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 mtDNA copy number is also reported as associated with cancer.
OBJECTIVE: Independent evaluation of these two potential prostate cancer biomarkers using formalin-fixed paraffin-embedded (FFPE) prostate tissue and matched urine and serum from a high risk cohort of men with and without prostate cancer.
METHODS: Biomarker levels were detected via qPCR.
RESULTS: Both 3.4kb. and mtDNA levels were significantly higher in cancer patient FFPE cores (p = 0.045 and p = 0.070 respectively at >90% confidence). Urine from cancer patients contained significantly higher levels of mtDNA (p = 0.006, 64.3% sensitivity, 86.7% specificity). Combining the 3.4kb Delta and mtDNA gave better performance of detecting prostate cancer than either biomarker alone (FFPE 73.7% sensitivity, 65% specificity; urine 64.3% sensitivity, 100% specificity). In serum, there was no difference for any of the biomarkers.
CONCLUSIONS: This is the first report on detecting the 3.4kb. in urine and evaluating mtDNA levels as a prostate cancer biomarker. A confirmation study with increased sample size and possibly with additional biomarkers would need to be conducted to corroborate and extend these observations.
C1 [Maragh, Samantha] NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA.
[Veltri, Robert W.; Mangold, Leslie; Isharwal, Sumit; Partin, Alan W.; Humphreys, Elizabeth B.] Johns Hopkins Univ, Sch Med, Dept Urol, Brady Urol Inst, Baltimore, MD 21205 USA.
[Lund, Steven P.] NIST, Stat Engn Div, Gaithersburg, MD 20899 USA.
[Christudass, Christhunesa S.] Christian Med Coll & Hosp, Dept Neurol Sci, Vellore, Tamil Nadu, India.
[Sorbara, Lynn; Srivastava, Sudhir; Wagner, Paul D.] NCI, Div Canc Prevent, Rockville, MD USA.
RP Maragh, S (reprint author), 100 Bur Dr,MS 8312, Gaithersburg, MD 20899 USA.
EM Samantha@nist.gov
FU National Cancer Institute [Y1-CN-0001]
FX This study was funded by interagency agreement (Y1-CN-0001) from the
National Cancer Institute. This study was a collaborative effort between
the National Institute of Standards and Technology (NIST) and the
National Cancer Institute's Early Detection Research Network (EDRN).
NR 27
TC 0
Z9 0
U1 2
U2 3
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 1574-0153
EI 1875-8592
J9 CANCER BIOMARK
JI Cancer Biomark.
PY 2015
VL 15
IS 6
BP 763
EP 773
DI 10.3233/CBM-150518
PG 11
WC Oncology
SC Oncology
GA DA4WJ
UT WOS:000367802400006
PM 26406418
ER
PT S
AU Hauser, BR
Hoffman, MP
AF Hauser, Belinda R.
Hoffman, Matthew P.
BE Chai, Y
TI Regulatory Mechanisms Driving Salivary Gland Organogenesis
SO CRANIOFACIAL DEVELOPMENT
SE Current Topics in Developmental Biology
LA English
DT Review; Book Chapter
ID MOUSE SUBMANDIBULAR-GLAND; EPITHELIAL-CELL DYNAMICS; BRANCHING
MORPHOGENESIS; BASEMENT-MEMBRANE; EMBRYONIC-DEVELOPMENT;
SELF-DUPLICATION; PROGENITOR CELLS; STEM; REGENERATION; INNERVATION
AB Salivary glands develop as highly branched structures designed to produce and secrete saliva. Advances in mouse genetics, stem cell biology, and regenerative medicine are having a tremendous impact on our understanding of salivary gland organogenesis. Understanding how submandibular gland (SMG) initiation, branching morphogenesis, and cell differentiation occur, as well as defining the progenitor/stem cells and cell and tissue interactions that drive SMG development will help guide regenerative approaches for patients suffering from loss of salivary gland function. This review focuses on recent literature from the past 5 years investigating the regulatory mechanisms driving SMG organogenesis.
C1 [Hauser, Belinda R.; Hoffman, Matthew P.] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
EM mhoffman@mail.nih.gov
FU Intramural NIH HHS
NR 47
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 0070-2153
BN 978-0-12-408141-3
J9 CURR TOP DEV BIOL
JI Curr. Top. Dev. Biol.
PY 2015
VL 115
BP 111
EP 130
DI 10.1016/bs.ctdb.2015.07.029
PG 20
WC Developmental Biology
SC Developmental Biology
GA BE3CF
UT WOS:000370512300006
PM 26589923
ER
PT J
AU Omura, Y
Lu, D
Jones, MK
Nihrane, A
Duvvi, H
Yapor, D
Shimotsuura, Y
Ohki, M
AF Omura, Yoshiaki
Lu, Dominic
Jones, Marilyn K.
Nihrane, Abdallah
Duvvi, Harsha
Yapor, Dario
Shimotsuura, Yasuhiro
Ohki, Motomu
TI Using new non-invasive quick method to detect Borrelia Burgdorferi (BB)
infection from specific parts of the heart in "seemingly normal" ECGs,
and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are
found to have: 1) Significant BB infection, 2) Markedly increased ANP,
3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4
factors were mainly localized at infected areas of the SA node area,
R-&L-Atria & pulmonary veins at the L-atrium.
SO ACUPUNCTURE & ELECTRO-THERAPEUTICS RESEARCH
LA English
DT Article
DE Atrial Fibrillation; Lyme disease; Lyme carditis; Borrelia Burgdorferi
(BB) spirochete; Atrial Natriuretic Peptide (ANP); Cardiac Troponin I;
Taurine; Vitamin D-3; SA Node; Right & Left atrium; AV Node; Acupuncture
at painful joint; Amoxicillin; Doxycycline
ID LYME CARDITIS; DIAGNOSIS; CATHETER; BLOCK; WELL
AB Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224 similar to 600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224 similar to 600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100 similar to 400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4 similar to 6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times/day + Taurine 175mg x3 times/day, with or without EPA 180mg & DHA 120mg, to avoid serious current limitations in the use of Doxycycline 100mg 2 times/day, for 4 weeks.
C1 [Omura, Yoshiaki] New York Med Coll, Dept Family & Community Med, Valhalla, NY 10595 USA.
[Omura, Yoshiaki] Heart Dis Res Fdn, Med Res, Brooklyn, NY USA.
[Omura, Yoshiaki] Int Coll Acupuncture & Electrotherapeut, New York, NY USA.
[Lu, Dominic] Univ Penn, Oral Med, Philadelphia, PA 19104 USA.
[Lu, Dominic] Amer Soc Adv Anesthesia & Sedat, New York, NY USA.
[Jones, Marilyn K.] Holist Dent Ctr Houston, Houston, TX USA.
[Jones, Marilyn K.] Univ Houston, Chem, Houston, TX 77004 USA.
