Mofenson, LM
Shearer, WT
Colan, SD
AF Lipshultz, Steven E.
Williams, Paige L.
Zeldow, Bret
Wilkinson, James D.
Rich, Kenneth C.
van Dyke, Russell B.
Seage, George R., III
Dooley, Laurie B.
Kaltman, Jonathan R.
Siberry, George K.
Mofenson, Lynne M.
Shearer, William T.
Colan, Steven D.
CA Pediat HIV AIDS Cohort Study PHACS
TI Cardiac effects of in-utero exposure to antiretroviral therapy in
HIV-uninfected children born to HIV-infected mothers
SO AIDS
LA English
DT Article
DE antiretroviral drugs; cardiac; HIV; pediatrics; toxicity
ID POSSIBLE MITOCHONDRIAL DYSFUNCTION; IDIOPATHIC DILATED CARDIOMYOPATHY;
ZIDOVUDINE; TRANSMISSION; MYOCARDITIS; PREVENTION; TOXICITY; ALCOHOL;
INFANTS; DESIGN
AB Objectives: We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children.
Design and methods: We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs.
Results: There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores.
Conclusion: There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Lipshultz, Steven E.; Wilkinson, James D.] Wayne State Univ, Sch Med, Detroit, MI 48201 USA.
[Lipshultz, Steven E.; Wilkinson, James D.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Lipshultz, Steven E.] Univ Miami, Leonard M Miller Sch Med, Miami, FL USA.
[Williams, Paige L.; Zeldow, Bret; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Rich, Kenneth C.] Univ Illinois, Chicago, IL USA.
[van Dyke, Russell B.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA.
[Dooley, Laurie B.] Frontier Sci Technol & Res Fdn, Amherst, NY USA.
[Kaltman, Jonathan R.] NHLBI, Bethesda, MD 20892 USA.
[Siberry, George K.; Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Shearer, William T.] Baylor Coll Med, Houston, TX 77030 USA.
[Shearer, William T.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Colan, Steven D.] Boston Childrens Hosp, Boston, MA USA.
RP Lipshultz, SE (reprint author), Wayne State Univ, Sch Med, Dept Pediat, 3901 Beaubien Blvd,1K40, Detroit, MI 48201 USA.
EM slipshultz@med.wayne.edu
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 [HD052102];
Tulane University School of Medicine [HD052104]; National Institutes of
Health [HD052102, HD052104]
FX Funding/support: The study 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 (HD052102) and the Tulane University School of Medicine
(HD052104). Data management services were provided by Frontier Science
and Technology Research Foundation, and regulatory services and
logistical support were provided by Westat, Inc.; Sources of funding:
National Institutes of Health (HD052102; HD052104).
NR 37
TC 9
Z9 9
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 2
PY 2015
VL 29
IS 1
BP 91
EP 100
DI 10.1097/QAD.0000000000000499
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AU4NB
UT WOS:000345586900012
PM 25562493
ER
PT J
AU Brunoni, AR
Machado-Vieira, R
Zarate, CA
Vieira, ELM
Valiengo, L
Bensenor, IM
Lotufo, PA
Gattaz, WF
Teixeira, AL
AF Brunoni, Andre R.
Machado-Vieira, Rodrigo
Zarate, Carlos A., Jr.
Vieira, Erica L. M.
Valiengo, Leandro
Bensenor, Isabela M.
Lotufo, Paulo A.
Gattaz, Wagner F.
Teixeira, Antonio L.
TI Assessment of non-BDNF neurotrophins and GDNF levels after depression
treatment with sertraline and transcranial direct current stimulation in
a factorial, randomized, sham-controlled trial (SELECT-TDCS): An
exploratory analysis
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE GDNF; Major depressive disorder; Neurotrophins; Sertraline; Transcranial
direct current stimulation
ID ELECTRICAL-CURRENT THERAPY; LATE-LIFE DEPRESSION; NERVE GROWTH-FACTOR;
MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; MOOD DISORDERS; INDUCED
NEUROPLASTICITY; BRAIN-STIMULATION; DC STIMULATION; PLASMA-LEVELS
AB The neurotrophic hypothesis of depression states that the major depressive episode is associated with lower neurotrophic factors levels, which increase with amelioration of depressive symptoms. However, this hypothesis has not been extended to investigate neurotrophic factors other than the brain-derived neurotrophic factor (BDNF). We therefore explored whether plasma levels of neurotrophins 3 (NT-3) and 4 (NT-4), nerve growth factor (NGF) and glial cell line derived neurotrophic factor (GDNF) changed after antidepressant treatment and correlated with treatment response. Seventy-three patients with moderate-to-severe, antidepressant-free unipolar depression were assigned to a pharmacological (sertraline) and a non-pharmacological (transcranial direct current stimulation, tDCS) intervention in a randomized, 2 x 2, placebo-controlled design. The plasma levels of NT-3, NT-4, NGF and GDNF were determined by enzyme-linked immunosorbent assay before and after a 6-week treatment course and analyzed according to clinical response and allocation group. We found that tDCS and sertraline (separately and combined) produced significant improvement in depressive symptoms. Plasma levels of all neurotrophic factors were similar across groups at baseline and remained significantly unchanged regardless of the intervention and of clinical response. Also, baseline plasma levels were not associated with clinical response. To conclude, in this 6-week placebo-controlled trial, NT-3, NT-4, NGF and GDNF plasma levels did not significantly change with sertraline or tDCS. These data suggest that these neurotrophic factors are not surrogate biomarkers of treatment response or involved in the antidepressant mechanisms of tDCS. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Brunoni, Andre R.; Valiengo, Leandro; Bensenor, Isabela M.; Lotufo, Paulo A.] Univ Sao Paulo, Univ Hosp, Ctr Clin & Epidemiol Res, BR-05508000 Sao Paulo, Brazil.
[Brunoni, Andre R.; Valiengo, Leandro; Bensenor, Isabela M.; Lotufo, Paulo A.] Univ Sao Paulo, Univ Hosp, Interdisciplinary Ctr Appl Neuromodulat CINA, BR-05508000 Sao Paulo, Brazil.
[Brunoni, Andre R.; Valiengo, Leandro] Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, SIN, BR-05508000 Sao Paulo, Brazil.
[Brunoni, Andre R.; Machado-Vieira, Rodrigo; Valiengo, Leandro; Gattaz, Wagner F.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM27, BR-05508000 Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Intramural Res Program, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[Vieira, Erica L. M.; Teixeira, Antonio L.] Fac Med Minas Gerais, Interdisciplinary Lab Med Invest, Belo Horizonte, MG, Brazil.
RP Brunoni, AR (reprint author), Univ Sao Paulo, Univ Hosp, Ctr Clin & Epidemiol Res, Av Prof Lineu Prestes 2565,3o Andar, BR-05508000 Sao Paulo, Brazil.
EM brunoni@usp.br
RI Lotufo, Paulo/A-9843-2008; Brunoni, Andre/H-8394-2012; Vieira,
Erica/A-1976-2013; MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI Lotufo, Paulo/0000-0002-4856-8450; Brunoni, Andre/0000-0002-6310-3571;
Vieira, Erica/0000-0002-4147-5614; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190
FU FAPESP (Sao Paulo Research Foundation [2009/05728-7]; FAPEMIG; CNPq;
NARSAD Young Investigator from the Brain & Behavior Research Foundation
[20493]; FAPESP Young Researcher from the Sao Paulo State Foundation
[20911-5]; National Council for Scientific and Technological Development
(CNPq) [470904]; Associacao Beneficente Alzira Denise da Silva (ABADHS)
FX This study was partially funded by FAPESP (Sao Paulo Research
Foundation, Grant Number: 2009/05728-7), FAPEMIG and CNPq. The sponsors
played no role in the design and conduct of the study, collection,
management, analysis and interpretation of the data, and preparation,
review or approval of the manuscript. A.R.B. is supported by the
following grants: 2013 NARSAD Young Investigator from the Brain &
Behavior Research Foundation (Grant Number 20493), 2013 FAPESP Young
Researcher from the Sao Paulo State Foundation (Grant Number 20911-5)
and National Council for Scientific and Technological Development (CNPq,
Grant Number 470904). C.A.Z. is listed as a coinventor on a patent
application for the use of ketamine and its metabolites in major
depression. C.A.Z. has assigned his rights in the patent to the US
government but will share a percentage of any royalties that may be
received by the government. The Laboratory of Neuroscience receives
financial support from the Associacao Beneficente Alzira Denise da Silva
(ABADHS).
NR 59
TC 8
Z9 8
U1 2
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD JAN 2
PY 2015
VL 56
BP 91
EP 96
DI 10.1016/j.pnpbp.2014.08.009
PG 6
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AU3PR
UT WOS:000345526400012
PM 25172025
ER
PT J
AU Loch, AA
Zanetti, MV
de Sousa, RT
Chaim, TM
Serpa, MH
Gattaz, WF
Teixeira, AL
Machado-Vieira, R
AF Loch, Alexandre A.
Zanetti, Marcus V.
de Sousa, Rafael T.
Chaim, Tiffany M.
Serpa, Mauricio H.
Gattaz, Wagner F.
Teixeira, Antonio L.
Machado-Vieira, Rodrigo
TI Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated
bipolar depression and the effects of lithium
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Biomarkers; Bipolar disorder; Lithium; Neurotrophic; Treatment
ID OXIDATIVE STRESS; MOOD DISORDERS; IN-VIVO; NEURONS; EPISODES; SERUM;
BDNF; HIPPOCAMPAL; EXPRESSION; NT-3
AB Background: Bipolar disorder (BD) has been associated with diverse abnormalities in neural plasticity and cellular resilience. Neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) support synaptic neuronal survival and differentiation. NT-3 and NT-4/5 levels were found to be altered in BD, potentially representing a physiological response against cellular stress. However, the use of psychopharmacological agents and heterogeneous mood states may constitute important biases in such studies. Thus, we aimed to assess NT-3 and NT-4/5 levels in medication-free BD type I or II individuals in a current depressive episode, before and after 6weeks of lithium monotherapy and matched with healthy controls.
Methods: Twenty-three patients with BD type I or II during a depressive episode and 28 healthy controls were studied. Patients were required to have a 21-item Hamilton Depression Rating Scale score >= 18 and had not undergone any psychopharmacological treatment for at least 6 weeks prior to study entry. Patients were treated with lithium for 6 weeks and plasma NT-3 and NT-4/5 levels were determined at baseline and end point using ELISA method.
Results: Baseline plasma levels of both NT-3 and NT-4/5 were significantly increased in acutely depressed BD subjects in comparison to healthy controls (p = 0.040 and 0.039, respectively). The NT-3 and NT-4/5 levels did not significantly change after lithium treatment. NT-3 and NT-4/5 levels were positively correlated to illness duration in BD (p = 0.032 and 0.034, respectively).
Conclusion: Our findings suggest that NT-3 and NT-4/5 levels are increased in the depressive phase of BD, which seems directly associated with illness duration. The increased levels of NT-3 and NT-4/5 may underlie a biological response to cellular stress associated with the course of BD. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Loch, Alexandre A.; Zanetti, Marcus V.; de Sousa, Rafael T.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci, LIM 27, Sao Paulo, Brazil.
[Zanetti, Marcus V.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo, Brazil.
[Zanetti, Marcus V.; Chaim, Tiffany M.; Serpa, Mauricio H.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Psychiat Neuroimaging, LIM 21, Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo] NIMH, ETPB, NIH, Bethesda, MD USA.
[Teixeira, Antonio L.] Fac Med Minas Gerais, Interdisciplinary Lab Med Invest, Belo Horizonte, MG, Brazil.
RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM27, Rua Dr Ovidio Pires Campos 785, Sao Paulo, Brazil.
EM machadovieirar@gmail.com
RI Loch, Alexandre/C-8526-2011; MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI Loch, Alexandre/0000-0002-0006-8107; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190
FU Sao Paulo Research Foundation (FAPESP, Brazil) [2009/14891-9,
2013/03905-4]; CNPq; Fapemig
FX This study was sponsored by Sao Paulo Research Foundation (FAPESP,
Brazil) (2009/14891-9, RM-V), CNPq, and Fapemig. Dr. Marcus V. Zanetti
is funded by FAPESP, Brazil (process no. 2013/03905-4).
NR 32
TC 1
Z9 1
U1 1
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD JAN 2
PY 2015
VL 56
BP 243
EP 246
DI 10.1016/j.pnpbp.2014.09.014
PG 4
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AU3PR
UT WOS:000345526400034
PM 25290636
ER
PT J
AU Pecoraro, A
Mimiaga, M
O'Cleirigh, C
Safren, SA
Blokhina, E
Verbitskaya, E
Yaroslavtseva, T
Ustinov, A
Lioznov, DA
Zvartau, E
Krupitsky, E
Woody, GE
AF Pecoraro, Anna
Mimiaga, Matthew
O'Cleirigh, Conall
Safren, Steven A.
Blokhina, Elena
Verbitskaya, Elena
Yaroslavtseva, Tatiana
Ustinov, Andrey
Lioznov, Dmitry A.
Zvartau, Edwin
Krupitsky, Evgeny
Woody, George E.
TI Depression, substance use, viral load, and CD4+ count among patients who
continued or left antiretroviral therapy for HIV in St. Petersburg,
Russian Federation
SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
LA English
DT Article
DE attrition; retention; Russian Federation; AIDS; HIV
ID PREVENTING RELAPSE; RELEASE NALTREXONE; OPIOID DEPENDENCE; LENINGRAD
REGION; RANDOMIZED-TRIAL; ADHERENCE; DRUG; FACILITATORS; MEDICATION;
BARRIERS
AB Antiretroviral therapy (ART) became more widely available in the Russian Federation in 2006 when the Global Fund made a contribution to purchase ART with a mandate to increase numbers of patients receiving it. Funds were distributed to AIDS Centers and selected hospitals, and numbers quickly increased. Though ART is highly effective for adherent patients, dropout has been a problem; thus understanding characteristics of patients who remain on ART vs. those who leave treatment may provide information to facilitate engagement. We retrospectively assessed depression, hopelessness, substance use, viral load, and CD4+ counts of 120 patients who dropped out of ART for >= 12 months (Lost-to-Care, LTCs) and 120 who continued for >= 12 months (Engaged-in-Care, EICs). As expected, LTCs had higher viral loads and depression, lower CD4+ counts, more alcohol, heroin, and injection drug use in the past 30 days. A binary logistic regression with Center for Epidemiologic Studies Depression score, Beck Hopelessness score, whether drugs/alcohol had ever prevented them from taking ART, and past 30 days' alcohol use [chi(2)(4) = 64.27, p = .0.000] correctly classified 74.5% of participants as LTC or EIC, suggesting that integrated treatment for substance use, psychiatric, and HIV could reduce dropout and improve outcomes.
C1 [Pecoraro, Anna; Woody, George E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Pecoraro, Anna; Woody, George E.] NIDA Clin Trials Network, Philadelphia, PA USA.
[Mimiaga, Matthew] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Mimiaga, Matthew; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA.
[O'Cleirigh, Conall; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Blokhina, Elena; Verbitskaya, Elena; Yaroslavtseva, Tatiana; Ustinov, Andrey; Lioznov, Dmitry A.; Zvartau, Edwin; Krupitsky, Evgeny] First Pavlov State Med Univ, Valdman Inst Pharmacol, St Petersburg, Russia.
[Krupitsky, Evgeny] Bekhterev Res Psychoneurol Inst, St Petersburg, Russia.
RP Pecoraro, A (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
EM annp@mail.med.upenn.edu
RI Verbitskaya, Elena/N-3867-2015; Lioznov, Dmitry/J-2539-2013
OI Verbitskaya, Elena/0000-0003-3770-993X; Lioznov,
Dmitry/0000-0003-3643-7354
FU NIDA NIH HHS [R01 DA026336]; PEPFAR
NR 25
TC 8
Z9 8
U1 0
U2 9
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0954-0121
EI 1360-0451
J9 AIDS CARE
JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv
PD JAN 2
PY 2015
VL 27
IS 1
BP 86
EP 92
DI 10.1080/09540121.2014.959464
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychology, Multidisciplinary; Respiratory System; Social Sciences,
Biomedical
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychology; Respiratory System; Biomedical Social Sciences
GA AS6UL
UT WOS:000344397500015
PM 25264710
ER
PT J
AU Walsh, KS
Paltin, I
Gioia, GA
Isquith, P
Kadan-Lottick, NS
Neglia, JP
Brouwers, P
AF Walsh, Karin S.
Paltin, Iris
Gioia, Gerard A.
Isquith, Peter
Kadan-Lottick, Nina S.
Neglia, Joseph P.
Brouwers, Pim
TI Everyday executive function in standard-risk acute lymphoblastic
leukemia survivors
SO CHILD NEUROPSYCHOLOGY
LA English
DT Article
DE Central nervous system; Neuropsychology; Leukemia; Neurobehavioral
manifestations; Survivors
ID TRAUMATIC BRAIN-INJURY; ACUTE LYMPHOCYTIC-LEUKEMIA; LONG-TERM SURVIVORS;
CHILDHOOD LEUKEMIA; COGNITIVE IMPAIRMENT; CRANIAL IRRADIATION; CHILDREN;
CHEMOTHERAPY; PERFORMANCE; ATTENTION
AB We aimed to evaluate parent-rated executive function (EF) in pediatric standard risk acute lymphoblastic leukemia (SR-ALL) survivors compared to a healthy comparison (HC) group. We hypothesized that SR-ALL survivors would have greater reported executive dysfunction compared to HC, and that those younger at the time of treatment would demonstrate greater EF difficulties. A sample of 256 SR-ALL survivors evaluated an average nine years after treatment were compared to HC matched for gender, assessment age, and maternal education. Profile analysis was used to compare the groups across EF scales on the BRIEF. The prevalence of clinical elevations in the groups was compared via chi square, and odds ratios were calculated. Regression models were applied to examine the role of age at diagnosis and age at assessment in reported EF. Results indicated that SR-ALL survivors' mean scores of EF are similar to HC, except for flexibility and initiation. Survivors were rated as having clinical impairments with flexibility, initiation, working memory, and emotional control at rates two to three times that of HC. The risk of working memory and self-monitoring deficits was greater in survivors who were older when assessed. There was no relationship between age at diagnosis or treatment regimen on EF. These findings suggest sparing of extensive and severe EF deficits in SR-ALL survivors overall. However, a subset of survivors displays clinically significant executive dysfunction. There appears to be a heightened susceptibility to disrupted metacognitive functions as survivors age. This has implications for how we monitor neurocognitive development and functioning of SR-ALL survivors, and highlights opportunities for cognitive interventions.
C1 [Walsh, Karin S.; Gioia, Gerard A.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Walsh, Karin S.; Gioia, Gerard A.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Paltin, Iris] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
[Paltin, Iris] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Isquith, Peter] Geisel Sch Med Dartmouth, Norwich, VT USA.
[Kadan-Lottick, Nina S.] Yale Univ, Sch Med, New Haven, CT USA.
[Kadan-Lottick, Nina S.] Yale Sect Pediat Hematol Oncol, New Haven, CT USA.
[Neglia, Joseph P.] Univ Minnesota, Amplatz Childrens Hosp, Minneapolis, MN USA.
[Brouwers, Pim] Baylor Coll Med, Houston, TX 77030 USA.
[Brouwers, Pim] NIMH, Div AIDS Res, NIH, Rockville, MD 20857 USA.
RP Walsh, KS (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave, Washington, DC 20010 USA.
EM kwalsh@childrensnational.org
OI Walsh, Karin/0000-0001-9637-2164
FU American Cancer Society; St. Baldrick's Foundation
FX This study was supported by research funding by the American Cancer
Society to Joseph Neglia and Nina Kadan-Lottick. Dr. Kadan-Lottick's
effort was additionally funded as a St. Baldrick's Foundation Scholar.
NR 38
TC 6
Z9 6
U1 1
U2 20
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0929-7049
EI 1744-4136
J9 CHILD NEUROPSYCHOL
JI Child Neuropsychol.
PD JAN 2
PY 2015
VL 21
IS 1
BP 78
EP 89
DI 10.1080/09297049.2013.876491
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA AS6TC
UT WOS:000344394100005
PM 24428397
ER
PT J
AU Resnik, DB
Neal, T
Raymond, A
Kissling, GE
AF Resnik, David B.
Neal, Talicia
Raymond, Austin
Kissling, Grace E.
TI Research Misconduct Definitions Adopted by U.S. Research Institutions
SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE
LA English
DT Article
DE research misconduct; policies; ethics; integrity; definitions
AB In 2000, the U.S. federal government adopted a uniform definition of research misconduct as fabrication, falsification, or plagiarism (FFP), which became effective in 2001. Institutions must apply this definition of misconduct to federally-funded research to receive funding. While institutions are free to adopt definitions of misconduct that go beyond the federal standard, it is not known how many do. We analyzed misconduct policies from 183 U.S. research institutions and coded them according to thirteen different types of behavior mentioned in the misconduct definition. We also obtained data on the institution's total research funding and public vs. private status, and the year it adopted the definition. We found that more than half (59%) of the institutions in our sample had misconduct policies that went beyond the federal standard. Other than FFP, the most common behaviors included in definitions were "other serious deviations" (45.4%), "significant or material violations of regulations" (23.0%), "misuse of confidential information" (15.8%), "misconduct related to misconduct" (14.8%), "unethical authorship other than plagiarism" (14.2%), "other deception involving data manipulation" (13.1%), and "misappropriation of property/theft" (10.4%). Significantly more definitions adopted in 2001 or later went beyond the federal standard than those adopted before 2001 (73.2% vs. 26.8%), and significantly more definitions adopted by institutions in the lower quartile of total research funding went beyond the federal standard than those adopted by institutions in the upper quartiles. Public vs. private status was not significantly associated with going beyond the federal standard.
C1 [Resnik, David B.; Kissling, Grace E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Neal, Talicia] Charlotte Sch Law, Charlotte, NC USA.
[Raymond, Austin] Elon Law Sch, Greensboro, NC USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-01]
NR 9
TC 5
Z9 6
U1 2
U2 32
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 JAN 2
PY 2015
VL 22
IS 1
BP 14
EP 21
DI 10.1080/08989621.2014.891943
PG 8
WC Medical Ethics
SC Medical Ethics
GA AS4KS
UT WOS:000344245200002
PM 25275621
ER
PT J
AU Matsunaga, F
Gao, L
Huang, XP
Saven, JG
Roth, BL
Liu, RY
AF Matsunaga, Felipe
Gao, Lu
Huang, Xi-Ping
Saven, Jeffery G.
Roth, Bryan L.
Liu, Renyu
TI Molecular interactions between general anesthetics and the 5HT(2B)
receptor
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Article
DE propofol; anesthetics; serotonin receptor; isoflurane
ID PROTEIN-COUPLED RECEPTORS; 5-HT3 RECEPTORS; CARDIOVASCULAR-SYSTEM;
VOLATILE ANESTHETICS; ENDOTHELIAL-CELLS; XENOPUS OOCYTES; NITRIC-OXIDE;
PROPOFOL; SEROTONIN; BINDING
AB Background: Serotonin modulates many processes through a family of seven serotonin receptors. However, no studies have screened for interactions between general anesthetics currently in clinical use and serotonergic G-protein-coupled receptors (GPCRs). Given that both intravenous and inhalational anesthetics have been shown to target other classes of GPCRs, we hypothesized that general anesthetics might interact directly with some serotonin receptors and thus modify their function. Methods: Radioligand binding assays were performed to screen serotonin receptors for interactions with propofol and isoflurane as well as for affinity determinations. Docking calculations using the crystal structure of 5-HT2B were performed to computationally confirm the binding assay results and locate anesthetic binding sites. Results: The 5-HT2B class of receptors interacted significantly with both propofol and isoflurane in the primary screen. The affinities for isoflurane and propofol were determined to be 7.78 and .95 mu M, respectively, which were at or below the clinical concentrations for both anesthetics. The estimated free energy derived from docking calculations for propofol (-6.70 kcal/mol) and isoflurane (-5.10 kcal/mol) correlated with affinities from the binding assay. The anesthetics were predicted to dock at a pharmacologically relevant binding site of 5HT(2B). Conclusions: The molecular interactions between propofol and isoflurane with the 5-HT2B class of receptors were discovered and characterized. This finding implicates the serotonergic GPCRs as potential anesthetic targets.
C1 [Matsunaga, Felipe; Liu, Renyu] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Gao, Lu; Saven, Jeffery G.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC USA.
RP Liu, RY (reprint author), Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, 336 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA.
EM liur@uphs.upenn.edu
RI Roth, Bryan/F-3928-2010
FU Department of Anesthesiology and Critical Care at University of
Pennsylvania; Foundation for Anesthesia Education and Research; NIH
[K08-GM-093115-01, P01GM055876]; NSF [DMR-1120901]; National Institute
of Mental Health's Psychoactive Drug Screening Program
[HHSN-271-2008-00025-C]
FX This research was supported by departmental funding from the Department
of Anesthesiology and Critical Care at University of Pennsylvania (PI
RL), funding from the Foundation for Anesthesia Education and Research
(PI, RL), NIH [grant number K08-GM-093115-01] (PI: RL). Jeffery G. Saven
acknowledges support from NIH [grant number P01GM055876] and NSF [grant
number DMR-1120901]. This work is also supported by the National
Institute of Mental Health's Psychoactive Drug Screening Program,
Contract # HHSN-271-2008-00025-C (NIMH PDSP), which is directed by Bryan
L. Roth MD, PhD at the University of North Carolina at Chapel Hill and
Project Officer Jamie Driscol at NIMH, Bethesda MD, USA.
NR 55
TC 2
Z9 2
U1 3
U2 27
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0739-1102
EI 1538-0254
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JAN 2
PY 2015
VL 33
IS 1
BP 211
EP 218
DI 10.1080/07391102.2013.869483
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AR9QP
UT WOS:000343910000017
PM 24365264
ER
PT J
AU Gu, DY
Yang, Y
Xin, XL
Aisa, HA
Ito, Y
AF Gu, Dongyu
Yang, Yi
Xin, Xuelei
Aisa, Haji Akber
Ito, Yoichiro
TI Novel Design for Centrifugal Counter-Current Chromatography: VI.
Ellipsoid Column
SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES
LA English
DT Article
DE rotary-seal-free centrifuge; hydrostatic counter-current chromatographic
system; centrifugal counter-current chromatography; retention of the
stationary phase; protein separation; peak resolution; ellipsoid column
ID LARGE-SCALE SEPARATION; ALKALOIDS
AB A novel ellipsoid column was designed for centrifugal counter-current chromatography. Performance of the ellipsoid column with a capacity of 3.4mL was examined with three different solvent systems composed of 1-butanol-acetic acid-water (4:1:5, v/v/v) (BAW), hexane-ethyl acetate-methanol-0.1M HCl (1:1:1:1, v/v/v/v) (HEMH), and 12.5% (w/w) PEG1000 and 12.5% (w/w) dibasic potassium phosphate in water (PEG-DPP) each with suitable test samples. In dipeptide separation with BAW system, both stationary phase retention (Sf) and peak resolution (Rs) of the ellipsoid column were much higher at 0 degrees column angle (column axis parallel to the centrifugal force) than at 90 degrees column angle (column axis perpendicular to the centrifugal force), where elution with the lower phase at a low flow rate produced the best separation yielding Rs at 2.02 with 27.8% Sf at a flow rate of 0.07mL/min. In the DNP-amino acid separation with HEMW system, the best results were obtained at a flow rate of 0.05ml/min with 31.6% Sf yielding high Rs values at 2.16 between DNP-DL-glu and DNP-beta-ala peaks and 1.81 between DNP-beta-ala and DNP-L-ala peaks. In protein separation with PEG-DPP system, lysozyme and myolobin were resolved at Rs of 1.08 at a flow rate of 0.03mL/min with 38.9% Sf. Most of those Rs values exceed those obtained from the figure-8 column under similar experimental conditions previously reported.
C1 [Gu, Dongyu; Yang, Yi; Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Gu, Dongyu; Yang, Yi; Xin, Xuelei; Aisa, Haji Akber] Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Key Lab Xinjiang Indigenous Med Plants Resource U, Urumqi, Peoples R China.
[Gu, Dongyu] Dalian Ocean Univ, Sch Marine Sci & Environm Engn, Dalian, Peoples R China.
RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
FU China National Funds for Distinguished Young Scientists [30925045]; West
Light Foundation of The Chinese Academy of Sciences [XBBS201011]; Major
State Basic Research Development Program [2011CB512013]
FX This work was funded by the China National Funds for Distinguished Young
Scientists (Grant No. 30925045), the West Light Foundation of The
Chinese Academy of Sciences (No. XBBS201011), and the Major State Basic
Research Development Program (Grant No. 2011CB512013).
NR 20
TC 2
Z9 2
U1 1
U2 12
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1082-6076
EI 1520-572X
J9 J LIQ CHROMATOGR R T
JI J. Liq. Chromatogr. Relat. Technol.
PD JAN 2
PY 2015
VL 38
IS 1
BP 68
EP 73
DI 10.1080/10826076.2014.883533
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AS6NZ
UT WOS:000344381300010
PM 25309116
ER
PT B
AU Ernst, M
Hale, EA
Balderston, N
Torrisi, S
AF Ernst, Monique
Hale, Elizabeth A.
Balderston, Nicholas
Torrisi, Salvatore
BE Ewing, SWF
Witkiewitz, K
Filbey, FM
TI Introduction to Functional Brain Connectivity: Potential Contributions
to Understanding Adolescent Vulnerability to Substance Abuse
SO Neuroimaging and Psychosocial Addiction Treatment: An Integrative Guide
for Researchers and Clinicians
LA English
DT Editorial Material; Book Chapter
ID RESTING STATE FMRI; INDEPENDENT COMPONENT ANALYSIS; INHIBITORY CONTROL;
LIFE-SPAN; NETWORKS; ARCHITECTURE; MRI; NEURODEVELOPMENT; CHILDHOOD;
ASYMMETRY
C1 [Ernst, Monique] NIMH, Dept Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
[Hale, Elizabeth A.; Balderston, Nicholas; Torrisi, Salvatore] NIMH, NIH, Bethesda, MD 20892 USA.
RP Ernst, M (reprint author), NIMH, Dept Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
NR 69
TC 0
Z9 0
U1 0
U2 0
PU PALGRAVE
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND
BN 978-1-137-36265-0; 978-1-137-36264-3
PY 2015
BP 181
EP 199
D2 10.1057/9781137362650
PG 19
WC Substance Abuse; Neuroimaging
SC Substance Abuse; Neurosciences & Neurology
GA BG4NC
UT WOS:000389017700013
ER
PT J
AU Bornstein, MH
AF Bornstein, Marc H.
BE Elliot, AJ
Fairchild, MD
Franklin, A
TI Emergence and early development of color vision and color perception
SO HANDBOOK OF COLOR PSYCHOLOGY
LA English
DT Article; Book Chapter
ID YOUNG HUMAN INFANTS; MODULATION-SENSITIVE MECHANISM; 2-MONTH-OLD HUMAN
INFANTS; WALLACHS RATIO RULE; SHORT-TERM-MEMORY; SPECTRAL SENSITIVITY;
CONTRAST SENSITIVITY; 4-MONTH-OLD INFANTS; CATEGORICAL PERCEPTION;
CHROMATIC DISCRIMINATION
C1 [Bornstein, Marc H.] NICHHD, Child & Family Res, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), NICHHD, Child & Family Res, Bethesda, MD 20892 USA.
NR 211
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND
BN 978-1-107-04323-7
PY 2015
BP 149
EP 179
D2 10.1017/CBO9781107337930
PG 31
WC Neurosciences; Psychology; Psychology, Multidisciplinary
SC Neurosciences & Neurology; Psychology
GA BG4EL
UT WOS:000388685900008
ER
PT J
AU Azoury, SC
Crompton, JG
Straughan, DM
Klemen, ND
Reardon, ES
Beresnev, TH
Hughes, MS
AF Azoury, Said C.
Crompton, Joseph G.
Straughan, David M.
Klemen, Nicholas D.
Reardon, Emily S.
Beresnev, Tatiana H.
Hughes, Marybeth S.
TI Unknown primary nasopharyngeal melanoma presenting as severe recurrent
epistaxis and hearing loss following treatment and remission of
metastatic disease: A case report and literature review
SO INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS
LA English
DT Review
DE Nasopharyngeal; Head and neck; Mucosal; Melanoma; Metastasis
ID MUCOSAL MELANOMA; MALIGNANT-MELANOMA; SINONASAL MELANOMA; NASAL CAVITY;
HEAD; NECK; EPIDEMIOLOGY; RADIATION
AB INTRODUCTION: Primary nasopharyngeal melanoma is an exceedingly rare pathology with unclear etiology and oftentimes obscure clinical presentation. Despite improved diagnostic capabilities, these lesions are often diagnosed at an advanced stage and associated prognosis is poor, partly due to high rates of recurrences and metastasis.
PRESENTATION OF CASE: A 74-year-old woman was diagnosed with metastatic melanoma to the liver, of unknown primary. Just prior to the time of diagnosis, she experienced several episodes of severe epistaxis which she managed conservatively. Her symptoms eventually subsided without further medical evaluation. The patient was initially treated with interleukin-2 (IL-2) for her advanced disease, but her cancer progressed. She was then enrolled in a protocol for percutaneous hepatic perfusion (PHP) with melphalan and had complete radiographic resolution of disease, yet her nosebleeds recurred and persisted despite conservative measures. Six years after her initial diagnosis, a nasopharyngoscopy demonstrated a pigmented lesion in the posterior nasopharynx. Surgical resection was performed (pathology consistent with mucosal melanoma) followed by radiation therapy. She has since had complete resolution of bleeding and shows no evidence of cancer.
DISCUSSION: To our knowledge, this is the first report of a diagnosis of primary nasopharyngeal melanoma 6-years following complete remission of metastatic disease. Surgery remains the primary treatment for disease and symptom control in this setting.
CONCLUSION: Timely diagnosis of nasopharyngeal melanomas remains challenging. Thorough clinical evaluations should be performed in such patients, and attention should be paid to recurrent and persistent symptoms, such as epistaxis and hearing loss. This may allow for earlier detection of primary disease. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Azoury, Said C.; Crompton, Joseph G.; Straughan, David M.; Klemen, Nicholas D.; Reardon, Emily S.; Beresnev, Tatiana H.; Hughes, Marybeth S.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Azoury, Said C.] Johns Hopkins Univ, Sch Med, Dept Surg, Johns Hopkins Hosp, Baltimore, MD 21218 USA.
[Beresnev, Tatiana H.] Leidos Biomed Res Inc, Clin Monitoring Res Program, Frederick, MD USA.
RP Azoury, SC (reprint author), NCI, NIH, Baltimore, MD 21287 USA.
EM sazoury1@jhmi.edu
NR 20
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 2210-2612
J9 INT J SURG CASE REP
JI Int. J. Surg. Case Rep.
PY 2015
VL 10
BP 232
EP 235
DI 10.1016/j.ijscr.2015.03.053
PG 4
WC Surgery
SC Surgery
GA ED3FL
UT WOS:000388734800063
PM 25898283
ER
PT J
AU Neychev, V
Borruso, J
AF Neychev, Vladimir
Borruso, John
TI Bowel ischemia and necrosis in anorexia nervosa: A case report and
review of the literature
SO INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS
LA English
DT Review
ID NECROTIZING COLITIS; EATING-DISORDERS; COMPLICATIONS; POPULATION
AB INTRODUCTION: Bowel ischemia and necrosis is an uncommon complication of anorexia nervosa (AN), which may pose significant diagnostic and therapeutic challenges. The review of the existing literature shows that the mortality rate of this condition reaches 80%.
CASE: We present a case of a 30 year old woman with long-standing AN complicated by ischemia and necrosis of the entire small bowel and the right hemicolon.
CONCLUSION: A high index of suspicion of bowel ischemia is necessary when patients with AN present with abdominal symptoms. Timely diagnosis and treatment may prevent bowel necrosis and death. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd.
C1 [Neychev, Vladimir] NCI, Endocrine Oncol Branch, NIH, 10 Ctr Dr,CRC 3-5840, Bethesda, MD 20892 USA.
[Borruso, John] Danbury Hosp, Dept Surg, Danbury, CT 06810 USA.
RP Neychev, V (reprint author), NCI, Endocrine Oncol Branch, NIH, 10 Ctr Dr,CRC 3-5840, Bethesda, MD 20892 USA.
EM vladimir.neychev@nih.gov
NR 11
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2210-2612
J9 INT J SURG CASE REP
JI Int. J. Surg. Case Rep.
PY 2015
VL 8
BP 141
EP 143
DI 10.1016/j.ijscr.2015.01.035
PG 3
WC Surgery
SC Surgery
GA ED3ET
UT WOS:000388732900040
PM 25681813
ER
PT B
AU O'Toole, D
Tang, LH
Jensen, RT
Falconi, M
Pape, UF
Kwekkeboom, D
AF O'Toole, Dermot
Tang, Laura H.
Jensen, Robert T.
Falconi, Massimo
Pape, U. -F.
Kwekkeboom, Dik
BE OSullivan, B
Brierley, JD
DCruz, AK
Fey, MF
Pollock, R
Vermorken, JB
Huang, SH
TI Neuroendocrine tumours
SO UICC MANUAL OF CLINICAL ONCOLOGY, 9TH EDITION
LA English
DT Article; Book Chapter
ID ENETS CONSENSUS GUIDELINES; MANAGEMENT; NEOPLASMS; METASTASES; FOREGUT;
SYSTEM
C1 [O'Toole, Dermot] St James Hosp, Trinity Ctr Hlth Sci, Dept Clin Med & Gastroenterol, Dublin, Ireland.
[O'Toole, Dermot] Trinity Coll Dublin, Dublin, Ireland.
[O'Toole, Dermot] St Vincents Univ Hosp, Dept Neuroendocrine Tumours, Dublin, Ireland.
[Tang, Laura H.] Mem Sloan Kettering Canc, Dept Pathol, New York, NY USA.
[Jensen, Robert T.] NIDDK, Cell Biol Sect, Digest Dis Branch, NIH, Bethesda, MD USA.
[Falconi, Massimo] Salute & Vita Univ, Hosp San Raffaele, Pancreat Surg Unit, Milan, Italy.
[Pape, U. -F.] Campus Virchow Klinikum, Dept Internal Med, Div Hepatol & Gastroenterol, Berlin, Germany.
[Kwekkeboom, Dik] Erasmus MC, Dept Nucl Med, Rotterdam, Netherlands.
RP O'Toole, D (reprint author), St James Hosp, Trinity Ctr Hlth Sci, Dept Clin Med & Gastroenterol, Dublin, Ireland.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND
BN 978-1-119-01313-6; 978-1-4443-3244-5
PY 2015
BP 656
EP 673
D2 10.1002/9781119013143
PG 18
WC Oncology
SC Oncology
GA BG1BQ
UT WOS:000386636800054
ER
PT S
AU Shin, HC
Lu, L
Kim, L
Seff, A
Yao, JH
Summers, RM
AF Shin, Hoo-Chang
Lu, Le
Kim, Lauren
Seff, Ari
Yao, Jianhua
Summers, Ronald M.
GP IEEE
TI Interleaved Text/Image Deep Mining on a Large-Scale Radiology Database
SO 2015 IEEE CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION (CVPR)
SE IEEE Conference on Computer Vision and Pattern Recognition
LA English
DT Proceedings Paper
CT IEEE Conference on Computer Vision and Pattern Recognition (CVPR)
CY JUN 07-12, 2015
CL Boston, MA
SP IEEE
AB Despite tremendous progress in computer vision, effective learning on very large-scale (> 100K patients) medical image databases has been vastly hindered. We present an interleaved text/image deep learning system to extract and mine the semantic interactions of radiology images and reports from a national research hospital's picture archiving and communication system. Instead of using full 3D medical volumes, we focus on a collection of representative similar to 216K 2D key images/slices (selected by clinicians for diagnostic reference) with text-driven scalar and vector labels. Our system interleaves between unsupervised learning (e.g., latent Dirichlet allocation, recurrent neural net language models) on document-and sentence-level texts to generate semantic labels and supervised learning via deep convolutional neural networks (CNNs) to map from images to label spaces. Disease-related key words can be predicted for radiology images in a retrieval manner. We have demonstrated promising quantitative and qualitative results. The large-scale datasets of extracted key images and their categorization, embedded vector labels and sentence descriptions can be harnessed to alleviate the deep learning "datahungry" obstacle in the medical domain.
C1 [Shin, Hoo-Chang; Lu, Le; Kim, Lauren; Seff, Ari; Yao, Jianhua; Summers, Ronald M.] Natl Inst Hlth Clin Ctr, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Shin, HC (reprint author), Natl Inst Hlth Clin Ctr, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
EM hoochang.shin@nih.gov; le.lu@nih.gov; lauren.kim2@nih.gov;
ari.seff@nih.gov; jyao@cc.nih.gov; rms@nih.gov
NR 46
TC 1
Z9 1
U1 0
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1063-6919
BN 978-1-4673-6964-0
J9 PROC CVPR IEEE
PY 2015
BP 1090
EP 1099
PG 10
WC Computer Science, Artificial Intelligence
SC Computer Science
GA BG3KA
UT WOS:000387959201012
ER
PT B
AU Bennett, JE
AF Bennett, John E.
BE Hospenthal, DR
Rinaldi, MG
TI Diagnostic Histopathology
SO DIAGNOSIS AND TREATMENT OF FUNGAL INFECTIONS, SECOND EDITION
SE Infectious Disease-Series
LA English
DT Article; Book Chapter
C1 [Bennett, John E.] NIH, Lab Clin Infect Dis, Ctr Clin, Clin Ctr Room 12C103B,9000 Rockville Pike, Bethesda, MD USA.
RP Bennett, JE (reprint author), NIH, Lab Clin Infect Dis, Ctr Clin, Clin Ctr Room 12C103B,9000 Rockville Pike, Bethesda, MD USA.
EM jbennett@niaid.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
BN 978-3-319-13090-3; 978-3-319-13089-7
J9 INFECT DIS-SER
PY 2015
BP 37
EP 43
DI 10.1007/978-3-319-13090-3_4
D2 10.1007/978-3-319-13090-3
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA BF9SL
UT WOS:000385855800005
ER
PT B
AU von Geldern, G
Nath, A
AF von Geldern, Gloria
Nath, Avindra
BE Demaerschalk, BM
Wingerchuk, DM
TI Central nervous system infections
SO EVIDENCE-BASED NEUROLOGY: MANAGEMENT OF NEUROLOGICAL DISORDERS, 2ND
EDITION
LA English
DT Article; Book Chapter
ID HERPES-SIMPLEX ENCEPHALITIS; POLYMERASE-CHAIN-REACTION;
ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; ACUTE
BACTERIAL-MENINGITIS; RECONSTITUTION INFLAMMATORY SYNDROME; CHILDHOOD
TUBERCULOUS MENINGITIS; PLACEBO-CONTROLLED TRIAL; CRYPTOCOCCAL
MENINGITIS; AMPHOTERICIN-B
C1 [von Geldern, Gloria; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bldg 10-7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
RP von Geldern, G (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bldg 10-7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
NR 118
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND
BN 978-1-119-06732-0; 978-0-470-65778-2
PY 2015
BP 131
EP 142
D2 10.1002/9781119067344
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA BF7RF
UT WOS:000384349500015
ER
PT B
AU Rueda, C
Fernandez, MA
Barragan, S
Peddada, SD
AF Rueda, Cristina
Fernandez, Miguel A.
Barragan, Sandra
Peddada, Shyamal D.
BE Dryden, IL
Kent, JT
TI Some advances in constrained inference for ordered circular parameters
in oscillatory systems
SO GEOMETRY DRIVEN STATISTICS
LA English
DT Article; Book Chapter
ID CYCLE-REGULATED GENES; CELL-CYCLE; FISSION YEAST; CIRCUMPLEX MODEL;
CANCER TRIAL; EXPRESSION; REGRESSION; IDENTIFICATION; CLASSIFICATION;
COORDINATION
C1 [Rueda, Cristina; Fernandez, Miguel A.; Barragan, Sandra] Univ Valladolid, Dept Stat & OR, Valladolid, Spain.
[Peddada, Shyamal D.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Rueda, C (reprint author), Univ Valladolid, Dept Stat & OR, Valladolid, Spain.
NR 53
TC 0
Z9 0
U1 2
U2 2
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND
BN 978-1-118-86661-0; 978-1-118-86657-3
PY 2015
BP 97
EP 114
D2 10.1002/9781118866641
PG 18
WC Mathematics, Interdisciplinary Applications; Statistics & Probability
SC Mathematics
GA BF8SL
UT WOS:000385227600004
ER
PT S
AU Newman, DJ
Cragg, GM
AF Newman, David J.
Cragg, Gordon M.
BE Levin, JI
TI Bioactive Macrocycles from Nature
SO MACROCYCLES IN DRUG DISCOVERY
SE RSC Drug Discovery Series
LA English
DT Article; Book Chapter
ID HISTONE DEACETYLASE INHIBITOR; BRYOSTATIN ANTITUMOR MACROLIDES;
MICROTUBULE-STABILIZING AGENTS; AZUMAMIDES-A-E; RAPAMYCIN AY-22,989;
DRUG DISCOVERY; IN-VITRO; MYXOCOCCUS-XANTHUS; CANCER CELLS; HETEROLOGOUS
EXPRESSION
C1 [Newman, David J.; Cragg, Gordon M.] NCI, Nat Prod Branch, Dev Therapeut Program, DCTD,Frederick Natl Lab, POB B, Frederick, MD 21702 USA.
RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, DCTD,Frederick Natl Lab, POB B, Frederick, MD 21702 USA.
EM dn22a@nih.gov
NR 182
TC 4
Z9 4
U1 2
U2 2
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND
SN 2041-3203
BN 978-1-78262-311-3; 978-1-84973-701-2
J9 RSC DRUG DISCOV
JI RSC Drug Discov.
PY 2015
VL 40
BP 1
EP 36
PG 36
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA BG3NU
UT WOS:000388091100003
ER
PT B
AU Breggin, PR
AF Breggin, Peter R.
BE Kirkcaldy, B
TI Understanding and Overcoming Guilt, Shame, and Anxiety: Based on the
Theory of Negative Legacy Emotions
SO PROMOTING PSYCHOLOGICAL WELL-BEING IN CHILDREN AND FAMILIES
LA English
DT Article; Book Chapter
C1 [Breggin, Peter R.] Ctr Study Empath Therapy, Ithaca, NY 14850 USA.
[Breggin, Peter R.] NIMH, Bethesda, MD 20892 USA.
RP Breggin, PR (reprint author), Ctr Study Empath Therapy, Ithaca, NY 14850 USA.
NR 22
TC 0
Z9 0
U1 0
U2 0
PU PALGRAVE
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND
BN 978-1-137-47996-9; 978-1-137-47995-2
PY 2015
BP 68
EP 80
D2 10.1057/9781137479969
PG 13
WC Family Studies; Psychology, Multidisciplinary
SC Family Studies; Psychology
GA BG1GY
UT WOS:000386737000005
ER
PT B
AU Scholmerich, A
Agache, A
Leyendecker, B
AF Schoelmerich, Axel
Agache, Alexandra
Leyendecker, Birgit
BE Kirkcaldy, B
TI Child Well-Being: Indicators and. Measurement
SO PROMOTING PSYCHOLOGICAL WELL-BEING IN CHILDREN AND FAMILIES
LA English
DT Article; Book Chapter
ID INDEX; CULTURE; SELF
C1 [Schoelmerich, Axel; Leyendecker, Birgit] Ruhr Univ Bochum, Dev Psychol, Bochum, Germany.
[Schoelmerich, Axel] NICHHD, Bethesda, MD 20892 USA.
[Schoelmerich, Axel] Univ Halle Wittenberg, Flunitan Dev, Halle, Germany.
[Agache, Alexandra] Ruhr Univ Bochum, Fac Psychol, Bochum, Germany.
RP Scholmerich, A (reprint author), Ruhr Univ Bochum, Dev Psychol, Bochum, Germany.
NR 20
TC 0
Z9 0
U1 1
U2 1
PU PALGRAVE
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND
BN 978-1-137-47996-9; 978-1-137-47995-2
PY 2015
BP 123
EP 134
D2 10.1057/9781137479969
PG 12
WC Family Studies; Psychology, Multidisciplinary
SC Family Studies; Psychology
GA BG1GY
UT WOS:000386737000008
ER
PT B
AU Antoniou, AS
Mitsopoulou, E
Chrousos, GP
AF Antoniou, Alexander-Stamatios
Mitsopoulou, Eftychia
Chrousos, George P.
BE Kirkcaldy, B
TI Psychosocial Factors and Suicidal Behaviour in Adolescents
SO PROMOTING PSYCHOLOGICAL WELL-BEING IN CHILDREN AND FAMILIES
LA English
DT Article; Book Chapter
ID NESTED CASE-CONTROL; RISK-FACTORS; SELF-HARM; MENTAL-HEALTH;
YOUNG-PEOPLE; DEPRESSION; YOUTH; INTERVENTIONS; ASSOCIATIONS; PREVALENCE
C1 [Antoniou, Alexander-Stamatios] Univ Athens, Psychol, GR-10679 Athens, Greece.
[Antoniou, Alexander-Stamatios] Minist Justice, Inst Epanodos, Athens, Greece.
[Antoniou, Alexander-Stamatios] Natl Council Radio Televis ESR, Athens, Greece.
[Antoniou, Alexander-Stamatios] Hellen Psychol Soc, Div Org Psychol, Thessaloniki, Greece.
[Mitsopoulou, Eftychia] 2nd Model Expt Jr lhgh Sch Athens, Athens, Greece.
[Mitsopoulou, Eftychia] Univ Athens, Fac Primary Educ, Athens, Greece.
[Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, Athens, Greece.
[Chrousos, George P.] NICHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA.