[Nihrane, Abdallah] Mt Sinai Sch Med, Med, New York, NY USA.
[Nihrane, Abdallah] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Duvvi, Harsha] New York Med Coll, Valhalla, NY 10595 USA.
[Shimotsuura, Yasuhiro] Japan Bi Digital O Ring Test Assoc, New York, NY USA.
[Shimotsuura, Yasuhiro; Ohki, Motomu] ORT Life Sci Res Inst, Kurume, Fukuoka, Japan.
RP Omura, Y (reprint author), 800 Riverside Dr 8-I, New York, NY 10032 USA.
EM icaet@yahoo.com
NR 41
TC 1
Z9 1
U1 0
U2 1
PU COGNIZANT COMMUNICATION CORP
PI PUTNAM VALLEY
PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA
SN 0360-1293
EI 2167-9010
J9 ACUPUNCTURE ELECTRO
JI Acupunct. Electro-Ther. Res.
PY 2015
VL 40
IS 4
BP 297
EP 333
DI 10.3727/036012916X14533115160606
PG 37
WC Integrative & Complementary Medicine; Neurosciences
SC Integrative & Complementary Medicine; Neurosciences & Neurology
GA DE2WD
UT WOS:000370487000001
PM 26934795
ER
PT S
AU Verma, M
AF Verma, Mukesh
BE Scatena, R
TI The Role of Epigenomics in the Study of Cancer Biomarkers and in the
Development of Diagnostic Tools
SO ADVANCES IN CANCER BIOMARKERS: FROM BIOCHEMISTRY TO CLINIC FOR A
CRITICAL REVISION
SE Advances in Experimental Medicine and Biology
LA English
DT Article; Book Chapter
DE Biomarker; Bladder cancer; Blood cancer; Brain cancer; Breast cancer;
Cancer; Cancer epigenetics; Cervical cancer; Chromatin; Colorectal
cancer; Diagnosis; Early detection; Endometrial cancer; Epigenetic
inhibitors; Epigenetics; Epigenomic biomarkers; Gastric cancer; Genomic
instability; Glioma; Head and neck cancer; Histone; Kidney cancer;
Leukemia and lymphoma; Liver cancer; Lung cancer; Methylation; microRNA;
Ovarian cancer; Pancreatic cancer; Prognosis; Prostate cancer; Skin
cancer; Surveillance; Validation
ID SQUAMOUS-CELL CARCINOMA; GENE PROMOTER METHYLATION; CPG ISLAND
METHYLATION; GLOBAL HISTONE MODIFICATION; EPIGENETIC FIELD DEFECT;
TUMOR-SUPPRESSOR GENES; CERVICAL INTRAEPITHELIAL NEOPLASIA;
HELICOBACTER-PYLORI INFECTION; INDEPENDENT PROGNOSTIC-FACTOR; ACUTE
LYMPHOBLASTIC-LEUKEMIA
AB Epigenetics plays a key role in cancer development. Genetics alone cannot explain sporadic cancer and cancer development in individuals with no family history or a weak family history of cancer. Epigenetics provides a mechanism to explain the development of cancer in such situations. Alterations in epigenetic profiling may provide important insights into the etiology and natural history of cancer. Because several epigenetic changes occur before histopathological changes, they can serve as biomarkers for cancer diagnosis and risk assessment. Many cancers may remain asymptomatic until relatively late stages; in managing the disease, efforts should be focused on early detection, accurate prediction of disease progression, and frequent monitoring. This chapter describes epigenetic biomarkers as they are expressed during cancer development and their potential use in cancer diagnosis and prognosis. Based on epigenomic information, biomarkers have been identified that may serve as diagnostic tools; some such biomarkers also may be useful in identifying individuals who will respond to therapy and survive longer. The importance of analytical and clinical validation of biomarkers is discussed, along with challenges and opportunities in this field.
C1 [Verma, Mukesh] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Suite 4E102,9609 Med Ctr Dr,MSC 9763, Bethesda, MD 20892 USA.
RP Verma, M (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Suite 4E102,9609 Med Ctr Dr,MSC 9763, Bethesda, MD 20892 USA.
EM vermam@mail.nih.gov
NR 232
TC 4
Z9 4
U1 4
U2 11
PU SPRINGER
PI DORDRECHT
PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
SN 0065-2598
BN 978-94-017-7215-0; 978-94-017-7214-3
J9 ADV EXP MED BIOL
JI Adv.Exp.Med.Biol.
PY 2015
VL 867
BP 59
EP 80
DI 10.1007/978-94-017-7215-0_5
D2 10.1007/978-94-017-7215-0
PG 22
WC Biochemistry & Molecular Biology; Oncology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Oncology; Research & Experimental
Medicine
GA BE2YW
UT WOS:000370341700006
PM 26530360
ER
PT J
AU Kashiouris, MG
Miljkovic, M
Herasevich, V
Goldberg, AD
Albrecht, C
AF Kashiouris, Markos G.
Miljkovic, Milos
Herasevich, Vitaly
Goldberg, Andrew D.
Albrecht, Charles, III
TI Description and pilot evaluation of the Metabolic Irregularities
Narrowing down Device software: a case analysis of physician programming
SO JOURNAL OF COMMUNITY HOSPITAL INTERNAL MEDICINE PERSPECTIVES
LA English
DT Article
DE computerized decision support systems; medical calculator; differential
diagnosis software
ID CLINICAL DECISION-SUPPORT; OF-CARE; SYSTEMS; COMPUTERS; BEHAVIOR;
NETWORK; TOOL
AB Background: There is a gap between the abilities and the everyday applications of Computerized Decision Support Systems (CDSSs). This gap is further exacerbated by the different 'worlds' between the software designers and the clinician end-users. Software programmers often lack clinical experience whereas practicing physicians lack skills in design and engineering.
Objective: Our primary objective was to evaluate the performance of Metabolic Irregularities Narrowing down Device (MIND) intelligent medical calculator and differential diagnosis software through end-user surveys and discuss the roles of CDSS in the inpatient setting.
Setting: A tertiary care, teaching community hospital.
Study participants: Thirty-one responders answered the survey. Responders consisted of medical students, 24%; attending physicians, 16%, and residents, 60%.
Results: About 62.5% of the responders reported that MIND has the ability to potentially improve the quality of care, 20.8% were sure that MIND improves the quality of care, and only 4.2% of the responders felt that it does not improve the quality of care. Ninety-six percent of the responders felt that MIND definitely serves or has the potential to serve as a useful tool for medical students, and only 4% of the responders felt otherwise. Thirty-five percent of the responders rated the differential diagnosis list as excellent, 56% as good, 4% as fair, and 4% as poor.