[Chrousos, George P.] NIH, Bethesda, MD 20892 USA.
[Chrousos, George P.] Lib Congress, Technol & Soc, Washington, DC 20540 USA.
[Chrousos, George P.] European Soc Clin Invest, Utrecht, Netherlands.
RP Antoniou, AS (reprint author), Univ Athens, Psychol, GR-10679 Athens, Greece.
NR 82
TC 0
Z9 0
U1 1
U2 1
PU PALGRAVE
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND
BN 978-1-137-47996-9; 978-1-137-47995-2
PY 2015
BP 154
EP 171
D2 10.1057/9781137479969
PG 18
WC Family Studies; Psychology, Multidisciplinary
SC Family Studies; Psychology
GA BG1GY
UT WOS:000386737000010
ER
PT S
AU Nicastro, HL
Dunn, BK
AF Nicastro, Holly L.
Dunn, Barbara K.
BE Preedy, VR
TI The Selenium and Vitamin E Cancer Prevention Trial (SELECT): Prevention
of Prostate Cancer Using Selenium and/or Vitamin E in the SELECT Cancer
Prevention Trial
SO SELENIUM: CHEMISTRY, ANALYSIS, FUNCTION AND EFFECTS
SE Food and Nutritional Components in Focus
LA English
DT Article; Book Chapter
ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY;
ALPHA-TOCOPHEROL; MINERAL SUPPLEMENTATION; RISK; CARCINOGENESIS;
SURVIVAL; LINXIAN; COHORT; CHINA
C1 [Nicastro, Holly L.] NCI, Canc Prevent Fellowship Program, Nutr Sci Res Grp, Canc Prevent Div,NIH, 9609 Med Ctr Dr 5E-572, Bethesda, MD 20852 USA.
[Dunn, Barbara K.] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20852 USA.
RP Nicastro, HL (reprint author), NCI, Canc Prevent Fellowship Program, Nutr Sci Res Grp, Canc Prevent Div,NIH, 9609 Med Ctr Dr 5E-572, Bethesda, MD 20852 USA.
EM dunnb@mail.nih.gov
NR 33
TC 0
Z9 0
U1 0
U2 0
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND
SN 2045-1695
BN 978-1-78262-221-5; 978-1-84973-891-0
J9 FOOD NUTR COMPON FOC
PY 2015
IS 9
BP 428
EP 457
D2 10.1039/9781782622215
PG 30
WC Chemistry, Analytical; Food Science & Technology; Nutrition & Dietetics
SC Chemistry; Food Science & Technology; Nutrition & Dietetics
GA BG3LC
UT WOS:000387992800026
ER
PT B
AU Aravind, L
Zhang, DP
Iyer, LM
AF Aravind, L.
Zhang, Dapeng
Iyer, Lakshminarayan M.
BE Hausinger, RP
Schofield, CJ
TI The TET/JBP Family of Nucleic Acid Base-Modifying 2-Oxoglutarate and
Iron-Dependent Dioxygenases
SO 2-OXOGLUTARATE-DEPENDENT OXYGENASES
LA English
DT Article; Book Chapter
ID EMBRYONIC STEM-CELLS; MOUSE GERM-LINE; DNA DEMETHYLATION;
DEOXYRIBONUCLEIC-ACID; COMPLEX MODIFICATIONS; POSTNATAL-DEVELOPMENT;
PATERNAL GENOME; MAMMALIAN DNA; 5-HYDROXYMETHYLCYTOSINE; TET2
C1 [Aravind, L.; Zhang, Dapeng; Iyer, Lakshminarayan M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
NR 82
TC 0
Z9 0
U1 0
U2 0
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND
BN 978-1-78262-195-9; 978-1-84973-950-4
PY 2015
BP 289
EP 308
D2 10.1039/9781782621959
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BG2DI
UT WOS:000387272100012
ER
PT B
AU Wheeler, DC
Siangphoe, U
AF Wheeler, David C.
Siangphoe, Umaporn
BE Kanaroglou, P
Delmelle, E
Paez, A
TI Modeling Spatial Variation in Disease Risk in Epidemiologic Studies
SO SPATIAL ANALYSIS IN HEALTH GEOGRAPHY
SE Geographies of Health
LA English
DT Article; Book Chapter
ID NON-HODGKIN-LYMPHOMA; UNITED-STATES; TEMPORAL ANALYSIS;
CANCER-MORTALITY; BREAST-CANCER; CHILDHOOD LEUKEMIA; CLUSTER DETECTION;
BIRTH COHORT; LIFE-COURSE; SMALL-AREA
C1 [Wheeler, David C.] Virginia Commonwealth Univ, Sch Med, Dept Biostat, Richmond, VA 23284 USA.
[Wheeler, David C.] NCI, Bethesda, MD 20892 USA.
[Siangphoe, Umaporn] Virginia Commonwealth Univ, Biostat, Richmond, VA 23284 USA.
RP Wheeler, DC (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biostat, Richmond, VA 23284 USA.
NR 56
TC 0
Z9 0
U1 0
U2 0
PU ASHGATE PUBLISHING LTD
PI ALDERSHOT
PA GOWER HOUSE, CROFT ROAD, ALDERSHOT GU11 3HR, ENGLAND
BN 978-1-47-241620-9; 978-1-47-241619-3
J9 GEOGR HEALTH
PY 2015
BP 121
EP 137
PG 17
WC Geography; Public, Environmental & Occupational Health
SC Geography; Public, Environmental & Occupational Health
GA BG0RI
UT WOS:000386481100008
ER
PT J
AU Ramirez, DF
Zambrano, R
Cochran, E
Brown, R
AF Ramirez, Felipe D.
Zambrano, R.
Cochran, E.
Brown, R.
TI Metreleptin Use in Children with Congenital Generalized Lipodystrophy
SO HORMONE RESEARCH IN PAEDIATRICS
LA English
DT Meeting Abstract
C1 [Ramirez, Felipe D.; Zambrano, R.] LSU Hlth Sci Ctr, New Orleans, LA USA.
[Cochran, E.; Brown, R.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1663-2818
EI 1663-2826
J9 HORM RES PAEDIAT
JI Horm. Res. Paediatr.
PY 2015
VL 84
SU 2
MA O24
BP 30
EP 30
PG 1
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA DX1UO
UT WOS:000384152700056
ER
PT S
AU Van Waes, C
AF Van Waes, Carter
BE Miller, J
LePrell, CG
Rybak, L
TI Role of Free Radicals in Head and Neck Cancer
SO FREE RADICALS IN ENT PATHOLOGY
SE Oxidative Stress in Applied Basic Research and Clinical Practice
LA English
DT Article; Book Chapter
ID NF-KAPPA-B; SQUAMOUS-CELL CARCINOMA; FANCONI-ANEMIA; LUNG
CARCINOGENESIS; OXIDATIVE STRESS; TUMOR-GROWTH; IN-VIVO; EXPRESSION;
ACTIVATION; PATHWAY
C1 [Van Waes, Carter] NIDCD, Head & Neck Surg Branch, NIH, CRC Rm 4-2732,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Van Waes, C (reprint author), NIDCD, Head & Neck Surg Branch, NIH, CRC Rm 4-2732,10 Ctr Dr, Bethesda, MD 20892 USA.
EM vanwaesc@nidcd.nih.gov
NR 48
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2197-7224
BN 978-3-319-13473-4; 978-3-319-13472-7
J9 OXID STRESS APPL BAS
JI Oxid. Stress Appl. Basic Res. Clin. Pract.
PY 2015
BP 457
EP 466
DI 10.1007/978-3-319-13473-4_22
D2 10.1007/978-3-319-13473-4
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Medicine, Research & Experimental; Otorhinolaryngology
SC Biochemistry & Molecular Biology; Research & Experimental Medicine;
Otorhinolaryngology
GA BF9WT
UT WOS:000386013700022
ER
PT J
AU Gupta, R
Gupta, S
AF Gupta, Ramji
Gupta, Sarthak
TI Topical Adapalene in the Treatment of Plantar Warts; Randomized
Comparative Open Trial in Comparison with Cryo-Therapy
SO INDIAN JOURNAL OF DERMATOLOGY
LA English
DT Article
DE Adapalene; cryo-therapy; occlusion; plantar wart
ID IMIQUIMOD 5-PERCENT CREAM; CUTANEOUS WARTS; VIRAL WARTS;
DIFFERENTIATION; MANAGEMENT; EFFICACY; ACNE
AB Background: Various therapeutic modalities, which are available for treating plantar wart, have not been successful every time. Aims: To evaluate topical adapalene under occlusion in the treatment of plantar warts and compare it with cryo-therapy. Materials and Methods: 50 patients with 424 plantar warts were included in this single center, two arm, prospective, randomized, control, open study. Patients were allocated randomly into two groups consisting of 25 patients each. Group A patients having 299 plantar warts were treated using adapalene gel 0.1% under occlusion while Group B patients having 125 warts were treated using cryo-therapy. All the patients were evaluated weekly till the clearance of all the warts and the results compared. Result: All the warts of 25 patients of Group A that were treated using adapalene gel 0.1% cleared in 36.71 +/- 19.24 (55.95-17.47) days except those in one patient. In Group B, warts in all except one treated by cryo-therapy cleared in 52.17 +/- 30.06 (82.23-22.11) days. There were no side effects like scar formation, irritation, erythema, or infections with adapalene group while in the cryo group scar was seen in 2 patients, pain in 24, erythema in 10, and infection in 3 patients. Conclusion: Adapalene gel 0.1% under occlusion is an effective, safe and easy to use treatment for plantar warts and may help clear lesions faster than cryo-therapy.
C1 [Gupta, Ramji] Indraprastha Apollo Hosp, Dept Dermatol, New Delhi, India.
[Gupta, Sarthak] NIAMSD, Dept Rheumatol, NIH, Bethesda, MD 20892 USA.
RP Gupta, R (reprint author), M-54,Jal Vihar Rd,Lajpat Nagar 2, New Delhi 110024, India.
EM drramjigupta@yahoo.co.in
NR 19
TC 2
Z9 2
U1 0
U2 1
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 0019-5154
EI 1998-3611
J9 INDIAN J DERMATOL
JI Indian J. Dermatol.
PD JAN-FEB
PY 2015
VL 60
IS 1
DI 10.4103/0019-5154.147835
PG 4
WC Dermatology
SC Dermatology
GA DY3IY
UT WOS:000384986700029
PM 25657417
ER
PT J
AU Denniston, RW
AF Denniston, Robert W.
TI Commentary: The land of insurmountable opportunities
SO INTERNATIONAL JOURNAL OF ALCOHOL AND DRUG RESEARCH
LA English
DT Editorial Material
DE Alcohol policy; alcohol industry; evidence-based prevention;
environmental approaches
ID PUBLIC-HEALTH
AB Much is known about how to change alcohol policy to reduce harm, but despite the evidence little action has been taken at the national level in the United States. Government officials have shown little interest in putting prevention research results to work. The influence of the alcohol industry on policy-makers combined with free market ideology has thwarted change despite the efforts of advocacy groups working to reduce harm. The role of the alcohol industry at the national and international level serves as a powerful deterrent to policy change.
C1 [Denniston, Robert W.] NIAAA, Rockville, MD 20852 USA.
[Denniston, Robert W.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
[Denniston, Robert W.] Off Natl Drug Control Policy, Rockville, MD USA.
RP Denniston, RW (reprint author), NIAAA, Rockville, MD 20852 USA.
EM justdoitbob@hotmail.com
NR 9
TC 0
Z9 0
U1 0
U2 0
PU OHIO STATE UNIV, COLL SOCIAL WORK
PI COLUMBUS
PA 1947 COLLEGE RD, COLUMBUS, OH 43210 USA
SN 1925-7066
J9 INT J ALCOHOL DRUG R
JI Int. J. Alcohol Drug Res.
PY 2015
VL 4
IS 2
SI SI
BP 97
EP 99
DI 10.7895/ijadr.v4i2.207
PG 3
WC Behavioral Sciences
SC Behavioral Sciences
GA DY8HP
UT WOS:000385370400002
ER
PT S
AU Miller, DS
AF Miller, David S.
BE Schuetz, JD
Ishikawa, T
TI Regulation of ABC Transporters Blood-Brain Barrier: The Good, the Bad,
and the Ugly
SO ABC TRANSPORTERS AND CANCER
SE Advances in Cancer Research
LA English
DT Review; Book Chapter
ID P-GLYCOPROTEIN EXPRESSION; CANCER RESISTANCE PROTEIN; XENOBIOTIC EFFLUX
TRANSPORTERS; MEDIATED UP-REGULATION; NECROSIS-FACTOR-ALPHA; SPINAL CORD
BARRIERS; DISEASE MOUSE MODEL; ALZHEIMERS-DISEASE; DRUG-DELIVERY;
AMYLOID-BETA
AB The brain capillary endothelial cells that constitute the blood-brain barrier express multiple ABC transport proteins on the luminal, blood-facing, plasma membrane. These transporters function as ATP-driven efflux pumps for xenobiotics and endogenous metabolites. High expression of these ABC transporters at the barrier is a major obstacle to the delivery of therapeutics, including chemotherapeutics, to the CNS. Here, I review the signals that alter ABC transporter expression and transport function with an emphasis on P-glycoprotein, Mrp2, and breast cancer resistance protein (BCRP), the efflux transporters for which we have the most detailed picture of regulation. Recent work shows that transporter protein expression can be upregulated in response to inflammatory and oxidative stress, therapeutic drugs, diet, and persistent environmental pollutants; as a consequence, drug delivery to the brain is reduced (potentially bad and ugly). In contrast, basal transport activity of P-glycoprotein and BCRP can be reduced through complex signaling pathways that involve events in and on the brain capillary endothelial cells. Targeting these signaling events provides opportunities to rapidly and reversibly increase brain accumulation of drugs that are substrates for the transporters ( potentially good). The clinical usefulness of targeting signaling to reduce efflux transporter activity and improve drug delivery to the CNS remains to be established.
C1 [Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Miller, DS (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM miller@niehs.nih.gov
NR 69
TC 15
Z9 16
U1 8
U2 15
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0065-230X
BN 978-0-12-801361-8; 978-0-12-801251-2
J9 ADV CANCER RES
JI Adv.Cancer Res.
PY 2015
VL 125
BP 43
EP 70
DI 10.1016/bs.acr.2014.10.002
PG 28
WC Oncology
SC Oncology
GA BF8GH
UT WOS:000385012300003
PM 25640266
ER
PT S
AU Chufan, EE
Sim, HM
Ambudkar, SV
AF Chufan, Eduardo E.
Sim, Hong-May
Ambudkar, Suresh V.
BE Schuetz, JD
Ishikawa, T
TI Molecular Basis of the Polyspecificity of P-Glycoprotein (ABCB1): Recent
Biochemical and Structural Studies
SO ABC TRANSPORTERS AND CANCER
SE Advances in Cancer Research
LA English
DT Review; Book Chapter
ID DRUG-BINDING SITE; MULTIDRUG-RESISTANCE; ATP HYDROLYSIS;
CAENORHABDITIS-ELEGANS; CATALYTIC CYCLE; TRANSMEMBRANE SEGMENTS;
PHARMACOPHORE MODEL; ALTERNATING ACCESS; BOUND STATES; EFFLUX PUMP
AB ABCB1 (P-glycoprotein/P-gp) is an ATP-binding cassette transporter well known for its association with multidrug resistance in cancer cells. Powered by the hydrolysis of ATP, it effluxes structurally diverse compounds. In this chapter, we discuss current views on the molecular basis of the substrate polyspecificity of P-gp. One of the features that accounts for this property is the structural flexibility observed in P-gp. Several X-ray crystal structures of mouse P-gp have been published recently in the absence of nucleotide, with and without bound inhibitors. All the structures are in an inward-facing conformation exhibiting different degrees of domain separation, thus revealing a highly flexible protein. Biochemical and biophysical studies also demonstrate this flexibility in mouse as well as human P-gp. Site-directed mutagenesis has revealed the existence of multiple transport-active binding sites in P-gp for a single substrate. Thus, drugs can bind at either primary or secondary sites. Biochemical, molecular modeling, and structure-activity relationship studies suggest a large, common drug-binding pocket with overlapping sites for different substrates. We propose that in addition to the structural flexibility, the molecular or chemical flexibility also contributes to the binding of substrates to multiple sites forming the basis of polyspecificity.
C1 [Chufan, Eduardo E.; Sim, Hong-May; Ambudkar, Suresh V.] NCI, Ctr Canc Res, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ambudkar, SV (reprint author), NCI, Ctr Canc Res, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM ambudkar@helix.nih.gov
FU Intramural NIH HHS
NR 79
TC 15
Z9 17
U1 3
U2 12
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0065-230X
BN 978-0-12-801361-8; 978-0-12-801251-2
J9 ADV CANCER RES
JI Adv.Cancer Res.
PY 2015
VL 125
BP 71
EP 96
DI 10.1016/bs.acr.2014.10.003
PG 26
WC Oncology
SC Oncology
GA BF8GH
UT WOS:000385012300004
PM 25640267
ER
PT S
AU Wu, YM
Sinden, RE
Churcher, TS
Tsuboi, T
Yusibov, V
AF Wu, Yimin
Sinden, Robert E.
Churcher, Thomas S.
Tsuboi, Takafumi
Yusibov, Vidadi
BE Rollinson, D
Stothard, JR
TI Development of Malaria Transmission-Blocking Vaccines: From Concept to
Product
SO ADVANCES IN PARASITOLOGY, VOL 89
SE Advances in Parasitology
LA English
DT Review; Book Chapter
ID PLASMODIUM-FALCIPARUM MALARIA; OOKINETE-SURFACE PROTEIN;
MEMBRANE-FEEDING ASSAY; SEXUAL STAGE ANTIGENS; MONTANIDE ISA 720;
AERUGINOSA EXOPROTEIN-A; DOMAIN-RELATED PROTEIN; PAPUA-NEW-GUINEA;
PHASE-I TRIAL; MOSQUITO-MIDGUT
AB Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission- blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches.
C1 [Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, Rockville, MD USA.
[Sinden, Robert E.] Jenner Inst, Oxford, England.
[Churcher, Thomas S.] Imperial Coll London, MRC, Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol,Sch Publ Hlth, London, England.
[Tsuboi, Takafumi] Ehime Univ, Div Malaria Res, Matsuyama, Ehime, Japan.
[Yusibov, Vidadi] Fraunhofer USA Ctr Mol Biotechnol, Newark, DE USA.
RP Wu, YM (reprint author), PATH Malaria Vaccine Initiat, Washington, DC 20001 USA.
EM ywu@path.org
OI Churcher, Thomas/0000-0002-8442-0525
FU Intramural NIH HHS; Medical Research Council [MR/K010174/1]
NR 205
TC 14
Z9 15
U1 3
U2 5
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0065-308X
BN 978-0-12-803334-0; 978-0-12-803301-2
J9 ADV PARASIT
JI Adv.Parasitol.
PY 2015
VL 89
BP 109
EP 152
DI 10.1016/bs.apar.2015.04.001
PG 44
WC Infectious Diseases; Parasitology
SC Infectious Diseases; Parasitology
GA BF8KY
UT WOS:000385154500003
PM 26003037
ER
PT S
AU Pierson, TC
Diamond, MS
AF Pierson, Theodore C.
Diamond, Michael S.
BE Klasse, PJ
TI A Game of Numbers: The Stoichiometry of Antibody-Mediated Neutralization
of Flavivirus Infection
SO MOLECULAR BASIS OF VIRAL INFECTION
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
ID WEST-NILE-VIRUS; TICK-BORNE ENCEPHALITIS; YELLOW-FEVER VACCINE; PROTEIN
DOMAIN-III; DENGUE VIRUS; ENVELOPE PROTEIN; DEPENDENT ENHANCEMENT;
MONOCLONAL-ANTIBODY; JAPANESE ENCEPHALITIS; IN-VIVO
AB The humoral response contributes to the protection against viral pathogens. Although antibodies have the potential to inhibit viral infections via several mechanisms, an ability to neutralize viruses directly may be particularly important. Neutralizing antibody titers are commonly used as predictors of protection from infection, especially in the context of vaccine responses and immunity. Despite the simplicity of the concept, how antibody binding results in virus inactivation is incompletely understood despite decades of research. Flaviviruses have been an attractive system in which to seek a structural and quantitative understanding of how antibody interactions with virions modulate infection because of the contribution of antibodies to both protection and pathogenesis. This review will present a stoichiometric model of antibody-mediated neutralization of flaviviruses and discuss how these concepts can inform the development of vaccines and antibody-based therapeutics.
C1 [Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Immunol, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
RP Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM piersontc@niaid.nih.gov; diamond@borcim.wustl.edu
FU NIAID NIH HHS [R01 AI073755, R01 AI089591, R01AI073755]; PHS HHS
[R01A1089591]
NR 123
TC 3
Z9 3
U1 2
U2 3
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1877-1173
BN 978-0-12-802587-1; 978-0-12-802461-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 129
BP 141
EP 166
DI 10.1016/bs.pmbts.2014.10.005
PG 26
WC Biochemistry & Molecular Biology; Infectious Diseases; Virology
SC Biochemistry & Molecular Biology; Infectious Diseases; Virology
GA BF8GQ
UT WOS:000385020000006
PM 25595803
ER
PT S
AU Tedbury, PR
Freed, EO
AF Tedbury, Philip R.
Freed, Eric O.
BE Klasse, PJ
TI The Cytoplasmic Tail of Retroviral Envelope Glycoproteins
SO MOLECULAR BASIS OF VIRAL INFECTION
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
ID HUMAN-IMMUNODEFICIENCY-VIRUS; JAAGSIEKTE SHEEP RETROVIRUS;
MURINE-LEUKEMIA-VIRUS; POLARIZED EPITHELIAL-CELLS; ROUS-SARCOMA-VIRUS;
MEMBRANE-SPANNING DOMAIN; AMINO-ACID SUBSTITUTIONS; INFECTIOUS-ANEMIA
VIRUS; VIRAL PARTICLE RELEASE; N-LINKED GLYCOSYLATION
AB Retroviruses comprise a large, diverse group that infects a broad range of host organisms. Pathogenicity varies widely; the human immunodeficiency virus is the causative agent of acquired immunodeficiency syndrome, one of the world's leading infectious causes of death, while many nonhuman retroviruses cause cancer in the host. Retroviruses have been studied intensively, and great strides have been made in understanding aspects of retroviral biology. While the principal functions of the viral structural proteins are well understood, there remain many incompletely characterized domains. One of these is the cytoplasmic tail (CT) of the envelope glycoprotein. Several functions of the CT are highly conserved, whereas other properties are unique to a specific retrovirus. For example, the lentiviruses encode envelope glycoproteins with particularly large cytoplasmic domains. The functions of the long lentiviral envelope CT are still being deciphered. The reported functions of retroviral envelope CTs are discussed in this chapter.
C1 [Tedbury, Philip R.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM efreed@nih.gov
OI Tedbury, Philip/0000-0001-8151-4967
FU Intramural NIH HHS
NR 196
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1877-1173
BN 978-0-12-802587-1; 978-0-12-802461-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 129
BP 253
EP 284
DI 10.1016/bs.pmbts.2014.10.009
PG 32
WC Biochemistry & Molecular Biology; Infectious Diseases; Virology
SC Biochemistry & Molecular Biology; Infectious Diseases; Virology
GA BF8GQ
UT WOS:000385020000010
PM 25595807
ER
PT S
AU Evans, PR
Dudek, SM
Hepler, JR
AF Evans, Paul R.
Dudek, Serena M.
Hepler, John R.
BE Fisher, RA
TI Regulator of G Protein Signaling 14: A Molecular Brake on Synaptic
Plasticity Linked to Learning and Memory
SO RGS PROTEIN PHYSIOLOGY AND PATHOPHYSIOLOGY
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
ID HETEROTRIMERIC G-PROTEINS; VASOPRESSIN 1B RECEPTOR; LONG-TERM
POTENTIATION; HIPPOCAMPAL AREA CA2; CENTRAL-NERVOUS-SYSTEM;
GUANINE-NUCLEOTIDE EXCHANGE; MEDIAL ENTORHINAL CORTEX; G-ALPHA-I; RGS
PROTEINS; SUPRAMAMMILLARY NUCLEUS
AB The regulators of G protein signaling (RGS) proteins are a diverse family of proteins that function as central components of G protein and other signaling pathways. In the brain, regulator of G protein signaling 14 (RGS14) is enriched in neurons in the hippocampus where the mRNA and protein are highly expressed. This brain region plays a major role in processing learning and forming new memories. RGS14 is an unusual RGS protein that acts as a multifunctional scaffolding protein to integrate signaling events and pathways essential for synaptic plasticity, including conventional and unconventional G protein signaling, mitogen-activated protein kinase, and, possibly, calcium signaling pathways. Within the hippocampus of primates and rodents, RGS14 is predominantly found in the enigmatic CA2 subfield. Principal neurons within the CA2 subfield differ from neighboring hippocampal regions in that they lack a capacity for long-term potentiation (LTP) of synaptic transmission, which is widely viewed as the cellular substrate of learning and memory formation. RGS14 was recently identified as a natural suppressor of LTP in hippocampal CA2 neurons as well as forms of learning and memory that depend on the hippocampus. Although CA2 has only recently been studied, compelling recent evidence implicates area CA2 as a critical component of hippocampus circuitry with functional roles in mediating certain types of learning and memory. This review will highlight the known functions of RGS14 in cell signaling and hippocampus physiology, and discuss potential roles for RGS14 in human cognition and disease.
C1 [Evans, Paul R.; Hepler, John R.] Emory Univ, Sch Med, Dept Pharmacol, Rollins Res Ctr, Atlanta, GA 30322 USA.
[Dudek, Serena M.] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Hepler, JR (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Rollins Res Ctr, Atlanta, GA 30322 USA.
EM jhepler@emory.edu
OI Dudek, Serena M./0000-0003-4094-8368
FU Intramural NIH HHS; NIEHS NIH HHS [Z01-ES-100221]; NINDS NIH HHS
[1F31NS086174, F31 NS086174, 5R01 NS37112, 1R21NS074975]
NR 123
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1877-1173
BN 978-0-12-802954-1; 978-0-12-802938-1
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 133
BP 169
EP 206
DI 10.1016/bs.pmbts.2015.03.006
PG 38
WC Biochemistry & Molecular Biology; Physiology
SC Biochemistry & Molecular Biology; Physiology
GA BF8GO
UT WOS:000385016400010
PM 26123307
ER
PT J
AU Zhao, YD
Polley, EC
Li, MC
Lih, CJ
Palmisano, A
Sims, DJ
Rubinstein, LV
Conley, BA
Chen, AP
Williams, PM
Kummar, S
Doroshow, JH
Simon, RM
AF Zhao, Yingdong
Polley, Eric C.
Li, Ming-Chung
Lih, Chih-Jian
Palmisano, Alida
Sims, David J.
Rubinstein, Lawrence V.
Conley, Barbara A.
Chen, Alice P.
Williams, P. Mickey
Kummar, Shivaani
Doroshow, James H.
Simon, Richard M.
TI GeneMed: An Informatics Hub for the Coordination of Next-Generation
Sequencing Studies that Support Precision Oncology Clinical Trials
SO CANCER INFORMATICS
LA English
DT Article
DE GeneMed; MPACT; next-generation sequencing; precision medicine;
informatics system; clinical trial
ID GENOME
AB We have developed an informatics system, GeneMed, for the National Cancer Institute (NCI) molecular profiling-based assignment of cancer therapy (MPACT) clinical trial (NCT01827384) being conducted in the National Institutes of Health (NIH) Clinical Center. This trial is one of the first to use a randomized design to examine whether assigning treatment based on genomic tumor screening can improve the rate and duration of response in patients with advanced solid tumors. An analytically validated next-generation sequencing (NGS) assay is applied to DNA from patients' tumors to identify mutations in a panel of genes that are thought likely to affect the utility of targeted therapies available for use in the clinical trial. The patients are randomized to a treatment selected to target a somatic mutation in the tumor or with a control treatment. The GeneMed system streamlines the workflow of the clinical trial and serves as a communications hub among the sequencing lab, the treatment selection team, and clinical personnel. It automates the annotation of the genomic variants identified by sequencing, predicts the functional impact of mutations, identifies the actionable mutations, and facilitates quality control by the molecular characterization lab in the review of variants. The GeneMed system collects baseline information about the patients from the clinic team to determine eligibility for the panel of drugs available. The system performs randomized treatment assignments under the oversight of a supervising treatment selection team and generates a patient report containing detected genomic alterations. NCI is planning to expand the MPACT trial to multiple cancer centers soon. In summary, the GeneMed system has been proven to be an efficient and successful informatics hub for coordinating the reliable application of NGS to precision medicine studies.
C1 [Zhao, Yingdong; Polley, Eric C.; Li, Ming-Chung; Palmisano, Alida; Rubinstein, Lawrence V.; Simon, Richard M.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD 20850 USA.
[Lih, Chih-Jian; Sims, David J.; Williams, P. Mickey] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Mol Characterizat & Clin Assay Dev Lab, Frederick, MD USA.
[Conley, Barbara A.] NCI, Canc Diag Program, Div Canc Treatment & Diag, Rockville, MD USA.
[Chen, Alice P.; Kummar, Shivaani; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD USA.
RP Simon, RM (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD 20850 USA.
EM rsimon@nih.gov
RI Palmisano, Alida/C-2254-2015
OI Palmisano, Alida/0000-0002-1859-3719
NR 16
TC 8
Z9 8
U1 0
U2 1
PU LIBERTAS ACAD
PI AUCKLAND
PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND
SN 1176-9351
J9 CANCER INFORM
JI Cancer Inform.
PY 2015
VL 14
SU 2
BP 45
EP 55
DI 10.4137/CIN.S17282
PG 11
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DW9FH
UT WOS:000383960900006
PM 25861217
ER
PT J
AU Isokpehi, RD
Valero, KCW
Graham, BE
Pacurari, M
Sims, JN
Udensi, UK
Ndebele, K
AF Isokpehi, Raphael D.
Valero, Katharina C. Wollenberg
Graham, Barbara E.
Pacurari, Maricica
Sims, Jennifer N.
Udensi, Udensi K.
Ndebele, Kenneth
TI Secondary Data Analytics of Aquaporin Expression Levels in Glioblastoma
Stem-Like Cells
SO CANCER INFORMATICS
LA English
DT Article
DE aquaporins; aquaporin-1; aquaporin-4; brain; cancer; gliomas;
glioblastoma; hypoxia; neurospheres; visual analytics
ID VISUAL ANALYTICS; GLIOMA
AB Glioblastoma is the most common brain tumor in adults in which recurrence has been attributed to the presence of cancer stem cells in a hypoxic microenvironment. On the basis of tumor formation in vivo and growth type in vitro, two published microarray gene expression profiling studies grouped nine glioblastoma stem-like (GS) cell lines into one of two groups: full (GSf) or restricted (GSr) stem-like phenotypes. Aquaporin-1 (AQP1) and aquaporin-4 (AQP4) are water transport proteins that are highly expressed in primary glial-derived tumors. However, the expression levels of AQP1 and AQP4 have not been previously described in a panel of 92 glioma samples. Therefore, we designed secondary data analytics methods to determine the expression levels of AQP1 and AQP4 in GS cell lines and glioblastoma neurospheres. Our investigation also included a total of 2,566 expression levels from 28 Affymetrix microarray probe sets encoding 13 human aquaporins (AQP0-AQP12); CXCR4 (the receptor for stromal cell derived factor-1 [SDF-1], a potential glioma stem cell therapeutic target]); and PROM1 (gene encoding CD133, the widely used glioma stem cell marker). Interactive visual representation designs for integrating phenotypic features and expression levels revealed that inverse expression levels of AQP1 and AQP4 correlate with distinct phenotypes in a set of cell lines grouped into full and restricted stem-like phenotypes. Discriminant function analysis further revealed that AQP1 and AQP4 expression are better predictors for tumor formation and growth types in glioblastoma stem-like cells than are CXCR4 and PROM1. Future investigations are needed to characterize the molecular mechanisms for inverse expression levels of AQP1 and AQP4 in the glioblastoma stem-like neurospheres.
C1 [Isokpehi, Raphael D.; Valero, Katharina C. Wollenberg] Bethune Cookman Univ, Coll Sci Engn & Math, Daytona Beach, FL 32114 USA.
[Graham, Barbara E.; Sims, Jennifer N.; Ndebele, Kenneth] Jackson State Univ, Lab Canc Immunol Target Identificat & Validat, Dept Biol, Jackson, MS USA.
[Graham, Barbara E.; Udensi, Udensi K.; Ndebele, Kenneth] Jackson State Univ, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS USA.
[Pacurari, Maricica] Jackson State Univ, Dept Biol, Jackson, MS USA.
[Ndebele, Kenneth] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA.
RP Isokpehi, RD (reprint author), Bethune Cookman Univ, Coll Sci Engn & Math, Daytona Beach, FL 32114 USA.
EM isokpehir@cookman.edu
OI Wollenberg Valero, Katharina/0000-0001-8858-1804
FU NIGMS NIH HHS [T36 GM095335]; NIMHD NIH HHS [G12 MD007581, P20 MD006899]
NR 21
TC 0
Z9 0
U1 0
U2 0
PU LIBERTAS ACAD
PI AUCKLAND
PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND
SN 1176-9351
J9 CANCER INFORM
JI Cancer Inform.
PY 2015
VL 14
BP 95
EP 103
DI 10.4137/CIN.S22058
PG 9
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DW9EG
UT WOS:000383958200001
PM 26279619
ER
PT J
AU Finney, RP
Chen, QR
Nguyen, CV
Hsu, CH
Yan, CH
Hu, Y
Abawi, M
Bian, XP
Meerzaman, DM
AF Finney, Richard P.
Chen, Qing-Rong
Nguyen, Cu V.
Hsu, Chih Hao
Yan, Chunhua
Hu, Ying
Abawi, Massih
Bian, Xiaopeng
Meerzaman, Daoud M.
TI Alview: Portable Software for Viewing Sequence Reads in BAM Formatted
Files
SO CANCER INFORMATICS
LA English
DT Article
DE genomics; short read; alignment; visualization; BAM; open source
AB The name Alview is a contraction of the term Alignment Viewer. Alview is a compiled to native architecture software tool for visualizing the alignment of sequencing data. Inputs are files of short-read sequences aligned to a reference genome in the SAM/BAM format and files containing reference genome data. Outputs are visualizations of these aligned short reads. Alview is written in portable C with optional graphical user interface (GUI) code written in C, C++, and Objective-C. The application can run in three different ways: as a web server, as a command line tool, or as a native, GUI program. Alview is compatible with Microsoft Windows, Linux, and Apple OS X. It is available as a web demo at https://cgwb.nci.nih.gov/cgi-bin/alview. The source code and Windows/Mac/Linux executables are available via https://github.com/NCIP/alview.
C1 [Finney, Richard P.; Chen, Qing-Rong; Nguyen, Cu V.; Hsu, Chih Hao; Yan, Chunhua; Hu, Ying; Abawi, Massih; Bian, Xiaopeng; Meerzaman, Daoud M.] NCI, Computat Genom Res Grp, Ctr Bioinformat & Informat Technol, Bethesda, MD 20892 USA.
RP Finney, RP (reprint author), NCI, Computat Genom Res Grp, Ctr Bioinformat & Informat Technol, Bethesda, MD 20892 USA.
EM finneyr@mail.nih.gov
NR 9
TC 1
Z9 1
U1 1
U2 1
PU LIBERTAS ACAD
PI AUCKLAND
PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND
SN 1176-9351
J9 CANCER INFORM
JI Cancer Inform.
PY 2015
VL 14
BP 105
EP 107
DI 10.4137/CIN.S26470
PG 3
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DW9EI
UT WOS:000383958400001
PM 26417198
ER
PT S
AU Xu, ZY
Bagci, U
Udupa, JK
Mollura, DJ
AF Xu, Ziyue
Bagci, Ulas
Udupa, Jayaram K.
Mollura, Daniel J.
BE Gao, F
Shi, K
Li, S
TI Fuzzy Connectedness Image Co-segmentation for Hybrid PET/MRI and PET/CT
Scans
SO COMPUTATIONAL METHODS FOR MOLECULAR IMAGING
SE Lecture Notes in Computational Vision and Biomechanics
LA English
DT Article; Book Chapter
DE Co-segmentation; Fuzzy connectedness; PET/MRI; PET/CT; Image
segmentation
ID DELINEATION; DEFINITION
AB In this paper, we presented a 3-D computer-aided co-segmentation tool for tumor/lesion detection and quantification from hybrid PET/MRI and PET/CT scans. The proposed method was designed with a novel modality-specific visibility weighting scheme built upon a fuzzy connectedness (FC) image segmentation algorithm. In order to improve the determination of lesion margin, it is necessary to combine the complementary information of tissues from both anatomical and functional domains. Therefore, a robust image segmentation method that simultaneously segments tumors/lesions in each domain is required. However, this task, named co-segmentation, is a challenging problem due to (1) unique challenges brought by each imaging modality, and (2) a lack of one-to-one region and boundary correspondences of lesions in different imaging modalities. Owing to these hurdles, the algorithm is desired to have a sufficient flexibility to utilize the strength of each modality. In this work, seed points were first selected from high uptake regions within PET images. Then, lesion boundaries were delineated using a hybrid approach based on novel affinity function design within the FC framework. Further, an advanced extension of FC algorithm called iterative relative FC (IRFC) was used with automatically identified background seeds. The segmentation results were compared to the reference truths provided by radiologists. Experimental results showed that the proposed method effectively utilized multi-modality information for co-segmentation, with a high accuracy (mean DSC of 85%) and can be a viable alternative to the state-of-the art joint segmentation method of random walk (RW) with higher efficiency.
C1 [Bagci, Ulas] Univ Cent Florida, CRCV, Comp Sci, HEC 221, Orlando, FL 32816 USA.
[Xu, Ziyue; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Udupa, Jayaram K.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
RP Bagci, U (reprint author), Univ Cent Florida, CRCV, Comp Sci, HEC 221, Orlando, FL 32816 USA.
EM bagci@crcv.ucf.edu
OI Bagci, Ulas/0000-0001-7379-6829
NR 8
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2212-9391
BN 978-3-319-18431-9; 978-3-319-18430-2
J9 L N COMPUT VIS BIOME
PY 2015
VL 22
BP 15
EP 24
DI 10.1007/978-3-319-18431-9_2
D2 10.1007/978-3-319-18431-9
PG 10
WC Biophysics; Computer Science, Artificial Intelligence; Engineering,
Biomedical
SC Biophysics; Computer Science; Engineering
GA BF6NS
UT WOS:000383355200002
ER
PT J
AU Kaplan, RM
Smith, WB
AF Kaplan, Robert M.
Smith, Wendy B.
BE Jeste, DV
Palmer, BW
TI What Is Well-Being?
SO POSITIVE PSYCHIATRY: A CLINICAL HANDBOOK
LA English
DT Article; Book Chapter
ID QUALITY-OF-LIFE; HEALTH; TECHNOLOGY; PREVALENCE; PREVENTION; VALIDITY;
OUTCOMES; INDEXES; DISEASE; SF-36
C1 [Kaplan, Robert M.] US Dept HHS, Agcy Healthcare Res & Qual, Rockville, MD 20852 USA.
[Smith, Wendy B.] NIH, Res Dev & Outreach, Off Behav & Social Sci Res, Off Director, Bethesda, MD 20892 USA.
RP Kaplan, RM (reprint author), US Dept HHS, Agcy Healthcare Res & Qual, Rockville, MD 20852 USA.
NR 29
TC 0
Z9 0
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA
BN 978-1-58562-495-9
PY 2015
BP 111
EP 125
D2 10.1176/appi.books.9781615370818
PG 15
WC Psychiatry
SC Psychiatry
GA BF6IU
UT WOS:000383142600007
ER
PT J
AU Sharmin, M
Raij, A
Epstien, D
Nahum-Shani, I
Beck, JG
Vhaduri, S
Preston, K
Kumar, S
AF Sharmin, Moushumi
Raij, Andrew
Epstien, David
Nahum-Shani, Inbal
Beck, J. Gayle
Vhaduri, Sudip
Preston, Kenzie
Kumar, Santosh
GP ACM
TI Visualization of Time-Series Sensor Data to Inform the Design of
Just-In-Time Adaptive Stress Interventions
SO PROCEEDINGS OF THE 2015 ACM INTERNATIONAL JOINT CONFERENCE ON PERVASIVE
AND UBIQUITOUS COMPUTING (UBICOMP 2015)
LA English
DT Proceedings Paper
CT ACM International Joint Conference on Pervasive and Ubiquitous Computing
(UbiComp)
CY SEP 07-11, 2015
CL Osaka, JAPAN
SP Assoc Comp Machinery, ACM SIGCHI, ACM SIGMOBILE, Panasonic, Bell Labs, Microsoft, Google, Yahoo Japan, KDDI, FXPAL, Rakuten Inst Technol, ISTC PC, NTT DOCOMO, Telefonica Investigac & Desarrollo
DE Stress; Stress Management; Visualization; Just-in-time Adaptive
Interventions (JITAIs)
AB We investigate needs, challenges, and opportunities in visualizing time-series sensor data on stress to inform the design of just-in-time adaptive interventions (JITAIs). We identify seven key challenges: massive volume and variety of data, complexity in identifying stressors, scalability of space, multifaceted relationship between stress and time, a need for representation at multiple granularities, interperson variability, and limited understanding of JITAI design requirements due to its novelty. We propose four new visualizations based on one million minutes of sensor data (n = 70). We evaluate our visualizations with stress researchers (n = 6) to gain first insights into its usability and usefulness in JITAI design. Our results indicate that spatiotemporal visualizations help identify and explain between-and within-person variability in stress patterns and contextual visualizations enable decisions regarding the timing, content, and modality of intervention. Interestingly, a granular representation is considered informative but noise-prone; an abstract representation is the preferred starting point for designing JITAIs.
C1 [Sharmin, Moushumi; Beck, J. Gayle; Kumar, Santosh] Univ Memphis, Memphis, TN 38152 USA.
[Raij, Andrew] Univ Cent Florida, Orlando, FL 32816 USA.
[Epstien, David; Preston, Kenzie] NIDA IRP, Baltimore, MD USA.
[Nahum-Shani, Inbal] Univ Michigan, Ann Arbor, MI 48109 USA.
[Vhaduri, Sudip] Univ Notre Dame, Notre Dame, IN 46556 USA.
RP Sharmin, M (reprint author), Univ Memphis, Memphis, TN 38152 USA.
EM msharmin@memphis.edu; raij@ucf.edu; depstein@intra.nida.nih.gov;
inbal@umich.edu; jgbeck@memphis.edu; svhaduri@nd.edu;
kpreston@intra.nida.nih.gov; skumar4@memphis.edu
NR 40
TC 0
Z9 0
U1 0
U2 0
PU ASSOC COMPUTING MACHINERY
PI NEW YORK
PA 1515 BROADWAY, NEW YORK, NY 10036-9998 USA
BN 978-1-4503-3574-4
PY 2015
BP 505
EP 516
DI 10.1145/2750858.2807537
PG 12
WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic
SC Computer Science; Engineering
GA BF6WQ
UT WOS:000383742200046
ER
PT B
AU Ku, S
Klaessig, F
AF Ku, Sharon
Klaessig, Frederick
BE Schlaudt, O
Huber, L
TI A MATTER OF SIZE DOES NOT MATTER: MATERIAL AND INSTITUTIONAL AGENCIES IN
NANOTECHNOLOGY STANDARDIZATION
SO STANDARDIZATION IN MEASUREMENT: PHILOSOPHICAL, HISTORICAL AND
SOCIOLOGICAL ISSUES
SE History and Philosophy of Technoscience
LA English
DT Article; Book Chapter
C1 [Ku, Sharon] Drexel Univ, Dept Hist & Polit, Philadelphia, PA 19104 USA.
[Ku, Sharon] NIH, Off Hist, Bethesda, MD 20892 USA.
[Klaessig, Frederick] Evonik Degussa GmbH, Aerosil Business Line, Essen, Germany.
RP Ku, S (reprint author), Drexel Univ, Dept Hist & Polit, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI ABINGDON
PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND
BN 978-1-317-31669-5; 978-1-84893-571-6
J9 HIST PHILOS TECHNOSC
PY 2015
VL 7
BP 189
EP 206
PG 18
WC History & Philosophy Of Science
SC History & Philosophy of Science
GA BF6FQ
UT WOS:000383032900015
ER
PT J
AU Kim, IC
Thoma, GR
AF Kim, In Cheol
Thoma, George R.
GP IEEE
TI Automated Classification of Author's Sentiments in Citation Using
Machine Learning Techniques: A Preliminary Study
SO 2015 IEEE CONFERENCE ON COMPUTATIONAL INTELLIGENCE IN BIOINFORMATICS AND
COMPUTATIONAL BIOLOGY (CIBCB)
LA English
DT Proceedings Paper
CT IEEE Conference on Computational Intelligence in Bioinformatics and
Computational Biology CIBCB
CY AUG 12-15, 2015
CL Honolulu, HI
DE Citation analysis; author's sentiments; "Comment-on"; support vector
machine; n-grams word statistics; MEDLINE
ID TEXT CATEGORIZATION
AB Scientific papers generally include citations to external sources such as journal articles, books, or Web links to refer to works that are related in an important way to the research. The reason for the citation appears within the sentences surrounding the citation tag in the body text, and represents the relationship between the citation and cited works as supportive, contrastive, corrective, etc. This could be an important clue for researchers seeking relevant previous work or approaches for a certain research purpose. We propose to develop an automated method to identify the citing author's sentiments toward the cited external sources expressed in citation sentences using machine-learning techniques and linguistic cues. As a preliminary study, this paper presents a support vector machine (SVM)-based text categorization technique to classify the author's sentiments specifically toward Comment-on (CON) articles. CON, a MEDLINE citation field, indicates previously published articles commented on by authors of a given article expressing possibly complimentary or contradictory opinions. An SVM with a radial basis kernel function (RBF) is implemented, and Input feature vectors for the SVM are created based on n-grams word statistics representing the distribution of words in CON sentences. Experiments conducted on a set of CON sentences collected from 414 different online biomedical journal titles show that the SVM with a RBF yields the best result for an input feature vector combining uni-gram and bi-gram word statistics.
C1 [Kim, In Cheol; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Kim, IC (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4799-6926-5
PY 2015
BP 488
EP 494
PG 7
WC Computer Science, Information Systems; Mathematical & Computational
Biology
SC Computer Science; Mathematical & Computational Biology
GA BF1SY
UT WOS:000380434200049
ER
PT S
AU Cavalcante, FR
Carvalho, AB
Santos, WS
Lee, C
AF Cavalcante, F. R.
Carvalho Junior, A. B.
Santos, W. S.
Lee, Choonsik
BE Jaffray, DA
TI Monte Carlo simulation of interventional cardiac scenarios using a
newborn hybrid phantom and MCNPX code
SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS
1 AND 2
SE IFMBE Proceedings
LA English
DT Proceedings Paper
CT World Congress on Medical Physics and Biomedical Engineering
CY JUN 07-12, 2015
CL Toronto, CANADA
DE Dose conversion coefficients; interventional procedure; NURBS phantom;
MCNPX code
AB We developed exposure scenarios of pediatric interventional cardiology using a newborn hybrid phantom and the radiation transport code MCNPX. Six angiographic projections (AP, PA, LAO45, RAO45, LAO90 and RAO90) were simulated considering three X-ray energy spectra (60, 70 and 80 kVp), focus-skin distance (FSD) not less than 45 cm and a 7 x 7 cm(2) field size. The equivalent and effective doses were computed and normalized by the kerma-area product (KAP) resulting the conversion coefficients HT/KAP and E/KAP. The results showed highest HT/KAP values in AP projection (80 kVp). Increasing photon energy, average E/KAP values presented relative differences of 18% (60 to 70 kVp) and 15% (70 to 80 kVp). E/KAP values were compared with those published for mathematical newborn phantom. Results showed relative differences of 14% for AP projection (70 kVp) and 60% for lateral projections (60 kVp).
C1 [Cavalcante, F. R.; Carvalho Junior, A. B.] Univ Fed Sergipe, Dept Fis, Sao Cristovao, Brazil.
[Santos, W. S.] Comissao Nacl Energia Nucl, Inst Pesquisas Energet & Nucl, Sao Paulo, Brazil.
[Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
RP Cavalcante, FR (reprint author), Univ Fed Sergipe, Dept Fis, Sao Cristovao, Brazil.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1680-0737
BN 978-3-319-19387-8; 978-3-319-19386-1
J9 IFMBE PROC
PY 2015
VL 51
BP 173
EP 176
DI 10.1007/978-3-319-19387-8_42
PG 4
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA BF5AQ
UT WOS:000381813000042
ER
PT S
AU Oldfield, R
Jalilian, I
Song, MJ
Tate, MK
AF Oldfield, Richard
Jalilian, Iman
Song, Min Jae
Tate, Melissa Knothe
BE Jaffray, DA
TI Mapping the Stem Cell's Mechanome Using Paired Live Cell Multiplexed
Imaging and Modeling
SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS
1 AND 2
SE IFMBE Proceedings
LA English
DT Proceedings Paper
CT World Congress on Medical Physics and Biomedical Engineering
CY JUN 07-12, 2015
CL Toronto, CANADA
ID MECHANICAL MODULATION; TISSUE; FATE; SHAPE
C1 [Oldfield, Richard; Jalilian, Iman; Tate, Melissa Knothe] Univ New South Wales, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia.
[Song, Min Jae] NIH, Bethesda, MD 20892 USA.
RP Oldfield, R (reprint author), Univ New South Wales, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia.
EM m.knothetate@unsw.edu.au
NR 10
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1680-0737
BN 978-3-319-19387-8; 978-3-319-19386-1
J9 IFMBE PROC
PY 2015
VL 51
BP 275
EP 275
PG 1
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA BF5AQ
UT WOS:000381813000067
ER
PT J
AU Hafftka, A
Celik, H
Cloninger, A
Czaja, W
Spencer, RG
AF Hafftka, Ariel
Celik, Hasan
Cloninger, Alexander
Czaja, Wojciech
Spencer, Richard G.
GP IEEE
TI 2D Sparse Sampling Algorithm for N D Fredholm Equations with
Applications to NMR Relaxometry
SO 2015 INTERNATIONAL CONFERENCE ON SAMPLING THEORY AND APPLICATIONS
(SAMPTA)
LA English
DT Proceedings Paper
CT International Conference on Sampling Theory and Applications (SampTA)
CY MAY 25-29, 2015
CL Washington, DC
SP Univ Maryland, Army Res Lab
ID MATRIX COMPLETION
AB In [1], Cloninger, Czaja, Bai, and Basser developed an algorithm for compressive sampling based data acquisition for the solution of 2 D Fredholm equations. We extend the algorithm to N dimensional data, by randomly sampling in 2 dimensions and fully sampling in the remaining N - 2 dimensions. This new algorithm has direct applications to 3-dimensional nuclear magnetic resonance relaxometry and related experiments, such as T-1 - D - T-2 or T-1 - T-1,rho - T-2. In these experiments, the first two parameters are time-consuming to acquire, so sparse sampling in the first two parameters can provide significant experimental time savings, while compressive sampling is unnecessary in the third parameter.
C1 [Hafftka, Ariel] Univ Maryland, Appl Math & Sci Computat, College Pk, MD 20742 USA.
[Celik, Hasan; Spencer, Richard G.] NIA, Lab Clin Invest, NIH, Bethesda, MD 20892 USA.
[Cloninger, Alexander] Yale Univ, Appl Math, New Haven, CT 06520 USA.
[Czaja, Wojciech] Univ Maryland, Dept Math, College Pk, MD 20742 USA.
RP Hafftka, A (reprint author), Univ Maryland, Appl Math & Sci Computat, College Pk, MD 20742 USA.
EM ahafftka@math.umd.edu; hasan.celik@nih.gov;
alexander.cloninger@yale.edu; wojtek@math.umd.edu;
spencerri@mail.nih.gov
NR 22
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4673-7353-1
PY 2015
BP 367
EP 371
PG 5
WC Engineering, Electrical & Electronic; Mathematics, Interdisciplinary
Applications
SC Engineering; Mathematics
GA BF2UI
UT WOS:000380500800077
ER
PT J
AU Shamputa, IC
Cho, SN
Lebron, J
Via, LE
AF Shamputa, Isdore C.
Cho, Sang Nae
Lebron, Janette
Via, Laura E.
BE Mukundan, H
Chambers, MA
Waters, WR
Larsen, MH
TI Introduction and Epidemiology of Mycobacterium tuberculosis Complex in
Humans
SO TUBERCULOSIS, LEPROSY AND MYCOBACTERIAL DISEASES OF MAN AND ANIMALS: THE
MANY HOSTS OF MYCOBACTERIA
LA English
DT Editorial Material; Book Chapter
ID ANTITUBERCULOSIS-DRUG-RESISTANCE; HUMAN-IMMUNODEFICIENCY-VIRUS;
PULMONARY TUBERCULOSIS; CONGENITAL TUBERCULOSIS; GENETIC SUSCEPTIBILITY;
LATENT TUBERCULOSIS; CHINESE POPULATION; UPDATED ANALYSIS; PROPHIT
SURVEY; GLOBAL TRENDS
C1 [Shamputa, Isdore C.] NIH, TB Res Sect, Lab Clin Infect Dis, Bldg 10, Bethesda, MD 20892 USA.
[Lebron, Janette] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Via, Laura E.] NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Cho, Sang Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea.
RP Via, LE (reprint author), NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM icshamputa@itg.be; raycho@yonsei.ac.kr; jlebron1@jhmi.edu;
lvia@niaid.nih.gov
NR 118
TC 0
Z9 0
U1 0
U2 0
PU CABI PUBLISHING-C A B INT
PI WALLINGFORD
PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND
BN 978-1-78064-396-0
PY 2015
BP 1
EP 16
D2 10.1079/9781780643960.0000
PG 16
WC Infectious Diseases; Veterinary Sciences
SC Infectious Diseases; Veterinary Sciences
GA BF5FO
UT WOS:000381942700002
ER
PT J
AU Sizemore, C
Lacourciere, K
Parker, T
AF Sizemore, Christine
Lacourciere, Karen
Parker, Tina
BE Mukundan, H
Chambers, MA
Waters, WR
Larsen, MH
TI Introduction - The Many Hosts of Mycobacteria: An Interdisciplinary
Approach to Understanding Mycobacterial Diseases
SO TUBERCULOSIS, LEPROSY AND MYCOBACTERIAL DISEASES OF MAN AND ANIMALS: THE
MANY HOSTS OF MYCOBACTERIA
LA English
DT Editorial Material; Book Chapter
C1 [Sizemore, Christine; Lacourciere, Karen; Parker, Tina] NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Sizemore, C (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM csizemore@niaid.nih.gov; lacourcierek@niaid.nih.gov;
parkerti@niaid.nih.gov
NR 0
TC 2
Z9 2
U1 0
U2 0
PU CABI PUBLISHING-C A B INT
PI WALLINGFORD
PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND
BN 978-1-78064-396-0
PY 2015
BP XV
EP XVII
D2 10.1079/9781780643960.0000
PG 3
WC Infectious Diseases; Veterinary Sciences
SC Infectious Diseases; Veterinary Sciences
GA BF5FO
UT WOS:000381942700001
ER
PT J
AU Barry, CE
AF Barry, Clifton E., III
BE Mukundan, H
Chambers, MA
Waters, WR
Larsen, MH
TI The Continuing Co-evolution of Mycobacterium tuberculosis and Homo
sapiens
SO TUBERCULOSIS, LEPROSY AND MYCOBACTERIAL DISEASES OF MAN AND ANIMALS: THE
MANY HOSTS OF MYCOBACTERIA
LA English
DT Article; Book Chapter
ID TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; BEIJING GENOTYPE;
IMMUNE-RESPONSE; RNA-POLYMERASE; PA-824; RESISTANCE; COMPLEX; STRAINS;
OBESITY
C1 [Barry, Clifton E., III] NIAID, TB Res Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@niaid.nih.gov
NR 64
TC 0
Z9 0
U1 0
U2 0
PU CABI PUBLISHING-C A B INT
PI WALLINGFORD
PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND
BN 978-1-78064-396-0
PY 2015
BP 112
EP 123
D2 10.1079/9781780643960.0000
PG 12
WC Infectious Diseases; Veterinary Sciences
SC Infectious Diseases; Veterinary Sciences
GA BF5FO
UT WOS:000381942700007
ER
PT J
AU Sharpe, S
Via, LE
Verreck, FAW
Lin, PL
AF Sharpe, Sally
Via, Laura E.
Verreck, Frank A. W.
Lin, P. Ling
BE Mukundan, H
Chambers, MA
Waters, WR
Larsen, MH
TI Non-human Primate Laboratory Models of Tuberculosis
SO TUBERCULOSIS, LEPROSY AND MYCOBACTERIAL DISEASES OF MAN AND ANIMALS: THE
MANY HOSTS OF MYCOBACTERIA
LA English
DT Article; Book Chapter
ID MARMOSET CALLITHRIX-JACCHUS; MACAQUES MACACA-MULATTA;
BACILLUS-CALMETTE-GUERIN; SIMIAN IMMUNODEFICIENCY VIRUS; INDIAN RHESUS
MACAQUES; VIRULENT MYCOBACTERIUM-TUBERCULOSIS; MONKEYS SAIMIRI-SCIUREUS;
PLASMA ANTIBODY PROFILES; NECROSIS-FACTOR-ALPHA; T-CELL DEPLETION
C1 [Sharpe, Sally] Publ Hlth England, Porton Down, England.
[Via, Laura E.] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
[Verreck, Frank A. W.] Biomed Primate Res Ctr, Dept Parasitol, Rijswijk, Netherlands.
[Lin, P. Ling] Univ Pittsburgh, Dept Pediat, Childrens Hosp Pittsburgh, UPMC, Pittsburgh, PA 15260 USA.
RP Lin, PL (reprint author), Univ Pittsburgh, Dept Pediat, Childrens Hosp Pittsburgh, UPMC, Pittsburgh, PA 15260 USA.
EM sally.sharpe@phe.gov; lvia@niaid.nih.gov; verreck@bprc.nl;
philana.lin@chp.edu
NR 146
TC 1
Z9 1
U1 0
U2 1
PU CABI PUBLISHING-C A B INT
PI WALLINGFORD
PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND
BN 978-1-78064-396-0
PY 2015
BP 451
EP 469
D2 10.1079/9781780643960.0000
PG 19
WC Infectious Diseases; Veterinary Sciences
SC Infectious Diseases; Veterinary Sciences
GA BF5FO
UT WOS:000381942700026
ER
PT S
AU Briggman, KL
Kristan, WB
Gonzalez, JE
Kleinfeld, D
Tsien, RY
AF Briggman, Kevin L.
Kristan, William B.
Gonzalez, Jesus E.
Kleinfeld, David
Tsien, Roger Y.
BE Canepari, M
Zecevic, D
Bernus, O
TI Monitoring Integrated Activity of Individual Neurons Using FRET-Based
Voltage-Sensitive Dyes
SO MEMBRANE POTENTIAL IMAGING IN THE NERVOUS SYSTEM AND HEART
SE Advances in Experimental Medicine and Biology
LA English
DT Article; Book Chapter
DE Fluorescence resonance energy transfer (FRET); Voltage-sensitive dyes;
Invertebrate ganglia; Invertebrate neurons; Genetically encoded probes;
Functional connectivity
ID RESONANCE ENERGY-TRANSFER; FLUORESCENT PROTEIN; ELECTRICAL-ACTIVITY;
OPTICAL RECORDINGS; BEHAVIORAL CIRCUIT; ACTION-POTENTIALS; MEMBRANE
VOLTAGE; NEURAL CIRCUITS; CHANNEL; LEECH
AB Pairs of membrane-associated molecules exhibiting fluorescence resonance energy transfer (FRET) provide a sensitive technique to measure changes in a cell's membrane potential. One of the FRET pair binds to one surface of the membrane and the other is a mobile ion that dissolves in the lipid bilayer. The voltage-related signal can be measured as a change in the fluorescence of either the donor or acceptor molecules, but measuring their ratio provides the largest and most noise-free signal. This technology has been used in a variety of ways; three are documented in this chapter: (1) high throughput drug screening, (2) monitoring the activity of many neurons simultaneously during a behavior, and (3) finding synaptic targets of a stimulated neuron. In addition, we provide protocols for using the dyes on both cultured neurons and leech ganglia. We also give an updated description of the mathematical basis for measuring the coherence between electrical and optical signals. Future improvements of this technique include faster and more sensitive dyes that bleach more slowly, and the expression of one of the FRET pair genetically.
C1 [Briggman, Kevin L.] NINDS, Circuit Dynam & Connect Unit, NIH, Bethesda, MD 20892 USA.
[Kristan, William B.] Univ Calif San Diego, Neurobiol Sect, Div Biol Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA.
[Gonzalez, Jesus E.] Avelas Biosci, La Jolla, CA 92037 USA.
[Kleinfeld, David] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
[Tsien, Roger Y.] Univ Calif San Diego, Dept Pharmacol, Howard Hughes Med Inst, George Palade Labs 310, La Jolla, CA 92093 USA.
RP Kristan, WB (reprint author), Univ Calif San Diego, Neurobiol Sect, Div Biol Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM kevin.briggman@nih.gov; wkristan@ucsd.edu; txsandpiper@sbcglobal.net
FU NINDS NIH HHS [R01 NS027177]
NR 55
TC 0
Z9 0
U1 2
U2 5
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0065-2598
BN 978-3-319-17641-3; 978-3-319-17640-6
J9 ADV EXP MED BIOL
JI Adv.Exp.Med.Biol.
PY 2015
VL 859
BP 149
EP 169
DI 10.1007/978-3-319-17641-3_6
D2 10.1007/978-3-319-17641-3
PG 21
WC Cell Biology; Medicine, Research & Experimental; Physiology
SC Cell Biology; Research & Experimental Medicine; Physiology
GA BF4JM
UT WOS:000381082700007
PM 26238052
ER
PT S
AU Roth, HR
Lee, CT
Shin, HC
Seff, A
Kim, L
Yao, J
Lu, L
Summers, RM
AF Roth, Holger R.
Lee, Christopher T.
Shin, Hoo-Chang
Seff, Ari
Kim, Lauren
Yao, Jianhua
Lu, Le
Summers, Ronald M.
GP IEEE
TI ANATOMY-SPECIFIC CLASSIFICATION OF MEDICAL IMAGES USING DEEP
CONVOLUTIONAL NETS
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE Image Classification; Computed tomography (CT); Convolutional Networks;
Deep Learning
ID NEURAL-NETWORKS; ANNOTATION
AB Automated classification of human anatomy is an important prerequisite for many computer-aided diagnosis systems. The spatial complexity and variability of anatomy throughout the human body makes classification difficult. "Deep learning" methods such as convolutional networks (ConvNets) outperform other state-of-the-art methods in image classification tasks. In this work, we present a method for organ-or body-part-specific anatomical classification of medical images acquired using computed tomography (CT) with ConvNets. We train a ConvNet, using 4,298 separate axial 2D key-images to learn 5 anatomical classes. Key-images were mined from a hospital PACS archive, using a set of 1,675 patients. We show that a data augmentation approach can help to enrich the data set and improve classification performance. Using ConvNets and data augmentation, we achieve anatomy-specific classification error of 5.9 % and area-under-the-curve (AUC) values of an average of 0.998 in testing. We demonstrate that deep learning can be used to train very reliable and accurate classifiers that could initialize further computer-aided diagnosis.
C1 [Roth, Holger R.; Lee, Christopher T.; Shin, Hoo-Chang; Seff, Ari; Kim, Lauren; Yao, Jianhua; Lu, Le; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Roth, HR (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM holger.roth@nih.gov; rms@nih.gov
NR 16
TC 3
Z9 3
U1 3
U2 3
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 101
EP 104
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000025
ER
PT S
AU Ozarslan, E
Memic, M
Avram, AV
Afzali, M
Basser, PJ
Westin, CF
AF Ozarslan, E.
Memic, M.
Avram, A. V.
Afzali, M.
Basser, P. J.
Westin, C. -F.
GP IEEE
TI ROTATING FIELD GRADIENT (RFG) MR OFFERS IMPROVED ORIENTATIONAL
SENSITIVITY
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE MRI; diffusion; anisotropy; connectome; connectivity; tractography;
orientation; RFG; rotating; microstructure; white-matter
ID DIFFUSION; RESOLUTION; ANGLE; NMR
AB Rotating field gradients (RFGs), generated by simultaneously applying sine-and cosine-modulated gradient waveforms along two perpendicular directions, provide an alternative diffusion sensitization mechanism for magnetic resonance imaging and spectroscopy. Two RFGs with a 90-degree phase shift between them are applied around the 180-degree RF pulse in a spin echo sequence to measure the diffusion orientation distribution function (dODF) directly. The technique obviates transforming the data from a space reciprocal to the displacement space. Here, we compare RFG results with those obtained by two pulsed field gradient (PFG) techniques: q-ball imaging (QBI) and its extension to constant solid angles (CSA). Our results indicate that RFG provides more accuracy than QBI, while the spurious peaks encountered with the QBI-CSA approach are absent when the RFG-based technique is used. These observations suggest the superior performance of RFG-based methods for mapping the anatomical connections within the nervous system.
C1 [Ozarslan, E.; Memic, M.] Bogazici Univ, Dept Phys, Istanbul, Turkey.
[Ozarslan, E.; Westin, C. -F.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA.
[Avram, A. V.; Basser, P. J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD USA.
[Afzali, M.] Sharif Univ Technol, Dept Elect Engn, Tehran, Iran.
RP Ozarslan, E (reprint author), Bogazici Univ, Dept Phys, Istanbul, Turkey.
NR 17
TC 1
Z9 1
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 955
EP 958
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000228
ER
PT S
AU Liu, JM
Narayanan, D
Chang, K
Kim, L
Turkbey, E
Lu, L
Yao, JH
Summers, RM
AF Liu, Jiamin
Narayanan, Divya
Chang, Kevin
Kim, Lauren
Turkbey, Evrim
Lu, Le
Yao, Jianhua
Summers, Ronald M.
GP IEEE
TI AUTOMATED SEGMENTATION OF THE THYROID GLAND ON CT USING MULTI-ATLAS
LABEL FUSION AND RANDOM FOREST
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE thyroid gland segmentation; multi-atlas label fusion; random forest
AB The thyroid gland is an important endocrine organ. For a variety of clinical applications, a system for automated segmentation of the thyroid is desirable. Thyroid segmentation is challenging due to the inhomogeneous nature of the thyroid and the surrounding structures which have similar intensities. In this paper, we propose a fully automated method for thyroid detection and segmentation on CT scans. The thyroid gland is initially estimated by a multi-atlas segmentation with joint label fusion algorithm. The segmentation is then corrected by supervised statistical learning-based voxel labeling with a random forest algorithm. Multi-atlas label fusion transfers expert-labeled thyroids from atlases to a target image using deformable registration. Errors produced by label transfer are reduced by label fusion that combines the results produced by all atlases into a consensus solution. Then, random forest employs an ensemble of decision trees that are trained on labeled thyroids to recognize various features. The trained forest classifier is then applied to the estimated thyroid by voxel scanning to assign the class-conditional probability. Voxels from the expert-labeled thyroids in CT volumes are treated as positive classes and background non-thyroid voxels as negatives. We applied our method to 73 patients using 5 as atlases. The system achieved an overall 0.70 Dice Similarity Coefficient ( DSC) if using the multi-atlas label fusion only and was improved to 0.75 DSC after the random forest correction.
C1 [Liu, Jiamin; Narayanan, Divya; Chang, Kevin; Kim, Lauren; Turkbey, Evrim; Lu, Le; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA.
RP Liu, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 1114
EP 1117
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000266
ER
PT S
AU Xu, ZY
Bagci, U
Gao, MC
Mollura, DJ
AF Xu, Ziyue
Bagci, Ulas
Gao, Mingchen
Mollura, Daniel J.
GP IEEE
TI HIGHLY PRECISE PARTIAL VOLUME CORRECTION FOR PET IMAGES: AN ITERATIVE
APPROACH VIA SHAPE CONSISTENCY
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE Positron Emission Tomography; Partial Volume Correction; Shape
Consistency; Regional Means; Affinity Propagation
ID SEGMENTATION
AB Positron emission tomography ( PET) is capable of capturing the functional information. A major limitation for PET imaging is the low spatial resolution, leading to partial volume effects ( PVE). PVE introduces significant bias to the image quantification, causing compromised measurement for uptake regions, especially smaller ones. For quantitative PET, accurate uptake values are critical for diagnostic evaluation and treatment planning. Therefore, a partial volume correction ( PVC) technique is highly desirable in order to avoid size-dependent underestimation for true activities. In this paper, we present a new iterative PVC approach for PET images. The proposed method uses the state-of-the-art simultaneous delineation and noise removal algorithm to estimate the local uptake regions. The delineation is further utilized for weighted PVC with regard to a shape consistency measurement. The process is performed iteratively until delineation convergence. Qualitative and quantitative results demonstrate that the proposed framework successfully corrects the PVE and preserves local structures.
C1 [Xu, Ziyue; Bagci, Ulas; Gao, Mingchen; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
[Bagci, Ulas] Univ Cent Florida, CRCV, Orlando, FL 32816 USA.
RP Bagci, U (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
EM bagci@crcv.ucf.edu
OI Bagci, Ulas/0000-0001-7379-6829
NR 11
TC 1
Z9 1
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 1196
EP 1199
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000286
ER
PT S
AU Jacobs, M
Gorbachev, M
Benovoy, M
Chang, LC
Arai, AE
Hsu, LY
AF Jacobs, Matthew
Gorbachev, Mikhail
Benovoy, Mitchel
Chang, Lin-Ching
Arai, Andrew E.
Hsu, Li-Yueh
GP IEEE
TI AUTOMATED MEASUREMENT OF ARTERIAL INPUT FUNCTION IN FIRST-PASS
MYOCARDIAL PERFUSION MAGNETIC RESONANCE IMAGES USING INDEPENDENT
COMPONENT ANALYSIS
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE cardiovascular magnetic resonance; myocardial perfusion imaging;
arterial input function
ID CORONARY-ANGIOGRAPHY
AB Quantitative assessment of first-pass cardiac magnetic resonance (CMR) perfusion imaging is useful for detecting coronary artery disease, but it requires the measurement of the arterial input function (AIF) from the left ventricle. This is usually done manually, which is time consuming and subjective. This study presents an automated method for measuring the AIF from the first-pass CMR perfusion images. It was tested on 194 clinical perfusion studies and compared with manual reference measurements. Our results show the proposed method successfully measured 98.79% of the perfusion series, with manual and automated measurements strongly correlating. Temporal statistics were similar for both measurements, showing agreement between the automated and manual AIFs. The automated method, however, more accurately selected the brightest left ventricle pixels and excluded papillary muscles. These improvements may help make AIF measurement and quantitative CMR myocardial perfusion analysis more accurate and readily available.
C1 [Jacobs, Matthew; Gorbachev, Mikhail; Benovoy, Mitchel; Arai, Andrew E.; Hsu, Li-Yueh] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Jacobs, Matthew; Gorbachev, Mikhail; Chang, Lin-Ching] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
[Benovoy, Mitchel] Ecole Polytech Montreal, Montreal, PQ, Canada.
RP Jacobs, M (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 14
TC 1
Z9 1
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 1332
EP 1335
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000320
ER
PT S
AU Nandy, K
Gulda, PR
Chellappa, R
Lockett, SJ
AF Nandy, Kaustav
Gulda, Prabhkar R.
Chellappa, Rama
Lockett, Stephen J.
GP IEEE
TI PROBABILISTIC EDGE DETECTION IN 3D OPTICAL MICROSCOPY IMAGES OF TISSUE
SAMPLES
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE Probabilistic edge detection; fluorescence microscopy; 3D image
analysis; tissue sample; acinus
AB Inspired by a state of the art 2D algorithm for edge detection in natural images, in this work we report the development of an accurate 3D probabilistic edge detector for fluorescence optical microscopy images of tissue samples. The method utilizes multi-orientation and multi-scale brightness, textural and spectral properties of the data to compute a probabilistic edge map. To demonstrate the strengths and accuracy of the proposed algorithm, comparisons of the edge maps produced by our algorithm and several other popular edge detectors on simulated and real 3D microscopic volumes are provided.
C1 [Nandy, Kaustav; Gulda, Prabhkar R.; Lockett, Stephen J.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Opt Microscopy & Anal Lab, Frederick, MD 21702 USA.
[Chellappa, Rama] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA.
RP Nandy, K (reprint author), Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Opt Microscopy & Anal Lab, Frederick, MD 21702 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 1462
EP 1465
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000351
ER
PT S
AU Huang, S
Gao, MC
Yang, D
Huang, XL
Elgammal, A
Zhang, XH
AF Huang, Sheng
Gao, Mingchen
Yang, Dan
Huang, Xiaolei
Elgammal, Ahmed
Zhang, Xiaohong
GP IEEE
TI UNBALANCED GRAPH-BASED TRANSDUCTION ON SUPERPIXELS FOR AUTOMATIC
CERVIGRAM IMAGE SEGMENTATION
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE Image Segmentation; Transductive Learning; Unbalanced Classification;
Graph Learning; Semi supervised Learning
AB We propose a novel medical image segmentation algorithm by transductively inferring the labels. In this approach, super pixels are first generated to incorporate the local spatial information and also to speed up the segmentation. The segmentation task can be deemed as an unbalanced superpixels labeling problem due to the fact that the region of interest is only a small fraction compared to the whole image. We present a new transductive learning-based algorithm called Class Averaging Graph -based Transduction (CAGT) to avoid the biased labeling caused by the imbalance. The proposed algorithm was applied to the automatic cervigram image segmentation to demonstrate it effectiveness.
C1 [Huang, Sheng; Yang, Dan; Zhang, Xiaohong] Chongqing Univ, Minist Educ, Key Lab Dependable Serv Comp Cyber Phys Soc, Chongqing 400044, Peoples R China.
[Gao, Mingchen] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Elgammal, Ahmed] Rutgers State Univ, Piscataway, NJ 08854 USA.
[Huang, Xiaolei] Lehigh Univ, Bethlehem, PA 18015 USA.
RP Huang, S (reprint author), Chongqing Univ, Minist Educ, Key Lab Dependable Serv Comp Cyber Phys Soc, Chongqing 400044, Peoples R China.
NR 10
TC 0
Z9 0
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 1556
EP 1559
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000374
ER
PT S
AU Benovoy, M
Jacobs, M
Cheriet, F
Dahdah, N
Arai, AE
Hsu, LY
AF Benovoy, Mitchel
Jacobs, Matthew
Cheriet, Farida
Dahdah, Nagib
Arai, Andrew E.
Hsu, Li-Yueh
GP IEEE
TI AUTOMATIC NONRIGID MOTION CORRECTION FOR QUANTITATIVE FIRST-PASS CARDIAC
MR PERFUSION IMAGING
SO 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT IEEE 12th International Symposium on Biomedical Imaging
CY APR 16-19, 2015
CL New York, NY
SP NIBIB, NATL INST, IEEE, EMB
DE cardiac magnetic resonance; perfusion; nonrigid; motion correction
AB First-pass dynamic contrast-enhanced cardiac magnetic resonance imaging is an increasingly important diagnostic tool for coronary artery disease. It is typically performed with breath holding and electrocardiogram gating to minimize motion, but movement caused by residual respiration, cardiac arrhythmia, or missed gating triggers during image acquisition will induce nonrigid deformations of the myocardium that can hamper interpretation and perfusion quantification. We propose an automatic nonrigid image registration framework to correct motion in a series of cardiac magnetic resonance perfusion images. Our method employs reference frame detection combined with robust flow field estimation using a large displacement optical flow formulation coupled with post -hoc image warping and flow field distortion correction. This framework is multi-threadable and can be applied to standard myocardial series, arterial input function series, and proton density weighted images to facilitate perfusion quantification.
C1 [Benovoy, Mitchel; Jacobs, Matthew; Arai, Andrew E.; Hsu, Li-Yueh] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Benovoy, Mitchel; Cheriet, Farida] Ecole Polytech Montreal, Dept Biomed Engn, Montreal, PQ, Canada.
[Jacobs, Matthew] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
[Dahdah, Nagib] Ste Justine Univ Hosp Res Ctr, Montreal, PQ, Canada.
RP Benovoy, M (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 13
TC 1
Z9 1
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4799-2374-8
J9 I S BIOMED IMAGING
PY 2015
BP 1588
EP 1591
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic;
Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BF3IK
UT WOS:000380546000382
ER
PT J
AU Rossi, E
Fontelo, P
Ackerman, MJ
Pozzi, G
Marceglia, S
AF Rossi, Elena
Fontelo, Paul
Ackerman, Michael J.
Pozzi, Giuseppe
Marceglia, Sara
BE Balakrishnan, P
Srivatsava, J
Fu, WT
Harabagiu, S
Wang, F
TI A prototype of mobile app/EHR communication through standards for home
treatment of transcranial Direct Current Stimulation
SO 2015 IEEE INTERNATIONAL CONFERENCE ON HEALTHCARE INFORMATICS (ICHI 2015)
LA English
DT Proceedings Paper
CT International Conference on Healthcare Informatics (ICHI)
CY OCT 21-23, 2015
CL Dallas, TX
SP IEEE, IEEE comp soc, UT DALLAS
DE Electric Stimulation Therapy; Electronic Health Record; Mobile Health
App; Transcranial Direct Current Stimulation
ID ELECTRONIC HEALTH RECORDS; CARE
AB Daily management of neurodegenerative diseases by electrical neuromodulation techniques requires an integrated health care system for the continuous assistance to the patient. In this scenario, a direct bi-directional exchange of information between the patient's electronic health record (EHR) and patient's personal mobile health apps (mHealth) can boost the active contribution of patients and caregivers to safe homecare management.
Grounding on a recently proposed standards-based architecture, we describe here a prototype implementing the mHealth App/EHR bi-directional health information exchange for supporting homecare transcranial Direct Current Stimulation (tDCS) therapy. We first modeled the tDCS case study using the Unified Modeling Language (UML) and, then, we developed the mHealth app for the patient side in order to implement the exchange architecture. We then connected the app to an EHR system developed using a web-based platform (WebBioBank) based on a framework for EHR management. The neurologist, using the EHR system, can configure the patient's homecare plan sent to the mHealth App, and can see the patient's monitoring reports sent from the mHealth App to the EHR.
The integration architecture is implemented by CDA-2 compliant XML encrypted files. The current prototype proves that direct information exchange between mHealth Apps and EHR systems is possible by a standards-based architecture and can be effectively used to improve patient-neurologist communication as well as to support tDCS home therapy.
C1 [Rossi, Elena; Pozzi, Giuseppe] Politecn Milan, Dipartimento Elettron Informaz & Bioingn, Milan, Italy.
[Fontelo, Paul; Ackerman, Michael J.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA.
[Marceglia, Sara] Univ Trieste, Dipartimento Ingn & Architettura, Trieste, Italy.
RP Rossi, E (reprint author), Politecn Milan, Dipartimento Elettron Informaz & Bioingn, Milan, Italy.
EM elena.rossi@polimi.it; pfontelo@mail.nih.gov; mackerman@mail.nih.gov;
giuseppe.pozzi@polimi.it; sara.marceglia@units.it
NR 20
TC 0
Z9 0
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4673-9548-9
PY 2015
BP 310
EP 315
DI 10.1109/ICHI.2015.44
PG 6
WC Computer Science, Information Systems; Medical Informatics
SC Computer Science; Medical Informatics
GA BF1IC
UT WOS:000380399000038
ER
PT S
AU Wolcott, HN
Fouch, MJ
Hsu, E
Bernaciak, C
Corrigan, J
Williams, D
AF Wolcott, Holly N.
Fouch, Matthew J.
Hsu, Elizabeth
Bernaciak, Catherine
Corrigan, James
Williams, Duane
BE Salah, AA
Tonta, Y
Salah, AAA
Sugimoto, C
Al, U
TI Modeling Time-dependent and -independent Indicators to Facilitate
Identification of Breakthrough Research Papers
SO PROCEEDINGS OF ISSI 2015 ISTANBUL: 15TH INTERNATIONAL SOCIETY OF
SCIENTOMETRICS AND INFORMETRICS CONFERENCE
SE Proceedings of the International Conference on Scientometrics and
Informetrics
LA English
DT Proceedings Paper
CT 15th International Conference of the
International-Society-for-Scientometrics-and-Informetrics (ISSI) on
Scientometrics and Informetrics
CY JUN 29-JUL 04, 2015
CL Bogazici Univ, Istanbul, TURKEY
SP Int Soc Scientometr & Informetr, Hacettepe Univ, Sci & Technol Res Council Turkey, Turkish Acad Network & Informat Ctr
HO Bogazici Univ
AB Research funding organizations invest substantial resources to stay current with important research findings within their mission areas to identify and support promising new lines of inquiry. To that end, we continue to pursue the development of tools to identify research publications that have a strong likelihood of driving new avenues of research. This research-in-progress paper describes our work incorporating multiple time-dependent and-independent features of publications into a model that aims to identify candidate breakthrough papers as early as possible following publication. We used multiple Random Forest models to assess the ability of indicators to reliably distinguish a gold standard set of breakthrough publications as identified by subject matter experts from among a comparison group of similar Thomson Reuters Web of Science (TM) publications. These indicators will be selected for inclusion in a multi-variate model to test their predictive value. Prospective use of these indicators and models is planned to further establish their reliability.
C1 [Wolcott, Holly N.; Fouch, Matthew J.; Bernaciak, Catherine; Williams, Duane] Thomson Reuters, Intellectual Property & Sci, Rockville, MD 20850 USA.
[Hsu, Elizabeth; Corrigan, James] NCI, Off Sci Planning & Assessment, Bethesda, MD 20892 USA.
RP Wolcott, HN (reprint author), Thomson Reuters, Intellectual Property & Sci, Rockville, MD 20850 USA.
EM holly.wolcott@thomsonreuters.com; corrigan@mail.nih.gov
NR 16
TC 1
Z9 1
U1 3
U2 3
PU INT SOC SCIENTOMETRICS & INFORMETRICS-ISSI
PI LEUVEN
PA KATHOLIEKE UNIV LEUVEN, FACULTEIT E T E W, DEKENSTRAAT 2, LEUVEN,
B-3000, BELGIUM
SN 2175-1935
BN 978-975-518-381-7
J9 PRO INT CONF SCI INF
PY 2015
BP 403
EP 408
PG 6
WC Computer Science, Interdisciplinary Applications
SC Computer Science
GA BF2TX
UT WOS:000380499700056
ER
PT J
AU Marchell, R
Locatis, C
Ackerman, M
AF Marchell, Richard
Locatis, Craig
Ackerman, Michael
BE Smari, WW
McQuay, W
Nygard, M
Natarian, J
TI High Definition Live Interactive and Store and Forward Teledermatology:
Initial Qualitative Observations
SO PROCEEDINGS OF THE 2015 INTERNATIONAL CONFERENCE ON COLLABORATION
TECHNOLOGIES AND SYSTEMS
LA English
DT Proceedings Paper
CT Proceedings of the 2015 International Conference on Collaboration
Technologies and Systems
CY JUN 01-05, 2015
CL Atlanta, GA
SP Honeywell Int Inc, Knowledge Based Systems, Inc. (KBSI), Ball Aerospace and Technologies Corp, ClearFunnel, Inc, Intel Corp, LexisNexis Corp, Microsoft Res, PayPal, Inc., Springer Verlag
DE collaboration enabling technologies; information infrastructure for
collaboration; tele and collaboration technologies in healthcare
ID MANAGEMENT; DIAGNOSIS; TELEMEDICINE
AB Initial qualitative findings from a study of uncompressed and compressed high definition live interactive video, and store and forward teledermatology (photographs and written histories for later review) are presented. Quantitative data collected in the study are still being compiled and analyzed comparing diagnostic concordance and confidence with in-person exams. The early qualitative findings suggest bifurcated patient and physician preferences for the different remote exam methods.
C1 [Marchell, Richard] Med Univ S Carolina, Dept Dermatol, Charleston, SC 29425 USA.
[Locatis, Craig; Ackerman, Michael] Natl Lib Med, NIH, Bethesda, MD USA.
RP Marchell, R (reprint author), Med Univ S Carolina, Dept Dermatol, Charleston, SC 29425 USA.
EM marchell@musc.edu; locatis@nlm.nih.gov; ackerman@nlm.nih.gov
NR 14
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4673-7648-8
PY 2015
BP 446
EP 449
PG 4
WC Computer Science, Information Systems; Computer Science, Theory &
Methods
SC Computer Science
GA BF2HZ
UT WOS:000380469300075
ER
PT J
AU de Maturana, EL
Picornell, A
Masson-Lecomte, A
Kogevinas, M
Marquez, M
Carrato, A
Tardon, A
Lloreta, J
Garcia-Closas, M
Silverman, D
Rothman, N
Chanock, S
Real, F
Goddard, M
Malats, N
AF Lopez de Maturana, E.
Picornell, A.
Masson-Lecomte, A.
Kogevinas, M.
Marquez, M.
Carrato, A.
Tardon, A.
Lloreta, J.
Garcia-Closas, M.
Silverman, D.
Rothman, N.
Chanock, S.
Real, F.
Goddard, M.
Malats, N.
CA SBC EPICURO Investigators
TI A Bayesian Lasso Genome-Wide Multimarker Approach to Predict Prognosis:
An Application to Bladder Cancer Progression
SO HUMAN HEREDITY
LA English
DT Meeting Abstract
CT 44th European Mathematical Genetics Meeting (EMGM)
CY MAY 11-12, 2016
CL Newcastle upon Tyne, ENGLAND
C1 [Lopez de Maturana, E.; Picornell, A.; Masson-Lecomte, A.; Marquez, M.; Real, F.; Malats, N.] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain.
[Kogevinas, M.] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Carrato, A.] Hosp Univ Ramon y Cajal, Madrid, Spain.
[Tardon, A.] Univ Oviedo, Oviedo, Spain.
[Garcia-Closas, M.] Inst Canc Res, London, England.
[Silverman, D.; Rothman, N.; Chanock, S.] NCI, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Goddard, M.] Univ Melbourne, Melbourne, Vic, Australia.
RI Kogevinas, Manolis/C-3918-2017
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0001-5652
EI 1423-0062
J9 HUM HERED
JI Hum. Hered.
PY 2015
VL 80
IS 3
MA 38
BP 117
EP 117
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA DR8IA
UT WOS:000380140400039
ER
PT J
AU Wang, SL
Chen, F
Gu, JC
Fang, JW
AF Wang, Shulin
Chen, Fang
Gu, Jinchao
Fang, Jianwen
GP IEEE
TI Cancer Classification Using Collaborative Representation Classifier
Based on Non-convex Lp-norm and Novel Decision Rule
SO 2015 SEVENTH INTERNATIONAL CONFERENCE ON ADVANCED COMPUTATIONAL
INTELLIGENCE (ICACI)
LA English
DT Proceedings Paper
CT International Conference on Advanced Computational Intelligence
CY MAR 27-29, 2015
CL Fujian, PEOPLES R CHINA
ID ROBUST FACE RECOGNITION; GENE-EXPRESSION PROFILE; SPARSE REPRESENTATION;
TUMOR CLASSIFICATION; L(1)-MINIMIZATION; PREDICTION; ALGORITHMS;
LEUKEMIA
AB Sparse representation classification (SRC) and collaborative representation classification (CRC) are the most promising classifiers for classifying high dimensional data. However, they may suffer from outliers and noises, as l(2)-norm on signal fidelity is not effective enough to represent the test sample in that case. Recent studies show that non-convex l(p)-norm minimization can boost the performance of classifiers compared with l(1)- and l(2)-norm minimization in classification. In this paper, we present an improved collaborative representation classification method for the accurate identification of cancer subtype. We improve CRC method by adopting non-convex lp-norm on the signal fidelity term and introducing a new classification decision rule. We compute the coding coefficients over training samples for test sample via generalized iterated shrinkage algorithm (GISA) and classify the test sample into the subclass which has the maximum sum of coefficient (SoC). Extensive experiments on eight publicly available gene expression profde (GEP) datasets demonstrate the superiority of our proposed method.
C1 [Wang, Shulin; Chen, Fang; Gu, Jinchao] Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China.
[Fang, Jianwen] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD 20850 USA.
RP Wang, SL (reprint author), Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China.
EM smartforesting@gmail.com; keepmoving90@qq.com; gu0802@126.com;
jianwen.fang@nih.gov
NR 26
TC 0
Z9 0
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4799-7259-3
PY 2015
BP 189
EP 194
PG 6
WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic
SC Computer Science; Engineering
GA BF2MC
UT WOS:000380479600063
ER
PT S
AU Moakher, M
Basser, PJ
AF Moakher, Maher
Basser, Peter J.
BE Hotz, I
Schultz, T
TI Fiber Orientation Distribution Functions and Orientation Tensors for
Different Material Symmetries
SO VISUALIZATION AND PROCESSING OF HIGHER ORDER DESCRIPTORS FOR
MULTI-VALUED DATA
SE Mathematics and Visualization
LA English
DT Proceedings Paper
CT Workshop on the Visualization and Processing of Higher Order Descriptors
for Multi-Valued Data
CY FEB, 2014
CL Dagstuhl, GERMANY
ID DENSITY-FUNCTION; DIRECTIONAL-DATA; FABRIC TENSORS; DIFFUSION;
DECOMPOSITION; COMPOSITES; TRANSFORM; KERNEL
AB In this paper we give closed-form expressions of the orientation tensors up to the order four associated with some axially-symmetric orientation distribution functions (ODF), including the well-known von Mises-Fisher, Watson, and de la Vallee Poussin ODFs. Each is characterized by a mean direction and a concentration parameter. Then, we use these elementary ODFs as building blocks to construct new ones with a specified material symmetry and derive the corresponding orientation tensors. For a general ODF we present a systematic way of calculating the corresponding orientation tensors from certain coefficients of the expansion of the ODF in spherical harmonics.
C1 [Moakher, Maher] Univ Tunis El Manar, ENIT LAMSIN, Lab Math & Numer Modeling Engn Sci, Natl Engn Sch Tunis, BP 37, Tunis 1002, Tunisia.
[Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
RP Moakher, M (reprint author), Univ Tunis El Manar, ENIT LAMSIN, Lab Math & Numer Modeling Engn Sci, Natl Engn Sch Tunis, BP 37, Tunis 1002, Tunisia.
EM maher.moakher@gmail.com; pjbasser@helix.nih.gov
RI Moakher, Maher/A-6315-2010
OI Moakher, Maher/0000-0002-9432-0456
NR 35
TC 2
Z9 2
U1 1
U2 2
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 1612-3786
BN 978-3-319-15090-1; 978-3-319-15089-5
J9 MATH VIS
PY 2015
BP 37
EP 71
DI 10.1007/978-3-319-15090-1_3
PG 35
WC Computer Science, Artificial Intelligence; Mathematics, Applied; Imaging
Science & Photographic Technology
SC Computer Science; Mathematics; Imaging Science & Photographic Technology
GA BF2ER
UT WOS:000380461100003
ER
PT B
AU Richmond, BJ
AF Richmond, Barry J.
BE Liljenstrom, H
TI An Interaction Between Orbitofrontal and Rhinal Cortices Contributing to
Reward Seeking Behavior
SO ADVANCES IN COGNITIVE NEURODYNAMICS (IV)
LA English
DT Proceedings Paper
CT 4th International Conference on Cognitive Neurodynamics (ICCN)
CY JUN 23-27, 2013
CL Sigtuna, SWEDEN
SP Agora Biosystems, Sigtunastiftelsen, Vetenskapsradet, Springer, Uppsala Univ, Swedish Univ Agr Sci
DE Reward value; Orbitofrontal cortex; Rhinal cortex; Disconnection; Monkey
ID MEDIAL TEMPORAL-LOBE; CORTEX; SCHEDULES; NEURONS; MEMORY
AB Monkeys given a disconnection of rhinal cortex from orbitofrontal cortex do not distinguish among different reward sizes, in a manner similar to that seen in monkeys with a bilateral rhinal cortex removal. Thus, it seems that reacting to differences among rewards requires communication between rhinal and orbitofrontal cortices. We suggest that the orbitofrontal cortex assesses value and rhinal is important for remembering the relations among the different reward sizes. This interaction provides a platform for studying information exchange across brain regions.
C1 [Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA.
RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA.
EM bjr@ln.nimh.nih.gov
NR 12
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
BN 978-94-017-9548-7; 978-94-017-9547-0
PY 2015
BP 89
EP 92
DI 10.1007/978-94-017-9548-7_12
PG 4
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA BF1CJ
UT WOS:000380362800012
ER
PT B
AU Belic, JJ
Klaus, A
Plenz, D
Kotaleski, JH
AF Belic, Jovana J.
Klaus, Andreas
Plenz, Dietmar
Kotaleski, Jeanette Hellgren
BE Liljenstrom, H
TI Mapping of Cortical Avalanches to the Striatum
SO ADVANCES IN COGNITIVE NEURODYNAMICS (IV)
LA English
DT Proceedings Paper
CT 4th International Conference on Cognitive Neurodynamics (ICCN)
CY JUN 23-27, 2013
CL Sigtuna, SWEDEN
SP Agora Biosystems, Sigtunastiftelsen, Vetenskapsradet, Springer, Uppsala Univ, Swedish Univ Agr Sci
DE Neuronal avalanches; Striatum; Cortico-striatal network; Cortex; Basal
ganglia
ID NEURONAL AVALANCHES; NETWORKS
AB Neuronal avalanches are found in the resting state activity of the mammalian cortex. Here we studied whether and how cortical avalanches are mapped onto the striatal circuitry, the first stage of the basal ganglia. We first demonstrate using organotypic cortex-striatum-substantia nigra cultures from rat that indeed striatal neurons respond to cortical avalanches originating in superficial layers. We simultaneously recorded spontaneous local field potentials (LFPs) in the cortical and striatal tissue using high-density microelectrode arrays. In the cortex, spontaneous neuronal avalanches were characterized by intermittent spatiotemporal activity clusters with a cluster size distribution that followed a power law with exponent -1.5. In the striatum, intermittent spatiotemporal activity was found to correlate with cortical avalanches. However, striatal negative LFP peaks (nLFPs) did not show avalanche signatures, but formed a cluster size distribution that had a much steeper drop-off, i. e., lacked large spatial clusters that are commonly expected for avalanche dynamics. The underlying de-correlation of striatal activity could have its origin in the striatum through local inhibition and/ or could result from a particular mapping in the corticostriatal pathway. Here we show, usingmodeling, that highly convergent corticostriatal projections can map spatially extended cortical activity into spatially restricted striatal regimes.
C1 [Belic, Jovana J.; Kotaleski, Jeanette Hellgren] KTH Royal Inst Technol, Sch Comp Sci & Commun, S-10044 Stockholm, Sweden.
[Belic, Jovana J.] Univ Freiburg, Bernstein Ctr Freiburg, D-79104 Freiburg, Germany.
[Klaus, Andreas; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
RP Belic, JJ (reprint author), KTH Royal Inst Technol, Sch Comp Sci & Commun, S-10044 Stockholm, Sweden.
EM belic@kth.se
NR 14
TC 2
Z9 2
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
BN 978-94-017-9548-7; 978-94-017-9547-0
PY 2015
BP 291
EP 297
DI 10.1007/978-94-017-9548-7_41
PG 7
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA BF1CJ
UT WOS:000380362800041
ER
PT B
AU Kish, LB
Granqvist, CG
Bezrukov, SM
Horvath, T
AF Kish, Laszlo B.
Granqvist, Claes G.
Bezrukov, Sergey M.
Horvath, Tamas
BE Liljenstrom, H
TI Brain: Biological Noise-Based Logic
SO ADVANCES IN COGNITIVE NEURODYNAMICS (IV)
LA English
DT Proceedings Paper
CT 4th International Conference on Cognitive Neurodynamics (ICCN)
CY JUN 23-27, 2013
CL Sigtuna, SWEDEN
SP Agora Biosystems, Sigtunastiftelsen, Vetenskapsradet, Springer, Uppsala Univ, Swedish Univ Agr Sci
DE Neural logic; Deterministic logic; Logic variable; Neural spikes;
Stochastic signal
AB Neural spikes in the brain form stochastic sequences, i.e., belong to the class of pulse noises. This stochasticity is a counterintuitive feature because extracting information-such as the commonly supposed neural information of mean spike frequency-requires long times for reasonably low error probability. The mystery could be solved by noise-based logic, wherein randomness has an important function and allows large speed enhancements for special-purpose tasks, and the same mechanism is at work for the brain logic version of this concept.
C1 [Kish, Laszlo B.] Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA.
[Granqvist, Claes G.] Uppsala Univ, Dept Engn Sci, Angstrom Lab, SE-75121 Uppsala, Sweden.
[Bezrukov, Sergey M.] NICHD, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Horvath, Tamas] Schloss Birlinghoven, Fraunhofer IAIS, Div Knowledge Discovery, D-53754 St Augustin, Germany.
[Horvath, Tamas] Univ Bonn, Dept Comp Sci, Bonn, Germany.
RP Kish, LB (reprint author), Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA.
EM Laszlokish@tamu.edu
NR 3
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER
PI DORDRECHT
PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
BN 978-94-017-9548-7; 978-94-017-9547-0
PY 2015
BP 319
EP 322
DI 10.1007/978-94-017-9548-7_45
PG 4
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA BF1CJ
UT WOS:000380362800045
ER
PT S
AU Bourne, PE
AF Bourne, Philip E.
BE Huan, J
Miyano, S
Shehu, A
Hu, X
Ma, B
Rajasekaran, S
Gombar, VK
Schapranow, IM
Yoo, IH
Zhou, JY
Chen, B
Pai, V
Pierce, B
TI Big Data in Biomedicine - An NIH Perspective
SO PROCEEDINGS 2015 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND
BIOMEDICINE
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine
CY NOV 09-12, 2015
CL Washington, DC
SP IEEE, IEEE Comp Soc, Natl Sci Fdn
AB Biomedical research is becoming increasingly data driven, analytical and hence digital. In recognition of this evolution NIH has established the Office for Data Science with trans NIH responsibility for maximizing the value of this digital enterprise. This effort brings together communities, policy changes and new infrastructure to be applied to existing and new areas of research such as precision medicine. We will review these changes from the perspective of research advances that are underway and highlight how this community can further engage in these activities.
C1 [Bourne, Philip E.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Bourne, PE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2156-1125
BN 978-1-4673-6798-1
J9 IEEE INT C BIOINFORM
PY 2015
BP 1
EP 1
PG 1
WC Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology
SC Computer Science; Mathematical & Computational Biology
GA BE9EI
UT WOS:000377335600001
ER
PT S
AU Xue, ZY
Candemir, S
Antani, S
Long, LR
Jaeger, S
Demner-Fushman, D
Thoma, GR
AF Xue, Zhiyun
Candemir, Serna
Antani, Sameer
Long, L. Rodney
Jaeger, Stefan
Demner-Fushman, Dina
Thoma, George R.