Discussion: MIND is a suggesting, interpreting, alerting, and diagnosing CDSS with good performance and end-user satisfaction. In the era of the electronic medical record, the ongoing development of efficient CDSS platforms should be carefully considered by practicing physicians and institutions.
C1 [Kashiouris, Markos G.; Miljkovic, Milos; Albrecht, Charles, III] Sinai Hosp Baltimore, Internal Med Residency Program, Baltimore, MD USA.
[Kashiouris, Markos G.] Virginia Commonwealth Univ, Div Pulm & Crit Care, Richmond, VA USA.
[Miljkovic, Milos] NIH, Div Med Oncol, Bethesda, MD 20892 USA.
[Herasevich, Vitaly] Mayo Clin, Coll Med, Div Anesthesiol, Rochester, MN USA.
[Goldberg, Andrew D.] Oregon Hlth & Sci Univ, Div Emergency Med, Portland, OR 97201 USA.
RP Kashiouris, MG (reprint author), Virginia Commonwealth Univ, Div Pulm & Crit Care, Richmond, VA USA.
EM mkashiouris@vcu.edu
NR 28
TC 1
Z9 1
U1 1
U2 2
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2000-9666
J9 J COMMUNITY HOSP INT
JI J. Community Hosp. Intern. Med. Perspect.
PY 2015
VL 5
IS 1
AR 25793
DI 10.3402/jchimp.v5.25793
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DE6EG
UT WOS:000370725900003
PM 25656664
ER
PT S
AU Pearson, C
Martin, K
AF Pearson, Craig
Martin, Keith
BE Bagetta, G
Nucci, C
TI Stem cell approaches to glaucoma: from aqueous outflow modulation to
retinal neuroprotection
SO NEW TRENDS IN BASIC AND CLINICAL RESEARCH OF GLAUCOMA: A
NEURODEGENERATIVE DISEASE OF THE VISUAL SYSTEM, PT A
SE Progress in Brain Research
LA English
DT Review; Book Chapter
DE Glaucoma; Stem cells; Retina; Optic nerve; Neuroprotection; Replacement
ID NEURAL PROGENITOR CELLS; NECROSIS-FACTOR-ALPHA; CHONDROITIN SULFATE
PROTEOGLYCANS; LOADED BIODEGRADABLE MICROSPHERES; HUMAN TRABECULAR
MESHWORK; CENTRAL-NERVOUS-SYSTEM; GANGLION-LIKE CELLS;
SPINAL-CORD-INJURY; HUMAN MULLER GLIA; OPTIC-NERVE
AB Long-term pharmacological management of glaucoma currently relies on self-administered drugs to regulate intraocular pressure (IOP). A number of approaches using stem cells have recently shown promise as potential future treatment strategies complementary to IOP lowering. Several sources of endogenous stem cells have been identified in the eye, some of which may be able to repair the damaged trabecular meshwork and restore functional regulation of aqueous outflow. Neural and mesenchymal stem cells secrete growth factors which provide neuroprotective effects, reducing loss of retinal ganglion cells (RGCs) in animal models. In the future, stem cells may even replace RGCs to reform functional connections between the eye and the brain, although the complexity of such a repair task is formidable. With advances in biomaterial cell scaffolds and concurrent efforts in other neural systems, stem cell therapies are becoming a realistic option for treating multiple eye diseases, and despite ongoing challenges, there are reasons for optimism that stem cells may play a role in the treatment of human glaucoma in the future.
C1 [Pearson, Craig; Martin, Keith] Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge, England.
[Pearson, Craig; Martin, Keith] Cambridge NIHR Biomed Res Ctr, Cambridge, England.
[Pearson, Craig] NHLBI, NIH, Bethesda, MD 20892 USA.
[Martin, Keith] Wellcome Trust Res Labs, MRC, Cambridge Stem Cell Inst, Cambridge, England.
RP Martin, K (reprint author), Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge, England.
EM krgm2@cam.ac.uk
NR 121
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0079-6123
BN 978-0-444-63566-2
J9 PROG BRAIN RES
JI Prog. Brain Res.
PY 2015
VL 220
BP 241
EP 256
DI 10.1016/bs.pbr.2015.04.005
PG 16
WC Medicine, Research & Experimental; Neurosciences; Ophthalmology
SC Research & Experimental Medicine; Neurosciences & Neurology;
Ophthalmology
GA BE3CT
UT WOS:000370523000013
PM 26497794
ER
PT J
AU Little, DJ
Yuan, CM
Thurlow, JS
Gounden, V
Doi, SQ
Pruziner, A
Abbott, KC
Theeler, BJ
Olson, SW
AF Little, Dustin J.
Yuan, Christina M.
Thurlow, John S.
Gounden, Verena
Doi, Sonia Q.
Pruziner, Alison
Abbott, Kevin C.
Theeler, Brett J.
Olson, Stephen W.
TI Effects of Traumatic Amputation on beta-Trace Protein and beta
2-Microglobulin Concentrations in Male Soldiers
SO AMERICAN JOURNAL OF NEPHROLOGY
LA English
DT Article
DE Amputation; Beta 2 microglobulin; Beta trace protein; Glomerular
filtration rate estimation
ID GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION;
SERUM CREATININE; UNITED-STATES; CYSTATIN C; MORTALITY; AMPUTEES;
MARKERS; HEART
AB Background: Serum creatinine (SCr) levels are decreased following traumatic amputation, leading to the overestimation of glomerular filtration rate (GFR). beta-Trace protein (BTP) and beta(2) -microglobulin (B2M) strongly correlate with measured GFR and have not been studied following amputation. We hypothesized that BTP and B2M would be unaffected by traumatic amputation. Methods: We used the Department of Defense Serum Repository to compare pre-and post-traumatic amputation serum BTP and B2M levels in 33 male soldiers, via the N Latex BTP and B2M nephelometric assays (Siemens Diagnostics, Tarrytown, N.Y., USA). Osterkamp estimation using DEXA scan measurements was used to establish percent estimated body weight loss (%EBWL). Results were analyzed for small (3-5.9% EBWL), medium (6-13.5%), and large (> 13.5%) amputation subgroups; and for a control group matched 1: 1 to the 12 large amputation subjects. Paired Student's t test was used for comparisons. Results: Mean serum BTP levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. BTP appeared to decrease following large %EBWL amputation (p = 0.05). Mean serum B2M levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. B2M appeared to increase following large %EBWL amputation (p = 0.05). Conclusions: BTP and B2M levels are less affected than SCr by amputation, and should be considered for future study of GFR estimation. BTP and B2M changes following large %EBWL amputation require validation and may offer insight into non-GFR BTP and B2M determinants as well as increased cardiovascular disease and mortality following amputation. Published by S. Karger AG, Basel
C1 [Little, Dustin J.; Yuan, Christina M.; Olson, Stephen W.] Walter Reed Natl Mil Med Ctr, Dept Med, Serv Nephrol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
[Gounden, Verena] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Doi, Sonia Q.] Uniformed Serv Univ Hlth Sci, Nephrol, Bethesda, MD 20814 USA.
[Pruziner, Alison] DoD VA Extrem Trauma & Amputat Ctr Excellence, Bethesda, MD USA.
[Abbott, Kevin C.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Theeler, Brett J.] Walter Reed Natl Mil Med Ctr, Neurol Serv, Bethesda, MD USA.
[Thurlow, John S.] William Beaumont Army Med Ctr, Dept Med, Serv Nephrol, El Paso, TX 79920 USA.
RP Little, DJ (reprint author), Walter Reed Natl Mil Med Ctr, Dept Med, Serv Nephrol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM little.dustinj@gmail.com
NR 39
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0250-8095
EI 1421-9670
J9 AM J NEPHROL
JI Am. J. Nephrol.
PY 2015
VL 42
IS 6
BP 436
EP 442
DI 10.1159/000443775
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DD4NR
UT WOS:000369900200008
PM 26800100
ER
PT S
AU Vidalain, PO
Jacob, Y
Hagemeijer, MC
Jones, LM
Neveu, G
Roussarie, JP
Rottier, PJM
Tangy, F
de Haan, CAM
AF Vidalain, Pierre-Olivier
Jacob, Yves
Hagemeijer, Marne C.
Jones, Louis M.
Neveu, Gregory
Roussarie, Jean-Pierre
Rottier, Peter J. M.
Tangy, Frederic
de Haan, Cornelis A. M.
BE Maier, HJ
Bickerton, E
Britton, P
TI A Field-Proven Yeast Two-Hybrid Protocol Used to Identify
Coronavirus-Host Protein-Protein Interactions
SO CORONAVIRUSES: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Murine hepatitis virus; Host pathogen interactions; Yeast two-hybrid;
Interactomics; Proteomics
ID C-ELEGANS; SYSTEM; TRANSCRIPTION; LIBRARIES; NETWORK; DRAFT; MAP
AB Over the last 2 decades, yeast two-hybrid became an invaluable technique to decipher protein protein interaction networks. In the field of virology, it has proven instrumental to identify virus host interactions that are involved in viral embezzlement of cellular functions and inhibition of immune mechanisms. Here, we present a yeast two -hybrid protocol that has been used in our laboratory since 2006 to search for cellular partners of more than 300 viral proteins. Our aim was to develop a robust and straightforward pipeline, which minimizes false-positive interactions with a decent coverage of target cDNA libraries, and only requires a minimum of equipment. We also discuss reasons that motivated our technical choices and compromises that had to be made. This protocol has been used to screen most non-structural proteins of murine hepatitis virus (MHV), a member of betacoronavirus genus, against a mouse brain cDNA library. Typical results were obtained and are presented in this report.
C1 [Vidalain, Pierre-Olivier; Neveu, Gregory; Roussarie, Jean-Pierre; Tangy, Frederic] Inst Pasteur, Unite Genom Virale & Vaccinat, Paris, France.
[Vidalain, Pierre-Olivier; Jacob, Yves; Neveu, Gregory; Tangy, Frederic] CNRS, UMR3569, Paris, France.
[Jacob, Yves] Inst Pasteur, Dept Virol, Unite Genet Mol Virus ARN, Paris, France.
[Jacob, Yves] Univ Paris Diderot, Unite Genet Mol Virus ARN, Sorbonne Paris Cite, Paris, France.
[Hagemeijer, Marne C.; Rottier, Peter J. M.; de Haan, Cornelis A. M.] Univ Utrecht, Fac Vet Med, Div Virol, Dept Infect Dis & Immunol, Utrecht, Netherlands.
[Hagemeijer, Marne C.] NHLBI, Lab Host Pathogen Dynam, CBPC, NIH, Bethesda, MD 20892 USA.
[Jones, Louis M.] Inst Pasteur, Ctr Informat Biol, Paris, France.
[Neveu, Gregory] Stanford Univ, Dept Med, Sch Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA.
[Neveu, Gregory] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA.
[Roussarie, Jean-Pierre] Rockefeller Univ, Lab Mol & Cellular Neurosci, New York, NY 10021 USA.
RP Vidalain, PO (reprint author), Inst Pasteur, Unite Genom Virale & Vaccinat, Paris, France.
OI Neveu, Gregory/0000-0002-2363-6031
NR 29
TC 0
Z9 0
U1 1
U2 8
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2438-7; 978-1-4939-2437-0
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1282
BP 213
EP 229
DI 10.1007/978-1-4939-2438-7_18
D2 10.1007/978-1-4939-2438-7
PG 17
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Virology
SC Biochemistry & Molecular Biology; Virology
GA BE2UX
UT WOS:000370135700019
PM 25720483
ER
PT S
AU Hagemeijer, MC
de Haan, CAM
AF Hagemeijer, Marne C.
de Haan, Cornelis A. M.
BE Maier, HJ
Bickerton, E
Britton, P
TI Studying the Dynamics of Coronavirus Replicative Structures
SO CORONAVIRUSES: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Coronavirus; Nonstructural proteins; Live-cell imaging; Replication
transcription complex; Dynamics; Fluorescence recovery after
photobleaching; Fluorescence loss in photobleaching
ID MOUSE HEPATITIS-VIRUS; RESPIRATORY SYNDROME CORONAVIRUS; TRANSCRIPTION
COMPLEXES; VIRAL REPLICATION; MEMBRANE-VESICLES; GENE POLYPROTEIN;
RNA-SYNTHESIS; PROTEINS; LOCALIZATION; CELLS
AB Coronaviruses (CoVs) generate specialized membrane compartments, which consist of double membrane vesicles connected to convoluted membranes, the so-called replicative structures, where viral RNA synthesis takes place. These sites harbor the CoV replication transcription complexes (RTCs): multi -protein complexes consisting of 16 nonstructural proteins (nsps), the CoV nucleocapsid protein (N) and presumably host proteins. To successfully establish functional membrane -bound RTCs all of the viral and host constituents need to be correctly spatiotemporally organized during viral infection. Few studies, however, have investigated the dynamic processes involved in the formation and functioning of the (subunits of) CoV RTCs and the replicative structures in living cells. In this chapter we describe several protocols to perform time-lapse imaging of CoV-infected cells and to study the kinetics of (subunits of) the CoV replicative structures. The approaches described are not limited to CoV-infected cells; they can also be applied to other virus -infected or non -infected cells.
C1 [Hagemeijer, Marne C.; de Haan, Cornelis A. M.] Univ Utrecht, Fac Vet Med, Div Virol, Dept Infect Dis & Immunol, Utrecht, Netherlands.
[Hagemeijer, Marne C.] NHLBI, Lab Host Pathogen Dynam, CBPC, NIH, Bethesda, MD 20892 USA.