BE Huan, J
Miyano, S
Shehu, A
Hu, X
Ma, B
Rajasekaran, S
Gombar, VK
Schapranow, IM
Yoo, IH
Zhou, JY
Chen, B
Pai, V
Pierce, B
TI Foreign Object Detection in Chest X-rays
SO PROCEEDINGS 2015 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND
BIOMEDICINE
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine
CY NOV 09-12, 2015
CL Washington, DC
SP IEEE, IEEE Comp Soc, Natl Sci Fdn
DE chest X-ray; object detection; computer aided diagnosis; lung
segmentation
ID RADIOGRAPHS; SEGMENTATION; DATABASE
AB Automatic analysis of chest X-ray images is one important approach for screening/identifying pulmonary diseases. The existence of foreign objects in the images hinders the performance of such processing. In this paper, we focus on one type of foreign objects that is often shown in the images of a large dataset of chest X-rays we are working on-the buttons on the gown that the patient is wearing. The method we propose involves four major steps: intensity normalization, low contrast image identification and enhancement, segmentation of lung regions, and button object extraction. Based on the characteristics of the button objects, we applied two methods for the step of button object extraction. One was based on the circular Hough transform; the other was based on the Viola-Jones algorithm. We tested and compared both methods using a ground truth dataset containing 505 button objects. The results demonstrate the effectiveness of the proposed method.
C1 [Xue, Zhiyun; Candemir, Serna; Antani, Sameer; Long, L. Rodney; Jaeger, Stefan; Demner-Fushman, Dina; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
RP Xue, ZY (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
EM xuez@mail.nih.gov; candemirs@mail.nih.gov; santani@mail.nih.gov;
rlong@mail.nih.gov; jaegersr@mail.nih.gov; ddemner@mail.nih.gov;
gthoma@mail.nih.gov
NR 14
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2156-1125
BN 978-1-4673-6798-1
J9 IEEE INT C BIOINFORM
PY 2015
BP 956
EP 961
PG 6
WC Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology
SC Computer Science; Mathematical & Computational Biology
GA BE9EI
UT WOS:000377335600169
ER
PT S
AU Sung, H
Sorant, AJM
Sabourin, JA
Schwantes-An, TH
Justice, CM
Bailey-Wilson, JE
Wilson, AF
AF Sung, Heejong
Sorant, Alexa J. M.
Sabourin, Jeremy A.
Schwantes-An, Tae-Hwi
Justice, Cristina M.
Bailey-Wilson, Joan E.
Wilson, Alexander F.
BE Huan, J
Miyano, S
Shehu, A
Hu, X
Ma, B
Rajasekaran, S
Gombar, VK
Schapranow, IM
Yoo, IH
Zhou, JY
Chen, B
Pai, V
Pierce, B
TI Tiled regression reduces type I error rates in tests of association of
rare single nucleotide variants with non-normally distributed traits,
compared with simple linear regression
SO PROCEEDINGS 2015 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND
BIOMEDICINE
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine
CY NOV 09-12, 2015
CL Washington, DC
SP IEEE, IEEE Comp Soc, Natl Sci Fdn
DE type I error rate; tiled regression; minor allele frequency;
non-normality
AB The effects of the minor allele frequency of single nucleotide variants and the degree of departure from normality of a quantitative trait on type I error rates were evaluated using Genetic Analysis Workshop 17 mini-exome sequence data. Four simulated traits were generated: standard normal and gamma distributed traits and two transformations of the gamma distributed trait by log(10) and rank-based inverse normal functions. Tiled regression was compared with simple linear regression. Average type I error rates were obtained for minor allele frequency classes. The distribution of the type I error rate for tiled regression analysis followed a pattern similar to that of simple linear regression analysis, but with much lower type I error.
C1 [Sung, Heejong; Sorant, Alexa J. M.; Sabourin, Jeremy A.; Schwantes-An, Tae-Hwi; Justice, Cristina M.; Bailey-Wilson, Joan E.; Wilson, Alexander F.] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
RP Sung, H (reprint author), NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
EM sunghe@mail.nih.gov; ajms@mail.nih.gov; sabourinja@mail.nih.gov;
ant2@mail.nih.gov; cmj@mail.nih.gov; jebw@mail.nih.gov; afw@mail.nih.gov
NR 5
TC 1
Z9 1
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2156-1125
BN 978-1-4673-6798-1
J9 IEEE INT C BIOINFORM
PY 2015
BP 1336
EP 1340
PG 5
WC Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology
SC Computer Science; Mathematical & Computational Biology
GA BE9EI
UT WOS:000377335600229
ER
PT S
AU Du, W
Cheung, H
Johnson, CA
Goldberg, I
Thambisetty, M
Becker, K
AF Du, Wei
Cheung, Huey
Johnson, Calvin A.
Goldberg, Ilya
Thambisetty, Madhav
Becker, Kevin
BE Huan, J
Miyano, S
Shehu, A
Hu, X
Ma, B
Rajasekaran, S
Gombar, VK
Schapranow, IM
Yoo, IH
Zhou, JY
Chen, B
Pai, V
Pierce, B
TI A Longitudinal Support Vector Regression for Prediction of ALS Score
SO PROCEEDINGS 2015 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND
BIOMEDICINE
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine
CY NOV 09-12, 2015
CL Washington, DC
SP IEEE, IEEE Comp Soc, Natl Sci Fdn
DE longitudinal data; support vector regression; ALS; machine learning
AB Longitudinal studies play a key role in various fields, including epidemiology, clinical research, and genomic analysis. Currently, the most popular methods in longitudinal data analysis are model-driven regression approaches, which impose strong prior assumptions and are unable to scale to large problems in the manner of machine learning algorithms. In this work, we propose a novel longitudinal support vector regression (LSVR) algorithm that not only takes the advantage of one of the most popular machine learning methods, but also is able to model the temporal nature of longitudinal data by taking into account observational dependence within subjects. We test LSVR on publicly available data from the DREAM-Phil Bowen ALS Prediction Prize4Life challenge. Results suggest that LSVR is at a minimum competitive with favored machine learning methods and is able to outperform those methods in predicting ALS score one month in advance.
C1 [Du, Wei; Cheung, Huey; Johnson, Calvin A.] NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Goldberg, Ilya; Thambisetty, Madhav; Becker, Kevin] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Du, W (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM johnson@mail.nih.gov
OI Goldberg, Ilya/0000-0001-8514-6110
NR 11
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2156-1125
BN 978-1-4673-6798-1
J9 IEEE INT C BIOINFORM
PY 2015
BP 1586
EP 1590
PG 5
WC Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology
SC Computer Science; Mathematical & Computational Biology
GA BE9EI
UT WOS:000377335600269
ER
PT S
AU Park, HS
Chae, SH
Yoon, JW
Kim, J
Sudduth, A
Stanley, C
AF Park, Hyung-Soon
Chae, Sang Hoon
Yoon, Jung Won
Kim, Jonghyun
Sudduth, Amanda
Stanley, Christopher
GP IEEE
TI Implementing Overground Turning on a Linear Treadmill
SO 2015 12TH INTERNATIONAL CONFERENCE ON UBIQUITOUS ROBOTS AND AMBIENT
INTELLIGENCE (URAI)
SE International Conference on Ubiquitous Robots and Ambient Intelligence
LA English
DT Proceedings Paper
CT 12th International Conference on Ubiquitous Robots and Ambient
Intelligence (URAI)
CY OCT 28-30, 2015
CL Goyang, SOUTH KOREA
SP Korean Robot Soc, IEEE, Inst Control Robot & Syst, MySET, Robot Soc Japan
DE Gait Rehabilitation; Turning; User-driven Treadmill; Virtual Reality
ID WALKING
AB The purpose of treadmill-based locomotor training is to transfer walking skills obtained from training to real world walking (overground: OG). For optimal skill transfer, treadmill-based training should simulate OG as closely as possible. The constant speed of a standard treadmill encourages automaticity rather than engagement and fails to simulate the variable speeds encountered during OG walking. Our effort to overcome this limitation has focused on developing user-driven treadmill (UDT) velocity control schemes that allow the user to freely change walking speed and feel the same inertial force that they feel during OG walking. In this study, we have combined the user driven treadmill control with the virtual reality (VR) display to simulate realistic turning in a safe environment.
C1 [Park, Hyung-Soon; Chae, Sang Hoon] Korea Adv Inst Sci & Technol, Dept Mech Engn, Daejeon, South Korea.
[Yoon, Jung Won] Gyeongsang Natl Univ, Dept Mech Engn, Jinju, South Korea.
[Kim, Jonghyun] DGIST, Dept Robot Engn, Daegu, South Korea.
[Sudduth, Amanda; Stanley, Christopher] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Park, HS (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, Daejeon, South Korea.
EM hyungspark@kaist.ac.kr; jwyoon@gnu.ac.kr; jhkim@dgist.ac.kr;
stanleycl@cc.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2325-033X
BN 978-1-4673-7971-7
J9 INT CONF UBIQ ROBOT
PY 2015
BP 390
EP 391
PG 2
WC Computer Science, Artificial Intelligence; Robotics
SC Computer Science; Robotics
GA BF0PD
UT WOS:000379215900111
ER
PT S
AU De Castro, M
Zand, DJ
Lichter-Konecki, U
Kirmse, B
AF De Castro, Mauricio
Zand, Dina J.
Lichter-Konecki, Uta
Kirmse, Brian
BE Zschocke, J
Baumgartner, M
Morava, E
Patterson, M
Rahman, S
Peters, V
TI Severe Neonatal Holocarboxylase Synthetase Deficiency in West African
Siblings
SO JIMD REPORTS, VOL 20
SE JIMD Reports
LA English
DT Article; Book Chapter
ID MULTIPLE CARBOXYLASE DEFICIENCY; MOLECULAR ANALYSIS; JAPANESE PATIENTS;
DIAGNOSIS; GENE
AB In multiple carboxylase deficiency (MCD), the biotin-dependent carboxylases have decreased activity due to either biotinidase deficiency or holocarboxylase synthetase (HS) deficiency. We report the case of two siblings from Ghana, the first of which presented shortly after birth with profound lactic acidosis and a urine organic acid profile consistent with MCD. In the first sibling, treatment with pulverized biotin tablets (20 mg) was begun immediately, but the patient died at 10 days of age from cardiac arrest secondary to refractory metabolic acidosis. Autopsy revealed a biotin bezoar. Sequencing of HCLS showed homozygosity for a novel missense variant (p.G241W). The second sibling had a similar presentation at birth: severe metabolic acidosis and respiratory distress. A urine organic acid profile was consistent with HS deficiency; he was treated with biotin powder (20 mg), and after 24 h, the lactate decreased significantly; by day 5 of life, the patient was tolerating 40 mg of biotin, feeding by mouth and off all other medications and support. This is the first report of the p.G241W mutation. To our knowledge, this is also the first mutation described in West African patients with HS deficiency and the cases demonstrate that it is biotin responsive. Additionally, our experience suggests that the powdered form of biotin supplementation may be more digestible than tablets for the treatment of severe neonatal HS deficiency.
C1 [De Castro, Mauricio] NHGRI, Med Genet Branch, US Dept HHS, NIH, 35 Convent Dr,MSC 3717,Room 1B207, Bethesda, MD 20892 USA.
[Zand, Dina J.; Lichter-Konecki, Uta; Kirmse, Brian] Childrens Natl Hlth Syst, Genet & Metab, Washington, DC USA.
RP De Castro, M (reprint author), NHGRI, Med Genet Branch, US Dept HHS, NIH, 35 Convent Dr,MSC 3717,Room 1B207, Bethesda, MD 20892 USA.
EM mauricio.decastro-pretelt@nih.gov
NR 16
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 2192-8304
BN 978-3-662-46700-8; 978-3-662-46699-5
J9 JIMD REP
PY 2015
VL 20
BP 1
EP 4
DI 10.1007/8904_2014_367
D2 10.1007/978-3-662-46700-8
PG 4
WC Endocrinology & Metabolism; Genetics & Heredity
SC Endocrinology & Metabolism; Genetics & Heredity
GA BE8SM
UT WOS:000376984500001
PM 25690727
ER
PT S
AU Choi, EY
Patel, K
Haddad, MR
Yi, L
Holmes, C
Goldstein, DS
Dutra, A
Pak, E
Kaler, SG
AF Choi, Eun-Young
Patel, Keyur
Haddad, Marie Reine
Yi, Ling
Holmes, Courtney
Goldstein, David S.
Dutra, Amalia
Pak, Evgenia
Kaler, Stephen G.
BE Zschocke, J
Baumgartner, M
Morava, E
Patterson, M
Rahman, S
Peters, V
TI Tandem Duplication of Exons 1-7 Neither Impairs ATP7A Expression Nor
Causes a Menkes Disease Phenotype
SO JIMD REPORTS, VOL 20
SE JIMD Reports
LA English
DT Article; Book Chapter
ID COPPER TRANSPORT; MUTATIONS; LOCALIZATION; DIAGNOSIS; PLASMA; GENE
AB ATP7A duplications are estimated to represent the molecular cause of Menkes disease in 4-10% of affected patients. We identified a novel duplication of ATP7A exons 1-7 discovered in the context of a challenging prenatal diagnostic situation. All other reported ATP7A duplications (n - 24) involved intragenic tandem duplications, predicted to disrupt the normal translational reading frame and produce nonfunctional ATP7A proteins. In contrast, the exon 1-7 duplication occurred at the 50 end of the ATP7A gene rather than within the gene and did not correspond to any known copy number variants. We hypothesized that, if the exon 1-7 duplication was in tandem, functional ATP7A molecules could be generated depending on promoter selection, mRNA splicing, and the proximal and distal duplication breakpoints and that Menkes disease would be averted. Here, we present detailed molecular characterization of this novel duplication, as well as 2-year postnatal clinical and biochemical correlations. The case highlights the ongoing need for cautious interpretation of prenatal genetic test results.
C1 [Choi, Eun-Young; Patel, Keyur; Haddad, Marie Reine; Yi, Ling; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci,Mol Med Program, Porter Neurosci Res Ctr 2, NIH, Bldg 35,Room 2D-971,35A Convent Dr,MSC 3754, Bethesda, MD 20892 USA.
[Holmes, Courtney; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA.
[Dutra, Amalia; Pak, Evgenia] NHGRI, Cytogenet & Microscopy Core, NIH, Bethesda, MD 20892 USA.
RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci,Mol Med Program, Porter Neurosci Res Ctr 2, NIH, Bldg 35,Room 2D-971,35A Convent Dr,MSC 3754, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
NR 17
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 2192-8304
BN 978-3-662-46700-8; 978-3-662-46699-5
J9 JIMD REP
PY 2015
VL 20
BP 57
EP 63
DI 10.1007/8904_2014_391
D2 10.1007/978-3-662-46700-8
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity
SC Endocrinology & Metabolism; Genetics & Heredity
GA BE8SM
UT WOS:000376984500009
PM 25638460
ER
PT J
AU Conforto, AB
Anjos, SM
Menezes, I
Siqueira, IL
Machado, AG
Conti, J
Peckham, PH
Mello, EA
Cohen, LG
AF Conforto, A. B.
Anjos, S. M.
Menezes, I.
Siqueira, I. L.
Machado, A. G.
Conti, J.
Peckham, P. H.
Mello, E. A.
Cohen, L. G.
TI Central and peripheral stimulation to enhance effects of motor training
in patients with stroke - preliminary results
SO CEREBROVASCULAR DISEASES
LA English
DT Meeting Abstract
CT 24th European Stroke Conference
CY MAY 13-15, 2015
CL Vienna, AUSTRIA
C1 [Conforto, A. B.; Anjos, S. M.; Menezes, I.; Siqueira, I. L.; Conti, J.; Mello, E. A.] Univ Sao Paulo, Hosp Clin, BR-05508 Sao Paulo, Brazil.
[Conforto, A. B.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil.
[Machado, A. G.] Cleveland Clin, Cleveland, Brazil.
[Peckham, P. H.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Cohen, L. G.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 4
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1015-9770
EI 1421-9786
J9 CEREBROVASC DIS
JI Cerebrovasc. Dis.
PY 2015
VL 39
SU 2
BP 264
EP 264
PG 1
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DM0HD
UT WOS:000376023400404
ER
PT J
AU de Vlieger, JSB
Muhlebach, S
Shah, VP
McNeil, SE
Borchard, G
Weinstein, V
Fluhmann, B
Neervannan, S
Crommelin, DJA
AF de Vlieger, Jon S. B.
Muhlebach, Stefan
Shah, Vinod P.
McNeil, Scott E.
Borchard, Gerrit
Weinstein, Vera
Fluhmann, Beat
Neervannan, Sesha
Crommelin, Daan J. A.
TI Non-biological complex drugs (NBCDs) and their follow-on versions: time
for an editorial section
SO GABI JOURNAL-GENERICS AND BIOSIMILARS INITIATIVE JOURNAL
LA English
DT Article
DE Glatiramoids; iron-carbohydrate complexes; liposomes; nanomedicines;
Non-Biological Complex Drug (NBCD) products; therapeutic equivalence
ID INTRAVENOUS IRON SUCROSE; NANOMEDICINES
AB This paper discusses the group of non-biological complex drug (NBCD) products and presents the reasons why NBCDs should be assigned a special position in our arsenal of medicines as well as why from now on a special section will be devoted to report on these NBCD products in the GaBI Journal.
C1 [de Vlieger, Jon S. B.] Dutch Top Inst Pharma, POB 142, NL-2300 AC Leiden, Netherlands.
[Muhlebach, Stefan] Vifor Pharma Ltd, CH-8152 Glattbrugg, Switzerland.
[Muhlebach, Stefan] Univ Basel, Dept Pharmaceut Sci, Pharmactr, CH-4056 Basel, Switzerland.
[McNeil, Scott E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA.
[Borchard, Gerrit] Univ Lausanne 30, Univ Geneva, Sch Pharmaceut Sci, Biopharmaceut Sci, CH-1211 Geneva 4, Switzerland.
[Weinstein, Vera] Teva Pharmaceut Ind Ltd, Discovery & Prod Dev, Global Res & Dev, Netanya, Israel.
[Fluhmann, Beat] Vifor Fresenius Med Care Renal Pharma Ltd, CH-9001 St Gallen, Switzerland.
[Neervannan, Sesha] Allergan Plc, Pharmaceut Dev Brands R&D, Irvine, CA 92612 USA.
[Crommelin, Daan J. A.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut Sci, NL-3508 TC Utrecht, Netherlands.
RP de Vlieger, JSB (reprint author), Dutch Top Inst Pharma, POB 142, NL-2300 AC Leiden, Netherlands.
NR 30
TC 0
Z9 0
U1 0
U2 0
PU PRO PHARMA COMMUNICATIONS INT
PI MOL
PA POSTBUS 10001, MOL, 2400, BELGIUM
SN 2033-6403
EI 2033-6772
J9 GABI J
JI GaBI J.
PY 2015
VL 4
IS 4
BP 167
EP 170
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DP3JN
UT WOS:000378389400004
ER
PT S
AU Kleinerman, RA
Morton, LM
Wong, JR
Tucker, MA
AF Kleinerman, Ruth A.
Morton, Lindsay M.
Wong, Jeannette R.
Tucker, Margaret A.
BE Francis, JH
Abramson, DH
TI Second Tumors in Retinoblastoma Survivors
SO RECENT ADVANCES IN RETINOBLASTOMA TREATMENT
SE Essentials in Ophthalmology
LA English
DT Article; Book Chapter
ID LONG-TERM SURVIVORS; HEREDITARY RETINOBLASTOMA; CHILDHOOD-CANCER;
HERITABLE RETINOBLASTOMA; BREAST-CANCER; FOLLOW-UP; RISK; RADIOTHERAPY;
CHEMOTHERAPY; GENE
C1 [Kleinerman, Ruth A.; Morton, Lindsay M.; Wong, Jeannette R.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
EM kleinerr@mail.nih.gov
NR 40
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 1612-3212
BN 978-3-319-19467-7; 978-3-319-19466-0
J9 ESSENT OPHTHALMOL
PY 2015
BP 105
EP 112
DI 10.1007/978-3-319-19467-7_10
D2 10.1007/978-3-319-19467-7
PG 8
WC Ophthalmology
SC Ophthalmology
GA BE8LP
UT WOS:000376577700011
ER
PT S
AU Watkins, PV
Doolittle, LM
Krusienski, DJ
Anderson, NR
AF Watkins, Paul V.
Doolittle, Luke M.
Krusienski, Dean J.
Anderson, Nicholas R.
GP IEEE
TI A theoretical limit and simulation of time-domain event detection in the
EEG
SO 2015 7TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER)
SE International IEEE EMBS Conference on Neural Engineering
LA English
DT Proceedings Paper
CT 7th Annual International IEEE EMBS Conference on Neural Engineering
(NER)
CY APR 22-24, 2015
CL Montpellier, FRANCE
SP IEEE, EMBS
ID AUTOMATIC RECOGNITION; FREQUENCY-BANDS
AB Scalp recordings of cortical activations, Electroencephalography (EEG), are commonly used clinically to detect diseases or injuries to the underlying cortical physiology. Unfortunately, the EEG signal is also artifact prone and these artifacts can exhibit a similar temporal and spectral profile as that caused by the potential disease. We have created a model of simulated (synthetic) EEG and artifacts to explore their interplay and the theoretical limits of detection when artifacts may not be separable from clinical events of interest. A theoretical limit of separation without an EEG signal is derived and then simulated upper bounds for time-domain event detection are created using simulated EEG data.
C1 [Watkins, Paul V.] NINDS, NIH, Bethesda, MD 20892 USA.
[Doolittle, Luke M.] Natus Med, Madison, WI 53562 USA.
[Krusienski, Dean J.] Old Dominion Univ, Dept Elect & Comp Engn, Norfolk, VA 23529 USA.
[Anderson, Nicholas R.] Cortech Solut, Wilmington, NC 28403 USA.
RP Anderson, NR (reprint author), Cortech Solut, Wilmington, NC 28403 USA.
EM pwatkins@gmail.com; luke.doolittle@gmail.com; dkrusien@odu.edu;
nickr.anderson@gmail.com
NR 15
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1948-3546
BN 978-1-4673-6389-1
J9 I IEEE EMBS C NEUR E
PY 2015
BP 1020
EP 1023
PG 4
WC Engineering, Biomedical; Neurosciences
SC Engineering; Neurosciences & Neurology
GA BE9FT
UT WOS:000377414600256
ER
PT J
AU Adjemian, J
Olivier, KN
Prevots, DR
AF Adjemian, J.
Olivier, K. N.
Prevots, D. R.
TI Predictors Of Prolonged Nontuberculous Mycobacterial Infections In
Patients With Cystic Fibrosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Adjemian, J.; Prevots, D. R.] NIAID, Bethesda, MD 20892 USA.
[Olivier, K. N.] NHLBI, Bethesda, MD 20892 USA.
EM jennifer.adjemian@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A5255
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582807075
ER
PT J
AU Akrami, K
Pondo, J
Nunes, E
Sousa, J
Figueiredo, I
Cossa, A
Teixiera, J
Hassane, A
AF Akrami, K.
Pondo, J.
Nunes, E.
Sousa, J.
Figueiredo, I.
Cossa, A.
Teixiera, J.
Hassane, A.
TI Pleurodesis: A Comparison Of Two Sclerosing Agents For Pleural Effusions
In A Resource Poor Area
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Akrami, K.] NIH, Bethesda, MD 20892 USA.
[Pondo, J.; Nunes, E.; Sousa, J.; Figueiredo, I.; Cossa, A.; Teixiera, J.; Hassane, A.] Maputo Cent Hosp, Maputo, Mozambique.
EM kevan.akrami@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A1119
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800120
ER
PT J
AU Al-Naamani, N
Chirinos, JA
Finkelman, M
Zamani, P
Paulus, JK
Roberts, KE
Barr, RG
Lima, JAC
Bluemke, DA
Kronmal, R
Kawut, SM
AF Al-Naamani, N.
Chirinos, J. A.
Finkelman, M.
Zamani, P.
Paulus, J. K.
Roberts, K. E.
Barr, R. G.
Lima, J. A. C.
Bluemke, D. A.
Kronmal, R.
Kawut, S. M.
CA MESA-Right Ventricle Study
TI Systemic Vascular Changes Are Associated With Right Ventricular Mass:
The MESA-Right Ventricle Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Al-Naamani, N.; Roberts, K. E.] Tufts Med Ctr, Boston, MA USA.
[Chirinos, J. A.; Zamani, P.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Chirinos, J. A.; Zamani, P.] Vet Adm Med Ctr, Philadelphia, PA 19104 USA.
[Finkelman, M.; Paulus, J. K.] Tufts Clin & Translat Sci Inst, Boston, MA USA.
[Barr, R. G.] Columbia Univ, Med Ctr, New York, NY USA.
[Lima, J. A. C.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Bluemke, D. A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Kronmal, R.] Univ Washington, Seattle, WA 98195 USA.
[Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
EM nalnaamani@tuftsmedicalcenter.org
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A5534
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582807395
ER
PT J
AU An, S
Tang, WY
Ahn, K
Mitzner, W
Huang, J
Kumar, S
Biswal, S
Panettieri, RA
Solway, J
Liggett, SB
AF An, S.
Tang, W. -Y.
Ahn, K.
Mitzner, W.
Huang, J.
Kumar, S.
Biswal, S.
Panettieri, R. A.
Solway, J.
Liggett, S. B.
TI Inflammation-Independent Regulation Of Airway Smooth Muscle Mechanical
Properties In Asthma
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [An, S.; Tang, W. -Y.; Mitzner, W.; Huang, J.; Kumar, S.; Biswal, S.] Johns Hopkins Univ, Baltimore, MD USA.
[Ahn, K.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Panettieri, R. A.] Univ Penn, Philadelphia, PA 19104 USA.
[Solway, J.] Univ Chicago, Chicago, IL 60637 USA.
[Liggett, S. B.] Univ S Florida, Tampa, MD USA.
EM san3@jhu.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2466
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802320
ER
PT J
AU Antkowiak, MC
Burg, E
Ubags, N
Fessler, MB
Poynter, ME
Suratt, BT
AF Antkowiak, M. C.
Burg, E.
Ubags, N.
Fessler, M. B.
Poynter, M. E.
Suratt, B. T.
TI Low Density Lipoprotein Activates Neutrophils Via Tlr4 And The Map
Kinase And Nfkb Pathways
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Antkowiak, M. C.; Burg, E.; Ubags, N.; Suratt, B. T.] Univ Vermont, Burlington, VT USA.
[Antkowiak, M. C.; Fessler, M. B.] Natl Inst Environm Hlth, Res Triangle Pk, NC USA.
[Poynter, M. E.] Univ Vermont, Coll Med, Burlington, VT USA.
NR 0
TC 0
Z9 0
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.
PY 2015
VL 191
MA A4351
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582805410
ER
PT J
AU Barochia, AV
Kaler, M
Cuento, RA
Mushaben, E
Weir, N
Sampson, ML
Fontana, JR
MacDonald, SD
Moss, J
Mangianello, V
Remaley, AT
Levine, SJ
AF Barochia, A. V.
Kaler, M.
Cuento, R. A.
Mushaben, E.
Weir, N.
Sampson, M. L.
Fontana, J. R.
MacDonald, S. D.
Moss, J.
Mangianello, V.
Remaley, A. T.
Levine, S. J.
TI Serum Apolipoprotein A-I And Large High-Density Lipoprotein (hdl)
Particles Are Positively Correlated With Fev1 In Atopic Asthma
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Barochia, A. V.; Kaler, M.; Cuento, R. A.; Mushaben, E.; Weir, N.; Sampson, M. L.; Fontana, J. R.; MacDonald, S. D.; Moss, J.; Mangianello, V.; Remaley, A. T.; Levine, S. J.] NIH, Bethesda, MD 20892 USA.
EM barochiaav@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A4331
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582805390
ER
PT J
AU Biller, JA
Eagle, G
McGinnis, JP
Micioni, L
Daley, CL
Winthrop, KL
Ruoss, SJ
Addrizzo-Harris, DJ
Flume, PA
Dorgan, DJ
Salathe, M
Brown-Elliott, BA
Wallace, RJ
Griffith, DE
Olivier, KN
AF Biller, J. A.
Eagle, G.
McGinnis, J. P.
Micioni, L.
Daley, C. L.
Winthrop, K. L.
Ruoss, S. J.
Addrizzo-Harris, D. J.
Flume, P. A.
Dorgan, D. J.
Salathe, M.
Brown-Elliott, B. A.
Wallace, R. J.
Griffith, D. E.
Olivier, K. N.
TI Efficacy Of Liposomal Amikacin For Inhalation (lai) In Achieving
Nontuberculous Mycobacteria (ntm) Culture Negativity In Patients Whose
Lung Infection Is Refractory To Guideline-Based Therapy
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Biller, J. A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Eagle, G.; McGinnis, J. P.; Micioni, L.] Insmed Inc, Bridgewater, NJ USA.
[Daley, C. L.] Natl Jewish Hlth, Denver, CO USA.
[Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Ruoss, S. J.] Stanford Univ, Stanford, CA 94305 USA.
[Addrizzo-Harris, D. J.] NYU, Sch Med, New York, NY USA.
[Flume, P. A.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Dorgan, D. J.] Univ Penn, Philadelphia, PA 19104 USA.
[Salathe, M.] Univ Miami, Miami, FL USA.
[Brown-Elliott, B. A.] Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA.
[Wallace, R. J.] Univ Texas Hlth Sci Ctr, Tyler, TX USA.
[Griffith, D. E.] Univ Texas Hlth Ctr Tyler, Tyler, TX USA.
[Olivier, K. N.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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.
PY 2015
VL 191
MA A6295
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582808530
ER
PT J
AU Burkart, KM
Stilp, AM
Sofer, T
London, S
Davis, S
Celedon, JC
Barr, RG
AF Burkart, K. M.
Stilp, A. M.
Sofer, T.
London, S.
Davis, S.
Celedon, J. C.
Barr, R. G.
TI Genome-Wide Association Study (gwas) Of Lung Function Among
Hispanic/latino Individuals Of Diverse Backgrounds. The Hispanic
Community Health Study/study Of LatINOS (hchs/sol)
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Burkart, K. M.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Burkart, K. M.; Stilp, A. M.] Univ Washington, Seattle, WA 98195 USA.
[Sofer, T.] Univ Washington, Seattle, WA 98195 USA.
[London, S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Davis, S.] Univ N Carolina, Chapel Hill, NC USA.
[Celedon, J. C.] Univ Pittsburgh, Childrens Hosp Pittsburgh UPMC, Pittsburgh, PA USA.
[Barr, R. G.] Columbia Univ, Presbyterian Hosp, New York, NY USA.
EM kb2319@columbia.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A1069
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800070
ER
PT J
AU Chang, H
Adjemian, J
Dell, SDM
Ferkol, TW
Leigh, MW
Milla, CE
Rosenfeld, M
Sagel, SD
Knowles, MR
Olivier, KN
AF Chang, H.
Adjemian, J.
Dell, S. D. M.
Ferkol, T. W.
Leigh, M. W.
Milla, C. E.
Rosenfeld, M.
Sagel, S. D.
Knowles, M. R.
Olivier, K. N.
TI Prevalence Of Airway Microbial Flora In Primary Ciliary Dyskinesia
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Chang, H.] NIAID, Bethesda, MD 20892 USA.
[Adjemian, J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Dell, S. D. M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Ferkol, T. W.] Washington Univ, St Louis, MO USA.
[Leigh, M. W.] Univ N Carolina, Chapel Hill, NC USA.
[Milla, C. E.] Stanford Univ, Palo Alto, CA 94304 USA.
[Rosenfeld, M.] Childrens Hosp Reg Med Ctr, Seattle, WA USA.
[Sagel, S. D.] Univ Colorado Denver, Childrens Hosp, Aurora, CO USA.
[Knowles, M. R.] Univ N Carolina, Chapel Hill, NC USA.
[Olivier, K. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM kenneth.olivier@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A1798
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582801197
ER
PT J
AU Chen, MY
Yao, J
Schuzer, J
Haughey, ME
Jones, AM
Julien-Williams, P
Moss, J
AF Chen, M. Y.
Yao, J.
Schuzer, J.
Haughey, M. E.
Jones, A. M.
Julien-Williams, P.
Moss, J.
TI Iterative Reconstruction Enables Nearly 75% Radiation Dose Reduction For
Automated Quantitative Assessment Of Lymphangioleiomyomatosis Cyst Score
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Chen, M. Y.; Haughey, M. E.; Jones, A. M.; Julien-Williams, P.; Moss, J.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Yao, J.] NIH, Bethesda, MD 20892 USA.
[Schuzer, J.] Toshiba Med Res Inst, Vernon Hills, IL USA.
EM marcus.chen@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A1398
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800397
ER
PT J
AU Cui, Y
Ma, D
Nwokeji, A
Maynard, D
Cullinane, A
George, G
D'Agostino, E
Gochuico, BR
Handin, R
El-Chemaly, S
AF Cui, Y.
Ma, D.
Nwokeji, A.
Maynard, D.
Cullinane, A.
George, G.
D'Agostino, E.
Gochuico, B. R.
Handin, R.
El-Chemaly, S.
TI Dysregulated Angiotensin Ii Receptor Type-1 And Myosin Iib-Mediated
Migration Of Hermansky-Pudlak Syndrome Fibroblasts
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Cui, Y.; Ma, D.; Nwokeji, A.; George, G.; D'Agostino, E.; Handin, R.; El-Chemaly, S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Maynard, D.; Cullinane, A.; Gochuico, B. R.] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A4947
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582806381
ER
PT J
AU Duncan, EA
Ortega, H
Gleich, G
Price, R
Yancey, S
Klion, A
AF Duncan, E. A.
Ortega, H.
Gleich, G.
Price, R.
Yancey, S.
Klion, A.
TI Observational Experience Describing The Use Of Mepolizumab In Patients
With Hypereosinophilic Syndrome
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Duncan, E. A.; Ortega, H.; Yancey, S.] GSK, Res Triangle Pk, NC USA.
[Gleich, G.] Univ Utah, Salt Lake City, UT USA.
[Price, R.] GSK, Uxbridge, Middx, England.
[Klion, A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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.
PY 2015
VL 191
MA A1365
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800364
ER
PT J
AU Ferrada, M
Decker, B
Mennow, R
Munro, N
Kent, T
O'Grady, NP
Palmore, T
AF Ferrada, M.
Decker, B.
Mennow, R.
Munro, N.
Kent, T.
O'Grady, N. P.
Palmore, T.
TI Empiric Use Of Empiric Antimicrobial Drugs In Neutropenic Icu Patients
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Ferrada, M.; Decker, B.; Mennow, R.; Munro, N.; Kent, T.; O'Grady, N. P.; Palmore, T.] NIH, Bethesda, MD 20892 USA.
EM marcela.ferrada@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A4536
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582805595
ER
PT J
AU Gesthalter, YB
Kusko, RL
Holland, WP
Allen-Ziegler, K
Limburg, PJ
Aubry, MC
Mandrekar, SJ
Lenburg, M
Wigle, D
Szabo, E
Spira, A
Beane, J
AF Gesthalter, Y. B.
Kusko, R. L.
Holland, W. P.
Allen-Ziegler, K.
Limburg, P. J.
Aubry, M. C.
Mandrekar, S. J.
Lenburg, M.
Wigle, D.
Szabo, E.
Spira, A.
Beane, J.
TI Pioglitazone Reverses Oncogenic Pathways In Airway Epithelium Of Lung
Cancer Patients
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Gesthalter, Y. B.; Beane, J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Kusko, R. L.; Lenburg, M.; Spira, A.] Boston Univ, Boston, MA 02215 USA.
[Holland, W. P.; Allen-Ziegler, K.; Limburg, P. J.; Aubry, M. C.; Mandrekar, S. J.; Wigle, D.] Mayo Clin, Rochester, MN 55905 USA.
[Szabo, E.] NCI, Bethesda, MD 20892 USA.
EM ygesty@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2428
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802222
ER
PT J
AU Gowdy, KM
Madenspacher, JH
Thomas, SY
Nakano, H
Cook, DN
Fessler, MB
AF Gowdy, K. M.
Madenspacher, J. H.
Thomas, S. Y.
Nakano, H.
Cook, D. N.
Fessler, M. B.
TI Novel Role For Scavenger Receptor B-I In Neutrophilic Asthma
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Gowdy, K. M.] E Carolina Univ, Greenville, NC USA.
[Madenspacher, J. H.; Thomas, S. Y.; Nakano, H.; Cook, D. N.; Fessler, M. B.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2501
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802355
ER
PT J
AU Henkle, E
Daley, CL
Griffith, DE
Walsh, JW
Leitman, P
Malanga, E
Aksamit, TR
O'Donnell, AE
Thomashow, B
Olivier, KN
Knowles, MR
Barker, AF
Metersky, ML
Tino, G
Eden, E
Salathe, M
Johnson, M
Wilkins, T
Prieto, D
Winthrop, KL
AF Henkle, E.
Daley, C. L.
Griffith, D. E.
Walsh, J. W.
Leitman, P.
Malanga, E.
Aksamit, T. R.
O'Donnell, A. E.
Thomashow, B.
Olivier, K. N.
Knowles, M. R.
Barker, A. F.
Metersky, M. L.
Tino, G.
Eden, E.
Salathe, M.
Johnson, M.
Wilkins, T.
Prieto, D.
Winthrop, K. L.
CA Bronchiectasis Res Registry
TI Patterns Of Pharmacotherapy For Non-Cystic Fibrosis Bronchiectasis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Henkle, E.; Barker, A. F.; Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Daley, C. L.] Natl Jewish Hlth, Denver, CO USA.
[Griffith, D. E.] Univ Texas Hlth Ctr Tyler, Tyler, TX USA.
[Walsh, J. W.] COPD Fdn, Miami, FL USA.
[Leitman, P.] NTM Info & Res, Coral Gables, FL USA.
[Malanga, E.; Prieto, D.] COPD Fdn, Washington, DC USA.
[Aksamit, T. R.] Mayo Clin, Rochester, MN USA.
[O'Donnell, A. E.] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Thomashow, B.] Columbia Univ, New York, NY USA.
[Olivier, K. N.] NHLBI, Bethesda, MD 20892 USA.
[Knowles, M. R.; Wilkins, T.] Univ N Carolina, Chapel Hill, NC USA.
[Metersky, M. L.] Univ Connecticut, Sch Med, Farmington, CT USA.
[Tino, G.] Hosp Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Eden, E.] Columbia Univ St Lukes, New York, NY USA.
[Salathe, M.] Univ Miami, Miami, FL USA.
[Johnson, M.] Mayo Clin Florida, Jacksonville, FL USA.
EM henkle@ohsu.edu
NR 0
TC 1
Z9 1
U1 0
U2 0
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.
PY 2015
VL 191
MA A2445
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802299
ER
PT J
AU Hoppin, J
Umbach, D
Long, S
London, S
Henneberger, PK
Blair, A
Freeman, LB
Sandler, DP
AF Hoppin, J.
Umbach, D.
Long, S.
London, S.
Henneberger, P. K.
Blair, A.
Freeman, L. Beane
Sandler, D. P.
TI Pesticides Are Associated With Allergic And Non-Allergic Wheeze Among
Male Farmers
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Hoppin, J.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Umbach, D.] NIEHS, Res Triangle Pk, NC USA.
[Long, S.] Westat Corp, Durham, NC USA.
[London, S.; Sandler, D. P.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Henneberger, P. K.] NIOSH, CDC, Morgantown, WV USA.
[Blair, A.; Freeman, L. Beane] NCI, Rockville, MD USA.
EM jahoppin@ncsu.edu
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A6263
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582808498
ER
PT J
AU Hussain, S
Bushel, P
Gerrish, K
Garantziotis, S
AF Hussain, S.
Bushel, P.
Gerrish, K.
Garantziotis, S.
TI Human Bronchial Epithelia From Healthy And Asthmatic Subjects Show
Differential Sensitivity Towards Toxic Effects Of Multi-Walled Carbon
Nanotubes
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Hussain, S.; Bushel, P.; Gerrish, K.; Garantziotis, S.] NIEHS, Res Triangle Pk, NC 27709 USA.
EM salik.hussain@nih.gov
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
NR 0
TC 0
Z9 0
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.
PY 2015
VL 191
MA A3227
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582803502
ER
PT J
AU Jaswal, DS
Remy, KE
Cui, X
Puch, IC
Solomon, S
Sun, J
Eichacker, PQ
AF Jaswal, D. S.
Remy, K. E.
Cui, X.
Puch, I. Cortes
Solomon, S.
Sun, J.
Eichacker, P. Q.
TI The Effect Of Anthrax Immunoglobulin (aig) On Survival In A Canine Model
Of B. Anthracis Lethal And Edema Toxin Associated Shock
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Jaswal, D. S.; Remy, K. E.; Cui, X.; Puch, I. Cortes; Solomon, S.; Sun, J.; Eichacker, P. Q.] NIH, Bethesda, MD 20892 USA.
EM dharmvir.jaswal@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2550
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802404
ER
PT J
AU Jaswal, DS
Namagerdi, LO
Sampath-Kumar, H
Fitz, Y
Li, Y
Cui, X
Eichacker, PQ
AF Jaswal, D. S.
Namagerdi, L. Ohanjanian
Sampath-Kumar, H.
Fitz, Y.
Li, Y.
Cui, X.
Eichacker, P. Q.
TI The Development And Implementation Of An Isolated Perfused Rat Kidney
Model To Study Renal Tubular Function
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Jaswal, D. S.; Namagerdi, L. Ohanjanian; Sampath-Kumar, H.; Fitz, Y.; Li, Y.; Cui, X.; Eichacker, P. Q.] NIH, Bethesda, MD 20892 USA.
EM dharmvir.jaswal@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2552
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802406
ER
PT J
AU Jaswal, DS
Sampath-Kumar, H
Namagerdi, LO
Fitz, Y
Li, Y
Cui, X
Eichacker, PQ
AF Jaswal, D. S.
Sampath-Kumar, H.
Namagerdi, L. Ohanjanian
Fitz, Y.
Li, Y.
Cui, X.
Eichacker, P. Q.
TI B. Anthracis Edema Toxin Increases Fractional Free Water Reabsorption In
An Isolated Perfused Rat Kidney Model
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Jaswal, D. S.; Sampath-Kumar, H.; Namagerdi, L. Ohanjanian; Fitz, Y.; Li, Y.; Cui, X.; Eichacker, P. Q.] NIH, Bethesda, MD 20892 USA.
EM dharmvir.jaswal@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2551
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802405
ER
PT J
AU Laslett, DB
Kawut, SM
Praestgaard, A
Barr, G
Bluemke, DM
Kronmal, RA
Lima, J
Ventetuolo, CE
AF Laslett, D. B.
Kawut, S. M.
Praestgaard, A.
Barr, G.
Bluemke, D. M.
Kronmal, R. A.
Lima, J.
Ventetuolo, C. E.
TI Association Of Non-Steroidal Anti-Inflammatory Drug (nsaid) Use With
Right Ventricular (rv) Morphology: The MESA-Right Ventricle Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Laslett, D. B.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Praestgaard, A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Bluemke, D. M.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kronmal, R. A.] Univ Washington, Seattle, WA 98195 USA.
[Lima, J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Ventetuolo, C. E.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA.
EM DAVID.LASLETT@uphs.upenn.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A6452
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582807225
ER
PT J
AU Li, Y
Namagerdi, LO
Sampath-Kumar, H
Cui, X
Fitz, Y
Eichacker, PQ
AF Li, Y.
Namagerdi, L. Ohanjanian
Sampath-Kumar, H.
Cui, X.
Fitz, Y.
Eichacker, P. Q.
TI Nitric Oxide Synthase Inhibition Improves Hemodynamics And Survival In
B. Anthracis Edema Toxin Challenged Rats
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Li, Y.; Namagerdi, L. Ohanjanian; Sampath-Kumar, H.; Cui, X.; Fitz, Y.; Eichacker, P. Q.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM yli@mail.cc.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2549
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802403
ER
PT J
AU Marzec, JM
Ciencewicki, J
Serra, ME
Gerek, M
Polack, F
Kleeberger, SR
AF Marzec, J. M.
Ciencewicki, J.
Serra, M. E.
Gerek, M.
Polack, F.
Kleeberger, S. R.
TI Macrophage Associated Receptor With Collagenous Structure (marco)
Variant Modulates Susceptibility To Respiratory Syncytial Virus (rsv)
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Marzec, J. M.; Ciencewicki, J.; Kleeberger, S. R.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Serra, M. E.; Gerek, M.] Fundacian Infant, Buenos Aires, DF, Argentina.
[Polack, F.] Vanderbilt Univ, Nashville, TN 37235 USA.
EM marzec@niehs.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A3239
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582803514
ER
PT J
AU Mathias, RA
Johnston, HR
Torgerson, D
Levin, AM
Lange, LA
Ortega, VE
Hu, Y
Caraballo, L
Foreman, MG
Hartert, T
Herrera-Paz, E
Knight-Madden, JM
Kumar, R
Mayorga, A
Olopade, C
Ware, LB
Marrugo, J
Oliveira, RR
Yazdanbakhsh, M
Wilson, JG
Williams, L
Watson, H
Faruque, MU
Rotimi, C
Ober, C
Meyers, D
Bleecker, ER
Burchard, EG
Qin, Z
Taub, M
Beaty, TH
Ruczinski, I
Barnes, KC
AF Mathias, R. A.
Johnston, H. R.
Torgerson, D.
Levin, A. M.
Lange, L. A.
Ortega, V. E.
Hu, Y.
Caraballo, L.
Foreman, M. G.
Hartert, T.
Herrera-Paz, E.
Knight-Madden, J. M.
Kumar, R.
Mayorga, A.
Olopade, C.
Ware, L. B.
Marrugo, J.
Oliveira, R. R.
Yazdanbakhsh, M.
Wilson, J. G.
Williams, L.
Watson, H.
Faruque, M. U.
Rotimi, C.
Ober, C.
Meyers, D.
Bleecker, E. R.
Burchard, E. G.
Qin, Z.
Taub, M.
Beaty, T. H.
Ruczinski, I.
Barnes, K. C.
TI The Value Of Whole Genome Sequencing In Identifying Genetic Determinants
Of Asthma In Populations Of African Ancestry
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Mathias, R. A.] Johns Hopkins Med, Baltimore, MD USA.
[Johnston, H. R.; Hu, Y.; Qin, Z.] Emory Univ, Atlanta, GA 30322 USA.
[Torgerson, D.; Burchard, E. G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Levin, A. M.; Williams, L.] Henry Ford Hlth Syst, Detroit, MI USA.
[Lange, L. A.; Meyers, D.; Bleecker, E. R.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Ortega, V. E.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Caraballo, L.; Marrugo, J.] Univ Cartagena, Cartagena, Colombia.
[Foreman, M. G.] Morehouse Sch Med, Atlanta, GA 30310 USA.
[Hartert, T.; Ware, L. B.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Herrera-Paz, E.] Univ Catol Honduras, San Pedro Sula, Honduras.
[Knight-Madden, J. M.] Univ W Indies, Kingston 7, Jamaica.
[Kumar, R.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Mayorga, A.] Ctr Neumol & Alergias, San Pedro Sula, Honduras.
[Olopade, C.; Ober, C.] Univ Chicago, Chicago, IL 60637 USA.
[Oliveira, R. R.] Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil.
[Yazdanbakhsh, M.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Wilson, J. G.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Watson, H.] Univ W Indies, St Michael, Barbados.
[Faruque, M. U.] Howard Univ, Washington, DC 20059 USA.
[Rotimi, C.] NHGRI, Bethesda, MD 20892 USA.
[Taub, M.; Ruczinski, I.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Beaty, T. H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Barnes, K. C.] Johns Hopkins Univ, Baltimore, MD USA.
EM kbarnes@jhmi.edu
NR 0
TC 0
Z9 0
U1 2
U2 2
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.
PY 2015
VL 191
MA A1063
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800064
ER
PT J
AU Mushaben, E
Dai, C
Yao, X
Nugent, G
Keeran, K
Yu, Z
Aponte, A
Gucek, M
Levine, SJ
AF Mushaben, E.
Dai, C.
Yao, X.
Nugent, G.
Keeran, K.
Yu, Z.
Aponte, A.
Gucek, M.
Levine, S. J.
TI The Macrophage Scavenger Receptor Cd163 Binds The German Cockroach
Protein, Vitellogenin, And Attenuates Allergic Sensitization And Airway
Hyperreactivity In A Murine Model Of Experimental Cockroach-Induced
Asthma
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Mushaben, E.; Dai, C.; Yao, X.; Nugent, G.; Keeran, K.; Yu, Z.; Aponte, A.; Gucek, M.; Levine, S. J.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A5661
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582807522
ER
PT J
AU Nick, JA
Caceres, SM
Kret, JE
Poch, KR
Strand, M
Faino, A
Nichols, D
Saavedra, M
Taylor-Cousar, JL
Coldren, CD
Geraci, M
Burnham, EL
Suratt, BT
Fessler, M
Abraham, E
Moss, M
Malcolm, KC
AF Nick, J. A.
Caceres, S. M.
Kret, J. E.
Poch, K. R.
Strand, M.
Faino, A.
Nichols, D.
Saavedra, M.
Taylor-Cousar, J. L.
Coldren, C. D.
Geraci, M.
Burnham, E. L.
Suratt, B. T.
Fessler, M.
Abraham, E.
Moss, M.
Malcolm, K. C.
TI Association Of Interferon-Stimulated Gene Expression With Worse Outcomes
In The Acute Respiratory Distress Syndrome
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Nick, J. A.; Caceres, S. M.; Poch, K. R.; Strand, M.; Faino, A.; Nichols, D.; Saavedra, M.; Taylor-Cousar, J. L.; Malcolm, K. C.] Natl Jewish Hlth, Denver, CO USA.
[Kret, J. E.] Dist Columbia Dept Hlth, Washington, DC USA.
[Faino, A.; Coldren, C. D.; Geraci, M.; Burnham, E. L.; Moss, M.] Univ Colorado Denver, Aurora, CO USA.
[Suratt, B. T.] Univ Vermont, Coll Med, Burlington, VT USA.