RP Hagemeijer, MC (reprint author), Univ Utrecht, Fac Vet Med, Div Virol, Dept Infect Dis & Immunol, Utrecht, Netherlands.
NR 21
TC 0
Z9 0
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2438-7; 978-1-4939-2437-0
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1282
BP 261
EP 269
DI 10.1007/978-1-4939-2438-7_22
D2 10.1007/978-1-4939-2438-7
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Virology
SC Biochemistry & Molecular Biology; Virology
GA BE2UX
UT WOS:000370135700023
PM 25720487
ER
PT J
AU Dubey, SK
Hejtmancik, JF
Krishnadas, SR
Sharmila, R
Haripriya, A
Sundaresan, P
AF Dubey, Sushil K.
Hejtmancik, James F.
Krishnadas, Subbaiah R.
Sharmila, Rajendrababu
Haripriya, Aravind
Sundaresan, Periasamy
TI Evaluation of Genetic Polymorphisms in Clusterin and Tumor Necrosis
Factor-Alpha Genes in South Indian Individuals with Pseudoexfoliation
Syndrome
SO CURRENT EYE RESEARCH
LA English
DT Article
DE CLU; pseudoexfoliation glaucoma; pseudoexfoliation syndrome; SNP;
TNF-alpha
ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; EXFOLIATION GLAUCOMA;
LOXL1 GENE; ALZHEIMERS-DISEASE; MATRIX METALLOPROTEINASES; IDENTIFIES
VARIANTS; SEQUENCE VARIANTS; AQUEOUS-HUMOR; UNITED-STATES
AB Purpose: The aim of this study was to explore the potential association of genetic variants across clusterin (CLU) and tumor necrosis factor-alpha (TNF-alpha) genes in South Indian individuals with pseudoexfoliation syndrome (PEXS) and pseudoexfoliation glaucoma (PEXG).
Materials and Methods: A total of 523 individuals including 299 unrelated cases (150 PEXS and 149 PEXG) and 224 age- and ethnically-matched healthy controls were recruited for genetic analysis. Six single-nucleotide polymorphisms (SNPs) including, five CLU SNPs (rs11136000, rs2279590, rs9331888, rs9331931, rs3087554) and one promoter SNP (rs1800629) of TNF-alpha were genotyped in all study subjects. Genotyping of CLU SNPs were performed using the TaqMan allelic discrimination assay while TNF-alpha SNP was genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis. Association analysis was performed by determining the distributions of genotype and allele frequencies, Hardy-Weinberg equilibrium, and chi-square p values and odds ratios as implemented in the Golden Helix SNP & Variation Suite (SVS).
Results: Five CLU SNPs did not show any significant differences in allele frequencies between patients and control subjects (rs3087554, p = 0.919, OR= 1.01, 95% CI: 0.77-1.33; rs2279590, p = 0.432, OR= 1.12, 95% CI: 0.84-1.51; rs9331931, p = 0.310, OR= 1.24, 95% CI: 0.81-1.89; rs11136000, p = 0.072, OR= 1.31, 95% CI: 0.97-1.76; rs9331888, p = 0.911, OR= 1.01, 95% CI: 0.78-1.31). The investigation of TNF-alpha SNP established a significant association with PEXS and PEXG (p = 0.042, OR= 0.61, 95% CI: 0.38-0.99). However, this association did not remain significant after Bonferroni correction.
Conclusions: Our data suggest that genetic variants in CLU and TNF-alpha genes do not play a major role in the development of PEXS and PEXG in the South Indian population.
C1 [Dubey, Sushil K.; Sundaresan, Periasamy] Aravind Med Res Fdn, Dr G Venkataswamy Eye Res Inst, Dept Genet, 1 Anna Nagar, Madurai, Tamil Nadu, India.
[Hejtmancik, James F.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Rockville, MD USA.
[Krishnadas, Subbaiah R.; Sharmila, Rajendrababu] Aravind Eye Hosp, Glaucoma Clin, Madurai, Tamil Nadu, India.
[Haripriya, Aravind] Aravind Eye Hosp, Intraocular Lens & Cataract Clin, Madurai, Tamil Nadu, India.
RP Sundaresan, P (reprint author), Aravind Med Res Fdn, Dr G Venkataswamy Eye Res Inst, Dept Genet, 1 Anna Nagar, Madurai, Tamil Nadu, India.
EM sundar@aravind.org
FU ALCON - Aravind Eye Care System, India
FX This study was supported by research grant from ALCON - Aravind Eye Care
System, India. The authors have no competing interests to declare.
NR 48
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2015
VL 40
IS 12
BP 1218
EP 1224
DI 10.3109/02713683.2014.997884
PG 7
WC Ophthalmology
SC Ophthalmology
GA DD4KP
UT WOS:000369891900005
PM 25849827
ER
PT J
AU Provinciali, N
Lazzeroni, M
Cazzaniga, M
Gorlero, F
Dunn, BK
DeCensi, A
AF Provinciali, Nicoletta
Lazzeroni, Matteo
Cazzaniga, Massimiliano
Gorlero, Franco
Dunn, Barbara K.
DeCensi, Andrea
TI Metformin: risk-benefit profile with a focus on cancer
SO EXPERT OPINION ON DRUG SAFETY
LA English
DT Review
DE clinical trials; metformin; neoplasm; safety
ID ACTIVATED PROTEIN-KINASE; RANDOMIZED PRESURGICAL TRIAL; TYPE-2
DIABETES-MELLITUS; LIFE-STYLE INTERVENTION; ABERRANT CRYPT FOCI; EARLY
BREAST-CANCER; ENDOMETRIAL CANCER; LACTIC-ACIDOSIS; NONDIABETIC WOMEN;
CONSENSUS REPORT
AB Introduction: Epidemiological evidence suggests an increased incidence of cancer in obese, prediabetic, and diabetic patients and a reduced risk of cancer incidence and mortality in diabetic patients on metformin compared with other antidiabetic drugs. In vitro studies support the efficacy of metformin in cancer therapy and prevention. Although metformin seems to be promising as a cancer chemopreventive or therapeutic drug, the principal consideration is whether metformin will be effective in cancer clinical trials for nondiabetic subjects or only in diabetics or subjects with insulin resistance. Safety of metformin is even more important in treating nondiabetic patients.
Areas covered: The present review focuses on epidemiological data and clinical trials testing the efficacy of metformin on cancer, the safety in nondiabetic patients and the future development of this promising drug.
Expert opinion: Meta-analyses of epidemiological in which metformin treatment has been used for diabetic patients show a positive trend for benefit; nevertheless, clinical data outcomes are preliminary and the results of ongoing trials are awaited. The different types of cancer, heterogeneity of populations and presence of comorbidity make it difficult to determine the benefits of metformin in cancer prevention and treatment.
C1 [Provinciali, Nicoletta; DeCensi, Andrea] EO Osped Galliera, Div Med Oncol, Genoa, Italy.
[Lazzeroni, Matteo; Cazzaniga, Massimiliano; DeCensi, Andrea] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Gorlero, Franco] EO Osped Galliera, Div Obstet & Gynecol, Genoa, Italy.
[Gorlero, Franco] Univ Genoa, Genoa, Italy.
[Dunn, Barbara K.] NCI, NIH, Canc Prevent Div, Bethesda, MD 20892 USA.
[DeCensi, Andrea] Queen Mary Univ London, Wolfson Inst Prevent Med, London, England.
RP DeCensi, A (reprint author), EO Osped Galliera, Div Med Oncol, Genoa, Italy.
EM andrea.decensi@galliera.it
OI Lazzeroni, Matteo/0000-0002-2162-4002
NR 76
TC 4
Z9 4
U1 1
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1474-0338
EI 1744-764X
J9 EXPERT OPIN DRUG SAF
JI Expert Opin. Drug Saf.
PY 2015
VL 14
IS 10
BP 1573
EP 1585
DI 10.1517/14740338.2015.1084289
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DD4ST
UT WOS:000369913600007
PM 26359221
ER
PT J
AU Selva-O'Callaghan, A
Alvarado-Cardenas, M
Marin, A
Pinal-Fernandez, I
AF Selva-O'Callaghan, Albert
Alvarado-Cardenas, Marcelo
Marin, Ana
Pinal-Fernandez, Iago
TI Statins and myositis: the role of anti-HMGCR antibodies
SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
DE anti-HMGCR; immune mediated necrotizing myopathy; myalgia; myositis;
statins
ID REDUCTASE AUTOANTIBODIES; AUTOIMMUNE MYOPATHY;
ANTI-3-HYDROXY-3-METHYLGLUTARYL-COENZYME
C1 [Selva-O'Callaghan, Albert; Alvarado-Cardenas, Marcelo; Pinal-Fernandez, Iago] Univ Autonoma Barcelona, Dept Internal Med, Vall Dhebron Gen Hosp, E-08193 Barcelona, Spain.
[Marin, Ana] Univ Autonoma Barcelona, Dept Immunol, Vall Dhebron Gen Hosp, E-08193 Barcelona, Spain.
[Pinal-Fernandez, Iago] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Selva-O'Callaghan, A (reprint author), Univ Autonoma Barcelona, Dept Internal Med, Vall Dhebron Gen Hosp, E-08193 Barcelona, Spain.
EM aselva@vhebron.net
NR 16
TC 1
Z9 1
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1744-666X
EI 1744-8409
J9 EXPERT REV CLIN IMMU
JI Expert Rev. Clin. Immunol.
PY 2015
VL 11
IS 12
BP 1277
EP 1279
DI 10.1586/1744666X.2015.1102632
PG 3
WC Immunology
SC Immunology
GA DD4RR
UT WOS:000369910800001
PM 26492593
ER
PT S
AU Le Grice, SFJ
AF Le Grice, Stuart F. J.
BE Torbett, BE
Goodsell, DS
Richman, DD
TI Targeting the HIV RNA Genome: High-Hanging Fruit Only Needs a Longer
Ladder
SO FUTURE OF HIV-1 THERAPEUTICS: RESISTANCE IS FUTILE?
SE Current Topics in Microbiology and Immunology
LA English
DT Review; Book Chapter
ID HUMAN-IMMUNODEFICIENCY-VIRUS; REV-RESPONSE ELEMENT; CELL-PENETRATING
PEPTIDES; STRAND DNA-SYNTHESIS; PRIMER ACTIVATION SIGNAL; MAJOR SPLICE
DONOR; REVERSE TRANSCRIPTION; VIRAL-RNA; TAR RNA; ANTISENSE
OLIGONUCLEOTIDES
AB Small molecules targeting the enzymes responsible for human immunodeficiency virus (HIV) maturation, DNA synthesis and its subsequent chromosomal integration as ribonucleotide-free double-stranded DNA remain the mainstay of combination antiretroviral therapy. For infected individuals harboring drug-susceptible virus, this approach has afforded complete or near-complete viral suppression. However, in the absence of a curative strategy, the predictable emergence of drug-resistant variants requires continued development of improved antiviral strategies, inherent to which is the necessity of identifying novel targets. Regulatory elements that mediate transcription, translation, nucleocytoplasmic transport, dimerization, packaging and reverse transcription of the (+) strand RNA genome should now be considered viable targets for small molecule, peptide-and oligonucleotide-based therapeutics. Where target specificity and cellular penetration and toxicity have been the primary obstacle to successful "macromolecule therapeutics", this chapter summarizes (a) novel approaches targeting RNA motifs whose three-dimensional structure is critical for biological function and consequently may be less prone to resistance-conferring mutations and (b) improved methods for delivery.
C1 [Le Grice, Stuart F. J.] NCI, RT Biochem Sect, Basic Res Lab, Frederick, MD 21702 USA.
RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, Basic Res Lab, Frederick, MD 21702 USA.
FU Intramural NIH HHS
NR 81
TC 5
Z9 5
U1 0
U2 3
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0070-217X
BN 978-3-319-18518-7; 978-3-319-18517-0
J9 CURR TOP MICROBIOL
JI Curr.Top.Microbiol.Immunol.
PY 2015
VL 389
BP 147
EP 169
DI 10.1007/82_2015_434
D2 10.1007/978-3-319-18518-7
PG 23
WC Immunology; Microbiology
SC Immunology; Microbiology
GA BE2XU
UT WOS:000370245500007
PM 25735922
ER
PT S
AU Tedbury, PR
Freed, EO
AF Tedbury, Philip R.
Freed, Eric O.
BE Torbett, BE
Goodsell, DS
Richman, DD
TI HIV-1 Gag: An Emerging Target for Antiretroviral Therapy
SO FUTURE OF HIV-1 THERAPEUTICS: RESISTANCE IS FUTILE?
SE Current Topics in Microbiology and Immunology
LA English
DT Review; Book Chapter
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MATURATION INHIBITOR BEVIRIMAT; TYPE-1
MATRIX PROTEIN; CA-SP1 CLEAVAGE SITE; ENVELOPE GLYCOPROTEIN
INCORPORATION; BETULINIC ACID-DERIVATIVES; GP41 CYTOPLASMIC TAIL;
N-TERMINAL DOMAIN; CAPSID PROTEIN; NUCLEOCAPSID PROTEIN
AB The advances made in the treatment of HIV-1 infection represent a major success of modern biomedical research, prolonging healthy life and reducing virus transmission. There remain, however, many challenges relating primarily to side effects of long-term therapy and the ever-present danger of the emergence of drug-resistant strains. To counter these threats, there is a continuing need for new and better drugs, ideally targeting multiple independent steps in the HIV-1 replication cycle. The most successful current drugs target the viral enzymes: protease (PR), reverse transcriptase (RT), and integrase (IN). In this review, we outline the advances made in targeting the Gag protein and its mature products, particularly capsid and nucleocapsid, and highlight possible targets for future pharmacological intervention.