[Fessler, M.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Abraham, E.] Wake Forest, Winston Salem, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2376
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802170
ER
PT J
AU Obeidat, M
Nie, Y
Hao, K
Bosse, Y
Laviolette, M
Nickle, D
Postma, DS
Timens, W
Gharib, S
Tobin, M
Hall, I
London, S
Sin, D
Pare, P
AF Obeidat, M.
Nie, Y.
Hao, K.
Bosse, Y.
Laviolette, M.
Nickle, D.
Postma, D. S.
Timens, W.
Gharib, S.
Tobin, M.
Hall, I.
London, S.
Sin, D.
Pare, P.
CA T SpiroMeta-Consortium
T CHARGE-Consortium
SpiroMeta-CHARGE Consortia
TI Systems Genetics Approach Identifies Nicotine Receptor Antagonist As A
Potential Therapeutic Target In COPD
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Obeidat, M.; Nie, Y.; Sin, D.; Pare, P.] Univ British Columbia, Ctr Heart Lung Innovat, St Pauls Hosp, Vancouver, BC V5Z 1M9, Canada.
[Hao, K.] Mt Sinai Sch Med, New York, NY USA.
[Bosse, Y.; Laviolette, M.] Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
[Nickle, D.] Merck Res Labs, Boston, MA USA.
[Postma, D. S.; Timens, W.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Tobin, M.] Univ Leicester, Leicester, Leics, England.
[T SpiroMeta-Consortium] Univ Nottingham, Nottingham NG7 2RD, England.
[T CHARGE-Consortium] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Gharib, S.] Univ Washington, Dept Med, Seattle, MA USA.
[Hall, I.] Univ Nottingham Hosp, Nottingham NG7 2UH, England.
[London, S.] NIEHS, Res Triangle Pk, NC 27709 USA.
EM maen.obeidat@hli.ubc.ca
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2202
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582801594
ER
PT J
AU Park, I
Olivier, KN
Holland, SM
Sampaio, EP
Zelazny, AM
AF Park, I.
Olivier, K. N.
Holland, S. M.
Sampaio, E. P.
Zelazny, A. M.
TI The Shift In Lipid Metabolism In Mycobacterium Abscessus During Early
Stage Of Human Lung Infection May Set The Stage For Its Persistence
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Park, I.; Holland, S. M.; Sampaio, E. P.] NIAID, NIH, Bethesda, MD 20892 USA.
[Olivier, K. N.] NHLBI, Bethesda, MD 20892 USA.
[Zelazny, A. M.] NIAID, Bethesda, MD USA.
EM inkwon.park@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2182
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582801574
ER
PT J
AU Patlolla, H
Miller, AC
AF Patlolla, H.
Miller, A. C.
TI Pulmonary Mycobacterium Tuberculosis Associated Immune Thrombocytopenia
Purpura
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Patlolla, H.] Mt Sinai Hosp, Chicago, IL USA.
[Miller, A. C.] NIH, Bethesda, MD 20892 USA.
EM harish.patlolla@sinai.org
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A3256
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582803531
ER
PT J
AU Pepper, DJ
Danner, RL
Suffredini, AF
AF Pepper, D. J.
Danner, R. L.
Suffredini, A. F.
TI High Dose Phenylephrine Causing Atypical Takotsubo-Like Cardiac
Dysfunction
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
ID CARDIOMYOPATHY
C1 [Pepper, D. J.; Danner, R. L.; Suffredini, A. F.] NIH, Bethesda, MD 20892 USA.
EM dominique.pepper@nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A4525
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582805584
ER
PT J
AU Pepper, DJ
Harris, AL
AF Pepper, D. J.
Harris, A. L.
TI Lemierre Syndrome: The Forgotten Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Pepper, D. J.] NIH, Bethesda, MD 20892 USA.
[Pepper, D. J.; Harris, A. L.] Univ MS, Med Ctr, GV Sonny Montgomery VAMC, Jackson, MS USA.
EM dominique.pepper@nih.gov
NR 2
TC 0
Z9 0
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.
PY 2015
VL 191
MA A1828
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582801227
ER
PT J
AU Remy, KE
Cortes-Puch, I
Solomon, SB
Sun, J
Lertora, JJ
Gladwin, MT
Kim-Shapiro, DB
Klein, HG
Natanson, C
AF Remy, K. E.
Cortes-Puch, I.
Solomon, S. B.
Sun, J.
Lertora, J. J.
Gladwin, M. T.
Kim-Shapiro, D. B.
Klein, H. G.
Natanson, C.
TI Haptoglobin Administration Improves Lung Injury And Survival In Canines
Challenged With S. Aureus Pneumonia And Exchange Transfused Fresh But
Not Older Stored Blood
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Remy, K. E.; Cortes-Puch, I.; Solomon, S. B.; Sun, J.; Lertora, J. J.; Klein, H. G.; Natanson, C.] NIH, Bethesda, MD 20892 USA.
[Remy, K. E.; Gladwin, M. T.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kim-Shapiro, D. B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
EM kenneth.remy@nih.gov
NR 0
TC 0
Z9 0
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.
PY 2015
VL 191
MA A2556
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802410
ER
PT J
AU Ruoss, SJ
Eagle, G
McGinnis, JP
Micioni, L
Daley, CL
Winthrop, KL
Addrizzo-Harris, DJ
Flume, PA
Dorgan, DJ
Salathe, M
Griffith, DE
Olivier, KN
AF Ruoss, S. J.
Eagle, G.
McGinnis, J. P.
Micioni, L.
Daley, C. L.
Winthrop, K. L.
Addrizzo-Harris, D. J.
Flume, P. A.
Dorgan, D. J.
Salathe, M.
Griffith, D. E.
Olivier, K. N.
TI Analysis Of Functional Exercise Capacity (via The Six-Minute Walk Test
[6mwt]) And Culture Negativity In Patients With Nontuberculous
Mycobacteria (ntm) Lung Infection Refractory To Guideline-Based Therapy
Treated With Liposomal Amikacin For Inhalation (lai)
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Ruoss, S. J.] Stanford Univ, Stanford, CA 94305 USA.
[Eagle, G.; McGinnis, J. P.; Micioni, L.] Insmed Inc, Bridgewater, NJ USA.
[Daley, C. L.] Natl Jewish Hlth, Denver, CO USA.
[Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Addrizzo-Harris, D. J.] NYU, Sch Med, New York, NY USA.
[Flume, P. A.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Dorgan, D. J.] Univ Penn, Philadelphia, PA 19104 USA.
[Salathe, M.] Univ Miami, Miami, FL USA.
[Griffith, D. E.] Univ Texas Hlth Ctr Tyler, Tyler, TX USA.
[Olivier, K. N.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
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.
PY 2015
VL 191
MA A6296
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582808531
ER
PT J
AU Sato, T
Shibata, Y
Yamamoto, M
Kudo, M
Kaneko, T
Ishigatsubo, Y
Klinman, D
AF Sato, T.
Shibata, Y.
Yamamoto, M.
Kudo, M.
Kaneko, T.
Ishigatsubo, Y.
Klinman, D.
TI Effect Of Intratracheal Immunostimulatory-Oligonucleotides With
Biodegradable Polyketal Nanoparticles On Murine Lung Cancer
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Sato, T.; Shibata, Y.; Yamamoto, M.; Kudo, M.; Kaneko, T.; Ishigatsubo, Y.] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa 232, Japan.
[Klinman, D.] NCI, Frederick, MD 21701 USA.
EM takashisato1220@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A2426
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582802220
ER
PT J
AU Snyder, RJ
Hussain, S
Rice, AB
Miller-DeGraff, L
Randell, SH
Garantziotis, S
AF Snyder, R. J.
Hussain, S.
Rice, A. B.
Miller-DeGraff, L.
Randell, S. H.
Garantziotis, S.
TI Exposure To Multi-Walled Carbon Nanotubes May Impair Mucociliary
Differentiation Of Human Bronchial Epithelia In Air Liquid Interface
Culture
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Snyder, R. J.; Randell, S. H.] Univ N Carolina, Chapel Hill, NC USA.
[Hussain, S.; Rice, A. B.; Miller-DeGraff, L.; Garantziotis, S.] NIEHS, Durham, NC USA.
EM rjsnyder@email.unc.edu
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
NR 0
TC 0
Z9 0
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.
PY 2015
VL 191
MA A3228
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582803503
ER
PT J
AU Strollo, SE
Adjemian, J
Prevots, DR
AF Strollo, S. E.
Adjemian, J.
Prevots, D. R.
TI The Burden Of Pulmonary Nontuberculous Mycobacterial Disease In The
United States: State-Specific Case Estimates And Associated Cost
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Strollo, S. E.; Adjemian, J.; Prevots, D. R.] NIAID, NIH, Bethesda, MD 20892 USA.
EM sara.strollo@nih.gov
NR 0
TC 0
Z9 0
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.
PY 2015
VL 191
MA A5260
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582807079
ER
PT J
AU Taveira-DaSilva, AM
Julien-Williams, PA
Jones, AM
Moss, J
AF Taveira-DaSilva, A. M.
Julien-Williams, P. A.
Jones, A. M.
Moss, J.
TI Prevalence Of Pneumothoraces In Lymphangioleiomyomatosis Patients
Undergoing Pulmonary Function And Exercise Testing
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Taveira-DaSilva, A. M.; Julien-Williams, P. A.; Jones, A. M.; Moss, J.] NHLBI, NIH, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A1395
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800394
ER
PT J
AU Taveira-DaSilva, AM
Jones, A
Julien-Williams, P
Moss, J
AF Taveira-DaSilva, A. M.
Jones, A.
Julien-Williams, P.
Moss, J.
TI Long-Term Effect Of Sirolimus Treatment On Serum Levels Of VEGF-D In
Lymphangioleiomyomatosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Taveira-DaSilva, A. M.; Jones, A.; Julien-Williams, P.; Moss, J.] NHLBI, NIH, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A1394
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800393
ER
PT J
AU Thomas, SY
Whitehead, GS
Gowdy, KM
Ward, JM
Nakano, K
Malhotra, AF
Nakano, H
Cook, DN
AF Thomas, S. Y.
Whitehead, G. S.
Gowdy, K. M.
Ward, J. M.
Nakano, K.
Malhotra, A. F.
Nakano, H.
Cook, D. N.
TI Myd88-Dependent Epithelial And Dendritic Cell Signaling And Crosstalk
Trigger Distinct Types Of Allergic Inflammatory Responses In The Lung
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Thomas, S. Y.; Whitehead, G. S.; Ward, J. M.; Nakano, K.; Malhotra, A. F.; Nakano, H.; Cook, D. N.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Gowdy, K. M.] E Carolina Univ, Greenville, NC USA.
EM seddon.thomas@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A6432
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582807205
ER
PT J
AU Ventetuolo, CE
Mitra, N
Wan, F
Manichaikul, A
Barr, RG
Johnson, C
Bluemke, D
Lima, J
Tandri, H
Ouyang, P
Kawut, SM
AF Ventetuolo, C. E.
Mitra, N.
Wan, F.
Manichaikul, A.
Barr, R. G.
Johnson, C.
Bluemke, D.
Lima, J.
Tandri, H.
Ouyang, P.
Kawut, S. M.
TI Genetic Variation In Sex Hormone Pathways And Right Ventricular
Structure And Function: The Multi-Ethnic Study Of Atherosclerosis-Right
Ventricle Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Ventetuolo, C. E.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA.
[Ventetuolo, C. E.; Mitra, N.; Wan, F.] Univ Penn, Philadelphia, PA 19104 USA.
[Manichaikul, A.] Univ Virginia, Charlottesville, VA USA.
[Barr, R. G.] Columbia Univ, Med Ctr, New York, NY USA.
[Johnson, C.] Univ Washington, Seattle, WA 98195 USA.
[Bluemke, D.] NIH, Bethesda, MD 20892 USA.
[Lima, J.; Tandri, H.; Ouyang, P.] Johns Hopkins Univ, Baltimore, MD USA.
[Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A1042
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582800043
ER
PT J
AU Ventetuolo, CE
Baird, G
Barr, RG
Bluemke, D
Fritz, JS
Hill, NS
Klinger, JR
Krishnan, I
Lima, J
Ouyang, P
Palevsky, HI
Palmisciano, A
Pinder, D
Preston, IR
Roberts, KE
Kawut, SM
AF Ventetuolo, C. E.
Baird, G.
Barr, R. G.
Bluemke, D.
Fritz, J. S.
Hill, N. S.
Klinger, J. R.
Krishnan, I.
Lima, J.
Ouyang, P.
Palevsky, H. I.
Palmisciano, A.
Pinder, D.
Preston, I. R.
Roberts, K. E.
Kawut, S. M.
TI Sex Hormones In Men With Pulmonary Arterial Hypertension: A Case-Control
Study Using The Multi-Ethnic Study Of Atherosclerosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Ventetuolo, C. E.; Klinger, J. R.; Krishnan, I.; Palmisciano, A.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA.
[Baird, G.] Rhode Isl Hosp, Providence, RI USA.
[Barr, R. G.] Columbia Univ, Med Ctr, New York, NY USA.
[Bluemke, D.] NIH, Bethesda, MD 20892 USA.
[Fritz, J. S.; Palevsky, H. I.; Pinder, D.; Kawut, S. M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hill, N. S.; Preston, I. R.; Roberts, K. E.] Tufts Med Ctr, Boston, MA USA.
[Lima, J.; Ouyang, P.] Johns Hopkins, Baltimore, MD USA.
EM corey_ventetuolo@brown.edu
NR 0
TC 1
Z9 1
U1 0
U2 0
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.
PY 2015
VL 191
MA A4093
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582805152
ER
PT J
AU Wenger, DS
Ding, J
Barr, RG
Bluemke, DA
Hough, CL
Kronmal, R
Lima, J
Tracy, RP
Kawut, SM
Leary, PJ
AF Wenger, D. S.
Ding, J.
Barr, R. G.
Bluemke, D. A.
Hough, C. L.
Kronmal, R.
Lima, J.
Tracy, R. P.
Kawut, S. M.
Leary, P. J.
TI Relationship Of Pericardial Fat With Right Ventricular Structure And
Function: The Multi-Ethnic Study Of Atherosclerosis- Right Ventricle
Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Wenger, D. S.; Kronmal, R.; Kawut, S. M.; Leary, P. J.] Univ Washington, Seattle, WA 98195 USA.
[Ding, J.] Wake Forest Sch Med, Winston Salem, NC USA.
[Barr, R. G.] Columbia Univ, Med Ctr, New York, NY USA.
[Bluemke, D. A.] NIH, Bethsda, MD USA.
[Hough, C. L.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA.
[Lima, J.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Tracy, R. P.] Univ Vermont, Burlington, VT USA.
[Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A4855
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582806289
ER
PT J
AU Wills, A
Adjemian, J
Manganiello, VC
Fontanta, JR
Prevots, DR
AF Wills, A.
Adjemian, J.
Manganiello, V. C.
Fontanta, J. R.
Prevots, D. R.
TI Prevalence Of Sarcoidosis Among U.s. Medicare Part B Beneficiaries Aged
>= 65 Years, 2000-2007
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Wills, A.; Adjemian, J.; Prevots, D. R.] NIAID, Epidemiol Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Wills, A.; Manganiello, V. C.; Fontanta, J. R.] NHLBI, NIH, Bethesda, MD 20892 USA.
EM aprielle.wills@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A3751
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582804393
ER
PT J
AU Winthrop, KL
Eagle, G
McGinnis, JP
Micioni, L
Daley, CL
Ruoss, SJ
Addrizzo-Harris, DJ
Flume, PA
Dorgan, DJ
Salathe, M
Brown-Elliott, BA
Wallace, RJ
Griffith, DE
Olivier, KN
AF Winthrop, K. L.
Eagle, G.
McGinnis, J. P.
Micioni, L.
Daley, C. L.
Ruoss, S. J.
Addrizzo-Harris, D. J.
Flume, P. A.
Dorgan, D. J.
Salathe, M.
Brown-Elliott, B. A.
Wallace, R. J.
Griffith, D. E.
Olivier, K. N.
TI Subgroup Analyses Of Baseline Demographics And Efficacy In Patients With
Refractory Nontuberculous Mycobacteria (ntm) Lung Infection Treated With
Liposomal Amikacin For Inhalation (lai)
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Eagle, G.; McGinnis, J. P.; Micioni, L.] Insmed Inc, Bridgewater, NJ USA.
[Daley, C. L.] Natl Jewish Hlth, Denver, CO USA.
[Ruoss, S. J.] Stanford Univ, Stanford, CA 94305 USA.
[Addrizzo-Harris, D. J.] NYU, Sch Med, New York, NY USA.
[Flume, P. A.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Dorgan, D. J.] Univ Penn, Philadelphia, PA 19104 USA.
[Salathe, M.] Univ Miami, Miami, FL USA.
[Brown-Elliott, B. A.] Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA.
[Wallace, R. J.] Univ Texas Hlth Sci Ctr, Tyler, TX USA.
[Griffith, D. E.] Univ Texas Hlth Ctr Tyler, Tyler, TX USA.
[Olivier, K. N.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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.
PY 2015
VL 191
MA A6294
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582808529
ER
PT J
AU Wyss, AB
House, JS
Hoppin, JA
Henneberger, PK
London, S
AF Wyss, A. B.
House, J. S.
Hoppin, J. A.
Henneberger, P. K.
London, S.
CA Agr Lung Hlth Study
TI Raw Milk Consumption And Pulmonary Function In Adults In The
Agricultural Lung Health Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Wyss, A. B.; House, J. S.; London, S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Wyss, A. B.; Hoppin, J. A.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Henneberger, P. K.] NIOSH, Morgantown, WV USA.
NR 0
TC 0
Z9 0
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.
PY 2015
VL 191
MA A4675
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582806110
ER
PT J
AU Yan, X
Chu, JH
Gomez, JL
Koenigs, M
Holm, C
He, X
Perez, MF
Zhao, H
Mane, S
Martinez, FD
Ober, C
Nicolae, DL
Barnes, KC
London, SJ
Gilliland, FD
Weiss, ST
Raby, BA
Cohn, LE
Chupp, GL
AF Yan, X.
Chu, J. -H.
Gomez, J. L.
Koenigs, M.
Holm, C.
He, X.
Perez, M. F.
Zhao, H.
Mane, S.
Martinez, F. D.
Ober, C.
Nicolae, D. L.
Barnes, K. C.
London, S. J.
Gilliland, F. D.
Weiss, S. T.
Raby, B. A.
Cohn, L. E.
Chupp, G. L.
TI Non-Invasive Analysis Of The Airway Transcriptome Discriminates Clinical
Phenotypes Of Asthma
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Yan, X.; Gomez, J. L.; Holm, C.; He, X.; Perez, M. F.; Mane, S.; Cohn, L. E.; Chupp, G. L.] Yale Univ, Sch Med, New Haven, CT USA.
[Yan, X.; Chu, J. -H.; Weiss, S. T.; Raby, B. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Koenigs, M.] Ohio State Univ, Columbus, OH 43210 USA.
[Zhao, H.] Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT USA.
[Martinez, F. D.] Univ Arizona, Tucson, AZ USA.
[Ober, C.] Unviers Chicago, Chicago, IL USA.
[Nicolae, D. L.] Univ Chicago, Chicago, IL 60637 USA.
[Barnes, K. C.] Johns Hopkins, Baltimore, MD USA.
[London, S. J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Gilliland, F. D.] Univ So Calif, Los Angeles, CA USA.
EM xiting.yan@yale.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A6056
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582808305
ER
PT J
AU Yang, IV
Pedersen, BS
Liu, A
O'Connor, GT
Teach, SJ
Kattan, M
Misiak, RT
Gruchalla, R
Steinbach, SF
Szefler, SJ
Gill, MA
Calatroni, A
David, G
Hennessy, CE
Davidson, EJ
Gergen, P
Togias, A
Busse, WW
Schwartz, DA
AF Yang, I. V.
Pedersen, B. S.
Liu, A.
O'Connor, G. T.
Teach, S. J.
Kattan, M.
Misiak, R. T.
Gruchalla, R.
Steinbach, S. F.
Szefler, S. J.
Gill, M. A.
Calatroni, A.
David, G.
Hennessy, C. E.
Davidson, E. J.
Gergen, P.
Togias, A.
Busse, W. W.
Schwartz, D. A.
TI Dna Methylation Changes In Nasal Epithelia Assoicated With Allergic
Asthma In The Inner City
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Yang, I. V.; Hennessy, C. E.; Davidson, E. J.] Univ Colorado, Aurora, CO USA.
[Pedersen, B. S.; Schwartz, D. A.] Univ Colorado, Denver, CO 80202 USA.
[Liu, A.; Szefler, S. J.] Natl Jewish Hlth, Denver, CO USA.
[O'Connor, G. T.; Steinbach, S. F.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Teach, S. J.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Kattan, M.] Columbia Univ, Med Ctr, New York, NY USA.
[Misiak, R. T.] Henry Ford Hosp, Detroit, MI 48202 USA.
[Gruchalla, R.] Univ Texas Southwestern Med Sch, Dallas, TX USA.
[Gill, M. A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Calatroni, A.; David, G.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Gergen, P.; Togias, A.] NIAID, Bethesda, MD 20892 USA.
[Busse, W. W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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.
PY 2015
VL 191
MA A5379
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582807247
ER
PT J
AU Yang, JX
Parikh, M
Carr, J
Gomes, A
Habibi, M
Hueper, K
Hoffman, EA
Lima, J
Kawut, SM
Prince, M
Smith, B
Swift, AJ
Sun, Y
Vogel-Claussen, J
Wild, JM
Bluemke, DM
Barr, RG
AF Yang, J. X.
Parikh, M.
Carr, J.
Gomes, A.
Habibi, M.
Hueper, K.
Hoffman, E. A.
Lima, J.
Kawut, S. M.
Prince, M.
Smith, B.
Swift, A. J.
Sun, Y.
Vogel-Claussen, J.
Wild, J. M.
Bluemke, D. M.
Barr, R. G.
TI Cardiac Hemodynamics In COPD And Emphysema Estimated By Magnetic
Resonance Imaging
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 15-20, 2015
CL Denver, CO
SP Amer Thorac Soc
C1 [Yang, J. X.; Prince, M.; Sun, Y.; Barr, R. G.] Columbia Univ, Med Ctr, New York, NY USA.
[Parikh, M.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Carr, J.] Northwestern Univ, Chicago, IL 60611 USA.
[Gomes, A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Habibi, M.; Hueper, K.] Johns Hopkins Univ, Baltimore, MD USA.
[Hoffman, E. A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Lima, J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Swift, A. J.; Wild, J. M.] Univ Sheffield, Sheffield, S Yorkshire, England.
[Vogel-Claussen, J.] Hannover Med Sch, Hannover, Germany.
[Bluemke, D. M.] NIH, Bethesda, MD 20892 USA.
EM jxy2002@columbia.edu
NR 0
TC 0
Z9 0
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.
PY 2015
VL 191
MA A6380
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO2AW
UT WOS:000377582803349
ER
PT S
AU Berezovskaya, FS
Karev, GP
AF Berezovskaya, Faina S.
Karev, Georgiy P.
BE Cojocaru, MG
Kotsireas, IS
Makarov, RN
Melnik, RVN
Shodiev, H
TI Stabilizing Role of Predators in Niche Construction Modeling
SO INTERDISCIPLINARY TOPICS IN APPLIED MATHEMATICS, MODELING AND
COMPUTATIONAL SCIENCE
SE Springer Proceedings in Mathematics & Statistics
LA English
DT Proceedings Paper
CT Interdisciplinary International Conference on Applied Mathematics,
Modelling and Computational Science (AMMCS)
CY AUG 26-30, 2013
CL Wilfrid Laurier Univ, Waterloo Campus, Waterloo, CANADA
HO Wilfrid Laurier Univ, Waterloo Campus
AB In this chapter a question of "how much over-consumption a renewable resource can tolerate" is addressed using a mathematical model, where a consumer population competes for the common resource, can contribute to resource restoration, and is subject to attacks of predators. The bifurcation analysis of the system shows that well-adapted predators can keep the system in a stable equilibrium even for "strong" prey over-consumption, when the initial system of resource-consumer goes to extinct. Thus, predators may extend the domain of total model system coexistence in niche.
C1 [Berezovskaya, Faina S.] Howard Univ, Dept Math, Washington, DC 20059 USA.
[Karev, Georgiy P.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Berezovskaya, FS (reprint author), Howard Univ, Dept Math, Washington, DC 20059 USA.
EM fberezovskaya@howard.edu; karev@ncbi.nlm.nih.gov
NR 6
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 2194-1009
BN 978-3-319-12307-3; 978-3-319-12306-6
J9 SPRINGER P MATH STAT
PY 2015
VL 117
BP 73
EP 79
DI 10.1007/978-3-319-12307-3_11
PG 7
WC Mathematics, Applied; Mathematics; Statistics & Probability
SC Mathematics
GA BE9FG
UT WOS:000377391500011
ER
PT J
AU Drgonova, J
Walther, D
Wang, KJ
Hartstein, GL
Lochte, B
Troncoso, J
Uetani, N
Iwakura, Y
Uhl, GR
AF Drgonova, Jana
Walther, Donna
Wang, Katherine J.
Hartstein, G. Luke
Lochte, Bryson
Troncoso, Juan
Uetani, Noriko
Iwakura, Yoichiro
Uhl, George R.
TI Mouse Model for Protein Tyrosine Phosphatase D (PTPRD) Associations with
Restless Leg Syndrome or Willis-Ekbom Disease and Addiction: Reduced
Expression Alters Locomotion, Sleep Behaviors and Cocaine-Conditioned
Place Preference
SO MOLECULAR MEDICINE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SMOKING-CESSATION SUCCESS; MOLECULAR-GENETICS;
NICOTINE REPLACEMENT; ALCOHOL DEPENDENCE; MICE; DELTA; TRIAL;
PARTICIPANTS; KNOCKOUT
AB The receptor type protein tyrosine phosphatase D (PTPRD) gene encodes a cell adhesion molecule likely to influence development and connections of addiction-, locomotion-and sleep-related brain circuits in which it is expressed. The PTPRD gene harbors genome-wide association signals in studies of restless leg syndrome (Willis-Ekbom disease [WED]/restless leg syndrome [RLS]; p < 10(-8)) and addiction-related phenotypes (clusters of nearby single nucleotide polymorphisms [SNPs] with 10(-2) > p > 10(-8) associations in several reports). We now report work that seeks (a) association between PTPRD genotypes and expression of its mRNA in postmortem human brains and (b) RLS-related, addiction-related and comparison behavioral phenotypes in hetero-and homozygous PTPRD knockout mice. We identify associations between PTPRD SNPs and levels of PTPRD mRNA in human brain samples that support validity of mouse models with altered PTPRD expression. Knockouts display less behaviorally defined sleep at the end of their active periods. Heterozygotes move more despite motor weakness/impersistence. Heterozygotes display shifted dose-response relationships for cocaine reward. They display greater preference for places paired with 5 mg/kg cocaine and less preference for places paired with 10 or 20 mg/kg. The combined data provide support for roles for common, level-of-expression PTPRD variation in locomotor, sleep and drug reward phenotypes relevant to RLS and addiction. Taken together, mouse and human results identify PTPRD as a novel therapeutic target for RLS and addiction phenotypes.
C1 [Drgonova, Jana; Walther, Donna; Wang, Katherine J.; Hartstein, G. Luke; Lochte, Bryson; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, Intramural Res Program, Baltimore, MD USA.
[Troncoso, Juan] Johns Hopkins Sch Med, Div Neuropathol, Baltimore, MD USA.
[Uetani, Noriko] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Montreal, PQ, Canada.
[Iwakura, Yoichiro] Univ Tokyo, Ctr Med Expt, Tokyo, Japan.
[Uhl, George R.] New Mexico VA Hlth Care Syst, Res, Albuquerque, NM USA.
RP Uhl, GR (reprint author), NMVAHCS, Res, Albuquerque, NM 87108 USA.
EM guhl@intra.nida.nih.gov
RI Iwakura, Yoichiro/E-5457-2011
OI Iwakura, Yoichiro/0000-0002-9934-5775
FU NIH-IRP; NIDA; U.S. Department of Health and Human Services (HHS); New
Mexico VA Health Care System (NMVAHCS)
FX This work was supported by the NIH-IRP, NIDA, U.S. Department of Health
and Human Services (HHS) (GR Uhl) and by New Mexico VA Health Care
System (NMVAHCS) (GR Uhl). We are grateful for help from C Johnson, D
Arking, D Naimen, J Bader and J Schroder; for access to brain samples
from the University of Maryland Brain Tissue Bank; and for access to
data for PTPRD from A Hart and A Palmer. All human and/or animal studies
were approved by the appropriate institutional committees.
NR 38
TC 1
Z9 1
U1 5
U2 5
PU FEINSTEIN INST MED RES
PI MANHASSET
PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA
SN 1076-1551
EI 1528-3658
J9 MOL MED
JI Mol. Med.
PY 2015
VL 21
BP 717
EP 725
DI 10.2119/molmed.2015.00017
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DN7QE
UT WOS:000377271200004
ER
PT J
AU Djoumerska-Alexieva, I
Roumenina, L
Pashov, A
Dimitrov, J
Hadzhieva, M
Lindig, S
Voynova, E
Dimitrova, P
Ivanovska, N
Bockmeyer, C
Stefanova, Z
Fitting, C
Blass, M
Claus, R
von Gunten, S
Kaveri, S
Cavaillon, JM
Bauer, M
Vassilev, T
AF Djoumerska-Alexieva, Iglika
Roumenina, Lubka
Pashov, Anastas
Dimitrov, Jordan
Hadzhieva, Maya
Lindig, Sandro
Voynova, Elisaveta
Dimitrova, Petya
Ivanovska, Nina
Bockmeyer, Clemens
Stefanova, Zvetanka
Fitting, Catherine
Blaess, Markus
Claus, Ralf
von Gunten, Stephan
Kaveri, Srini
Cavaillon, Jean-Marc
Bauer, Michael
Vassilev, Tchavdar
TI Intravenous Immunoglobulin with Enhanced Polyspecificity Improves
Survival in Experimental Sepsis and Aseptic Systemic Inflammatory
Response Syndromes
SO MOLECULAR MEDICINE
LA English
DT Article
ID SEPTIC SHOCK; IVIG PREPARATIONS; IMMUNE GLOBULIN; COMPLEMENT;
METAANALYSIS; ACTIVATION; MECHANISMS; ANTIBODIES; DISEASES; BINDING
AB Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as "genomic storm" in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous "danger" signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes.
C1 [Djoumerska-Alexieva, Iglika; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Dimitrova, Petya; Ivanovska, Nina; Stefanova, Zvetanka; Vassilev, Tchavdar] Bulgarian Acad Sci, Dept Immunol, Stefan Angelov Inst Microbiol, 26 Acad Georgi Bonchev St, Sofia 1113, Bulgaria.
[Roumenina, Lubka; Dimitrov, Jordan; Kaveri, Srini] INSERM UMRS 1138, Ctr Rech Cordeliers, Paris, France.
[Lindig, Sandro; Blaess, Markus; Claus, Ralf; Bauer, Michael; Vassilev, Tchavdar] Univ Jena, Univ Hosp, Ctr Sepsis Control & Care, Jena, Germany.
[Voynova, Elisaveta] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Bockmeyer, Clemens] Hannover Med Sch, Inst Pathol, Hannover, Germany.
[Fitting, Catherine; Cavaillon, Jean-Marc] Inst Pasteur, Cytokines & Inflammat Unit, Paris, France.
[von Gunten, Stephan] Univ Bern, Inst Pharmacol, Bern, Switzerland.
RP Vassilev, T (reprint author), Bulgarian Acad Sci, Dept Immunol, Stefan Angelov Inst Microbiol, 26 Acad Georgi Bonchev St, Sofia 1113, Bulgaria.
EM vassilev@microbio.bas.bg
RI Dimitrov, Jordan/N-2141-2014
FU Bulgarian-Swiss Research Programme [BSRP IZEBZO_142967]; Bulgarian
National Science Fund [DFNI B02/29]; Pasteur Institute [ACIP A07-2012];
NATO Science for Peace Program [SfP 982158]; German Federal Ministry of
Education and Research (BMBF) [01EO1002, 03Z2J521]
FX This work was supported by grants from the Bulgarian-Swiss Research
Programme (BSRP IZEBZO_142967), the Bulgarian National Science Fund
(DFNI B02/29), the Pasteur Institute (ACIP A07-2012), the NATO Science
for Peace Program (SfP 982158), and the German Federal Ministry of
Education and Research (BMBF; grant 01EO1002) and grant 03Z2J521
(Meta-ZIK), both to the Centre for Sepsis Control and Care. We thank D
Himsel for technical assistance.
NR 38
TC 2
Z9 2
U1 2
U2 2
PU FEINSTEIN INST MED RES
PI MANHASSET
PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA
SN 1076-1551
EI 1528-3658
J9 MOL MED
JI Mol. Med.
PY 2015
VL 21
BP 1002
EP 1010
DI 10.2119/molmed.2014.00224
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DN7QE
UT WOS:000377271200031
ER
PT J
AU Etemadi, A
Abnet, C
Kamangar, F
Wacholder, S
Islami, F
Brennan, P
Boffetta, P
Malekzadeh, R
Dawsey, S
AF Etemadi, A.
Abnet, C.
Kamangar, F.
Wacholder, S.
Islami, F.
Brennan, P.
Boffetta, P.
Malekzadeh, R.
Dawsey, S.
TI Impact of Body Size and Physical Activity during Adolescence and Adult
Life on Overall and Cause-specific Mortality in a Large Cohort Study
from Iran
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th IEA World Congress of Epidemiology (WCE)
CY AUG 17-21, 2014
CL Anchorage, AK
SP Int Epidemiol Assoc
C1 [Etemadi, A.; Abnet, C.; Wacholder, S.; Dawsey, S.] NCI, Bethesda, MD 20892 USA.
[Etemadi, A.; Islami, F.; Malekzadeh, R.] Univ Tehran Med Sci, Tehran, Iran.
[Kamangar, F.] Morgan State Univ, Baltimore, MD 21239 USA.
[Brennan, P.] Int Agcy Res Canc, Lyon, MD USA.
[Boffetta, P.] Mt Sinai Sch Med, New York, NY USA.
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PY 2015
VL 44
SU 1
MA 2480
BP 79
EP 79
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM9BV
UT WOS:000376659900178
ER
PT J
AU Alvarez-Hernandez, G
Murillo-Benitez, C
Candia-Plata, MC
Moro, M
AF Alvarez-Hernandez, G.
Murillo-Benitez, C.
Candia-Plata, M. C.
Moro, M.
TI Rocky Mountain Spotted Fever Reemergence in children from Sonora,
Mexico. 2004-12.
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th IEA World Congress of Epidemiology (WCE)
CY AUG 17-21, 2014
CL Anchorage, AK
SP Int Epidemiol Assoc
C1 [Alvarez-Hernandez, G.; Candia-Plata, M. C.] Univ Sonora, Hermosillo 83000, Sonora, Mexico.
[Murillo-Benitez, C.] Inst Tecnolo & Estudios Super Monterrey, Monterrey, Mexico.
[Moro, M.] 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 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PY 2015
VL 44
SU 1
MA 3030
BP 243
EP 243
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM9BV
UT WOS:000376659900631
ER
PT J
AU Hoffman, HJ
Li, CM
Bainbridge, KE
Losonczy, KG
Chiu, MS
Rice, ML
AF Hoffman, H. J.
Li, C. M.
Bainbridge, K. E.
Losonczy, K. G.
Chiu, M. S.
Rice, M. L.
TI Voice, Speech, and Language Problems in the US Pediatric Population: The
2012 National Health Interview Survey (NHIS).
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th IEA World Congress of Epidemiology (WCE)
CY AUG 17-21, 2014
CL Anchorage, AK
SP Int Epidemiol Assoc
C1 [Hoffman, H. J.; Li, C. M.; Bainbridge, K. E.; Losonczy, K. G.; Chiu, M. S.] NIDCD, NIH, Bethesda, MD USA.
[Rice, M. L.] Univ Kansas, Lawrence, KS 66045 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 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PY 2015
VL 44
SU 1
MA 3852
BP 260
EP 260
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM9BV
UT WOS:000376659900680
ER
PT S
AU Demner-Fushman, D
Shooshan, SE
Rodriguez, L
Antani, S
Thoma, GR
AF Demner-Fushman, Dina
Shooshan, Sonya E.
Rodriguez, Laritza
Antani, Sameer
Thoma, George R.
BE Muller, H
DelToro, OAJ
Hanbury, A
Langs, G
Rodriguez, AF
TI Annotation of Chest Radiology Reports for Indexing and Retrieval
SO MULTIMODAL RETRIEVAL IN THE MEDICAL DOMAIN, MRMD 2015
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 1st International Workshop on Multimodal Retrieval in the Medical Domain
(MRMD)
CY MAR 29, 2015
CL Vienna, AUSTRIA
DE Information storage and retrieval; Vocabulary; controlled; Radiology
ID DISEASES
AB Annotation of MEDLINE citations with controlled vocabulary terms improves the quality of retrieval results. Due to variety in descriptions of similar clinical phenomena and abundance of negation and uncertainty, annotation of clinical radiology reports for subsequent indexing and retrieval with a search engine is even more important. Provided with an opportunity to add about 4,000 radiology reports to collections indexed with NLM image retrieval engine Open-i, we needed to assure good retrieval quality. To accomplish this, we explored automatic and manual approaches to annotation, as well as developed a small controlled vocabulary of chest x-ray indexing terms and guidelines for manual annotation. Manual annotation captured the most salient findings in the reports and normalized the sparse distinct descriptions of similar findings to one controlled vocabulary term. This paper presents the vocabulary and the manual annotation process, as well as an evaluation of the automatic annotation of the reports.
C1 [Demner-Fushman, Dina; Shooshan, Sonya E.; Rodriguez, Laritza; Antani, Sameer; Thoma, George R.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA.
RP Demner-Fushman, D (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA.
EM ddemner@mail.nih.gov; sshooshan@mail.nih.gov; rodriguezlm2@mail.nih.gov;
santani@mail.nih.gov; gthoma@mail.nih.gov
NR 22
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24471-6; 978-3-319-24470-9
J9 LECT NOTES COMPUT SC
PY 2015
VL 9059
BP 99
EP 111
DI 10.1007/978-3-319-24471-6_9
PG 13
WC Computer Science, Artificial Intelligence; Computer Science, Information
Systems; Computer Science, Theory & Methods; Medical Informatics
SC Computer Science; Medical Informatics
GA BE7EI
UT WOS:000375149600009
ER
PT S
AU Cruz-Chan, JV
Valenzuela, J
Dumonteil, E
AF Vladimir Cruz-Chan, Julio
Valenzuela, Jesus
Dumonteil, Eric
BE FrancoParedes, C
SantosPreciado, JI
TI Leishmaniasis in the Americas
SO NEGLECTED TROPICAL DISEASES - LATIN AMERICA AND THE CARIBBEAN
SE Neglected Tropical Diseases
LA English
DT Article; Book Chapter
DE Leishmania; Sand fly; Lutzomyia; Visceral leishmaniasis; Cutaneous
leishmaniasis; New world
ID VISCERAL-LEISHMANIASIS; CUTANEOUS LEISHMANIASIS; CANINE LEISHMANIASIS;
NEW-WORLD; TEGUMENTARY LEISHMANIASIS; CHICLEROS ULCER; SAND FLIES;
MOLECULAR EPIDEMIOLOGY; MUCOSAL LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS
AB Leishmaniasis is a neglected tropical disease caused by kinetoplastid protozoan parasites belonging to the Leishmania genus. Infection causes a wide diversity of clinical manifestations, ranging in severity from asymptomatic infections, self-healing cutaneous lesions (cutaneous leishmaniasis (CL)), mucocutaneous lesions (mucocutaneous leishmaniasis (MCL)), diffuse leishmaniasis, and visceral leishmaniasis (VL) which can be lethal when untreated. Leishmania parasites are transmitted to vertebrate hosts through the bite of female sandflies of the genus Lutzomyia in the New World. We review here some of the key aspects of leishmaniasis in Latin America and highlight some of the specificities of the disease in the American continent. The diversity of vector and parasite species poses additional challenges compared to the situation in the Old World. Indeed, this diversity implies that most tools for disease surveillance and control, including diagnostics, vector control interventions, therapeutic treatments, and vaccines, need to be adapted to ensure their efficacy. Further research is thus needed to optimize leishmaniasis control and surveillance in the Americas.
C1 [Vladimir Cruz-Chan, Julio; Dumonteil, Eric] Univ Autonoma Yucatan, Ctr Invest Reg Dr Hideyo Noguchi, Lab Parasitol, Ave Itzaes 490 X 59, Merida 97000, Yucatan, Mexico.
[Valenzuela, Jesus] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Dumonteil, Eric] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA 70118 USA.
RP Dumonteil, E (reprint author), Univ Autonoma Yucatan, Ctr Invest Reg Dr Hideyo Noguchi, Lab Parasitol, Ave Itzaes 490 X 59, Merida 97000, Yucatan, Mexico.
EM oliver@uady.mx
NR 79
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 2194-8275
BN 978-3-7091-1422-3; 978-3-7091-1421-6
J9 NEGLECT TROP DIS
PY 2015
BP 113
EP 128
DI 10.1007/978-3-7091-1422-3_6
D2 10.1007/978-3-7091-1422-3
PG 16
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA BE6QN
UT WOS:000374638500007
ER
PT S
AU Varshney, GK
Sood, R
Burgess, SM
AF Varshney, Gaurav K.
Sood, Raman
Burgess, Shawn M.
BE Friedmann, T
Dunlap, JC
Goodwin, SF
TI Understanding and Editing the Zebrafish Genome
SO ADVANCES IN GENETICS, VOL 92
SE Advances in Genetics
LA English
DT Review; Book Chapter
ID ZINC-FINGER NUCLEASES; DEVELOPMENTAL GENE-EXPRESSION; ENU-INDUCED
MUTATIONS; TARGETED MUTAGENESIS; IN-VIVO; INSERTIONAL MUTAGENESIS;
CRISPR/CAS9 SYSTEM; TAL EFFECTORS; HUMAN-DISEASE; DNA-CLEAVAGE
AB In the last two decades, zebrafish has become one of the fastest growing model organisms in terms of publications, however it has been plagued with the absence of a key tool in the genetics toolbox: the ability to systematically make targeted mutations in the genome. That all changed with the recent emergence of custom-built, sequence-specific nucleases, i.e., zinc finger nucleases (ZFNs), TAL-effector nucleases (TALENs), or clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas9. Here, we provide a comprehensive review of the application of these genome-editing tools to generate targeted knockout and knock-in mutants in zebrafish. These technologies have allowed us to transition from targeted knockouts in zebrafish being a difficult, resource intensive undertaking, to something that can be done in virtually any lab with modest molecular biology experience. Furthermore, this review provides a comprehensive listing of genetic and genomic resources and online tools that zebrafish researchers can use to help find a desired mutation or design effective ZFNs, TALENs, or CRISPR guide RNAs for their targeting experiments.
C1 [Varshney, Gaurav K.; Sood, Raman; Burgess, Shawn M.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Burgess, SM (reprint author), NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
EM burgess@mail.nih.gov
OI Varshney, Gaurav K./0000-0002-0429-1904
FU Intramural NIH HHS
NR 190
TC 8
Z9 8
U1 6
U2 12
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0065-2660
BN 978-0-12-804079-9; 978-0-12-804014-0
J9 ADV GENET
JI Adv. Genet.
PY 2015
VL 92
BP 1
EP 52
DI 10.1016/bs.adgen.2015.09.002
PG 52
WC Genetics & Heredity
SC Genetics & Heredity
GA BE8AJ
UT WOS:000376148000001
PM 26639914
ER
PT S
AU Le Roy, A
Wang, K
Schaack, B
Schuck, P
Breyton, C
Ebel, C
AF Le Roy, Aline
Wang, Kai
Schaack, Beatrice
Schuck, Peter
Breyton, Cecile
Ebel, Christine
BE Cole, JL
TI AUC and Small-Angle Scattering for Membrane Proteins
SO ANALYTICAL ULTRACENTRIFUGATION
SE Methods in Enzymology
LA English
DT Review; Book Chapter
ID VELOCITY ANALYTICAL ULTRACENTRIFUGATION; DETECTED
SEDIMENTATION-VELOCITY; DETERGENT-SOLUBILIZED STATE; SIZE-DISTRIBUTION
ANALYSIS; RECEPTOR-BINDING PROTEIN; NEUTRON-SCATTERING; X-RAY;
MOLECULAR-WEIGHT; STRUCTURAL-CHARACTERIZATION; SAXS DATA
AB Analytical ultracentrifugation is a key tool to assess homogeneity of membrane protein samples, to determine protein association state and detergent concentration, and to characterize protein-protein equilibrium. Combining absorbance and interference detections gives information on the amount of the detergent and lipid bound to proteins. Changing the solvent density affects specifically the buoyancy of each of the different components, and can also be used to gain information on particle composition and interaction. We will present the related tools, recently implemented in the softwares Sedphat (sedfitsedphat.nibib.nih.gov/software) and Gussi (http://biophysics.swmed.edu/MBR/software.html), which help to measure the amount of detergent bound to the protein, and ascertain the protein association state within the protein-detergent complex. In addition, fluorescence detection allows focusing specifically on a labeled component within a complex mixture. We present two examples of sedimentation velocity experiments, allowing on one hand to evidence complex formation between an unpurified GFP-labeled protein and a membrane protein, and on the other hand to characterize fluorescent lipid vesicles. Small-angle X-ray and neutron scattering are techniques that give insights into the structure and conformation of macromolecules in solution. However, the detergents used to purify membrane protein are often imperfectly masked due to their amphipathic character. Particular strategies addressing membrane proteins were recently proposed, which are shortly presented.
C1 [Le Roy, Aline; Wang, Kai; Schaack, Beatrice; Breyton, Cecile; Ebel, Christine] Univ Grenoble Alpes, IBS, Grenoble, France.
[Le Roy, Aline; Wang, Kai; Schaack, Beatrice; Breyton, Cecile; Ebel, Christine] CNRS, IBS, Grenoble, France.
[Le Roy, Aline; Wang, Kai; Schaack, Beatrice; Breyton, Cecile; Ebel, Christine] CEA, IBS, Grenoble, France.
[Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA.
RP Ebel, C (reprint author), Univ Grenoble Alpes, IBS, Grenoble, France.
EM christine.ebel@ibs.fr
OI Schuck, Peter/0000-0002-8859-6966
FU Intramural NIH HHS
NR 59
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0076-6879
BN 978-0-12-802909-1; 978-0-12-802908-4
J9 METHOD ENZYMOL
JI Methods Enzymol.
PY 2015
VL 562
BP 257
EP 286
DI 10.1016/bs.mie.2015.06.010
PG 30
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE8AP
UT WOS:000376153000013
PM 26412656
ER
PT S
AU Sastry, M
Bewley, CA
Kwong, PD
AF Sastry, Mallika
Bewley, Carole A.
Kwong, Peter D.
BE Kelman, Z
TI Effective Isotope Labeling of Proteins in a Mammalian Expression System
SO ISOTOPE LABELING OF BIOMOLECULES - LABELING METHODS
SE Methods in Enzymology
LA English
DT Review; Book Chapter
ID DICTYOSTELIUM-DISCOIDEUM; NMR-SPECTROSCOPY; HUMAN CD2; RESONANCE
ASSIGNMENTS; ADHESION DOMAIN; MESSENGER-RNAS; HSQC-SPECTRA; CELL-LINES;
ADENOVIRUS; VECTORS
AB Isotope labeling of biologically interesting proteins is a prerequisite for structural and dynamics studies by NMR spectroscopy. Many of these proteins require mammalian cofactors, chaperons, or posttranslational modifications such as myristoylation, glypiation, disulfide bond formation, or N- or O-linked glycosylation; and mammalian cells have the necessary machinery to produce them in their functional forms. Here, we describe recent advances in mammalian expression, including an efficient adenoviral vector-based system, for the production of isotopically labeled proteins. This system enables expression of mammalian proteins and their complexes, including proteins that require posttranslational modifications. We describe a roadmap to produce isotopically labeled N-15 and C-13 posttranslationally modified proteins, such as the outer domain of HIV-1 gp120, which has four disulfide bonds and 15 potential sites of N-linked glycosylation. These methods should allow NMR spectroscopic analysis of the structure and function of posttranslationally modified and secreted, cytoplasmic, or membrane-bound proteins.
C1 [Sastry, Mallika; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bewley, Carole A.] Natl Inst Diabet & Digest & Kidney Dis, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
RP Sastry, M (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sastrym@niaid.nih.gov; CaroleB@mail.nih.gov; pdkwong@nih.gov
NR 68
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0076-6879
BN 978-0-12-803080-6; 978-0-12-803048-6
J9 METHOD ENZYMOL
JI Methods Enzymol.