C1 [Tedbury, Philip R.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM efreed@nih.gov
OI Tedbury, Philip/0000-0001-8151-4967
NR 178
TC 4
Z9 5
U1 0
U2 6
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0070-217X
BN 978-3-319-18518-7; 978-3-319-18517-0
J9 CURR TOP MICROBIOL
JI Curr.Top.Microbiol.Immunol.
PY 2015
VL 389
BP 171
EP 201
DI 10.1007/82_2015_436
D2 10.1007/978-3-319-18518-7
PG 31
WC Immunology; Microbiology
SC Immunology; Microbiology
GA BE2XU
UT WOS:000370245500008
PM 25731773
ER
PT J
AU Miyazaki, T
Lin, TY
Ito, K
Lee, CH
Stopfer, M
AF Miyazaki, Takaaki
Lin, Tzu-Yang
Ito, Kei
Lee, Chi-Hon
Stopfer, Mark
TI A gustatory second-order neuron that connects sucrose-sensitive primary
neurons and a distinct region of the gnathal ganglion in the Drosophila
brain
SO JOURNAL OF NEUROGENETICS
LA English
DT Article
DE Higher-order circuits; interneuron; taste; subesophageal zone
ID SPECTRAL PREFERENCE; MOLECULAR-BASIS; MOSAIC ANALYSIS; TASTE;
NEUROBIOLOGY; EXPRESSION; CIRCUIT; SYSTEMS; PROTEIN; REPRESENTATION
AB Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons (G2Ns) in Drosophila. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate G2Ns, we screened similar to 5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of Gr5a-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single-cell analysis by FLP-out recombination, revealed a pair of neurons that contact Gr5a axon terminals in both brain hemispheres and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (D alpha 7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to Gr5a neurons, while presynaptic sites were broadly distributed throughout the neurons' arborizations. GRASP analysis and further tests with the Syb-GRASP method suggested that the identified G2Ns receive synaptic inputs from Gr5a-expressing GSNs, but not Gr66a-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from Gr5a-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system.
C1 [Miyazaki, Takaaki; Stopfer, Mark] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Sensory Coding & Neural Ensembles, NIH, Bethesda, MD USA.
[Lin, Tzu-Yang; Lee, Chi-Hon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, NIH, Bethesda, MD USA.
[Ito, Kei] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan.
RP Stopfer, M (reprint author), Bldg 35A,Rm 3E-623,35 Convent Dr,MSC 3715, Bethesda, MD 20892 USA.
EM stopferm@mail.nih.gov
OI Miyazaki, Takaaki/0000-0002-9376-0839
FU Intramural Research Programs of the National Institutes of Health (NIH),
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [1ZIAHD008760, Z01-HD008776]; Japan Society for Promotion of
Science Research Fellowship for Japanese Biomedical and Behavioral
Researchers at NIH
FX We thank Moyi Li and Peter Nguyen for helping to maintain fly stocks,
Mihaela Serpe for sharing fly resources, and Chunyuan Ting, Yan Li,
Kazumichi Shimizu, and members of the Stopfer Lab for helpful discussion
and technical advice. We thank Kristin Scott (UC Berkeley), Marco Gallio
(North-western University), Craig Montell (UC Santa Barbara), and
Bloomington Drosophila Stock Center (Indiana University) for providing
fly strains. This work was supported by the Intramural Research Programs
of the National Institutes of Health (NIH), Eunice Kennedy Shriver
National Institute of Child Health and Human Development (grant
1ZIAHD008760 to M.S.; grant Z01-HD008776 to C.-H.L). T. M. received a
Japan Society for Promotion of Science Research Fellowship for Japanese
Biomedical and Behavioral Researchers at NIH (Mar., 2011-Feb., 2013).
NR 39
TC 4
Z9 4
U1 0
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0167-7063
EI 1563-5260
J9 J NEUROGENET
JI J. Neurogenet.
PY 2015
VL 29
IS 2-3
BP 144
EP 155
DI 10.3109/01677063.2015.1054993
PG 12
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA DD4KQ
UT WOS:000369892000014
PM 26004543
ER
PT J
AU Hirt, C
Camargo, MC
Yu, KJ
Hewitt, SM
Dolken, G
Rabkin, CS
AF Hirt, Carsten
Camargo, M. Constanza
Yu, Kelly J.
Hewitt, Stephen M.
Doelken, Gottfried
Rabkin, Charles S.
TI Risk of follicular lymphoma associated with BCL2 translocations in
peripheral blood
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
DE Lymphoma and Hodgkin disease; molecular genetics; prognostication
ID HEALTHY-INDIVIDUALS; T(14/18) TRANSLOCATION; B-CELLS; FREQUENCY; GENES
AB Many adults have circulating lymphocytes with the BCL2 gene translocation characteristic of follicular lymphoma. We therefore conducted a nested case-control study of incident lymphomas with peripheral blood obtained a median 4.9 years pre-diagnosis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Overall, 13 of 26 cases of lymphoma and 14 of 47 controls had BCL2 major breakpoint region (MBR) translocations in pre-diagnosis blood (odds ratio [OR] = 2.8). Nine cases had BCL2-MBR-positive tumors; eight of these nine had BCL2-MBR translocations in paired blood versus five of the 17 with BCL2-MBR-negative tumors (p = 0.01). Comparing both tumor types to controls, blood BCL2-MBR translocations had a strong, statistically significant association with BCL2-MBR-positive tumors (OR = 26), but not with BCL2-MBR-negative tumors (OR = 0.9). All eight BCL2-MBR-positive tumors with pre-diagnosis BCL2 translocations were clonally related to these circulating cells, based on similarity of recombination sequences. These data indicate that blood BCL2-MBR translocations represent lymphoma precursor clones with malignant potential.
C1 [Hirt, Carsten; Doelken, Gottfried] Ernst Moritz Arndt Univ Greifswald, Clin Internal Med C, Hematol & Oncol, Greifswald, Germany.