PY 2015
VL 565
BP 289
EP 307
DI 10.1016/bs.mie.2015.09.021
PG 19
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE8AO
UT WOS:000376152000013
PM 26577736
ER
PT S
AU Kumari, G
Sen, R
AF Kumari, Gita
Sen, Ranjan
BE Murre, C
TI Chromatin Interactions in the Control of Immunoglobulin Heavy Chain Gene
Assembly
SO MOLECULAR MECHANISMS THAT ORCHESTRATE THE ASSEMBLY OF ANTIGEN RECEPTOR
LOCI
SE Advances in Immunology
LA English
DT Review; Book Chapter
ID HISTONE LYSINE METHYLATION; CLASS-SWITCH RECOMBINATION;
B-CELL-DEVELOPMENT; ANTISENSE INTERGENIC TRANSCRIPTION; NUCLEAR LAMINA
INTERACTIONS; 3' REGULATORY REGION; CIS-ACTING ELEMENTS; V(D)J
RECOMBINATION; IGH LOCUS; INTRONIC ENHANCER
AB Expression of antibody heavy chain occurs via precisely timed developmental activation of the immunoglobulin heavy chain (IgH) gene locus during B cell development. IgH locus activation permits coordinated gene rearrangements that assemble variable (V-H), diversity (D-H), and joining (J(H)) gene segments into functional genes. Chromosomal conformation changes and epigenetic mechanisms play critical roles in ensuring rearrangement fidelity while minimizing hazardous consequences of broken DNA ends generated during recombination. In this review, we summarize the current status of regulatory mechanisms that underpin effective IgH gene assembly. For this, the germline locus is divided into two parts: a 2.4 Mb 50 part that contains all V-H gene segments and a 300 kb 30 domain that contains D-H and J(H) gene segments, as well as exons that encode IgH isotypes. Structural features of each part are discussed individually, followed by consideration of how the two parts come together to complete IgH recombination. Throughout we emphasize current insights, propose plausible mechanisms, and highlight key questions for future studies.
C1 [Kumari, Gita; Sen, Ranjan] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
RP Sen, R (reprint author), NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
EM senranja@grc.nia.nih.gov
FU Intramural NIH HHS
NR 199
TC 3
Z9 3
U1 3
U2 3
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0065-2776
BN 978-0-12-803330-2; 978-0-12-803296-1
J9 ADV IMMUNOL
JI Adv.Immunol.
PY 2015
VL 128
BP 41
EP 92
DI 10.1016/bs.ai.2015.08.001
PG 52
WC Immunology
SC Immunology
GA BE8AN
UT WOS:000376151400003
PM 26477365
ER
PT S
AU Zhang, JW
Ferre-D'Amare, AR
AF Zhang, Jinwei
Ferre-D'Amare, Adrian R.
BE Ponchon, L
TI Post-crystallization Improvement of RNA Crystal Diffraction Quality
SO RNA SCAFFOLDS: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE X-ray crystallography; Crystal dehydration; Ion replacement; Riboswitch;
T-box RNA; tRNA
ID ANGSTROM RESOLUTION; SECONDARY STRUCTURE; DEHYDRATION; RIBOSWITCH;
RIBOZYME; MOTIF; ANTITERMINATION; COMPLEX; ELEMENT; TURNS
AB The crystallization and structural determination of large RNAs and their complexes remain major bottle-necks in the mechanistic analysis of cellular and viral RNAs. Here, we describe a protocol that combines post-crystallization dehydration and ion replacement that dramatically improved the diffraction quality of crystals of a large gene-regulatory tRNA-mRNA complex. Through this method, the resolution limit of X-ray data extended from 8.5 to 3.2 angstrom, enabling structure determination. Although this protocol was developed for a particular RNA complex, the general importance of solvent and counterions in nucleic acid structure may render it generally useful for crystallographic analysis of other RNAs.
C1 [Zhang, Jinwei; Ferre-D'Amare, Adrian R.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
RP Zhang, JW (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [, Z99 HL999999, ZIA HL006102-04]; NIGMS NIH HHS [P41
GM103403]
NR 30
TC 0
Z9 0
U1 1
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2730-2; 978-1-4939-2729-6
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1316
BP 13
EP 24
DI 10.1007/978-1-4939-2730-2_2
D2 10.1007/978-1-4939-2730-2
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE6YK
UT WOS:000374927600003
PM 25967049
ER
PT J
AU Imai, CM
Halldorsson, TI
Eiriksdottir, G
Cotch, MF
Stein-Grimsdottir, L
Thorsdottir, I
Launer, LJ
Harris, T
Gudnason, V
Gunnarsdottir, I
AF Imai, Cindy Mari
Halldorsson, Thorhallur Ingi
Eiriksdottir, Gudny
Cotch, Mary Frances
Stein-Grimsdottir, Laufey
Thorsdottir, Inga
Launer, Lenore J.
Harris, Tamara
Gudnason, Vilmundur
Gunnarsdottir, Ingibjorg
TI Depression and serum 25-hydroxyvitamin D in older adults living at
northern latitudes-AGES-Reykjavik Study
SO ANNALS OF NUTRITION AND METABOLISM
LA English
DT Meeting Abstract
DE vitamin D; depression; older adults; nutrition epidemiology
C1 [Imai, Cindy Mari] Univ Iceland, Unit Nutr Res, Reykjavik, Iceland.
[Halldorsson, Thorhallur Ingi; Stein-Grimsdottir, Laufey; Thorsdottir, Inga; Gunnarsdottir, Ingibjorg] Landspitali, Unit Nutr Res, Reykjavik, Iceland.
[Halldorsson, Thorhallur Ingi; Stein-Grimsdottir, Laufey; Thorsdottir, Inga; Gunnarsdottir, Ingibjorg] Univ Iceland, Fac Food Sci & Nutr, Sch Hlth Sci, Reykjavik, Iceland.
[Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Launer, Lenore J.; Harris, Tamara] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0250-6807
EI 1421-9697
J9 ANN NUTR METAB
JI Ann. Nutr. Metab.
PY 2015
VL 67
SU 1
MA 149/73
BP 306
EP 306
PG 1
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA DK5VM
UT WOS:000374988801238
ER
PT J
AU Vermeulen, E
Stronks, K
Visser, M
Brouwer, I
Schene, A
Mocking, R
Colpo, M
Bandinelli, S
Ferrucci, L
Nicolaou, M
AF Vermeulen, Esther
Stronks, Karien
Visser, Marjolein
Brouwer, Ingeborg
Schene, Aart
Mocking, Roel
Colpo, Marco
Bandinelli, Stefania
Ferrucci, Luigi
Nicolaou, Mary
TI Diet in Tuscan population associated with lower depressive symptoms over
time
SO ANNALS OF NUTRITION AND METABOLISM
LA English
DT Meeting Abstract
DE diet; dietary pattern; depression; depressive symptoms; Reduced Rank
Regression
C1 [Vermeulen, Esther; Nicolaou, Mary] Acad Med Ctr, Dept Publ Hlth, Nutr, Amsterdam, Netherlands.
[Stronks, Karien] Acad Med Ctr, Social Med, Amsterdam, Netherlands.
[Visser, Marjolein] Vrije Univ Amsterdam, Dept Hlth Sci, Hlth Aging, Amsterdam, Netherlands.
[Brouwer, Ingeborg] Vrije Univ Amsterdam, Inst Hlth Sci, Amsterdam, Netherlands.
[Schene, Aart] Amsterdam Med Ctr, Dept Psychiat, Psychiat, Amsterdam, Netherlands.
[Mocking, Roel] Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Colpo, Marco] Azienda Sanit Firenze, InCHIANTI Study Grp, Stat, Florence, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, InCHIANTI Study Grp, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0250-6807
EI 1421-9697
J9 ANN NUTR METAB
JI Ann. Nutr. Metab.
PY 2015
VL 67
SU 1
MA 149/152
BP 315
EP 316
PG 2
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA DK5VM
UT WOS:000374988801260
ER
PT J
AU Kim, YM
Chaemsaithong, P
Romero, R
Shaman, M
Kim, CJ
Kim, JS
Qureshi, F
Jacques, SM
Ahmed, AI
Chaiworapongsa, T
Hassan, SS
Yeo, L
Korzeniewski, SJ
AF Kim, Yeon Mee
Chaemsaithong, Piya
Romero, Roberto
Shaman, Majid
Kim, Chong Jai
Kim, Jung-Sun
Qureshi, Faisal
Jacques, Suzanne M.
Ahmed, Ahmed I.
Chaiworapongsa, Tinnakorn
Hassan, Sonia S.
Yeo, Lami
Korzeniewski, Steven J.
TI The frequency of acute atherosis in normal pregnancy and preterm labor,
preeclampsia, small-for-gestational age, fetal death and midtrimester
spontaneous abortion
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Atherosclerosis; CD68; fibrinoid; foam cells; macrophage; spiral artery
ID C-REACTIVE-PROTEIN; INTRAUTERINE GROWTH-RETARDATION;
TUMOR-NECROSIS-FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CIRCULATING
IMMUNE-COMPLEXES; PRO-INFLAMMATORY CYTOKINES; MATERNAL VASCULAR-LESIONS;
LATE-ONSET PREECLAMPSIA; CORONARY-HEART-DISEASE; BED SPIRAL ARTERIES
AB Objective: Acute atherosis is characterized by subendothelial lipid-filled foam cells, fibrinoid necrosis and perivascular lymphocytic infiltration. This lesion is generally confined to non-transformed spiral arteries and is frequently observed in patients with preeclampsia. However, the frequency of acute atherosis in the great obstetrical syndromes is unknown. The purpose of this study was to determine the frequency and topographic distribution of acute atherosis in placentas and placental bed biopsy samples obtained from women with normal pregnancy and those affected by the "great obstetrical syndromes''. We also examined the relationship between acute atherosis and pregnancy outcome in patients with preeclampsia.
Material and methods: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women's Hospital/Detroit Medical Center was conducted to examine 16 345 placentas. Patients were classified into the following groups: (1) uncomplicated pregnancy; (2) spontaneous preterm labor (sPTL) and preterm prelabor rupture of membranes (PPROM); (3) preeclampsia; (4) gestational hypertension; (5) small-for-gestational age (SGA); (6) chronic hypertension; (5) fetal death; (6) spontaneous abortion and (7) others. A subset of patients had placental bed biopsy. The incidence of acute atherosis was compared among the different groups.
Results: (1) The prevalence of acute atherosis in uncomplicated pregnancies was 0.4% (29/6961) based upon examination of nearly 7000 placentas; (2) the frequency of acute atherosis was 10.2% (181/1779) in preeclampsia, 9% (26/292) in fetal death, 2.5% (3/120) in midtrimester spontaneous abortion, 1.7% (22/1,298) in SGA neonates and 1.2% (23/1,841) in sPTL and PPROM; (3) among patients with preeclampsia, those with acute atherosis than in those without the lesion had significantly more severe disease, earlier onset, and a greater frequency of SGA neonates (p<0.05 all) and (4) the lesion was more frequently observed in the decidua (parietalis or basalis) than in the decidual segment of the spiral arteries in patients with placental bed biopsies.
Conclusions: Acute atherosis is rare in normal pregnancy, and occurs more frequently in patients with pregnancy complications, including preeclampsia, sPTL, preterm PROM, midtrimester spontaneous abortion, fetal death and SGA.
C1 [Kim, Yeon Mee] Inje Univ, Coll Med, Haeundae Paik Hosp, Dept Pathol, Busan, South Korea.
[Chaemsaithong, Piya; Romero, Roberto; Shaman, Majid; Kim, Chong Jai; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M.; Ahmed, Ahmed I.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Korzeniewski, Steven J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Chaemsaithong, Piya; Romero, Roberto; Shaman, Majid; Kim, Chong Jai; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M.; Ahmed, Ahmed I.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Korzeniewski, Steven J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Chaemsaithong, Piya; Shaman, Majid; Ahmed, Ahmed I.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Korzeniewski, Steven J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI USA.
[Kim, Chong Jai] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea.
[Kim, Jung-Sun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea.
[Qureshi, Faisal; Jacques, Suzanne M.] Harper Univ Hosp, Dept Pathol, Detroit, MI USA.
[Qureshi, Faisal; Jacques, Suzanne M.] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM ykim.haeundae@gmail.com; romeror@mail.nih.gov
FU Intramural NIH HHS [ZIA HD002400-23]; NICHD NIH HHS [HHSN275201300006C];
PHS HHS [HHSN275201300006C]
NR 143
TC 7
Z9 7
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PY 2015
VL 28
IS 17
BP 2001
EP 2009
DI 10.3109/14767058.2014.976198
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DK2OP
UT WOS:000374754600001
PM 25308204
ER
PT S
AU Hollingsworth, JW
Nadadur, SS
AF Hollingsworth, John W.
Nadadur, Srikanth S.
BE Nadadur, SS
Hollingsworth, JW
TI Air Pollution and Health Effects Preface
SO AIR POLLUTION AND HEALTH EFFECTS
SE Molecular and Integrative Toxicology
LA English
DT Editorial Material; Book Chapter
ID AMERICAN-HEART-ASSOCIATION; CARDIOVASCULAR-DISEASE; STATEMENT
C1 [Hollingsworth, John W.] Ohio State Univ, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA.
[Nadadur, Srikanth S.] Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA.
RP Hollingsworth, JW (reprint author), Ohio State Univ, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA.
NR 5
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER-VERLAG LONDON LTD
PI GODALMING
PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY,
ENGLAND
SN 2168-4219
BN 978-1-4471-6669-6; 978-1-4471-6668-9
J9 MOLEC INTEGR TOXICOL
PY 2015
BP V
EP VII
D2 10.1007/978-1-4471-6669-6
PG 3
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BE5XX
UT WOS:000373624200001
ER
PT S
AU Chae, JJ
Kastner, DL
AF Chae, Jae Jin
Kastner, Daniel L.
BE Gattorno, M
TI Pathogenesis
SO FAMILIAL MEDITERRANEAN FEVER
SE Rare Diseases of the Immune System
LA English
DT Article; Book Chapter
ID FAMILIAL MEDITERRANEAN FEVER; DEATH-DOMAIN-FOLD; NF-KAPPA-B; COLD
AUTOINFLAMMATORY SYNDROME; MUCKLE-WELLS-SYNDROME; PYRIN DOMAIN;
COLCHICINE-RESISTANT; INFLAMMASOME ACTIVATION; NLRP3 INFLAMMASOME;
EXPANDING FAMILY
C1 [Chae, Jae Jin; Kastner, Daniel L.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Chae, JJ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM chaej@exchange.nih.gov; kastnerd@mail.nih.gov
NR 77
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2282-6505
BN 978-3-319-14615-7; 978-3-319-14614-0
J9 RARE DIS IMMUNE SYST
PY 2015
VL 3
BP 13
EP 30
DI 10.1007/978-3-319-14615-7_2
D2 10.1007/978-3-319-14615-7
PG 18
WC Immunology; Pathology
SC Immunology; Pathology
GA BE5ZS
UT WOS:000373700500003
ER
PT J
AU Rekik, I
Allassonniere, S
Luby, M
Carpenter, TK
Wardlaw, JM
AF Rekik, Islem
Allassonniere, Stephanie
Luby, Marie
Carpenter, Trevor K.
Wardlaw, Joanna M.
TI Phase-based metamorphosis of diffusion lesion in relation to perfusion
values in acute ischemic stroke
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Metamorphosis; Ischemic stroke; Lesion evolution; Diffusion imaging;
Perfusion imaging; Magnetic resonance imaging
ID MAGNETIC-RESONANCE; IMAGE-ANALYSIS; HETEROGENEITY; PREDICTION; INSIGHTS;
OUTCOMES; VOLUME; MRI
AB Examining the dynamics of stroke ischemia is limited by the standard use of 2D-volume or voxel-based analysis techniques. Recently developed spatiotemporal models such as the 4D metamorphosis model showed promise for capturing ischemia dynamics. We used a 4D metamorphosis model to evaluate acute ischemic stroke lesion morphology from the acute diffusion-weighted imaging (DWI) to final T2-weighted imaging (T2-w). In 20 representative patients, we metamorphosed the acute lesion to subacute lesion to final infarct. From the DWI lesion deformation maps we identified dynamic lesion areas and examined their association with perfusion values inside and around the lesion edges, blinded to reperfusion status. We then tested the model in ten independent patients from the STroke Imaging Repository (STIR). Perfusion values varied widely between and within patients, and were similar in contracting and expanding DWI areas in many patients in both datasets. In 25% of patients, the perfusion values were higher in DWI-contracting than DWI-expanding areas. A similar wide range of perfusion values and ongoing expansion and contraction of the DWI lesion were seen subacutely. There was more DWI contraction and less expansion in patients who received thrombolysis, although with widely ranging perfusion values that did not differ. 4D metamorphosis modeling shows promise as a method to improve use of multimodal imaging to understand the evolution of acute ischemic tissue towards its fate. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
C1 [Rekik, Islem; Carpenter, Trevor K.; Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Div Neuroimaging Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Rekik, Islem; Carpenter, Trevor K.; Wardlaw, Joanna M.] SINAPSE Collaborat, Brain Res Imaging Ctr, London, England.
[Rekik, Islem; Allassonniere, Stephanie] Ecole Polytech, CMAP, F-91128 Palaiseau, France.
[Luby, Marie] NINDS, NIH, Bethesda, MD 20892 USA.
[Luby, Marie] UT Southwestern Med Ctr, Dept Neurol & Neurotherapeut, Seton UT Southwestern Clin Res Inst Austin, Austin, TX USA.
RP Rekik, I (reprint author), Univ Edinburgh, Brain Res Imaging Ctr, Div Neuroimaging Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
EM islem.rekik@gmail.com; stephanie.allassonniere@polytechnique.edu;
LubyM@ninds.nih.gov; trevor.carpenter@ed.ac.uk; joanna.wardlaw@ed.ac.uk
FU Scottish Funding Council through the Scottish Imaging Network; Platform
for Scientific Excellence (SINAPSE) Collaboration; Centre for Clinical
Brain Sciences; Tony Watson Bequest and a Scottish Overseas Research
Award from the University of Edinburgh; Scottish Funding Council SINAPSE
Collaboration; Cohen Charitable Trust; Chief Scientist Office of the
Scottish Government; Seton/UT Southwestern Clinical Research Institute
of Austin; Department of Neurology and Neurotherapeutics; UT
Southwestern Medical Center, Austin, TX, USA; National Institute of
Neurological Disorders and Stroke (NINDS); National Institutes of Health
(NIH), Bethesda, MD, USA
FX This study was funded by the Scottish Funding Council through the
Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE)
Collaboration (http://www.sinapse.ac.uk/), the Centre for Clinical Brain
Sciences, the Tony Watson Bequest and a Scottish Overseas Research Award
from the University of Edinburgh (PhD for Islem Rekik), the Scottish
Funding Council SINAPSE Collaboration (to Prof. Joanna Wardlaw), the
Cohen Charitable Trust (to Dr. Trevor Carpenter and Dr Islem Rekik), and
the Chief Scientist Office of the Scottish Government.; This work was
also supported by the Seton/UT Southwestern Clinical Research Institute
of Austin, the Department of Neurology and Neurotherapeutics, the UT
Southwestern Medical Center, Austin, TX, USA, the National Institute of
Neurological Disorders and Stroke (NINDS), and the National Institutes
of Health (NIH), Bethesda, MD, USA.
NR 16
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 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 9
BP 44
EP 49
DI 10.1016/j.nicl.2015.07.007
PG 6
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0LR
UT WOS:000373188400006
PM 26288755
ER
PT J
AU Maestu, F
Pena, JM
Garces, P
Gonzalez, S
Bajo, R
Bagic, A
Cuesta, P
Funke, M
Makela, JP
Menasalvas, E
Nakamura, A
Parkkonen, L
Lopez, ME
del Pozo, F
Sudre, G
Zamrini, E
Pekkonen, E
Henson, RN
Becker, JT
AF Maestu, Fernando
Pena, Jose-Maria
Garces, Pilar
Gonzalez, Santiago
Bajo, Ricardo
Bagic, Anto
Cuesta, Pablo
Funke, Michael
Makela, Jyrki P.
Menasalvas, Ernestina
Nakamura, Akinori
Parkkonen, Lauri
Lopez, Maria E.
del Pozo, Francisco
Sudre, Gustavo
Zamrini, Edward
Pekkonen, Eero
Henson, Richard N.
Becker, James T.
CA Magnetoencephalography Int
TI A multicenter study of the early detection of synaptic dysfunction in
Mild Cognitive Impairment using Magnetoencephalography-derived
functional connectivity
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Magnetoencephalography; Mild Cognitive Impairment; Functional
connectivity; Data mining; Machine learning; Synaptic dysfunction;
Multicenter study
ID SIGNAL SPACE SEPARATION; RESTING-STATE FMRI; ALZHEIMERS-DISEASE;
NEURODEGENERATION; CLASSIFICATION; VALIDATION; NETWORK
AB Synaptic disruption is an early pathological sign of the neurodegeneration of Dementia of the Alzheimer's type (DAT). The changes in network synchronization are evident in patients with Mild Cognitive Impairment (MCI) at the group level, but there are very few Magnetoencephalography (MEG) studies regarding discrimination at the individual level. In an international multicenter study, we used MEG and functional connectivity metrics to discriminate MCI from normal aging at the individual person level. A labeled sample of features (links) that distinguished MCI patients from controls in a training dataset was used to classify MCI subjects in two testing datasets from four other MEG centers. We identified a pattern of neuronal hypersynchronization in MCI, in which the features that best discriminated MCI were fronto-parietal and interhemispheric links. The hypersynchronization pattern found in the MCI patients was stable across the five different centers, and may be considered an early sign of synaptic disruption and a possible preclinical biomarker for MCI/DAT. (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 [Maestu, Fernando; Pena, Jose-Maria; Garces, Pilar; Gonzalez, Santiago; Bajo, Ricardo; Cuesta, Pablo; Menasalvas, Ernestina; Lopez, Maria E.; del Pozo, Francisco] Univ Complutense Madrid, Ctr Biomed Technol, Lab Cognit & Computat Neurosci, Madrid, Spain.
[Maestu, Fernando; Pena, Jose-Maria; Garces, Pilar; Gonzalez, Santiago; Bajo, Ricardo; Cuesta, Pablo; Menasalvas, Ernestina; Lopez, Maria E.; del Pozo, Francisco] Tech Univ Madrid, Madrid, Spain.
[Bagic, Anto; Becker, James T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Funke, Michael] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Houston, TX 77030 USA.
[Makela, Jyrki P.] Univ Helsinki, Cent Hosp, HUS Med Imaging Ctr, BioMag Lab, Helsinki, Finland.
[Nakamura, Akinori] Natl Ctr Geriatr & Gerontol, Dept Clin & Expt Neuroimaging, Obu, Japan.
[Parkkonen, Lauri] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, Espoo, Finland.
[Parkkonen, Lauri] Elekta Oy, Helsinki, Finland.
[Sudre, Gustavo] NIH, Human Genome Res Inst, Bethesda, MD 20892 USA.
[Zamrini, Edward] Univ Utah, Dept Neurol, Salt Lake City, UT USA.
[Pekkonen, Eero] Univ Helsinki, Dept Neurol, FIN-00014 Helsinki, Finland.
[Henson, Richard N.] Med Res Council Cognit & Brain Sci Unit, Cambridge, England.
[Becker, James T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Becker, James T.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
RP Maestu, F (reprint author), Ctr Biomed Technol, Lab Cognit & Computat Neurosci, Campus Montegancedo, Madrid 28223, Spain.
RI Maestu, Fernando/E-3213-2012; Lopez, Maria Eugenia/E-9311-2016;
Parkkonen, Lauri/G-6755-2012;
OI Maestu, Fernando/0000-0002-3195-0071; Lopez, Maria
Eugenia/0000-0002-3928-2629; Parkkonen, Lauri/0000-0002-0130-0801;
Cuesta Prieto, Pablo/0000-0002-8459-3354; Henson,
Richard/0000-0002-0712-2639
FU National Institutes of Health [P01AG05133, R21MH098745]; Spanish
Ministry of Innovation and Science [PSI2009-14415-C03-01,
PSI2012-38375-C03-01]; SalWe Research Program for Mind and Body
[1104/10]; UK Medical Research Council [MC_A060_5PR10]; JSPS KAKENHI
[24590908]
FX This research was supported in part by funds from the National
Institutes of Health (P01AG05133, R21MH098745), the Spanish Ministry of
Innovation and Science (PSI2009-14415-C03-01 and PSI2012-38375-C03-01),
SalWe Research Program for Mind and Body (grant number: 1104/10), the UK
Medical Research Council (MC_A060_5PR10), and JSPS KAKENHI grant number
24590908. Thanks to Lisa Brindley and Elisa Cooper for helping to
collect the Cambridge MEG data, and Peter Nestor for referring the
Cambridge patients. We are also grateful to Melissa Fabrizio and Wiltrud
Fassbinder for collecting the Pittsburgh MEG data.
NR 36
TC 4
Z9 4
U1 3
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 9
BP 103
EP 109
DI 10.1016/j.nicl.2015.07.011
PG 7
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0LR
UT WOS:000373188400013
PM 26448910
ER
PT J
AU Hwang, S
White, SF
Nolan, ZT
Williams, WC
Sinclair, S
Blair, RJR
AF Hwang, Soonjo
White, Stuart F.
Nolan, Zachary T.
Williams, W. Craig
Sinclair, Stephen
Blair, R. J. R.
TI Executive attention control and emotional responding in
attention-deficit/hyperactivity disorder - A functional MRI study
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Attention-deficit/hyperactivity disorder; Affective Stroop; Executive
attention; Emotion regulation; fMRI
ID DEFICIT HYPERACTIVITY DISORDER; PEDIATRIC BIPOLAR DISORDER;
PSYCHIATRIC-DISORDERS; STIMULANT-MEDICATION; COGNITIVE CONTROL;
WORKING-MEMORY; ADHD; CHILDREN; FMRI; AMYGDALA
AB Background: There are suggestions that patients with attention-deficit/hyperactivity disorder (ADHD) show impairment in executive attention control and emotion regulation. This study investigated emotion regulation as a function of the recruitment of executive attention in patients with ADHD.
Methods: Thirty-five healthy children/adolescents (mean age = 13.91) and twenty-six children/adolescents with ADHD (mean age = 14.53) participated in this fMRI study. They completed the affective Stroop paradigm viewing positive, neutral and negative images under varying cognitive loads. A 3-way ANOVA (diagnosis-by-condition-by-emotion) was conducted on the BOLD response data. Following this, 2 3-way ANOVAs (diagnosis-by-condition-by-emotion) were applied to context-dependent psychophysiological interaction (gPPI) analyses generated from a dorsomedial frontal cortex and an amygdala seed (identified from the BOLD response ANOVA main effects of condition and emotion respectively).
Results: A diagnosis-by-condition interaction within dorsomedial frontal cortex revealed reduced recruitment of dorsomedial frontal cortex as a function of increased task demands in the children/adolescents with ADHD relative to healthy children/adolescents. The level of reduction in recruitment of dorsomedial frontal cortex was significantly correlated with symptom severity (total and hyperactivity) measured by Conner's Parent Report Scale in the children/adolescents with ADHD. In addition, analysis of gPPI data from a dorsomedial frontal cortex seed revealed significant diagnosis-by-condition interactions within lateral frontal cortex; connectivity between dorsomedial frontal cortex and lateral frontal cortex was reduced in the patients with ADHD relative to comparison youth during congruent and incongruent task trials relative to view trials. There were no interactions of group, or main effect of group, within the amygdala in the BOLD response ANOVA (though children/adolescents with ADHD showed increased responses to positive images within temporal cortical regions during task trials; identified by the diagnosis-by-condition-by-emotion interaction). However, analysis of gPPI data from an amygdala seed revealed decreased connectivity between amygdala and lentiform nucleus in the presence of emotional stimuli in children/adolescents with ADHD (diagnosis-by-emotion interaction).
Conclusion: The current study demonstrated disrupted recruitment of regions implicated in executive function and impaired connectivity within those regions in children/adolescents with ADHD. There were also indications of heightened representation of emotional stimuli in patients with ADHD. However, as the findings were specific for positive stimuli, the suggestion of a general failure in emotion regulation in ADHD was not supported. Published by Elsevier Inc.
C1 [Hwang, Soonjo; White, Stuart F.; Sinclair, Stephen; Blair, R. J. R.] NIMH, Sect Affect Cognit Neurosci, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Nolan, Zachary T.] Penn State Univ, Coll Med, Hershey, PA USA.
[Williams, W. Craig] Stanford Univ, Dept Psychol, Stanford, CA USA.
RP Hwang, S (reprint author), 9000 Rockville Pike,Bldg 15 K,Room 204, Bethesda, MD 20892 USA.
EM soonjo.hwang@nih.gov
FU National Institute of Mental Health, National Institutes of Health
[1-ZIA-MH002860-08]
FX This work was supported by the Intramural Research Program at the
National Institute of Mental Health, National Institutes of Health under
grant number 1-ZIA-MH002860-08 to Dr. Blair. Ethics approval for this
study was granted by the NIH Combined Neuroscience Institutional Review
Board under protocol number 05-M-0105.
NR 64
TC 0
Z9 0
U1 6
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 9
BP 545
EP 554
DI 10.1016/j.nicl.2015.10.005
PG 10
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0LR
UT WOS:000373188400058
PM 26640766
ER
PT J
AU White, SF
Costanzo, ME
Blair, JR
Roy, MJ
AF White, Stuart F.
Costanzo, Michelle E.
Blair, James R.
Roy, Michael J.
TI PTSD symptom severity is associated with increased recruitment of
top-down attentional control in a trauma-exposed sample
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Post-traumatic stress disorder; Emotion attention; Amygdala; Top down
attention
ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; COGNITIVE
CONTROL; VISUAL-ATTENTION; EMOTION; AMYGDALA; FACES; INDIVIDUALS;
MODULATION; MECHANISMS
AB Background: Recent neuroimaging work suggests that increased amygdala responses to emotional stimuli and dysfunction within regions mediating top down attentional control (dorsomedial frontal, lateral frontal and parietal cortices) may be associated with the emergence of anxiety disorders, including posttraumatic stress disorder (PTSD). This report examines amygdala responsiveness to emotional stimuli and the recruitment of top down attention systems as a function of task demands in a population of U.S. military service members who had recently returned from combat deployment in Afghanistan/Iraq. Given current interest in dimensional aspects of pathophysiology, it is worthwhile examining patients who, while not meeting full PTSD criteria, show clinically significant functional impairment.
Methods: Fifty-seven participants with sub-threshold levels of PTSD symptoms completed the affective Stroop task while undergoing fMRI. Participants with PTSD or depression at baseline were excluded.
Results: Greater PTSD symptom severity scores were associated with increased amygdala activation to emotional, particularly positive, stimuli relative to neutral stimuli. Furthermore, greater PTSD symptom severity was associated with increased superior/middle frontal cortex response during task conditions relative to passive viewing conditions. In addition, greater PTSD symptom severity scores were associated with: (i) increased activation in the dorsolateral prefrontal, lateral frontal, inferior parietal cortices and dorsomedial frontal cortex/dorsal anterior cingulate cortex (dmFC/dACC) in response to emotional relative to neutral stimuli; and (ii) increased functional connectivity during emotional trials, particularly positive trials, relative to neutral trials between the right amygdala and dmFC/dACC, left caudate/anterior insula cortex, right lentiform nucleus/caudate, bilateral inferior parietal cortex and left middle temporal cortex.
Conclusions: We suggest that these data may reflect two phenomena associated with increased PTSD symptomatology in combat-exposed, but PTSD negative, armed services members. First, these data indicate increased emotional responsiveness by: (i) the positive relationship between PTSD symptom severity and amygdala responsiveness to emotional relative to neutral stimuli; (ii) greater BOLD response as a function of PTSD symptom severity in regions implicated in emotion (striatum) and representation (occipital and temporal cortices) during emotional relative to neutral conditions; and (iii) increased connectivity between the amygdala and regions implicated in emotion (insula/caudate) and representation (middle temporal cortex) as a function of PTSD symptom severity during emotional relative to neutral trials. Second, these data indicate a greater need for the recruitment of regions implicated in top down attention as indicated by (i) greater BOLD response in superior/middle frontal gyrus as a function of PTSD symptom severity in task relative to view conditions; (ii) greater BOLD response in dmFC/dACC, lateral frontal and inferior parietal cortices as a function of PTSD symptom severity in emotional relative to neutral conditions and (iii) greater functional connectivity between the amygdala and inferior parietal cortex as a function of PTSD symptom severity during emotional relative to neutral conditions. Published by Elsevier Inc.
C1 [White, Stuart F.; Blair, James R.] NIMH, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Costanzo, Michelle E.; Roy, Michael J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Costanzo, Michelle E.; Roy, Michael J.] Walter Reed Natl Mil Ctr, Bethesda, MD 20814 USA.
[Costanzo, Michelle E.] Henry M Jackson Fdn, Bethesda, MD USA.
RP White, SF (reprint author), NIMH, 9000 Rockville Pike,Bldg 15k,Room 205,MSC 2670, Bethesda, MD 20892 USA.
EM stuart.white@nih.gov; stuart.white@nih.gov
FU National Institute of Mental Health, National Institutes of Health
[1-ZIA-MH002860]; Center for Neuroscience and Regenerative Medicine
[300601 8.01 60855510005]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health under
grant number 1-ZIA-MH002860 to James Blair and the Center for
Neuroscience and Regenerative Medicine under grant number 300601 8.01
60855510005 to Michael Roy. This work was approved under the Uniformed
Services University of the Health Sciences Institutional Review Board
protocol 11N-0090. NCT number: NCT01296126.
NR 41
TC 9
Z9 9
U1 2
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 7
BP 19
EP 27
DI 10.1016/j.nicl.2014.11.012
PG 9
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0GE
UT WOS:000373172600004
PM 25610763
ER
PT J
AU Meoded, A
Morrissette, AE
Katipally, R
Schanz, O
Gotts, SJ
Floeter, MK
AF Meoded, Avner
Morrissette, Arthur E.
Katipally, Rohan
Schanz, Olivia
Gotts, Stephen J.
Floeter, Mary Kay
TI Cerebro-cerebellar connectivity is increased in primary lateral
sclerosis
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Motor neuron disease; Resting state functional MRI; Connectivity;
Cerebellum; Primary lateral sclerosis
ID STATE FUNCTIONAL CONNECTIVITY; DIFFUSION-TENSOR MRI; STRUCTURAL
CONNECTIVITY; ALZHEIMERS-DISEASE; HUMAN BRAIN; FRONTOTEMPORAL DEMENTIA;
DIAGNOSTIC-CRITERIA; MOTOR NETWORK; TRACT DAMAGE; ALS
AB Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Conneclivily matrices were constructed from resting stale fMRI in 16 PLS patients lo identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used lo examine structural connections between regions of differing connecLivily.PLS patients had 12 regions with increased functional connectivity compared Lo controls, with a predominance of cerebrocerebellar connections. Increased functional connectivily was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber Lracking defected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact. Published by Elsevier Inc.
C1 [Meoded, Avner; Morrissette, Arthur E.; Katipally, Rohan; Schanz, Olivia; Floeter, Mary Kay] NINDS, NIH, Bethesda, MD 20892 USA.
[Gotts, Stephen J.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Floeter, MK (reprint author), Room 7-5680,10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA.
EM floeterm@ninds.nih.gov
OI Gotts, Stephen/0000-0002-7903-1832
FU National Institutes of Health, NINDS [Z01 NS002976]; National Institutes
of Health, NIMH [Z01 MH002920]
FX The research was supported by the intramural programs of the National
Institutes of Health, NINDS (Z01 NS002976) and NIMH (Z01 MH002920). The
assistance of Laura Danielian with image acquisition and processing is
gratefully acknowledged.
NR 63
TC 4
Z9 5
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 7
BP 288
EP 296
DI 10.1016/j.nicl.2014.12.009
PG 9
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0GE
UT WOS:000373172600033
PM 25610792
ER
PT J
AU Plitt, M
Barnes, KA
Martin, A
AF Plitt, Mark
Barnes, Kelly Anne
Martin, Alex
TI Functional connectivity classification of autism identifies highly
predictive brain features but falls short of biomarker standards
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Autism; Bioimarkers; Machine learning classification; Social brain
ID SPECTRUM DISORDERS; CHILDREN; FMRI
AB Objectives: Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MR1 (rs-IMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis.
Methods: Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrcorg/incli/abidc/) were included for replication.
Results: High classification accuracy was achieved through several rs-IMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASDIfMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning.
Conclusions: While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing. Published by Elsevier Inc.
C1 [Plitt, Mark; Barnes, Kelly Anne; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Plitt, M (reprint author), 10 Ctr Dr,MSC 1366,Bldg 10,4C214, Bethesda, MD 20892 USA.
EM mark.plitt@nih.gov
FU NARSAD Young Investigator Grant from the Brain & Behavior Research
Foundation; Intramural Research Program at NIMH
FX Thanks go to Steve Gotts, PhD for helpful discussion regarding methods
and statistics. The authors declare no competing interests. This work
was supported by a NARSAD Young Investigator Grant from the Brain &
Behavior Research Foundation (KAB) and by the Intramural Research
Program at NIMH (AM). Ethics approval for this study was granted by the
NIH Combined Neuroscience Institutional Review Board under protocol
number 10-M-0027. The clinical trial number (clinicaltrials.gov) for
this protocol is NCT01031407.
NR 40
TC 11
Z9 11
U1 3
U2 16
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 7
BP 359
EP 366
DI 10.1016/j.nicl.2014.12.013
PG 8
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0GE
UT WOS:000373172600040
PM 25685703
ER
PT J
AU Li, XZ
van Gelderen, P
Sati, P
de Zwart, JA
Reich, DS
Duyn, JH
AF Li, Xiaozhen
van Gelderen, Peter
Sati, Pascal
de Zwart, Jacco A.
Reich, Daniel S.
Duyn, Jeff H.
TI Detection of demyelination in multiple sclerosis by analysis of T-2*
relaxation at 7 T
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE T-2* relaxation; Water compartment; Multiple sclerosis; Demyelination
ID MYELIN WATER FRACTION; HIGH-FIELD MRI; WHITE-MATTER;
MAGNETIZATION-TRANSFER; BRAIN; FREQUENCY; RESONANCE; MICROSTRUCTURE;
HISTOPATHOLOGY; ORIENTATION
AB Multiple sclerosis (MS) is a relatively common cause of inflammatory demyelinating lesions of the central nervous system. In an attempt to detect and characterize ongoing demyelination in MS patient brains, we used a novel magnetic resonance imaging (MRI) technique, involving the fitting of a three-component model to the T-2* relaxation behavior at high-field (7 T). This model allowed estimation of the amount of myelin water (and thus indirectly myelin content), axonal water, and interstitial water. In this study, 25 relapsing-remitting MS patients underwent a 7 T MRI from which 12 gadolinium-enhancing lesions, 61 non-enhancing lesions, and their corresponding contralateral normal appearing white matter (NAWM) regions were analyzed. In both enhancing and non-enhancing lesions, the amplitude of myelin water was significantly decreased, and interstitial and axonal water were increased relative to the contralateral NAWM. Longer relaxation time T-2* of interstitial and axonal water, and lower frequency shift of axonal water, were also observed in both enhancing and non-enhancing lesions when compared to the contralateral NAWM. No significant difference was found between enhancing lesions and non-enhancing lesions. These findings suggest that the fitting of a three-component model to the T-2* decay curve in MS lesions may help to quantify myelin loss. Published by Elsevier Inc.
C1 [Li, Xiaozhen; van Gelderen, Peter; de Zwart, Jacco A.; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Li, Xiaozhen] Karolinska Inst, Ctr Alzheimer Dis Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, SE-14157 Stockholm, Sweden.
[Sati, Pascal; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Div Neuroimmunol & Neurovirol, NIH, Bethesda, MD 20892 USA.
RP Li, XZ (reprint author), Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Novum 5th Floor,Blickagangen 6, S-14157 Huddinge, Sweden.
EM xiaozhen.li@nih.gov
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU NINDS
FX We thank the National Institute of Neurological Disorders and Stroke
(NINDS) Neuroimmunology Clinic for coordinating the recruitment of human
subjects. We acknowledge the NINDS Intramural Research Program for
support, as well as the National Institutes of Health - Karolinska
Institutet Graduate Programme for International PhDs.
NR 26
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 7
BP 709
EP 714
DI 10.1016/j.nicl.2015.02.021
PG 6
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0GE
UT WOS:000373172600076
PM 26594617
ER
PT J
AU Shinohara, RT
Sweeney, EM
Goldsmith, J
Shiee, N
Mateen, FJ
Calabresi, PA
Jarso, S
Pham, DL
Reich, DS
Crainiceanu, CM
AF Shinohara, Russell T.
Sweeney, Elizabeth M.
Goldsmith, Jeff
Shiee, Navid
Mateen, Farrah J.
Calabresi, Peter A.
Jarso, Samson
Pham, Dzung L.
Reich, Daniel S.
Crainiceanu, Ciprian M.
CA Australian Imaging Biomarkers
Alzheimer's Dis Neuroimaging
TI Statistical normalization techniques for magnetic resonance imaging (vol
6, pg 9, 2014)
SO NEUROIMAGE-CLINICAL
LA English
DT Correction
C1 [Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Sweeney, Elizabeth M.; Reich, Daniel S.] NINDS, Translat Neurol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Sweeney, Elizabeth M.; Reich, Daniel S.; Crainiceanu, Ciprian M.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Goldsmith, Jeff] Columbia Univ, Dept Biostat, New York, NY 10032 USA.
[Shiee, Navid; Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA.
[Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Calabresi, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA.
[Jarso, Samson; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA.
RP Shinohara, RT (reprint author), Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, 210 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM rshi@upenn.edu
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 1
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 7
BP 848
EP 848
DI 10.1016/j.nicl.2015.02.011
PG 1
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0GE
UT WOS:000373172600093
PM 26082894
ER
PT J
AU Wang, JC
Cao, HB
Liao, YH
Liu, WQ
Tan, LW
Tang, YQ
Chen, JD
Xu, XF
Li, HJ
Luo, CR
Liu, CY
Merikangas, KR
Calhoun, V
Tang, JS
Shugart, YY
Chen, XG
AF Wang, Jicai
Cao, Hongbao
Liao, Yanhui
Liu, Weiqing
Tan, Liwen
Tang, Yanqing
Chen, Jindong
Xu, Xiufeng
Li, Haijun
Luo, Chunrong
Liu, Chunyu
Merikangas, Kathleen Ries
Calhoun, Vince
Tang, Jinsong
Shugart, Yin Yao
Chen, Xiaogang
TI Three dysconnectivity patterns in treatment-resistant schizophrenia
patients and their unaffected siblings
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Schizophrenia; TRS; Brain plasticity; Functional connectivity; Sibling
controls
ID FUNCTIONAL NETWORK CONNECTIVITY; RESTING-STATE FMRI; 1ST-DEGREE
RELATIVES; PREFRONTAL CORTEX; NONPSYCHOTIC SIBLINGS; COGNITIVE DEFICITS;
TIME-SERIES; BRAIN; ABNORMALITIES; HEALTHY
AB Among individuals diagnosed with schizophrenia, approximately 20%-33% are recognized as treatment-resistant schizophrenia (TRS) patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophreniamay be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL) brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs. control. To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level) on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1) 69 patient-specific connectivity (PCN); 2) 102 shared connectivity (SCN); and 3) 457 unshared connectivity (UCN). While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Wang, Jicai; Liao, Yanhui; Liu, Weiqing; Tan, Liwen; Chen, Jindong; Tang, Jinsong; Chen, Xiaogang] Cent S Univ, Xiangya Hosp 2, Inst Mental Hlth, Changsha 410011, Hunan, Peoples R China.
[Cao, Hongbao; Tang, Jinsong; Shugart, Yin Yao] NIMH, Unit Stat Genom, NIH, Bethesda, MD 20892 USA.
[Wang, Jicai; Liu, Weiqing; Xu, Xiufeng] Kunming Med Univ, Affiliated Hosp 1, Dept Psychiat, Kunming 650032, Yunnan, Peoples R China.
[Tang, Yanqing] China Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China.
[Liu, Chunyu; Chen, Xiaogang] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.
[Merikangas, Kathleen Ries] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Calhoun, Vince] Mind Res Network, Albuquerque, NM 87131 USA.
[Calhoun, Vince] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87106 USA.
[Chen, Xiaogang] Cent S Univ, Natl Technol Inst Psychiat, Changsha 410011, Hunan, Peoples R China.
[Li, Haijun; Luo, Chunrong] First Peoples Hosp Kunming, Dept Radiol, Kunming 650011, Yunnan, Peoples R China.
RP Tang, JS (reprint author), Cent S Univ, Xiangya Hosp 2, Inst Mental Hlth, Changsha 410011, Hunan, Peoples R China.
EM tangjinsonghn@gmail.com; kay1yao@mail.nih.gov; chenxghn@gmail.com
RI Liao, Yanhui/L-1590-2016
OI Liao, Yanhui/0000-0003-4735-3252
FU Natural Science Foundation of China [30900486, 81371480, 81100996,
81471361, 81271484, 81071099, 81271499]; National Key Basic Research and
Development Program (973) [2012CB517904]; Sheng-Hua Yuying project of
Central South University; Sheng-Hua Lieying project of Central South
University; program of China Scholarships Council; Intramural Research
Program of the National Institute of Mental Health, National Institutes
of Health (IRP, NIMH, NIH) [MH002930-03]; [NIBIB2R01EB000840];
[COBRE5P20RR021938/P20GM103472]
FX This work was supported by the Natural Science Foundation of China
(grant nos. 30900486 and 81371480 to JT, 81100996 to YL, 81471361 and
81271484 to XC, 81071099, and 81271499 to YT) and the National Key Basic
Research and Development Program (973) (grant no. 2012CB517904 to XC).
JT was supported by the Sheng-Hua Yuying project of Central South
University; YL was supported by the Sheng-Hua Lieying project of Central
South University; Financial support from the program of China
Scholarships Council to JT; Drs. Cao and Shugart gratefully acknowledge
the support of the Intramural Research Program of the National Institute
of Mental Health, National Institutes of Health (IRP, NIMH, NIH)
(project number MH002930-03). This work was also in part supported by
grants NIBIB2R01EB000840 and COBRE5P20RR021938/P20GM103472 (to Dr.
Calhoun). The authors have no conflicts of interest to disclose,
financial or otherwise.
NR 54
TC 1
Z9 2
U1 7
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 8
BP 95
EP 103
DI 10.1016/j.nicl.2015.03.017
PG 9
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0LE
UT WOS:000373187100009
PM 26106532
ER
PT J
AU Hanley, AP
Blumenthal, JD
Lee, NR
Baker, EH
Clasen, LS
Giedd, JN
AF Hanley, Alli P.
Blumenthal, Jonathan D.
Lee, Nancy Raitano
Baker, Eva H.
Clasen, Liv S.
Giedd, Jay N.
TI Brain and behavior in 48, XXYY syndrome
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Sex chromosomes aneuploidy; 48,XXYY; Brain anatomy; White matter lesions
ID KLINEFELTERS-SYNDROME; SEX-CHROMOSOMES; X-CHROMOSOME; MRI DATA;
HYPERINTENSITIES; NEUROANATOMY; ORIGIN
AB The phenotype of 48, XXYY syndrome (referred to as XXYY) is associated with characteristic but variable developmental, cognitive, behavioral and physical abnormalities. To discern the neuroanatomical phenotype of the syndrome, we conducted quantitative and qualitative analyses on MRI brain scans from 25 males with XXYY and 92 age and SES matched typically developing XY males. Quantitatively, males in the XXYY group had smaller gray and white matter volumes of the frontal and temporal lobes. Conversely, both gray and white matter volumes of the parietal lobe as well as lateral ventricular volume were larger in the XXYY group. Qualitatively, males in the XXYY group had a higher incidence of colpocephaly (84% vs. 34%, p <= 0.001), white matter lesions (25% vs. 5%, p = 0.007), and thin posterior body of the corpus callosum (28% vs. 3%, p = 0.001). The specificity of these findings may shed light on the role of the X and Y chromosomes in typical and atypical brain development and help provide direction for future studies of brain-behavior relationships in males with XXYY syndrome. Published by Elsevier Inc.
C1 [Hanley, Alli P.; Blumenthal, Jonathan D.; Clasen, Liv S.] NIMH, Child Psychiat Branch, NIH, DHHS, Bethesda, MD 20892 USA.
[Lee, Nancy Raitano] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA.
[Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, DHHS, Bethesda, MD USA.
[Giedd, Jay N.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
RP Blumenthal, JD (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Room 4C110,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jb364e@nih.gov
RI Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016
OI Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713
FU Intramural Research Program of the NIMH
FX The Intramural Research Program of the NIMH supported this research. The
authors were solely responsible for the study design; collection,
analysis and interpretation of data; the writing of the report; and the
decision to submit for publication. We thank the families who
participated in this research, and the Association of X and Y Chromosome
Variations for their assistance with recruitment of participants.
NR 43
TC 1
Z9 2
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 8
BP 133
EP 139
DI 10.1016/j.nicl.2015.04.009
PG 7
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0LE
UT WOS:000373187100014
PM 26106537
ER
PT J
AU Chu, RKO
Braun, AR
Meltzer, JA
AF Chu, Ron K. O.
Braun, Allen R.
Meltzer, Jed A.
TI MEG-based detection and localization of perilesional dysfunction in
chronic stroke
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Magnetoencephalography; Beamformer source reconstruction; Time-frequency
analysis; Chronic stroke
ID LOW-FREQUENCY RTMS; MULTISCALE ENTROPY ANALYSIS; CHRONIC NONFLUENT
APHASIA; INTENSIVE SPEECH-THERAPY; POSTSTROKE APHASIA; BRAIN PLASTICITY;
ISCHEMIC-STROKE; SAMPLE ENTROPY; APPROXIMATE ENTROPY; LANGUAGE RECOVERY
AB Post-stroke impairment is associated not only with structural lesions, but also with dysfunction in surviving perilesional tissue. Previous studies using equivalent current dipole source localization of MEG/EEG signals have demonstrated a preponderance of slow-wave activity localized to perilesional areas. Recent studies have also demonstrated the utility of nonlinear analyses such as multiscale entropy (MSE) for quantifying neuronal dysfunction in a wide range of pathologies. The current study utilized beamformer-based reconstruction of signals in source space to compare spectral and nonlinear measures of electrical activity in perilesional and healthy cortices. Data were collected from chronic stroke patients and healthy controls, both young and elderly. We assessed relative power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (15-30 Hz) frequency bands, and also measured the nonlinear complexity of electrical activity using MSE. Perilesional tissue exhibited a general slowing of the power spectrum(increased delta/theta, decreased beta) as well as a reduction in MSE. All measures tested were similarly sensitive to changes in the posterior perilesional regions, but anterior perilesional dysfunction was detected better by MSE and beta power. The findings also suggest that MSE is specifically sensitive to electrophysiological dysfunction in perilesional tissue, while spectral measures were additionally affected by an increase in rolandic beta power with advanced age. Furthermore, perilesional electrophysiological abnormalities in the left hemisphere were correlated with the degree of language task-induced activation in the right hemisphere. Finally, we demonstrate that single subject spectral and nonlinear analyses can identify dysfunctional perilesional regions within individual patients that may be ideal targets for interventions with non-invasive brain stimulation. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Chu, Ron K. O.; Meltzer, Jed A.] Univ Toronto, Dept Psychol, 100 St George St,4th Floor,Smith Hall, Sidney, ON M5S 3G3, Canada.
[Meltzer, Jed A.] Univ Toronto, Dept Speech Language Pathol, Toronto, ON M5G 1V7, Canada.
[Chu, Ron K. O.; Meltzer, Jed A.] Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON M6A 2E1, Canada.
[Meltzer, Jed A.] Heart & Stroke Fdn Canadian Partnership Stroke Re, Ottawa, ON K1G 5Z3, Canada.
[Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD USA.
RP Chu, RKO (reprint author), 3560 Bathurst St, Toronto, ON, Canada.
EM ron.chu@utoronto.ca
OI Meltzer, Jed/0000-0002-4301-1901
FU Intramural Research Program of the National Institute on Deafness and
Other Communication Disorders; Heart and Stroke Foundation Canadian
Partnership for Stroke Recovery; Alzheimer's Association
FX We thank the participating patients and their families. Data collection
was funded by the Intramural Research Program of the National Institute
on Deafness and Other Communication Disorders. Later analyses were
supported by grants from the Heart and Stroke Foundation Canadian
Partnership for Stroke Recovery and the Alzheimer's Association.
NR 73
TC 2
Z9 2
U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 8
BP 157
EP 169
DI 10.1016/j.nicl.2015.03.019
PG 13
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0LE
UT WOS:000373187100017
PM 26106540
ER
PT J
AU Kutch, JJ
Yani, MS
Asavasopon, S
Kirages, DJ
Rana, M
Cosand, L
Labus, JS
Kilpatrick, LA
Ashe-McNalley, C
Farmer, MA
Johnson, KA
Ness, TJ
Deutsch, G
Harris, RE
Apkarian, AV
Clauw, DJ
Mackey, SC
Mullins, C
Mayer, EA
AF Kutch, Jason J.
Yani, Moheb S.
Asavasopon, Skulpan
Kirages, Daniel J.
Rana, Manku
Cosand, Louise
Labus, Jennifer S.
Kilpatrick, Lisa A.
Ashe-McNalley, Cody
Farmer, Melissa A.
Johnson, Kevin A.
Ness, Timothy J.
Deutsch, Georg
Harris, Richard E.
Apkarian, A. Vania
Clauw, Daniel J.
Mackey, Sean C.
Mullins, Chris
Mayer, Emeran A.
TI Altered resting state neuromotor connectivity in men with chronic
prostatitis/chronic pelvic pain syndrome: A MAPP Research Network
Neuroimaging Study
SO NEUROIMAGE-CLINICAL
LA English
DT Article
ID LOW-BACK-PAIN; ANTERIOR CINGULATE CORTEX; FUNCTIONAL CONNECTIVITY; MOTOR
CORTEX; FLOOR; HEALTHY; INSULA
AB Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N=28), as well as group of age-matched healthy male controls (N=27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Kutch, Jason J.; Yani, Moheb S.; Kirages, Daniel J.; Rana, Manku] Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA USA.
[Asavasopon, Skulpan] Loma Linda Univ, Phys Therapy Dept, Loma Linda, CA 92350 USA.
[Cosand, Louise] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
[Labus, Jennifer S.; Kilpatrick, Lisa A.; Ashe-McNalley, Cody; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, PAIN, Oppenheimer Ctr Neurobiol Stress, Los Angeles, CA 90095 USA.
[Farmer, Melissa A.; Apkarian, A. Vania] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA.
[Johnson, Kevin A.; Mackey, Sean C.] Stanford Univ, Med Ctr, Dept Anesthesiol Perioperat & Pain Med, Div Pain Med, Stanford, CA 94305 USA.
[Ness, Timothy J.; Deutsch, Georg] Univ Alabama Birmingham, Dept Radiol, Birmingham Med Ctr, Birmingham, AL USA.
[Ness, Timothy J.; Deutsch, Georg] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham Med Ctr, Birmingham, AL USA.
[Harris, Richard E.; Clauw, Daniel J.] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA.
[Mullins, Chris] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Kutch, JJ (reprint author), Univ So Calif, 1540 E Alcazar St,CHP 155, Los Angeles, CA 90033 USA.
EM kutch@usc.edu
RI Kirages, Daniel/J-7974-2016;
OI Apkarian, A. Vania/0000-0002-9788-7458
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), National Institutes of Health (NIH) [DK82370, DK82342, DK82315,
DK82344, DK82325, DK82345, DK82333, DK82316]; USC Division of
Biokinesiology and Physical Therapy [USCBKN/PT-2013A]; Loma Linda
University Physical Therapy Department [LLU-647525-2007]; National
Center for Medical Rehabilitation Research of the National Institutes of
Health [T32 HD064578]
FX We thank all of the volunteers who participated in the study. We would
like to thank Nina Bradley, Bruce Naliboff, and Kirsten Tillisch for
helpful discussions. Funding for the MAPP Research Network was obtained
under a cooperative agreement from National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), National Institutes of Health
(NIH) (DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333,
and DK82316). This work was also supported, in part, by the USC Division
of Biokinesiology and Physical Therapy under award number
USCBKN/PT-2013A, the Loma Linda University Physical Therapy Department
under award number LLU-647525-2007, and National Center for Medical
Rehabilitation Research of the National Institutes of Health under award
number T32 HD064578. We declare the following interests: financial
interest and/or other relationship with Pfizer, Cerephex, Lilly, Merck,
Nuvo, Furest, Tonix, Purdue, Therauance and Johnson & Johnson (DJC),
financial interest and/or other relationship with National Institutes of
Health and Medtronic (TJN), financial interest and/or other relationship
with National Institutes of Health (CM).
NR 50
TC 10
Z9 11
U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2015
VL 8
BP 493
EP 502
DI 10.1016/j.nicl.2015.05.013
PG 10
WC Neuroimaging
SC Neurosciences & Neurology
GA DI0LE
UT WOS:000373187100053
PM 26106574
ER
PT S
AU Candia, J
Banavar, JR
Losert, W
AF Candia, Julian
Banavar, Jayanth R.
Losert, Wolfgang
BE Wang, X
TI Uncovering Phenotypes with Supercells: Applications to Single-Cell
Sequencing
SO SINGLE CELL SEQUENCING AND SYSTEMS IMMUNOLOGY
SE Translational Bioinformatics
LA English
DT Article; Book Chapter
DE Single-cell biology; Single-cell genomics; Cell heterogeneity; Machine
learning; Supercells
ID TUMOR HETEROGENEITY; STEM-CELLS; HEMATOPOIETIC STEM; HUMAN BRAIN;
CANCER; RETROTRANSPOSITION; PLASTICITY; GENOMES; SEQ
AB The so-called "Supercell paradigm" is a method for phenotyping based on single-cell multidimensional data, which has been recently proposed by the authors of this Chapter and collaborators within the larger context of single-cell biology. Supercells are multidimensional objects that represent the collective behavior of groups of cells and carry a distinct phenotype, which is often obscured at the single-cell level due to high cell-to-cell variability. The Supercell framework provides a quantitative assessment of the critical sample size and the number of simultaneous single-cell measurements needed to build a phenotype, which is a key piece of information given the fact that, in many single-cell applications, the number of measured cells and the number of measurements per cell are severely limited due to a variety of constraints, such as experimental costs, technological capabilities, specimen collection procedures, the availability of specialized personnel, and others. In this Chapter, we review the Supercell method and explore the potential for its application to single-cell sequencing datasets.
C1 [Candia, Julian] NIH, Ctr Human Immunol, 10 7N115,9000 Rockville Pike, Bethesda, MD 20892 USA.
[Banavar, Jayanth R.; Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
RP Candia, J (reprint author), NIH, Ctr Human Immunol, 10 7N115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM julian.candia@nih.gov
OI Candia, Julian/0000-0001-5793-8989
NR 35
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
SN 2213-2783
BN 978-94-017-9753-5; 978-94-017-9752-8
J9 TRANSL BIOINFORM
PY 2015
BP 11
EP 30
DI 10.1007/978-94-017-9753-5_2
D2 10.1007/978-94-017-9753-5
PG 20
WC Mathematical & Computational Biology; Immunology
SC Mathematical & Computational Biology; Immunology
GA BE5PI
UT WOS:000373182700003
ER
PT S
AU Wenger, C
Salvador, R
Basser, PJ
Miranda, PC
AF Wenger, Cornelia
Salvador, Ricardo
Basser, Peter J.
Miranda, Pedro C.
GP IEEE
TI Modeling Tumor Treating Fields (TTFields) application within a realistic
human head model
SO 2015 37TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN
MEDICINE AND BIOLOGY SOCIETY (EMBC)
SE IEEE Engineering in Medicine and Biology Society Conference Proceedings
LA English
DT Proceedings Paper
CT 37th Annual International Conference of the IEEE Engineering in Medicine
and Biology Society (EMBC)
CY AUG 25-29, 2015
CL Milan, ITALY
ID ALTERNATING ELECTRIC-FIELDS; WHITE-MATTER; ANISOTROPIC CONDUCTIVITY;
GLIOBLASTOMA; BRAIN
AB Tumor Treating Fields (TTFields) are an antimitotic treatment against brain and other tumors. They are applied regionally and non-invasively by inducing intermediate frequency (100-300 kHz) alternating electric field of intensities between 1 to 3 V/cm through transducer arrays placed on the patient's skin close to the tumor. All TTFields studies predicted variability in treatment response among patients, whereas in vitro experiments indicate that the magnitude and direction of the electric field in the tumor might be crucial determinants of efficacy. Differences in the field might arise from varying tumor positions or array placement. By investigating different scenarios within a realistic human head model we hope to advance our understanding of TTFields therapy in clinical practice.
We constructed a model from MRI data to calculate the electric field distribution in the brain using the Finite Element Method. An anisotropic electrical conductivity tensor was estimated using diffusion tensor imaging data. The head model contained different tissue types: scalp, skull, cerebrospinal fluid, gray and white matter. Additionally a virtual spherical tumor was included, two positions for the tumor were considered. Transducer arrays were placed on the scalp to model the commonly used device for TTFields delivery. One additional setup of the two transducer pairs was specifically adapted to the second tumor position.
The results predict that the electric field strength exceeds the assumed therapeutic threshold value of 1 V/cm in both tumors for both active array pairs. For the second tumor the adapted transducer layout improved field delivery. The average field strength in the tumor further depends on tumor electrical properties. Yet a cystic and a solid tumor experience the same average field strength when treated with TTFields. As a next step towards personalized TTFields therapy, we will explore possible benefits of individualized treatment planning.
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;
OI Miranda, Pedro/0000-0002-6793-8111; Wenger, Cornelia/0000-0001-7889-9093
NR 18
TC 0
Z9 0
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1557-170X
BN 978-1-4244-9270-1
J9 IEEE ENG MED BIO
PY 2015
BP 2555
EP 2558
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic
SC Engineering
GA BE4HD
UT WOS:000371717202207
ER
PT S
AU Wenger, C
Giladi, M
Bomzon, Z
Salvador, R
Basser, PJ
Miranda, PC
AF Wenger, Cornelia
Giladi, Moshe
Bomzon, Ze'ev
Salvador, Ricardo
Basser, Peter J.
Miranda, Pedro C.
GP IEEE
TI Modeling Tumor Treating Fields (TTFields) application in single cells
during metaphase and telophase
SO 2015 37TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN
MEDICINE AND BIOLOGY SOCIETY (EMBC)
SE IEEE Engineering in Medicine and Biology Society Conference Proceedings
LA English
DT Proceedings Paper
CT 37th Annual International Conference of the IEEE Engineering in Medicine
and Biology Society (EMBC)
CY AUG 25-29, 2015
CL Milan, ITALY
ID ALTERNATING ELECTRIC-FIELDS; DIELECTROPHORESIS; ELECTROROTATION;
DISRUPTION; MEMBRANES; MITOSIS; VOLUME
AB Effects of electric fields on biological cells have been extensively studied but primarily in the low and high frequency regimes. Low frequency AC fields have been investigated for applications to nerve and muscle stimulation or to examine possible environmental effects of 60 Hz excitation. High frequency fields have been studied to understand tissue heating and tumor ablation. Biological effects at intermediate frequencies (in the 100-500 kHz regime) have only recently been discovered and are now being used clinically to disrupt cell division, primarily for the treatment of recurrent glioblastoma multiforme. In this study, we develop a computational framework to investigate the mechanisms of action of these Tumor Treating Fields (TTFields) and to understand in vitro findings observed in cell culture. Using Finite Element Method models of isolated cells we show that the intermediate frequency range is unique because it constitutes a transition region in which the intracellular electric field, shielded at low frequencies, increases significantly. We also show that the threshold at which this increase occurs depends on the dielectric properties of the cell membrane. Furthermore, our models of different stages of the cell cycle and of the morphological changes associated with cytokinesis show that peak dielectrophoretic forces develop within dividing cells exposed to TTFields. These findings are in agreement with in vitro observations, and enhance our understanding of how TTFields disrupt cellular function.
C1 [Wenger, Cornelia; Salvador, Ricardo; Miranda, Pedro C.] Univ Lisbon, Fac Ciencias, Inst Biophys & Biomed Engn, P-1749016 Lisbon, Portugal.
[Giladi, Moshe; Bomzon, Ze'ev] Novocure, Root, Switzerland.
[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; mosheg@novocure.com; zbomzon@novocure.com;
rnsalvador@fc.ul.pt; pjbasser@helix.niv.gov; pcmiranda@fc.ul.pt
RI Miranda, Pedro/A-5643-2013;
OI Miranda, Pedro/0000-0002-6793-8111; Wenger, Cornelia/0000-0001-7889-9093
NR 24
TC 2
Z9 2
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1557-170X
BN 978-1-4244-9270-1
J9 IEEE ENG MED BIO
PY 2015
BP 6892
EP 6895
PG 4
WC Engineering, Biomedical; Engineering, Electrical & Electronic
SC Engineering
GA BE4HD
UT WOS:000371717207042
ER
PT S
AU Wessel, AW
Hanson, EP
AF Wessel, Alex W.
Hanson, Eric P.
BE May, MJ
TI A Method for the Quantitative Analysis of Stimulation-Induced Nuclear
Translocation of the p65 Subunit of NF-kappa B from Patient-Derived
Dermal Fibroblasts
SO NF-KAPPA B: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE NF-kappa B; p65; Nuclear translocation; Fibroblasts; IL-1R; TNFR; TLR;
RLR; Microscopy
ID MUTATION; MODULATOR
AB Developmental and immune-mediated disease has been linked to genetic mutation of key signaling components involved in NF-kappa B activation that leads to impaired activation or regulation of the canonical IKK complex. We identify patients with suspected or known defects of the NF-kappa B signaling pathway through clinical phenotyping and genetic sequencing. To help understand how mutations cause disease, we quantitate the kinetics and dose-response of NF-kappa B activation signaling events in their cells. Following activation of the canonical IKK complex, phosphorylation of the inhibitor of NF-kappa B proteins (I kappa B) leads to their degradation and the subsequent translocation of NF-kappa B family members from the cell cytoplasm to the nucleus. Here, we provide a method to obtain patient-derived dermal fibroblasts and quantitatively assess the integrity of the signal transduction pathway from receptor activation to nuclear p65 translocation.
C1 [Wessel, Alex W.; Hanson, Eric P.] NIH, Immunodeficiency & Inflammat Unit, Arthrit & Rheumatism Branch, Bldg 10, Bethesda, MD 20892 USA.
RP Wessel, AW (reprint author), NIH, Immunodeficiency & Inflammat Unit, Arthrit & Rheumatism Branch, Bldg 10, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2422-6; 978-1-4939-2421-9
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1280
BP 413
EP 426
DI 10.1007/978-1-4939-2422-6_25
D2 10.1007/978-1-4939-2422-6
PG 14
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE5GD
UT WOS:000372806300026
PM 25736764
ER
PT J
AU Hristovski, D
Kastrin, A
Rindflesch, TC
AF Hristovski, Dimitar
Kastrin, Andrej
Rindflesch, Thomas C.
BE Pei, J
Silvestri, F
Tang, J
TI Semantics-Based Cross-domain Collaboration Recommendation in the Life
Sciences: Preliminary Results
SO PROCEEDINGS OF THE 2015 IEEE/ACM INTERNATIONAL CONFERENCE ON ADVANCES IN
SOCIAL NETWORKS ANALYSIS AND MINING (ASONAM 2015)
LA English
DT Proceedings Paper
CT IEEE/ACM International Conference on Advances in Social Networks
Analysis and Mining (ASONAM)
CY AUG 25-28, 2015
CL Paris, FRANCE
SP IEEE, Assoc Comp Machinery, ACM SIGKDD, IEEE Comp Soc, IEEE TCDE, Springer, Cisco, Telecom ParisTech
DE Research collaboration; Recommendation system; Literature-based
discovery; Semantic MEDLINE
ID KNOWLEDGE
AB In this work we propose a novel approach for semantics-based cross-domain recommendation for research collaboration. First, we construct a large network representing authors, their expertize, current collaborations, and biomedical knowledge in general. We constructed the network from the bibliographic database MEDLINE and from semantic relations extracted from MEDLINE with the SemRep natural language processing system. Then, by using the literature-based discovery paradigm, we recommend novel collaborations, which include not only pairs of authors, but also novel topics for collaboration and an explanation why the collaboration makes sense.
C1 [Hristovski, Dimitar] Univ Ljubljana, Fac Med, Ljubljana, Slovenia.
[Kastrin, Andrej] Fac Informat Studies, Novo Mesto, Slovenia.
[Rindflesch, Thomas C.] Natl Lib Med, Bethesda, MD USA.
RP Hristovski, D (reprint author), Univ Ljubljana, Fac Med, Ljubljana, Slovenia.
EM dimitar.hristovski@gmail.com; andrej.kastrin@guest.arnes.si;
trindflesch@mail.nih.gov
NR 8
TC 0
Z9 0
U1 4
U2 4
PU ASSOC COMPUTING MACHINERY
PI NEW YORK
PA 1515 BROADWAY, NEW YORK, NY 10036-9998 USA
BN 978-1-4503-3854-7
PY 2015
BP 805
EP 806
DI 10.1145/2808797.2809300
PG 2
WC Computer Science, Artificial Intelligence; Computer Science, Information
Systems
SC Computer Science
GA BE4JN
UT WOS:000371793500122
ER
PT S
AU Wang, SL
Chen, F
Fang, JW
AF Wang, Shulin
Chen, Fang
Fang, Jianwen
GP IEEE
TI Spectral Clustering of High-dimensional Data via Nonnegative Matrix
Factorization
SO 2015 INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS (IJCNN)
SE IEEE International Joint Conference on Neural Networks (IJCNN)
LA English
DT Proceedings Paper
CT International Joint Conference on Neural Networks (IJCNN)
CY JUL 12-17, 2015
CL Killarney, IRELAND
DE Nonnegative Matrix Factorization; affinity matrix; spectral clustering;
cosine similarity; high-dimensional data
ID EXPRESSION; CLASSIFICATION; PREDICTION; DISCOVERY; LEUKEMIA
AB Spectral clustering has become a popular subspace clustering algorithm in machine learning and data mining, which aims at finding a low-dimensional representation by utilizing the spectrum of a Laplacian matrix. It is a key to construct a discriminative and reliable affinity matrix for spectral clustering to achieve impressive clustering quality. As the real word data increase with higher dimension of features and larger number of data samples, it is a challenge to construct a good affinity matrix. Recently, sparse representation based spectral clustering (SRSC) has proven its efficiency for clustering and lead to promising clustering results in high-dimensional data. SRSC constructs affinity matrix by using sparse representation coefficient vectors. However, it is very time consuming. Additionally, the dimension of the sparse coefficient vector is equal to the number of samples, which may make the affinity matrix not discriminative enough. Therefore, it is inefficient to apply SRSC in clustering large scale datasets. To remedy these issues, we propose a new spectral clustering algorithm which constructs affinity matrix via Nonnegative Matrix Factorization (NMF) coefficient vectors. We call our algorithm as NMF based spectral clustering (NMFSC). The dimension of NMF coefficient vector is independent on the number of the samples and significantly smaller than that of sparse coefficient vector. Therefore, the affinity matrix can be constructed via NMF coefficient vector with much lower computational cost. The experimental results on several public gene expression profiling (GEP) datasets demonstrate the advantage of NMF coefficient over sparse representation coefficient and suggest that NMFSC is promising in clustering high-dimensional data.
C1 [Wang, Shulin; Chen, Fang] Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China.
[Fang, Jianwen] NCI, Div Canc Treatment & Diag, Rockville, MD USA.
RP Wang, SL (reprint author), Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China.
EM smartforesting@gmail.com; jianwen.fang@nih.gov
NR 30
TC 0
Z9 0
U1 3
U2 3
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2161-4393
BN 978-1-4799-1959-8
J9 IEEE IJCNN
PY 2015
PG 8
WC Computer Science, Artificial Intelligence; Computer Science, Hardware &
Architecture; Engineering, Electrical & Electronic
SC Computer Science; Engineering
GA BE3HR
UT WOS:000370730601036
ER
PT S
AU Chadwick, RS
Cartagena-Rivera, AX
AF Chadwick, Richard S.
Cartagena-Rivera, Alexander X.
BE Karavitaki, KD
Corey, DP
TI Using Noncontact AFM Frequency Shifts to Determine Stereocilia Bundle
Stiffness and Tension in the Developing Cochlear Sensory Epithelium
SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION
SE AIP Conference Proceedings
LA English
DT Proceedings Paper
CT 12th International Workshop on the Mechanics of Hearing
CY JUN 23-29, 2014
CL Cape Sounio, GREECE
ID ATOMIC-FORCE MICROSCOPY; HAIR BUNDLES; CELLS
AB Measurement of frequency shifts of cantilevers having an attached microsphere oscillating at acoustic frequencies can be used to assess mechanical properties of cochlear structures. The method has already been reported for measuring elastic and viscous properties of the tectorial membrane. We describe here how the method can be used to examine other cochlear structures. Theory and formulas for relating hair bundle stiffness and tension in the developing cochlear sensory epithelium to measured frequency shifts are given to estimate the expected frequency shifts and show feasibility of the measurements. We show through a molecular model of myosin II located along the edges of confluent hexagons that myosin contractile forces are balanced by isotropic tension in the developing confluent sheet of cells.
C1 [Chadwick, Richard S.; Cartagena-Rivera, Alexander X.] Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mech, Lab Cellular Biol, NIH, Bethesda, MD USA.
RP Chadwick, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mech, Lab Cellular Biol, NIH, Bethesda, MD USA.
NR 11
TC 0
Z9 0
U1 0
U2 0
PU AMER INST PHYSICS
PI MELVILLE
PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA
SN 0094-243X
BN 978-0-7354-1350-4
J9 AIP CONF PROC
PY 2015
VL 1703
AR 030012
DI 10.1063/1.4939327
PG 4
WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology
SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology
GA BE4PY
UT WOS:000372065400014
ER
PT S
AU Iwasa, KH
Ricci, AJ
AF Iwasa, Kuni H.
Ricci, Anthony J.
BE Karavitaki, KD
Corey, DP
TI The Avian Tectorial Membrane: Why is it Tapered?
SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION
SE AIP Conference Proceedings
LA English
DT Proceedings Paper
CT 12th International Workshop on the Mechanics of Hearing
CY JUN 23-29, 2014
CL Cape Sounio, GREECE
ID BASILAR PAPILLA; HAIR-BUNDLE; AMPLIFICATION; MORPHOLOGY; MOTION; CHICK;
CELLS
AB While the mammalian-and the avian inner ears have well defined tonotopic organizations as well as hair cells specialized for motile and sensing roles, the structural organization of the avian ear is different from its mammalian cochlear counterpart. Presumably this difference stems from the difference in the way motile hair cells function. Short hair cells, whose role is considered analogous to mammalian outer hair cells, presumably depends on their hair bundles, and not motility of their cell body, in providing the motile elements of the cochlear amplifier. This report focuses on the role of the avian tectorial membrane, specifically by addressing the question, "Why is the avian tectorial membrane tapered from the neural to the abneural direction?"
C1 [Iwasa, Kuni H.; Ricci, Anthony J.] Stanford Univ, Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA.
[Iwasa, Kuni H.] NIDCD, NIH, Bethesda, MD USA.
[Ricci, Anthony J.] Stanford Univ, Mol & Cellular Physiol, Stanford, CA 94305 USA.
RP Iwasa, KH (reprint author), Stanford Univ, Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU AMER INST PHYSICS
PI MELVILLE
PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA
SN 0094-243X
BN 978-0-7354-1350-4
J9 AIP CONF PROC
PY 2015
VL 1703
AR 080005
DI 10.1063/1.4939396
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology
SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology
GA BE4PY
UT WOS:000372065400083
ER
PT J
AU Althabe, F
Moore, JL
Gibbons, L
Berrueta, M
Goudar, SS
Chomba, E
Derman, RJ
Patel, A
Saleem, S
Pasha, O
Esamai, F
Garces, A
Liechty, EA
Hambidge, KM
Krebs, NF
Hibberd, PL
Goldenberg, RL
Koso-Thomas, M
Carlo, WA
Cafferata, ML
Buekens, P
McClure, EM
AF Althabe, Fernando
Moore, Janet L.
Gibbons, Luz
Berrueta, Mabel
Goudar, Shivaprasad S.
Chomba, Elwyn
Derman, Richard J.
Patel, Archana
Saleem, Sarah
Pasha, Omrana
Esamai, Fabian
Garces, Ana
Liechty, Edward A.
Hambidge, K. Michael
Krebs, Nancy F.
Hibberd, Patricia L.
Goldenberg, Robert L.
Koso-Thomas, Marion
Carlo, Waldemar A.
Cafferata, Maria L.
Buekens, Pierre
McClure, Elizabeth M.
TI Adverse maternal and perinatal outcomes in adolescent pregnancies: The
Global Network's Maternal Newborn Health Registry study
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID TEENAGE PREGNANCY; AGE; POPULATION; BIRTHS
AB Background: Adolescent girls between 15 and 19 years give birth to around 16 million babies each year, around 11% of births worldwide. We sought to determine whether adolescent mothers are at higher risk of maternal and perinatal adverse outcomes compared with mothers aged 20-24 years in a prospective, population-based observational study of newborn outcomes in low resource settings.
Methods: We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in six low-middle income countries (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). The study population for this analysis was restricted to women aged 24 years or less, who gave birth to infants of at least 20 weeks' gestation and 500g or more. We compared adverse pregnancy maternal and perinatal outcomes among pregnant adolescents 15-19 years, < 15 years, and adults 20-24 years.
Results: A total of 269,273 women were enrolled from January 2010 to December 2013. Of all pregnancies 11.9% (32,097/269,273) were in adolescents 15-19 years, while 0.14% (370/269,273) occurred among girls < 15 years. Pregnancy among adolescents 15-19 years ranged from 2% in Pakistan to 26% in Argentina, and adolescent pregnancies < 15 year were only observed in sub-Saharan Africa and Latin America. Compared to adults, adolescents did not show increased risk of maternal adverse outcomes. Risks of preterm birth and LBW were significantly higher among both early and older adolescents, with the highest risks observed in the < 15 years group. Neonatal and perinatal mortality followed a similar trend in sub-Saharan Africa and Latin America, with the highest risk in early adolescents, although the differences in this age group were not significant. However, in South Asia the risks of neonatal and perinatal death were not different among adolescents 15-19 years compared to adults.
Conclusions: This study suggests that pregnancy among adolescents is not associated with worse maternal outcomes, but is associated with worse perinatal outcomes, particularly in younger adolescents. However, this may not be the case in regions like South Asia where there are decreasing rates of adolescent pregnancies, concentrated among older adolescents. The increased risks observed among adolescents seems more likely to be associated with biological immaturity, than with socio-economic factors, inadequate antenatal or delivery care.
C1 [Althabe, Fernando; Gibbons, Luz; Berrueta, Mabel] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Moore, Janet L.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Goudar, Shivaprasad S.] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, India.
[Chomba, Elwyn] Univ Zambia, Univ Teaching Hosp, Lusaka, Zambia.
[Derman, Richard J.] Christiana Care, Newark, DE USA.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Saleem, Sarah; Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya.
[Garces, Ana] FANCAP, Guatemala City, Guatemala.
[Liechty, Edward A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Hambidge, K. Michael] Univ Colorado, Sch Med, Denver, CO USA.
[Krebs, Nancy F.; Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Boston, MA USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet Gynecol, New York, NY USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Cafferata, Maria L.] UNICEM, Buenos Aires, DF, Argentina.
[Buekens, Pierre] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
RP Althabe, F (reprint author), Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
EM althabe@gmail.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This study was funded by grants from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 17
TC 9
Z9 10
U1 3
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S8
DI 10.1186/1742-4755-12-S2-S8
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400008
PM 26063350
ER
PT J
AU Bauserman, M
Lokangaka, A
Thorsten, V
Tshefu, A
Goudar, SS
Esamai, F
Garces, A
Saleem, S
Pasha, O
Patel, A
Manasyan, A
Berrueta, M
Kodkany, B
Chomba, E
Liechty, EA
Hambidge, KM
Krebs, NF
Derman, RJ
Hibberd, PL
Althabe, F
Carlo, WA
Koso-Thomas, M
Goldenberg, RL
Wallace, DD
McClure, EM
Bose, CL
AF Bauserman, Melissa
Lokangaka, Adrien
Thorsten, Vanessa
Tshefu, Antoinette
Goudar, Shivaprasad S.
Esamai, Fabian
Garces, Ana
Saleem, Sarah
Pasha, Omrana
Patel, Archana
Manasyan, Albert
Berrueta, Mabel
Kodkany, Bhala
Chomba, Elwyn
Liechty, Edward A.
Hambidge, K. Michael
Krebs, Nancy F.
Derman, Richard J.
Hibberd, Patricia L.
Althabe, Fernando
Carlo, Waldemar A.
Koso-Thomas, Marion
Goldenberg, Robert L.
Wallace, Dennis D.
McClure, Elizabeth M.
Bose, Carl L.
TI Risk factors for maternal death and trends in maternal mortality in low-
and middle-income countries: a prospective longitudinal cohort analysis
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID SYSTEMATIC ANALYSIS; NEWBORN; SURVEILLANCE; HEALTH; CARE
AB Background: Because large, prospective, population-based data sets describing maternal outcomes are typically not available in low-and middle-income countries, it is difficult to monitor maternal mortality rates over time and to identify factors associated with maternal mortality. Early identification of risk factors is essential to develop comprehensive intervention strategies preventing pregnancy-related complications. Our objective was to describe maternal mortality rates in a large, multi-country dataset and to determine maternal, pregnancy-related, delivery and postpartum characteristics that are associated with maternal mortality.
Methods: We collected data describing all pregnancies from 2010 to 2013 among women enrolled in the multinational Global Network for Women's and Children's Health Research Maternal and Neonatal Health Registry (MNHR). We reported the proportion of mothers who died per pregnancy and the maternal mortality ratio (MMR). Generalized linear models were used to evaluate the relationship of potential medical and social factors and maternal mortality and to develop point and interval estimates of relative risk associated with these factors. Generalized estimating equations were used to account for the correlation of outcomes within cluster to develop appropriate confidence intervals.
Results: We recorded 277,736 pregnancies and 402 maternal deaths for an MMR of 153/100,000 live births. We observed an improvement in the total MMR from 166 in 2010 to 126 in 2013. The MMR in Latin American sites (91) was lower than the MMR in Asian (178) and African sites (125). When adjusted for study site and the other variables, no formal education (RR 3.2 [1.5, 6.9]), primary education only (RR 3.4 [1.6, 7.5]), secondary education only (RR 2.5 [1.1, 5.7]), lack of antenatal care (RR 1.8 [1.2, 2.5]), caesarean section delivery (RR 1.9 [1.3, 2.8]), hemorrhage (RR 3.3 [2.2, 5.1]), and hypertensive disorders (RR 7.4 [5.2, 10.4]) were associated with higher risks of death.
Conclusions: The MNHR identified preventable causes of maternal mortality in diverse settings in low-and middle-income countries. The MNHR can be used to monitor public health strategies and determine their association with reducing maternal mortality.
C1 [Bauserman, Melissa; Bose, Carl L.] Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA.
[Lokangaka, Adrien; Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO.
[Thorsten, Vanessa; Wallace, Dennis D.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Goudar, Shivaprasad S.; Kodkany, Bhala] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, India.
[Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya.
[Garces, Ana] Fdn Alimentac & Nutr, Ctr Amer & Panama, Guatemala City, Guatemala.
[Saleem, Sarah; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Manasyan, Albert; Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia.
[Berrueta, Mabel; Althabe, Fernando] Univ Buenos Aires, Inst Clin Effectiveness & Hlth Policy, RA-1053 Buenos Aires, DF, Argentina.
[Liechty, Edward A.] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Hambidge, K. Michael; Krebs, Nancy F.] Univ Colorado, Sch Med, Boulder, CO 80309 USA.
[Derman, Richard J.] Christiana Hlth Care, Newark, DE USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Goldenberg, Robert L.] Columbia Univ, Sch Med, Dept Obstet & Gynecol, New York, NY 10027 USA.
RP Bauserman, M (reprint author), Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA.
EM Melissa_bauserman@med.unc.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the US National Institutes of Health [U01 HD040477,
U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457,
U10HD078439, U10HD078438, U10HD076474]
FX The project was funded by grants (U01 HD040477, U01HD040636,
U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439,
U10HD078438, and U10HD076474) from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the US National
Institutes of Health.
NR 19
TC 3
Z9 3
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S5
DI 10.1186/1742-4755-12-S2-S5
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400005
PM 26062992
ER
PT J
AU Bose, CL
Bauserman, M
Goldenberg, RL
Goudar, SS
McClure, EM
Pasha, O
Carlo, WA
Garces, A
Moore, JL
Miodovnik, M
Koso-Thomas, M
AF Bose, Carl L.
Bauserman, Melissa
Goldenberg, Robert L.
Goudar, Shivaprasad S.
McClure, Elizabeth M.
Pasha, Omrana
Carlo, Waldemar A.
Garces, Ana
Moore, Janet L.
Miodovnik, Menachem
Koso-Thomas, Marion
TI The Global Network Maternal Newborn Health Registry: a multi-national,
community-based registry of pregnancy outcomes
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID COUNTRIES; MORTALITY
AB Background: The Global Network for Women's and Children's Health Research (Global Network) supports and conducts clinical trials in resource-limited countries by pairing foreign and U.S. investigators, with the goal of evaluating low-cost, sustainable interventions to improve the health of women and children. Accurate reporting of births, stillbirths, neonatal deaths, maternal mortality, and measures of obstetric and neonatal care is critical to efforts to discover strategies for improving pregnancy outcomes in resource-limited settings. Because most of the sites in the Global Network have weak registration within their health care systems, the Global Network developed the Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnancies at the Global Network sites to provide precise data on health outcomes and measures of care.
Methods: Pregnant women are enrolled in the MNHR if they reside in or receive healthcare in designated groups of communities within sites in the Global Network. For each woman, demographic, health characteristics and major outcomes of pregnancy are recorded. Data are recorded at enrollment, the time of delivery and at 42 days postpartum.
Results: From 2010 through 2013 Global Network sites were located in Argentina, Guatemala, Belgaum and Nagpur, India, Pakistan, Kenya, and Zambia. During this period, 283,496 pregnant women were enrolled in the MNHR; this number represented 98.8% of all eligible women. Delivery data were collected for 98.8% of women and 42-day follow-up data for 98.4% of those enrolled. In this supplement, there are a series of manuscripts that use data gathered through the MNHR to report outcomes of these pregnancies.
Conclusions: Developing public policy and improving public health in countries with poor perinatal outcomes is, in part, dependent upon understanding the outcome of every pregnancy. Because the worst pregnancy outcomes typically occur in countries with limited health registration systems and vital records, alternative registration systems may prove to be highly valuable in providing data. The MNHR, an international, multicenter, population-based registry, assesses pregnancy outcomes over time in support of efforts to develop improved perinatal healthcare in resource-limited areas.
C1 [Bose, Carl L.; Bauserman, Melissa] Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Goudar, Shivaprasad S.] KLE Univ Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, India.
[McClure, Elizabeth M.; Moore, Janet L.] RTI Int, Durham, NC USA.
[Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Sch Med, Dept Pediat, Div Neonatol, Birmingham, AL USA.
[Garces, Ana] San Carlos Univ, Sch Med, Dept Pediat, Guatemala City, Guatemala.
[Miodovnik, Menachem; Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Bethesda, MD USA.
RP Bose, CL (reprint author), Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA.
EM carl_bose@med.unc.edu
FU NICHD NIH HHS [U10HD076474, U10HD076461, U10 HD078438, U10 HD076474,
U10HD078439, U01HD040636, U10HD076465, U10HD078437, U10HD076457, U01
HD040607, U10 HD076465, U10HD078438]
NR 24
TC 6
Z9 6
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S1
DI 10.1186/1742-4755-12-S2-S1
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400001
PM 26063166
ER
PT J
AU Bucher, S
Marete, I
Tenge, C
Liechty, EA
Esamai, F
Patel, A
Goudar, SS
Kodkany, B
Garces, A
Chomba, E
Althabe, F
Barreuta, M
Pasha, O
Hibberd, P
Derman, RJ
Otieno, K
Hambidge, KM
Krebs, NF
Carlo, WA
Chemweno, C
Goldenberg, RL
McClure, EM
Moore, JL
Wallace, DD
Saleem, S
Koso-Thomas, M
AF Bucher, Sherri
Marete, Irene
Tenge, Constance
Liechty, Edward A.
Esamai, Fabian
Patel, Archana
Goudar, Shivaprasad S.
Kodkany, Bhalchandra
Garces, Ana
Chomba, Elwyn
Althabe, Fernando
Barreuta, Mabel
Pasha, Omrana
Hibberd, Patricia
Derman, Richard J.
Otieno, Kevin
Hambidge, K. Michael
Krebs, Nancy F.
Carlo, Waldemar A.
Chemweno, Carolyne
Goldenberg, Robert L.
McClure, Elizabeth M.
Moore, Janet L.
Wallace, Dennis D.
Saleem, Sarah
Koso-Thomas, Marion
TI A prospective observational description of frequency and timing of
antenatal care attendance and coverage of selected interventions from
sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID MIDDLE-INCOME COUNTRIES; PREGNANT-WOMEN; WESTERN KENYA; BIRTH
PREPAREDNESS; MATERNAL HEALTH; RISK-FACTORS; STILLBIRTHS; DELIVERY;
MALARIA; ANEMIA
AB Background: The Global Network for Women's and Children's Health Research is one of the largest international networks for testing and generating evidence-based recommendations for improvement of maternal-child health in resource-limited settings. Since 2009, Global Network sites in six low and middle-income countries have collected information on antenatal care practices, which are important as indicators of care and have implications for programs to improve maternal and child health. We sought to: (1) describe the quantity of antenatal care attendance over a four-year period; and (2) explore the quality of coverage for selected preventative, screening, and birth preparedness components.
Methods: The Maternal Newborn Health Registry (MNHR) is a prospective, population-based birth and pregnancy outcomes registry in Global Network sites, including: Argentina, Guatemala, India (Belgaum and Nagpur), Kenya, Pakistan, and Zambia. MNHR data from these sites were prospectively collected from January 1, 2010 -December 31, 2013 and analyzed for indicators related to quantity and patterns of ANC and coverage of key elements of recommended focused antenatal care. Descriptive statistics were generated overall by global region (Africa, Asia, and Latin America), and for each individual site.
Results: Overall, 96% of women reported at least one antenatal care visit. Indian sites demonstrated the highest percentage of women who initiated antenatal care during the first trimester. Women from the Latin American and Indian sites reported the highest number of at least 4 visits. Overall, 88% of women received tetanus toxoid. Only about half of all women reported having been screened for syphilis (49%) or anemia (50%). Rates of HIV testing were above 95% in the Argentina, African, and Indian sites. The Pakistan site demonstrated relatively high rates for birth preparation, but for most other preventative and screening interventions, posted lower coverage rates as compared to other Global Network sites.
Conclusions: Results from our large, prospective, population-based observational study contribute important insight into regional and site-specific patterns for antenatal care access and coverage. Our findings indicate a quality and coverage gap in antenatal care services, particularly in regards to syphilis and hemoglobin screening. We have identified site-specific gaps in access to, and delivery of, antenatal care services that can be targeted for improvement in future research and implementation efforts.
C1 [Bucher, Sherri; Liechty, Edward A.; Chemweno, Carolyne] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Marete, Irene; Tenge, Constance; Esamai, Fabian; Otieno, Kevin] Moi Univ, Sch Med, Child Hlth & Paediat, Eldoret, Kenya.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Goudar, Shivaprasad S.; Kodkany, Bhalchandra] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, India.
[Garces, Ana] Fdn Alimentac & Nutr Ctr Amer & Panama, Guatemala City, Guatemala.
[Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia.
[Althabe, Fernando; Barreuta, Mabel] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Karachi, Pakistan.
[Hibberd, Patricia] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA.
[Hambidge, K. Michael; Krebs, Nancy F.] Univ Denver, Sch Med, Denver, CO USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet Gynecol, New York, NY USA.
[McClure, Elizabeth M.; Moore, Janet L.; Wallace, Dennis D.] RTI Int, Durham, NC USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Bucher, S (reprint author), Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
EM shbucher@iu.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the US National Institutes of Health [U01 HD040477,
U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457,
U10HD078439, U10HD078438, U10HD076474]
FX The project was funded by grants (U01 HD040477, U01HD040636,
U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439,
U10HD078438, and U10HD076474) from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the US National
Institutes of Health.
NR 68
TC 3
Z9 3
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S12
DI 10.1186/1742-4755-12-S2-S12
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400012
PM 26063483
ER
PT J
AU Dhaded, SM
Somannavar, MS
Vernekar, SS
Goudar, SS
Mwenche, M
Derman, R
Moore, JL
Patel, A
Pasha, O
Esamai, F
Garces, A
Althabe, F
Chomba, E
Liechty, EA
Hambidge, KM
Krebs, NF
Berrueta, M
Ciganda, A
Hibberd, PL
Goldenberg, RL
McClure, EM
Koso-Thomas, M
Manasyan, A
Carlo, WA
AF Dhaded, Sangappa M.
Somannavar, Manjunath S.
Vernekar, Sunil S.
Goudar, Shivaprasad S.
Mwenche, Musaku
Derman, Richard
Moore, Janet L.
Patel, Archana
Pasha, Omrana
Esamai, Fabian
Garces, Ana
Althabe, Fernando
Chomba, Elwyn
Liechty, Edward A.
Hambidge, K. Michael
Krebs, Nancy F.
Berrueta, Mabel
Ciganda, Alvaro
Hibberd, Patricia L.
Goldenberg, Robert L.
McClure, Elizabeth M.
Koso-Thomas, Marion
Manasyan, Albert
Carlo, Waldemar A.
TI Neonatal mortality and coverage of essential newborn interventions
2010-2013: a prospective, population-based study from low-middle income
countries
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID BORN TOO SOON; GLOBAL-NETWORK; RISK-FACTORS; DEATHS; BABIES; SURVIVAL;
COHORT; CARE
AB Background: Approximately 3 million neonatal deaths occur each year worldwide. Simple interventions have been tested and found to be effective in reducing the neonatal mortality. In order to effectively implement public health interventions, it is important to know the rates of neonatal mortality and understand the contributing risk factors. Hence, this prospective, population-based, observational study was carried out to inform these needs.
Methods: The Global Network's Maternal Newborn Health Registry was initiated in the seven sites in 2008. Registry administrators (RAs) attempt to identify and enroll all eligible women by 20 weeks gestation and collect basic health data, and outcomes after delivery and at 6 weeks post-partum. All study data were collected, reviewed, and edited by staff at each study site. The study was reviewed and approved by each sites' ethics review committee.
Results: Overall, the 7-day neonatal mortality rate (NMR) was 20.6 per 1000 live births and the 28-day NMR was 25.7 per 1000 live births. Higher neonatal mortality was associated with maternal age > 35 and < 20 years relative to women 20-35 years of age. Preterm births were at increased risk of both early and 28-day neonatal mortality (RR 8.1, 95% CI 7.5-8.8 and 7.5, 95% CI 6.9-8.1) compared to term as were those with low birth weight (< 2500g). Neonatal resuscitation rates were 4.8% for hospital deliveries compared to 0.9% for home births. In the hospital, 26.5% of deliveries were by cesarean section with an overall cesarean section rate of 12.5%. Neonatal mortality rates were highest in the Pakistan site and lowest in Argentina.
Conclusions: Using prospectively collected data with high follow up rates (99%), we documented characteristics associated with neonatal mortality. Low birth weight and prematurity are among the strongest predictors of neonatal mortality. Other risk factors for neonatal deaths included male gender, multiple gestation and major congenital anomalies. Breech presentation/transverse lie, and no antenatal care were also significant risk factors for neonatal death. Coverage of interventions varied by setting of delivery, with the overall population rate of most evidence-based interventions low. This study informs about risk factors for neonatal mortality which can serve to design strategies/interventions to reduce risk of neonatal mortality.
C1 [Dhaded, Sangappa M.; Somannavar, Manjunath S.; Vernekar, Sunil S.; Goudar, Shivaprasad S.] KLE Univ Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India.
[Mwenche, Musaku; Chomba, Elwyn] Univ Zambia, Univ Teaching Hosp, Lusaka, Zambia.
[Derman, Richard] Christiana Care Hlth Syst, Newark, DE USA.
[Moore, Janet L.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya.
[Garces, Ana] FANCAP, Guatemala City, Guatemala.
[Althabe, Fernando; Berrueta, Mabel; Ciganda, Alvaro] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Liechty, Edward A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Hambidge, K. Michael; Krebs, Nancy F.] Univ Colorado, Sch Med, Denver, CO USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Boston, MA USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet Gynecol, New York, NY USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Manasyan, Albert; Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
RP Dhaded, SM (reprint author), KLE Univ Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India.
EM drdhadedsm@gmail.com
OI Somannavar, Manjunath/0000-0002-8871-5072
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD040477, U01HD040636, U10HD078437, U10HD076461,
U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474]
FX The study was funded by grants (U01 HD040477, U01HD040636, U10HD078437,
U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, and
U10HD076474) from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development.
NR 23
TC 5
Z9 5
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S6
DI 10.1186/1742-4755-12-S2-S6
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400006
PM 26063125
ER
PT J
AU Goudar, SS
Goco, N
Somannavar, MS
Vernekar, SS
Mallapur, AA
Moore, JL
Wallace, DD
Sloan, NL
Patel, A
Hibberd, PL
Koso-Thomas, M
McClure, EM
Goldenberg, RL
AF Goudar, Shivaprasad S.
Goco, Norman
Somannavar, Manjunath S.
Vernekar, Sunil S.
Mallapur, Ashalata A.
Moore, Janet L.
Wallace, Dennis D.
Sloan, Nancy L.
Patel, Archana
Hibberd, Patricia L.
Koso-Thomas, Marion
McClure, Elizabeth M.
Goldenberg, Robert L.
TI Institutional deliveries and perinatal and neonatal mortality in
Southern and Central India
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID JANANI-SURAKSHA-YOJANA; LOW-RESOURCE SETTINGS; DEVELOPING-COUNTRIES;
MATERNAL MORTALITY; GLOBAL-NETWORK; OBSTETRIC CARE; STILLBIRTH;
INTRAPARTUM; KARNATAKA; IMPACT
AB Background: Skilled birth attendance and institutional delivery have been advocated for reducing maternal, perinatal and neonatal mortality (PMR and NMR). India has successfully implemented various strategies to promote skilled attendance and incentivize institutional deliveries in the last 5 years.
Objectives: The study evaluates the trends in institutional delivery, PMR, NMR, and their risk factors in two Eunice Kennedy Shriver NICHD Global Network for Women's and Children's Health Research sites, in Belgaum and Nagpur, India, between January 2010 and December 2013.
Design/methods: Descriptive data stratified by level of delivery care and key risk factors were analyzed for 36 geographic clusters providing 48 months of data from a prospective, population-based surveillance system that registers all pregnant permanent residents in the study area, and their pregnancy outcomes irrespective of where they deliver. Log binomial models with generalized estimating equations to control for correlation of clustered observations were used to test the trends significance
Results: 64,803 deliveries were recorded in Belgaum and 39,081 in Nagpur. Institutional deliveries increased from 92.6% to 96.1% in Belgaum and from 89.5% to 98.6% in Nagpur (both p< 0.0001); hospital rates increased from 63.4% to 71.0% (p= 0.002) and from 63.1% to 72.0% (p< 0.0001), respectively. PMR declined from 41.3 to 34.6 (p= 0.008) deaths per 1,000 births in Belgaum and from 47.4 to 40.8 (p= 0.09) in Nagpur. Stillbirths also declined, from 22.5 to 16.3 per 1,000 births in Belgaum and from 29.3 to 21.1 in Nagpur (both p= 0.002). NMR remained unchanged.
Conclusions: Significant increases in institutional deliveries, particularly in hospitals, were accompanied by reductions in stillbirths and PMR, but not by NMR.
C1 [Goudar, Shivaprasad S.; Somannavar, Manjunath S.; Vernekar, Sunil S.] KLE Univ Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India.
[Goco, Norman; Moore, Janet L.; Wallace, Dennis D.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Mallapur, Ashalata A.] S Nijalingappa Med Coll, Bagalkot, Karnataka, India.
[Sloan, Nancy L.] Christiana Care Hlth Syst, Newark, DE USA.
[Patel, Archana] Latta Med Res Fdn, Nagpur, Maharashtra, India.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Goldenberg, Robert L.] Columbia Univ, Sch Med, Dept Obstet & Gynecol, New York, NY USA.
RP Goudar, SS (reprint author), KLE Univ Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India.
EM sgoudar@jnmc.edu
OI Somannavar, Manjunath/0000-0002-8871-5072
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD040477, U01 HD043475, U01 HD043464, U01 HD040657, U01
HD042372, U01 HD040607, U01HD040636, U01 HD040574, U01 HD40636]
FX The study was funded by grants from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (U01 HD040477, U01
HD043475, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607,
U01HD040636, U01 HD040574, U01 HD40636).
NR 29
TC 3
Z9 3
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S13
DI 10.1186/1742-4755-12-S2-S13
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400013
PM 26063586
ER
PT J
AU Goudar, SS
Stolka, KB
Koso-Thomas, M
Honnungar, NV
Mastiholi, SC
Ramadurg, UY
Dhaded, SM
Pasha, O
Patel, A
Esamai, F
Chomba, E
Garces, A
Althabe, F
Carlo, WA
Goldenberg, RL
Hibberd, PL
Liechty, EA
Krebs, NF
Hambidge, MK
Moore, JL
Wallace, DD
Derman, RJ
Bhalachandra, KS
Bose, CL
AF Goudar, Shivaprasad S.
Stolka, Kristen B.
Koso-Thomas, Marion
Honnungar, Narayan V.
Mastiholi, Shivanand C.
Ramadurg, Umesh Y.
Dhaded, Sangappa M.
Pasha, Omrana
Patel, Archana
Esamai, Fabian
Chomba, Elwyn
Garces, Ana
Althabe, Fernando
Carlo, Waldemar A.
Goldenberg, Robert L.
Hibberd, Patricia L.
Liechty, Edward A.
Krebs, Nancy F.
Hambidge, Michael K.
Moore, Janet L.
Wallace, Dennis D.
Derman, Richard J.
Bhalachandra, Kodkany S.
Bose, Carl L.
TI Data quality monitoring and performance metrics of a prospective,
population-based observational study of maternal and newborn health in
low resource settings
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID BIRTH REGISTRY; IMPLEMENTATION; SYSTEMS; NORWAY
AB Background: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network's (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs).
Methods: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013.
Results: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e. g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time.
Conclusion: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health.
C1 [Goudar, Shivaprasad S.; Honnungar, Narayan V.; Mastiholi, Shivanand C.; Dhaded, Sangappa M.; Bhalachandra, Kodkany S.] KLE Univ, Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India.
[Stolka, Kristen B.; Moore, Janet L.; Wallace, Dennis D.] RTI Int, Durham, NC USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Bethesda, MD USA.
[Ramadurg, Umesh Y.] S Nijalingappa Med Coll, Belgaum, Karnataka, India.
[Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Esamai, Fabian] Univ Sch Med, Eldoret, Kenya.
[Chomba, Elwyn] Univ Zambia, Univ Teaching Hosp, Lusaka, Zambia.
[Garces, Ana] San Carlos Univ, Sch Med, Dept Pediat, Guatemala City, Guatemala.
[Althabe, Fernando] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Sch Med, Dept Pediat, Div Neonatol, Birmingham, AL USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Boston, MA USA.
[Liechty, Edward A.] Indiana Univ Sch Med, Indianapolis, IA USA.
[Krebs, Nancy F.; Hambidge, Michael K.] Univ Colorado, Sch Med, Denver, CO USA.
[Bose, Carl L.] Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA.
[Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA.
RP Stolka, KB (reprint author), RTI Int, Durham, NC USA.
EM kstolka@rti.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the US National Institutes of Health [U01 HD040477, U01
HD043475, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607,
U01HD040636, U01 HD040574, U01 HD40636]
FX The project was funded by grants (U01 HD040477, U01 HD043475, U01
HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01HD040636, U01
HD040574, U01 HD40636) from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the US National
Institutes of Health.
NR 25
TC 3
Z9 3
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S2
DI 10.1186/1742-4755-12-S2-S2
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400002
PM 26062714
ER
PT J
AU Harrison, MS
Ali, S
Pasha, O
Saleem, S
Althabe, F
Berrueta, M
Mazzoni, A
Chomba, E
Carlo, WA
Garces, A
Krebs, NF
Hambidge, KM
Goudar, SS
Dhaded, SM
Kodkany, B
Derman, RJ
Patel, A
Hibberd, PL
Esamai, F
Liechty, EA
Moore, JL
Koso-Thomas, M
McClure, EM
Goldenberg, RL
AF Harrison, Margo S.
Ali, Sumera
Pasha, Omrana
Saleem, Sarah
Althabe, Fernando
Berrueta, Mabel
Mazzoni, Agustina
Chomba, Elwyn
Carlo, Waldemar A.
Garces, Ana
Krebs, Nancy F.
Hambidge, K. Michael
Goudar, Shivaprasad S.
Dhaded, S. M.
Kodkany, Bhala
Derman, Richard J.
Patel, Archana
Hibberd, Patricia L.
Esamai, Fabian
Liechty, Edward A.
Moore, Janet L.
Koso-Thomas, Marion
McClure, Elizabeth M.
Goldenberg, Robert L.
TI A prospective population-based study of maternal, fetal, and neonatal
outcomes in the setting of prolonged labor, obstructed labor and failure
to progress in low- and middle-income countries
SO REPRODUCTIVE HEALTH
LA English
DT Article
AB Background: This population-based study sought to quantify maternal, fetal, and neonatal morbidity and mortality in low-and middle-income countries associated with obstructed labor, prolonged labor and failure to progress (OL/PL/FTP).
Methods: A prospective, population-based observational study of pregnancy outcomes was performed at seven sites in Argentina, Guatemala, India (2 sites, Belgaum and Nagpur), Kenya, Pakistan and Zambia. Women were enrolled in pregnancy and delivery and 6-week follow-up obtained to evaluate rates of OL/PL/FTP and outcomes resulting from OL/PL/FTP, including: maternal and delivery characteristics, maternal and neonatal morbidity and mortality and stillbirth.
Results: Between 2010 and 2013, 266,723 of 267,270 records (99.8%) included data on OL/PL/FTP with an overall rate of 110.4/1000 deliveries that ranged from 41.6 in Zambia to 200.1 in Pakistan. OL/PL/FTP was more common in women aged < 20, nulliparous women, more educated women, women with infants > 3500g, and women with a BMI > 25 (RR 1.4, 95% CI 1.3 -1.5), with the suggestion of OL/PL/FTP being less common in preterm deliveries. Protective characteristics included parity of = 3, having an infant < 1500g, and having a BMI < 18. Women with OL/ PL/FTP were more likely to die within 42 days (RR 1.9, 95% CI 1.4 -2.4), be infected (RR 1.8, 95% CI 1.5 -2.2), and have hemorrhage antepartum (RR 2.8, 95% CI 2.1 -3.7) or postpartum (RR 2.4, 95% CI 1.8 -3.3). They were also more likely to have a stillbirth (RR 1.6, 95% CI 1.3 -1.9), a neonatal demise at < 28 days (RR 1.9, 95% CI 1.6 -2.1), or a neonatal infection (RR 1.2, 95% CI 1.1 -1.3). As compared to operative vaginal delivery and cesarean section (CS), women experiencing OL/PL/FTP who gave birth vaginally were more likely to become infected, to have an infected neonate, to hemorrhage in the antepartum and postpartum period, and to die, have a stillbirth, or have a neonatal demise. Women with OL/PL/FTP were far more likely to deliver in a facility and be attended by a physician or other skilled provider than women without this diagnosis.
Conclusions: Women with OL/PL/FTP in the communities studied were more likely to be primiparous, younger than age 20, overweight, and of higher education, with an infant with birthweight of > 3500g. Women with this diagnosis were more likely to experience a maternal, fetal, or neonatal death, antepartum and postpartum hemorrhage, and maternal and neonatal infection. They were also more likely to deliver in a facility with a skilled provider. CS may decrease the risk of poor outcomes (as in the case of antepartum hemorrhage), but unassisted vaginal delivery exacerbates all of the maternal, fetal, and neonatal outcomes evaluated in the setting of OL/PL/FTP.
C1 [Harrison, Margo S.; Goldenberg, Robert L.] Columbia Univ, Dept Obstet Gynecol, New York, NY USA.
[Ali, Sumera; Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Althabe, Fernando; Berrueta, Mabel] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Mazzoni, Agustina] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Chomba, Elwyn] Univ Zambia, Univ Teaching Hosp, Lusaka, Zambia.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Garces, Ana] FANCAP, Guatemala City, Guatemala.
[Krebs, Nancy F.; Hambidge, K. Michael] Univ Colorado, Sch Med, Denver, CO USA.
[Goudar, Shivaprasad S.; Dhaded, S. M.; Kodkany, Bhala] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, India.
[Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Boston, MA USA.
[Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya.
[Liechty, Edward A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Moore, Janet L.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
RP Harrison, MS (reprint author), Columbia Univ, Dept Obstet Gynecol, New York, NY USA.
EM msh2154@cumc.columbia.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD040477, U01HD040636, U10HD078437, U10HD076461,
U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474]
FX The study was funded by grants (U01 HD040477, U01HD040636, U10HD078437,
U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, and
U10HD076474) from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development.
NR 11
TC 7
Z9 8
U1 3
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S9
DI 10.1186/1742-4755-12-S2-S9
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400009
PM 26063492
ER
PT J
AU Marete, I
Tenge, C
Chemweno, C
Bucher, S
Pasha, O
Ramadurg, UY
Mastiholi, SC
Chiwila, M
Patel, A
Althabe, F
Garces, A
Moore, JL
Liechty, EA
Derman, RJ
Hibberd, PL
Hambidge, KM
Goldenberg, RL
Carlo, WA
Koso-Thomas, M
McClure, EM
Esamai, F
AF Marete, Irene
Tenge, Constance
Chemweno, Carolyne
Bucher, Sherri
Pasha, Omrana
Ramadurg, Umesh Y.
Mastiholi, Shivanand C.
Chiwila, Melody
Patel, Archana
Althabe, Fernando
Garces, Ana
Moore, Janet L.
Liechty, Edward A.
Derman, Richard J.
Hibberd, Patricia L.
Hambidge, K. Michael
Goldenberg, Robert L.
Carlo, Waldemar A.
Koso-Thomas, Marion
McClure, Elizabeth M.
Esamai, Fabian
TI Lost to follow-up among pregnant women in a multi-site community based
maternal and newborn health registry: a prospective study
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID CARE; SERVICES; KENYA; HIV
AB Background: It is important when conducting epidemiologic studies to closely monitor lost to follow up (LTFU) rates. A high LTFU rate may lead to incomplete study results which in turn can introduce bias to the trial or study, threatening the validity of the findings. There is scarce information on LTFU in prospective community-based perinatal epidemiological studies. This paper reports the rates of LTFU, describes socio-demographic characteristics, and pregnancy/delivery outcomes of mothers LTFU in a large community-based pregnancy registry study.
Methods: Data were from a prospective, population-based observational study of the Global Network for Women's and Children's Health Research Maternal Newborn Health Registry (MNHR). This is a multi-centre, international study in which pregnant women were enrolled in mid-pregnancy, followed through parturition and 42 days post-delivery. Risk for LTFU was calculated within a 95% CI.
Results: A total of 282,626 subjects were enrolled in this study, of which 4,893 were lost to follow-up. Overall, there was a 1.7% LTFU to follow up rate. Factors associated with a higher LTFU included mothers who did not know their last menstrual period (RR 2.2, 95% CI 1.1, 4.4), maternal age of < 20 years (RR 1.2, 95% CI 1.1, 1.3), women with no formal education (RR 1.2, 95% CI 1.1, 1.4), and attending a government clinic for antenatal care (RR 2.0, 95% CI 1.4, 2.8). Post-natal factors associated with a higher LTFU rate included a newborn with feeding problems (RR 1.6, 94% CI 1.2, 2.2).
Conclusions: The LTFU rate in this community-based registry was low (1.7%). Maternal age, maternal level of education, pregnancy status at enrollment and using a government facility for ANC are factors associated with being LTFU. Strategies to ensure representation and high retention in community studies are important to informing progress toward public health goals.
C1 [Marete, Irene; Tenge, Constance; Chemweno, Carolyne; Esamai, Fabian] Moi Univ, Dept Child Hlth & Paediat, Sch Med, Eldoret, Kenya.
[Bucher, Sherri; Liechty, Edward A.] Indiana Univ, Riley Hosp, Dept Paediat, Indianapolis, IN 46204 USA.
[Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Serv, Karachi, Pakistan.
[Ramadurg, Umesh Y.] S Nijalingappa Med Coll, Bagalkot, Karnataka, India.
[Mastiholi, Shivanand C.] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India.
[Chiwila, Melody] Univ Teaching Hosp, Lusaka, Zambia.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Althabe, Fernando] Inst Clin Effectiveness, Buenos Aires, DF, Argentina.
[Garces, Ana] Francisco Marroquin Univ, Multidisciplinary Hlth Inst, Guatemala City, Guatemala.
[Moore, Janet L.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Derman, Richard J.] Christiana Care Hlth Syst, Wilmington, DC USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Div Global Hlth, Boston, MA 02114 USA.
[Hambidge, K. Michael] Univ Colorado, Dept Paediat, Denver, CO 80202 USA.
[Goldenberg, Robert L.] Columbia Univ, New York, NY USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Paediat, Birmingham, AL USA.
[Koso-Thomas, Marion] NICHHD, Bethesda, MD 20892 USA.
RP Marete, I (reprint author), Moi Univ, Dept Child Hlth & Paediat, Sch Med, Eldoret, Kenya.
EM mareteirene07@yahoo.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the US National Institutes of Health United State of
America [U01 HD040477, U01HD040636, U10HD078437, U10HD076461,
U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474]
FX We acknowledge the work of all the Registry Administrators in the seven
Global Network sites. This work was supported by grants (U01 HD040477,
U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457,
U10HD078439, U10HD078438, and U10HD076474) from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development of the
US National Institutes of Health United State of America.
NR 17
TC 1
Z9 1
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S4
DI 10.1186/1742-4755-12-S2-S4
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400004
PM 26062899
ER
PT J
AU McClure, EM
Saleem, S
Goudar, SS
Moore, JL
Garces, A
Esamai, F
Patel, A
Chomba, E
Althabe, F
Pasha, O
Kodkany, BS
Bose, CL
Berreuta, M
Liechty, EA
Hambidge, KM
Krebs, NF
Derman, RJ
Hibberd, PL
Buekens, P
Manasyan, A
Carlo, WA
Wallace, DD
Koso-Thomas, M
Goldenberg, RL
AF McClure, Elizabeth M.
Saleem, Sarah
Goudar, Shivaprasad S.
Moore, Janet L.
Garces, Ana
Esamai, Fabian
Patel, Archana
Chomba, Elwyn
Althabe, Fernando
Pasha, Omrana
Kodkany, Bhalachandra S.
Bose, Carl L.
Berreuta, Mabel
Liechty, Edward A.
Hambidge, K. Michael
Krebs, Nancy F.
Derman, Richard J.
Hibberd, Patricia L.
Buekens, Pierre
Manasyan, Albert
Carlo, Waldemar A.
Wallace, Dennis D.
Koso-Thomas, Marion
Goldenberg, Robert L.
TI Stillbirth rates in low-middle income countries 2010-2013: a
population-based, multi-country study from the Global Network
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID LOW-RESOURCE SETTINGS; PERINATAL-MORTALITY; CESAREAN DELIVERY; OBSTETRIC
CARE; PREGNANCY OUTCOMES; NEONATAL DEATHS; NEWBORN HEALTH; INTRAPARTUM;
DETERMINANTS; BANGLADESH
AB Background: Stillbirth rates remain nearly ten times higher in low-middle income countries (LMIC) than high income countries. In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented characteristics or care for mothers with stillbirths. Non-macerated stillbirths, those occurring around delivery, are generally considered preventable with appropriate obstetric care.
Methods: We undertook a prospective, population-based observational study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). Staff collected demographic and health care characteristics with outcomes obtained at delivery.
Results: From 2010 through 2013, 269,614 enrolled women had 272,089 births, including 7,865 stillbirths. The overall stillbirth rate was 28.9/1000 births, ranging from 13.6/1000 births in Argentina to 56.5/1000 births in Pakistan. Stillbirth rates were stable or declined in 6 of the 7 sites from 2010-2013, only increasing in Pakistan. Less educated, older and women with less access to antenatal care were at increased risk of stillbirth. Furthermore, women not delivered by a skilled attendant were more likely to have a stillbirth (RR 2.8, 95% CI 2.2, 3.5). Compared to live births, stillbirths were more likely to be preterm (RR 12.4, 95% CI 11.2, 13.6). Infants with major congenital anomalies were at increased risk of stillbirth (RR 9.1, 95% CI 7.3, 11.4), as were multiple gestations (RR 2.8, 95% CI 2.4, 3.2) and breech (RR 3.0, 95% CI 2.6, 3.5). Altogether, 67.4% of the stillbirths were non-macerated. 7.6% of women with stillbirths had cesarean sections, with obstructed labor the primary indication (36.9%).
Conclusions: Stillbirth rates were high, but with reductions in most sites during the study period. Disadvantaged women, those with less antenatal care and those delivered without a skilled birth attendant were at increased risk of delivering a stillbirth. More than two-thirds of all stillbirths were non-macerated, suggesting potentially preventable stillbirth. Additionally, 8% of women with stillbirths were delivered by cesarean section. The relatively high rate of cesarean section among those with stillbirths suggested that this care was too late or not of quality to prevent the stillbirth; however, further research is needed to evaluate the quality of obstetric care, including cesarean section, on stillbirth in these low resource settings.
C1 [McClure, Elizabeth M.; Moore, Janet L.] RTI Int, Durham, NC USA.
[Saleem, Sarah; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan.
[Goudar, Shivaprasad S.; Kodkany, Bhalachandra S.] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, India.
[Garces, Ana] Fdn Alimentac Nutr, Ctr Amer & Panama, Guatemala City, Guatemala.
[Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia.
[Althabe, Fernando; Berreuta, Mabel] Univ Buenos Aires, Inst Clin Effectiveness & Hlth Policy, RA-1053 Buenos Aires, DF, Argentina.
[Bose, Carl L.] Univ N Carolina, Chapel Hill, NC USA.
[Liechty, Edward A.] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Hambidge, K. Michael; Krebs, Nancy F.] Univ Denver, Sch Med, Denver, CO USA.
[Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Buekens, Pierre] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Manasyan, Albert; Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Goldenberg, Robert L.] Columbia Univ, Sch Med, Dept Obstet & Gynecol, New York, NY USA.
RP McClure, EM (reprint author), RTI Int, Durham, NC USA.
EM mcclure@rti.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD040477, U01HD040636, U10HD078437, U10HD076461,
U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474]
FX The study was funded by grants from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (U01 HD040477,
U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457,
U10HD078439, U10HD078438, and U10HD076474).
NR 31
TC 11
Z9 11
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S7
DI 10.1186/1742-4755-12-S2-S7
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400007
PM 26063292
ER
PT J
AU Pasha, O
Goudar, SS
Patel, A
Garces, A
Esamai, F
Chomba, E
Moore, JL
Kodkany, BS
Saleem, S
Derman, RJ
Liechty, EA
Hibberd, PL
Hambidge, KM
Krebs, NF
Carlo, WA
McClure, EM
Koso-Thomas, M
Goldenberg, RL
AF Pasha, Omrana
Goudar, Shivaprasad S.
Patel, Archana
Garces, Ana
Esamai, Fabian
Chomba, Elwyn
Moore, Janet L.
Kodkany, Bhalchandra S.
Saleem, Sarah
Derman, Richard J.
Liechty, Edward A.
Hibberd, Patricia L.
Hambidge, K. Michael
Krebs, Nancy F.
Carlo, Waldemar A.
McClure, Elizabeth M.
Koso-Thomas, Marion
Goldenberg, Robert L.
TI Postpartum contraceptive use and unmet need for family planning in five
low-income countries
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID SHORT INTERPREGNANCY INTERVALS; PERINATAL OUTCOMES; BIRTH OUTCOMES;
WOMEN; RISK; PREGNANCY; HEALTH; DEATH; DISCONTINUATION; QUALITY
AB Background: During the post-partum period, most women wish to delay or prevent future pregnancies. Despite this, the unmet need for family planning up to a year after delivery is higher than at any other time. This study aims to assess fertility intention, contraceptive usage and unmet need for family planning amongst women who are six weeks postpartum, as well as to identify those at greatest risk of having an unmet need for family planning during this period.
Methods: Using the NICHD Global Network for Women's and Children's Health Research's multi-site, prospective, ongoing, active surveillance system to track pregnancies and births in 100 rural geographic clusters in 5 countries (India, Pakistan, Zambia, Kenya and Guatemala), we assessed fertility intention and contraceptive usage at day 42 post-partum.
Results: We gathered data on 36,687 women in the post-partum period. Less than 5% of these women wished to have another pregnancy within the year. Despite this, rates of modern contraceptive usage varied widely and unmet need ranged from 25% to 96%. Even amongst users of modern contraceptives, the uptake of the most effective long-acting reversible contraceptives (intrauterine devices) was low. Women of age less than 20 years, parity of two or less, limited education and those who deliver at home were at highest risk for having unmet need.
Conclusions: Six weeks postpartum, almost all women wish to delay or prevent a future pregnancy. Even in sites where early contraceptive adoption is common, there is substantial unmet need for family planning. This is consistently highest amongst women below the age of 20 years. Interventions aimed at increasing the adoption of effective contraceptive methods are urgently needed in the majority of sites in order to reduce unmet need and to improve both maternal and infant outcomes, especially amongst young women.
C1 [Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Goudar, Shivaprasad S.; Kodkany, Bhalchandra S.] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Garces, Ana] FANCAP, Guatemala City, Guatemala.
[Esamai, Fabian] Moi Univ, Dept Pediat, Eldoret, Kenya.
[Chomba, Elwyn] Univ Zambia, Dept Pediat, Lusaka, Zambia.
[Moore, Janet L.] Social Stat & Environm Sci Res Triangle Inst, Durham, NC USA.
[Derman, Richard J.; McClure, Elizabeth M.] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA.
[Liechty, Edward A.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA.
[Hambidge, K. Michael; Krebs, Nancy F.] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Koso-Thomas, Marion] NICHD, Bethesda, MD USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
RP Pasha, O (reprint author), Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
EM Omrana.pasha@aku.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD040477, U01HD040636, U10HD078437, U10HD076461,
U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474]
FX This study was supported through grants from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (U01 HD040477,
U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457,
U10HD078439, U10HD078438, and U10HD076474).
NR 36
TC 5
Z9 5
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S11
DI 10.1186/1742-4755-12-S2-S11
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400011
PM 26063346
ER
PT J
AU Pasha, O
Saleem, S
Ali, S
Goudar, SS
Garces, A
Esamai, F
Patel, A
Chomba, E
Althabe, F
Moore, JL
Harrison, M
Berrueta, MB
Hambidge, KM
Krebs, NF
Hibberd, PL
Carlo, WA
Kodkany, B
Derman, RJ
Liechty, EA
Koso-Thomas, M
McClure, EM
Goldenberg, RL
AF Pasha, Omrana
Saleem, Sarah
Ali, Sumera
Goudar, Shivaprasad S.
Garces, Ana
Esamai, Fabian
Patel, Archana
Chomba, Elwyn
Althabe, Fernando
Moore, Janet L.
Harrison, Margo
Berrueta, Mabel B.
Hambidge, K. Michael
Krebs, Nancy F.
Hibberd, Patricia L.
Carlo, Waldemar A.
Kodkany, Bhala
Derman, Richard J.
Liechty, Edward A.
Koso-Thomas, Marion
McClure, Elizabeth M.
Goldenberg, Robert L.
TI Maternal and newborn outcomes in Pakistan compared to other low and
middle income countries in the Global Network's Maternal Newborn Health
Registry: an active, community-based, pregnancy surveillance mechanism
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID NEONATAL-MORTALITY; OBSTETRIC CARE; CHILD HEALTH; INTERVENTIONS;
STILLBIRTHS; DEATHS; RISK
AB Background: Despite global improvements in maternal and newborn health (MNH), maternal, fetal and newborn mortality rates in Pakistan remain stagnant. Using data from the Global Network's Maternal Newborn Health Registry (MNHR) the objective of this study is to compare the rates of maternal mortality, stillbirth and newborn mortality and levels of putative risk factors between the Pakistani site and those in other countries.
Methods: Using data collected through a multi-site, prospective, ongoing, active surveillance system to track pregnancies and births in communities in discrete geographical areas in seven sites across six countries including Pakistan, India, Kenya, Zambia, Guatemala and Argentina from 2010 to 2013, the study compared MNH outcomes and risk factors. The MNHR captures more than 60,000 deliveries annually across all sites with over 10,000 of them in Thatta, Pakistan.
Results: The Pakistan site had a maternal mortality ratio almost three times that of the other sites (313/100,000 vs 116/100,000). Stillbirth (56.5 vs 22.9/1000 births), neonatal mortality (50.0 vs 20.7/1000 livebirths) and perinatal mortality rates (95.2/1000 vs 39.0/1000 births) in Thatta, Pakistan were more than twice those of the other sites. The Pakistani site is the only one in the Global Network where maternal mortality increased (from 231/100,000 to 353/100,000) over the study period and fetal and neonatal outcomes remained stagnant. The Pakistan site lags behind other sites in maternal education, high parity, and appropriate antenatal and postnatal care. However, facility delivery and skilled birth attendance rates were less prominently different between the Pakistani site and other sites, with the exception of India. The difference in the fetal and neonatal outcomes between the Pakistani site and the other sites was most pronounced amongst normal birth weight babies.
Conclusions: The increase in maternal mortality and the stagnation of fetal and neonatal outcomes from 2010 to 2013 indicates that current levels of antenatal and newborn care interventions in Thatta, Pakistan are insufficient to protect against poor maternal and neonatal outcomes. Delivery care in the Pakistani site, while appearing quantitatively equivalent to the care in sites in Africa, is less effective in saving the lives of women and their newborns. By the metrics available from this study, the quality of obstetric and neonatal care in the site in Pakistan is poor.
C1 [Pasha, Omrana; Saleem, Sarah; Ali, Sumera] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Goudar, Shivaprasad S.; Kodkany, Bhala] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, India.
[Garces, Ana] FANCAP, Guatemala City, Guatemala.
[Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Chomba, Elwyn] Univ Zambia, Univ Teaching Hosp, Lusaka, Zambia.
[Althabe, Fernando; Berrueta, Mabel B.] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Moore, Janet L.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Harrison, Margo; Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Hambidge, K. Michael; Krebs, Nancy F.] Univ Colorado, Sch Med, Denver, CO USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Boston, MA USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA.
[Liechty, Edward A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Pasha, O (reprint author), Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
EM omrana.pasha@aku.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX The study was funded by grants from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 32
TC 2
Z9 2
U1 2
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S15
DI 10.1186/1742-4755-12-S2-S15
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400015
PM 26062610
ER
PT J
AU Patel, A
Bucher, S
Pusdekar, Y
Esamai, F
Krebs, NF
Goudar, SS
Chomba, E
Garces, A
Pasha, O
Saleem, S
Kodkany, BS
Liechty, EA
Kodkany, B
Derman, RJ
Carlo, WA
Hambidge, KM
Goldenberg, RL
Althabe, F
Berrueta, M
Moore, JL
McClure, EM
Koso-Thomas, M
Hibberd, PL
AF Patel, Archana
Bucher, Sherri
Pusdekar, Yamini
Esamai, Fabian
Krebs, Nancy F.
Goudar, Shivaprasad S.
Chomba, Elwyn
Garces, Ana
Pasha, Omrana
Saleem, Sarah
Kodkany, Bhalachandra S.
Liechty, Edward A.
Kodkany, Bhala
Derman, Richard J.
Carlo, Waldemar A.
Hambidge, K. Michael
Goldenberg, Robert L.
Althabe, Fernando
Berrueta, Mabel
Moore, Janet L.
McClure, Elizabeth M.
Koso-Thomas, Marion
Hibberd, Patricia L.
TI Rates and determinants of early initiation of breastfeeding and
exclusive breast feeding at 42 days postnatal in six low and
middle-income countries: A prospective cohort study
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; SECONDARY DATA-ANALYSIS;
NEONATAL-MORTALITY; NEWBORN-CARE; PERINATAL-MORTALITY; BIRTH ATTENDANTS;
GLOBAL-NETWORK; RURAL GHANA; HEALTH; INFANT
AB Background: Early initiation of breastfeeding after birth and exclusive breastfeeding through six months of age confers many health benefits for infants; both are crucial high impact, low-cost interventions. However, determining accurate global rates of these crucial activities has been challenging. We use population-based data to describe: (1) rates of early initiation of breastfeeding (defined as within 1 hour of birth) and of exclusive breastfeeding at 42 days post-partum; and (2) factors associated with failure to initiate early breastfeeding and exclusive breastfeeding at 42 days post-partum.
Methods: Prospectively collected data from women and their live-born infants enrolled in the Global Network's Maternal and Newborn Health Registry between January 1, 2010-December 31, 2013 included women-infant dyads in 106 geographic areas (clusters) at 7 research sites in 6 countries (Kenya, Zambia, India [2 sites], Pakistan, Argentina and Guatemala). Rates and risk factors for failure to initiate early breastfeeding were investigated for the entire cohort and rates and risk factors for failure to maintain exclusive breastfeeding was assessed in a sub-sample studied at 42 days post-partum.
Result: A total of 255,495 live-born women-infant dyads were included in the study. Rates and determinants for the exclusive breastfeeding sub-study at 42 days post-partum were assessed from among a sub-sample of 105,563 subjects. Although there was heterogeneity by site, and early initiation of breastfeeding after delivery was high, the Pakistan site had the lowest rates of early initiation of breastfeeding. The Pakistan site also had the highest rate of lack of exclusive breastfeeding at 42 days post-partum. Across all regions, factors associated with failure to initiate early breastfeeding included nulliparity, caesarean section, low birth weight, resuscitation with bag and mask, and failure to place baby on the mother's chest after delivery. Factors associated with failure to achieve exclusive breastfeeding at 42 days varied across the sites. The only factor significant in all sites was multiple gestation.
Conclusions: In this large, prospective, population-based, observational study, rates of both early initiation of breastfeeding and exclusive breastfeeding at 42 days post-partum were high, except in Pakistan. Factors associated with these key breastfeeding indicators should assist with more effective strategies to scale-up these crucial public health interventions.
C1 [Patel, Archana; Pusdekar, Yamini; Althabe, Fernando] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, Archana; Pusdekar, Yamini; Althabe, Fernando] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Bucher, Sherri; Liechty, Edward A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Esamai, Fabian] Moi Univ, Eldoret, Kenya.
[Krebs, Nancy F.; Hambidge, K. Michael] Univ Colorado, Sch Med, Denver, CO USA.
[Goudar, Shivaprasad S.; Kodkany, Bhalachandra S.; Kodkany, Bhala] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, India.
[Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia.
[Garces, Ana] FANCAP, Guatemala City, Guatemala.
[Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Karachi, Pakistan.
[Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Goldenberg, Robert L.] Columbia Univ, New York, NY USA.
[Berrueta, Mabel] IECS, Buenos Aires, DF, Argentina.
[Moore, Janet L.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Boston, MA USA.
RP Patel, A (reprint author), Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
EM dr_apatel@yahoo.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD040477, U01HD040636, U10HD078437, U10HD076461,
U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474]
FX This project was funded by grants (U01 HD040477, U01HD040636,
U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439,
U10HD078438, and U10HD076474) from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 61
TC 3
Z9 5
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PY 2015
VL 12
SU 2
AR S10
DI 10.1186/1742-4755-12-S2-S10
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG8LU
UT WOS:000372336400010
PM 26063291
ER
PT B
AU Hanson, RL
Malhotra, A
AF Hanson, Robert L.
Malhotra, Alka
BE Duggirala, R
Almasy, L
WilliamsBlangero, S
Paul, SFD
Kole, C
TI Association Studies to Map Genes for Disease-Related Traits in Humans
SO GENOME MAPPING AND GENOMICS IN HUMAN AND NON-HUMAN PRIMATES
SE Genome Mapping and Genomics in Animals
LA English
DT Article; Book Chapter
ID GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY LOCI;
SAMPLE-SIZE; CANCER SUSCEPTIBILITY; IMPUTATION ACCURACY;
GENOTYPE-IMPUTATION; DIABETES-MELLITUS; RESEQUENCING DATA;
AMERICAN-INDIANS
C1 [Hanson, Robert L.; Malhotra, Alka] NIDDK, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
RP Hanson, RL (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM rhanson@phx.niddk.nih.gov; alka@niddk.nih.gov
NR 70
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
BN 978-3-662-46306-2; 978-3-662-46305-5
J9 GENOME MAPP GENOMICS
JI Genome Mapp. Genomics Anim.
PY 2015
VL 5
BP 53
EP 66
DI 10.1007/978-3-662-46306-2_4
D2 10.1007/978-3-662-46306-2
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA BE4MT
UT WOS:000371927800005
ER
PT B
AU Mitchell, BD
Schaffer, AA
Pollin, TI
Streeten, EA
Horenstein, RB
Steinle, NI
Yerges-Armstrong, L
Shuldiner, AR
O'Connell, JR
AF Mitchell, Braxton D.
Schaeffer, Alejandro A.
Pollin, Toni I.
Streeten, Elizabeth A.
Horenstein, Richard B.
Steinle, Nanette I.
Yerges-Armstrong, Laura
Shuldiner, Alan R.
O'Connell, Jeffrey R.
BE Duggirala, R
Almasy, L
WilliamsBlangero, S
Paul, SFD
Kole, C
TI Mapping Genes in Isolated Populations: Lessons from the Old Order Amish
SO GENOME MAPPING AND GENOMICS IN HUMAN AND NON-HUMAN PRIMATES
SE Genome Mapping and Genomics in Animals
LA English
DT Article; Book Chapter
ID APOLIPOPROTEIN-C-III; A-I; PREMATURE ATHEROSCLEROSIS;
DIETARY-CHOLESTEROL; LANCASTER COUNTY; LINKAGE ANALYSIS; CORONARY
EVENTS; PLANT STEROLS; DISEASE; SITOSTEROLEMIA
C1 [Mitchell, Braxton D.; Pollin, Toni I.; Streeten, Elizabeth A.; Horenstein, Richard B.; Steinle, Nanette I.; Yerges-Armstrong, Laura; Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, 22 S Greene St, Baltimore, MD 21201 USA.
[Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, DHHS, 8600 Rockville Pike, Bethesda, MD 20894 USA.
[Streeten, Elizabeth A.; Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA.
[Steinle, Nanette I.] Vet Adm Med Ctr, Diabet & Endocrinol Sect, Baltimore, MD 21201 USA.
RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Dept Med, 22 S Greene St, Baltimore, MD 21201 USA.
EM bmitchel@medicine.umaryland.edu; aschaffe@helix.nih.gov;
tpollin@medicine.umaryland.edu; estreete@medicine.umaryland.edu;
rhorenst@medicine.umaryland.edu; nsteinle@medicine.umaryland.edu;
lyerges@medicine.umaryland.edu; ashuldin@medicine.umaryland.edu;
joconnel@medicine.umaryland.edu
OI Mitchell, Braxton/0000-0003-4920-4744
NR 53
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
BN 978-3-662-46306-2; 978-3-662-46305-5
J9 GENOME MAPP GENOMICS
JI Genome Mapp. Genomics Anim.
PY 2015
VL 5
BP 141
EP 153
DI 10.1007/978-3-662-46306-2_10
D2 10.1007/978-3-662-46306-2
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA BE4MT
UT WOS:000371927800011
ER
PT S
AU Rostovtseva, TK
Bezrukov, SM
AF Rostovtseva, Tatiana K.
Bezrukov, Sergey M.
BE Delcour, AH
TI Function and Regulation of Mitochondrial Voltage-Dependent Anion Channel
SO ELECTROPHYSIOLOGY OF UNCONVENTIONAL CHANNELS AND PORES
SE Springer Series in Biophysics
LA English
DT Article; Book Chapter
DE VDAC; Tubulin; Voltage gating; ATP transport; Lipid membranes;
Beta-barrel channels
ID ISCHEMIA-REPERFUSION INJURY; TUBULIN-BLOCKED STATE; VDAC1 N-TERMINUS;
OUTER-MEMBRANE; PHOSPHOLIPID-VESICLES; LIPID-COMPOSITION; ATP TRANSPORT;
CYTOCHROME-C; SUCCINIC ANHYDRIDE; SELECTIVE CHANNEL
AB The voltage-dependent anion channel (VDAC) is the major protein of the mitochondrial outer membrane (MOM). It is now generally accepted that this channel is responsible for most of the metabolite flux in and out of mitochondria. Small ions, adenine nucleotides such as ATP and ADP, and other water soluble mitochondrial respiratory substrates cross the MOM through VDAC. Therefore, any restriction to metabolite exchange through VDAC is able to lead to an essential disturbance of mitochondrial energetic functions and cell metabolism. This review discusses the mechanisms of regulation of these fluxes by VDAC through its ability to "gate" or adopt different conducting states. The focus of the first part is on the biophysical properties of this evolutionary conserved beta-barrel channel reconstituted into its "native" lipid environment and especially on the mechanisms of modification of VDAC gating by electrical field, medium pH, and membrane lipid composition. The second part of this review addresses the novel mechanism of VDAC regulation by dimeric tubulin, an abundant cytosolic protein, and the physiological implications of the uncovered VDAC-tubulin interaction. One of the intriguing consequences of VDAC regulation by tubulin is its coupling with the Warburg-type aerobic glycolysis characteristic of many tumor cells where the VDAC-tubulin complex may play a role of "glycolytic switch" moving cells between aerobic glycolysis and oxidative phosphorylation. The discussed biophysical insights of VDAC blockage by tubulin, obtained from experiments at the single-molecule level, could be also important for understanding the molecular mechanisms of functional interactions between water soluble and membrane proteins in general.
C1 [Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Rostovtseva, TK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM rostovtt@mail.nih.gov
NR 113
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0932-2353
BN 978-3-319-20149-8; 978-3-319-20148-1
J9 SPRINGER SER BIOPHYS
JI Springer Ser. Biophys.
PY 2015
VL 18
BP 3
EP 31
DI 10.1007/978-3-319-20149-8_1
D2 10.1007/978-3-319-20149-8
PG 29
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA BE4BQ
UT WOS:000371485200002
ER
PT J
AU Freeman, ML
Mudd, JC
Younes, SA
Panigrahi, S
Lee, SA
Hunt, PW
Gianella, S
Lederman, MM
AF Freeman, M. L.
Mudd, J. C.
Younes, S. A.
Panigrahi, S.
Lee, S. A.
Hunt, P. W.
Gianella, S.
Lederman, M. M.
TI CD8 T-cells expressing the fractalkine (endothelial homing) receptor
CX3CR1 in treated HIV infection are promoted by CMV co-infection and
functionally impaired by platelet interactions
SO ANTIVIRAL THERAPY
LA English
DT Meeting Abstract
CT 17th International Workshop on Co-Morbidities and Adverse Drug Reaction
in HIV
CY OCT 20-22, 2015
CL Barcelona, SPAIN
C1 [Freeman, M. L.; Mudd, J. C.; Younes, S. A.; Panigrahi, S.; Lederman, M. M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Mudd, J. C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Lee, S. A.; Hunt, P. W.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Gianella, S.] Univ Calif San Diego, La Jolla, CA 92093 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU INT MEDICAL PRESS LTD
PI LONDON
PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND
SN 1359-6535
J9 ANTIVIR THER
JI Antivir. Ther.
PY 2015
VL 20
SU 1
MA O07
BP A8
EP A8
PG 1
WC Infectious Diseases; Pharmacology & Pharmacy; Virology
SC Infectious Diseases; Pharmacology & Pharmacy; Virology
GA DE8VV
UT WOS:000370915700008
ER
PT J
AU Funderburg, NT
Xu, D
Playford, M
Andrade, A
Kuritzkes, D
Lederman, MM
Mehta, NN
AF Funderburg, N. T.
Xu, D.
Playford, M.
Andrade, A.
Kuritzkes, D.
Lederman, M. M.
Mehta, N. N.
TI Treatment of HIV disease with a raltegravir-based regimen increases LDL
levels, but improves HDL composition and function
SO ANTIVIRAL THERAPY
LA English
DT Meeting Abstract
CT 17th International Workshop on Co-Morbidities and Adverse Drug Reaction
in HIV
CY OCT 20-22, 2015
CL Barcelona, SPAIN
C1 [Funderburg, N. T.] Ohio State Univ, Columbus, OH 43210 USA.
[Xu, D.; Playford, M.; Mehta, N. N.] NHLBI, Bethesda, MD 20892 USA.
[Andrade, A.] Johns Hopkins Univ, Baltimore, MD USA.
[Kuritzkes, D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lederman, M. M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RI Funderburg, Nicholas/L-8022-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT MEDICAL PRESS LTD
PI LONDON
PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND
SN 1359-6535
J9 ANTIVIR THER
JI Antivir. Ther.
PY 2015
VL 20
SU 1
MA P02
BP A30
EP A30
PG 1
WC Infectious Diseases; Pharmacology & Pharmacy; Virology
SC Infectious Diseases; Pharmacology & Pharmacy; Virology
GA DE8VV
UT WOS:000370915700033
ER
PT J
AU Mulligan, K
Rutledge, B
Kapogiannis, BG
Siberry, GK
Anderson, PL
Landowitz, RJ
Rudy, B
Liu, N
Havens, PL
Wilson, CM
Hosek, S
AF Mulligan, K.
Rutledge, B.
Kapogiannis, B. G.
Siberry, G. K.
Anderson, P. L.
Landowitz, R. J.
Rudy, B.
Liu, N.
Havens, P. L.
Wilson, C. M.
Hosek, S.
CA Adolescent Trial Network ATN HIV A
TI Bone changes in young men ages 18-22 enrolled in a pre-exposure
prophylaxis (PrEP) safety and demonstration study using tenofovir
disoproxil fumarate/emtricitabine (TDF/FTC)
SO ANTIVIRAL THERAPY
LA English
DT Meeting Abstract
CT 17th International Workshop on Co-Morbidities and Adverse Drug Reaction
in HIV
CY OCT 20-22, 2015
CL Barcelona, SPAIN
C1 [Mulligan, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Rutledge, B.; Liu, N.] WESTAT Corp, Rockville, MD 20850 USA.
[Kapogiannis, B. G.; Siberry, G. K.] NICHHD, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Anderson, P. L.] Univ Colorado, Denver, CO 80202 USA.
[Landowitz, R. J.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Rudy, B.] NYU Med Ctr, New York, NY 10016 USA.
[Havens, P. L.] Med Coll Wisconsin, Milwaukee, WI USA.
[Wilson, C. M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Hosek, S.] John H Stroger Jr Hosp Cook Cty, Chicago, IL USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU INT MEDICAL PRESS LTD
PI LONDON
PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND
SN 1359-6535
J9 ANTIVIR THER
JI Antivir. Ther.
PY 2015
VL 20
SU 1
MA O26
BP A21
EP A22
PG 2
WC Infectious Diseases; Pharmacology & Pharmacy; Virology
SC Infectious Diseases; Pharmacology & Pharmacy; Virology
GA DE8VV
UT WOS:000370915700027
ER
PT J
AU Younes, SA
Freeman, ML
Mudd, JC
Shive, CL
Reynaldi, A
Panigrahi, S
Estes, JD
Deleage, C
Lucero, C
Anderson, J
Schacker, TW
Davenport, MP
McCune, JM
Hunt, PW
Lee, SA
Serano-Villar, S
Canaday, DH
Sekaly, RP
Rodriguez, B
Sieg, SF
Lederman, MM
AF Younes, S-A
Freeman, M. L.
Mudd, J. C.
Shive, C. L.
Reynaldi, A.
Panigrahi, S.
Estes, J. D.
Deleage, C.
Lucero, C.
Anderson, J.
Schacker, T. W.
Davenport, M. P.
McCune, J. M.
Hunt, P. W.
Lee, S. A.
Serano-Villar, S.
Canaday, D. H.
Sekaly, R-P
Rodriguez, B.
Sieg, S. F.
Lederman, M. M.
TI IL-15 and CMV co-infection drive CD8 T-cell expansion in HIV-1 infection
SO ANTIVIRAL THERAPY
LA English
DT Meeting Abstract
CT 17th International Workshop on Co-Morbidities and Adverse Drug Reaction
in HIV
CY OCT 20-22, 2015
CL Barcelona, SPAIN
C1 [Younes, S-A; Freeman, M. L.; Mudd, J. C.; Shive, C. L.; Panigrahi, S.; Canaday, D. H.; Sekaly, R-P; Rodriguez, B.; Sieg, S. F.; Lederman, M. M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Younes, S-A; Freeman, M. L.; Mudd, J. C.; Shive, C. L.; Panigrahi, S.; Canaday, D. H.; Sekaly, R-P; Rodriguez, B.; Sieg, S. F.; Lederman, M. M.] Univ Hosp, Cleveland, OH USA.
[Reynaldi, A.; Davenport, M. P.] Univ New S Wales, Sydney, NSW, Australia.
[Estes, J. D.; Deleage, C.; Lucero, C.] Frederick Natl Lab Canc Res, Frederick, MD USA.
[Anderson, J.; Schacker, T. W.] Univ Minnesota, Minneapolis, MN USA.
[McCune, J. M.; Hunt, P. W.; Lee, S. A.] Univ Calif Irvine, Irvine, CA USA.
[Serano-Villar, S.] Univ Hosp Ramon & Cajal, Madrid, Spain.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU INT MEDICAL PRESS LTD
PI LONDON
PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND
SN 1359-6535
J9 ANTIVIR THER
JI Antivir. Ther.
PY 2015
VL 20
SU 1
MA O08
BP A8
EP A9
PG 2
WC Infectious Diseases; Pharmacology & Pharmacy; Virology
SC Infectious Diseases; Pharmacology & Pharmacy; Virology
GA DE8VV
UT WOS:000370915700009
ER
PT S
AU Vecchiarelli, AG
Taylor, JA
Mizuuchi, K
AF Vecchiarelli, Anthony G.
Taylor, James A.
Mizuuchi, Kiyoshi
BE Ross, J
Marshall, WF
TI Reconstituting ParA/ParB-mediated transport of DNA cargo
SO BUILDING A CELL FROM ITS COMPONENT PARTS
SE Methods in Cell Biology
LA English
DT Review; Book Chapter
ID DIFFUSION-RATCHET MECHANISM; F-PLASMID; PATTERN-FORMATION; PARTITION;
PROTEIN; ATPASE; SOPA; SEGREGATION
AB Protein gradients play key roles in subcellular spatial organization. In bacteria, ParA adenosine triphosphatases, or ATPases, form dynamic gradients on the nucleoid surface, which imparts positional information for the segregation, transport, and positioning of chromosomes, plasmids, and large protein assemblies. Despite the apparent simplicity of these minimal and self-organizing systems, the mechanism remains unclear. The small size of bacteria along with the number of physical and biochemical processes involved in subcellular organization makes it difficult to study these systems under controlled conditions in vivo. We developed a cell-free reconstitution technique that allows for the visualization of ParA-mediated cargo transport on a DNA carpet, which acts as a biomimetic of the nucleoid surface. Here, we present methods to express, purify, and visualize the dynamic properties of the SopABC system from F plasmid, considered a paradigm for the study of ParA-type systems. We hope similar cell-free studies will be used to address the biochemical and biophysical underpinnings of this ubiquitous transport scheme in bacteria.
C1 [Vecchiarelli, Anthony G.; Taylor, James A.; Mizuuchi, Kiyoshi] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Vecchiarelli, AG (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM vecchiarelliag@mail.nih.gov
FU Intramural NIH HHS
NR 21
TC 2
Z9 2
U1 1
U2 8
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-679X
BN 978-0-12-802450-8
J9 METHOD CELL BIOL
JI Methods Cell Biol.
PY 2015
VL 128
BP 243
EP 269
DI 10.1016/bs.mcb.2015.01.021
PG 27
WC Cell Biology
SC Cell Biology
GA BE3BW
UT WOS:000370490800014
PM 25997351
ER
PT J
AU Maragh, S
Veltri, RW
Lund, SP
Mangold, L
Isharwal, S
Christudass, CS
Partin, AW
Humphreys, EB
Sorbara, L
Srivastava, S
Wagner, PD
AF Maragh, Samantha
Veltri, Robert W.
Lund, Steven P.
Mangold, Leslie
Isharwal, Sumit
Christudass, Christhunesa S.
Partin, Alan W.
Humphreys, Elizabeth B.
Sorbara, Lynn
Srivastava, Sudhir
Wagner, Paul D.
TI Evaluation of two mitochondrial DNA biomarkers for prostate cancer
detection
SO CANCER BIOMARKERS
LA English
DT Article
DE Prostate; cancer; biomarker; mitochondrial DNA; 3.4kb deletion; urine;
serum; FFPE; NIST; EDRN
ID DETECTION RESEARCH NETWORK; BIOPSY SPECIMENS; HEALTH INDEX; COPY NUMBER;
ANTIGEN; MUTATIONS; SERUM; MEN; REPRODUCIBILITY; PERCENT-P2PSA
AB BACKGROUND: A 3.4kb deletion (3.4kb.) in mitochondrial DNA (mtDNA) found in histologically normal prostate biopsy specimens has been reported to be a biomarker for the increased probability of prostate cancer. Increased m