[Camargo, M. Constanza; Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Yu, Kelly J.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Rabkin, CS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM rabkinc@mail.nih.gov
RI Camargo, M. Constanza/R-9891-2016;
OI Hewitt, Stephen/0000-0001-8283-1788
FU Intramural NIH HHS
NR 22
TC 1
Z9 1
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
EI 1029-2403
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PY 2015
VL 56
IS 9
BP 2625
EP 2629
DI 10.3109/10428194.2014.999324
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA DD3HG
UT WOS:000369812100024
PM 25549806
ER
PT S
AU Siriborvornratanakul, T
AF Siriborvornratanakul, Thitirat
BE Wang, L
Uesugi, S
Ting, IH
Okuhara, K
Wang, K
TI Social Media on a Piece of Paper: A Study of Hybrid and Sustainable
Media Using Active Infrared Vision
SO MULTIDISCIPLINARY SOCIAL NETWORKS RESEARCH, MISNC 2015
SE Communications in Computer and Information Science
LA English
DT Proceedings Paper
CT 2nd International Conference on Multidisciplinary Social Networks
Research (MISNC)
CY SEP 01-03, 2015
CL Matsuyama, JAPAN
SP IEEE Tech Comm Granular Comp, IEEE Computat Intelligence Soc, IEEE Soc Social Implicat Technol Japan Chapter, Matsuyama Univ, Int Acad Res Collaborat Funds, Hokyo Inc, KDDI Res Inst, Yamatoya Honten, Natl Univ Kaohsiung Social Network Innovat Ctr, ROC, Minist Sci & Technol, Taiwanese Assoc Social Networks, Harbin Inst Technol
DE Color printed paper; Mobile projector; Active infrared; Machine learning
AB In this world of digital and social media booms, a number of people spend their valuable times burying heads in smartphones, resulting in unintentional increased gaps in physical relationship with people nearby. A hybrid digital-physical medium is a possible solution for this problem by means of externalizing social media data and integrating them into a physical medium somehow. In this way, using social media will simultaneously connect us with both virtual and physical worlds.
This paper presents our first step towards implementation of such a hybrid system, using a mobile projector to project social media's digital data onto a physical color printed paper. With active infrared vision as an engine, we try to correlate physical printed colors with their infrared greyscale vision. A machine learning of multilayer perceptron is used to learn from samples whether there exists any reliable behavior that can be repeatedly used in the future. Nine color components from three well-known color models are combined, tested and evaluated before experimental results and future works are concluded and discussed.
C1 [Siriborvornratanakul, Thitirat] NIDA, Grad Sch Appl Stat, Bangkok 10240, Thailand.
RP Siriborvornratanakul, T (reprint author), NIDA, Grad Sch Appl Stat, 118 SeriThai Rd, Bangkok 10240, Thailand.
EM thitirat@as.nida.ac.th
NR 14
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 1865-0929
BN 978-3-662-48319-0; 978-3-662-48318-3
J9 COMM COM INF SC
PY 2015
VL 540
BP 331
EP 340
DI 10.1007/978-3-662-48319-0_26
PG 10
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Computer Science, Theory & Methods
SC Computer Science
GA BE2QR
UT WOS:000369889200026
ER
PT J
AU Evans, SR
Follmann, D
AF Evans, Scott R.
Follmann, Dean
TI Comment: Fundamentals and Innovation in Antibiotic Trials
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Editorial Material
ID NON-INFERIORITY TRIALS; CLINICAL-TRIALS; COLISTIN; INFECTIONS;
THERAPIES; ISSUES
C1 [Evans, Scott R.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
[Follmann, Dean] NIAID, NIH, 6700B Rockledge Dr,Rm 5231, Bethesda, MD USA.
RP Evans, SR (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM evans@sdac.harvard.edu; dfollmann@niaid.nih.gov
FU NIAID NIH HHS [UM1 AI104681]
NR 33
TC 3
Z9 3
U1 0
U2 2
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2015
VL 7
IS 4
BP 331
EP 336
DI 10.1080/19466315.2015.1094406
PG 6
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA DD4QW
UT WOS:000369908700011
PM 27087893
ER
PT J
AU Deak, T
Quinn, M
Cidlowski, JA
Victoria, NC
Murphy, AZ
Sheridan, JF
AF Deak, Terrence
Quinn, Matt
Cidlowski, John A.
Victoria, Nicole C.
Murphy, Anne Z.
Sheridan, John F.
TI Neuroimmune mechanisms of stress: sex differences, developmental
plasticity, and implications for pharmacotherapy of stress-related
disease
SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
LA English
DT Article
DE Corticosterone; cytokine; development; inflammation; neuroimmune; sex
differences; steroid receptors; stress
ID REPEATED SOCIAL DEFEAT; ANXIETY-LIKE BEHAVIOR; RECEPTOR ANTAGONIST
BLOCKS; SEXUALLY DIMORPHIC ACTIONS; UTERINE EPITHELIAL-CELLS; NEONATAL
PROCEDURAL PAIN; DEPRESSIVE-LIKE BEHAVIOR; LONG-TERM CONSEQUENCES;
BIRTH-WEIGHT CHILDREN; SPRAGUE-DAWLEY RATS
AB The last decade has witnessed profound growth in studies examining the role of fundamental neuroimmune processes as key mechanisms that might form a natural bridge between normal physiology and pathological outcomes. Rooted in core concepts from psychoneuroimmunology, this review utilizes a succinct, exemplar-driven approach of several model systems that contribute significantly to our knowledge of the mechanisms by which neuroimmune processes interact with stress physiology. Specifically, we review recent evidence showing that (i) stress challenges produce time-dependent and stressor-specific patterns of cytokine/chemokine expression in the CNS; (ii) inflammation-related genes exhibit unique expression profiles in males and females depending upon individual, cooperative or antagonistic interactions between steroid hormone receptors (estrogen and glucocorticoid receptors); (iii) adverse social experiences incurred through repeated social defeat engage a dynamic process of immune cell migration from the bone marrow to brain and prime neuroimmune function and (iv) early developmental exposure to an inflammatory stimulus (carageenin injection into the hindpaw) has a lasting influence on stress reactivity across the lifespan. As such, the present review provides a theoretical framework for understanding the role that neuroimmune mechanisms might play in stress plasticity and pathological outcomes, while at the same time pointing toward features of the individual (sex, developmental experience, stress history) that might ultimately be used for the development of personalized strategies for therapeutic intervention in stress-related pathologies.
C1 [Deak, Terrence] SUNY Binghamton, Dept Psychol, Behav Neurosci Program, Binghamton, NY 13902 USA.
[Quinn, Matt; Cidlowski, John A.] NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
[Victoria, Nicole C.; Murphy, Anne Z.] Georgia State Univ, Petit Sci Ctr, Inst Neurosci, Atlanta, GA 30303 USA.
[Sheridan, John F.] Ohio State Univ, Wexner Med Ctr, Coll Dent, Columbus, OH 43210 USA.
[Sheridan, John F.] Ohio State Univ, Wexner Med Ctr, Inst Behav Med Res, Columbus, OH 43210 USA.
RP Deak, T (reprint author), SUNY Binghamton, Dept Psychol, Behav Neurosci Program, Binghamton, NY 13902 USA.
EM tdeak@binghamton.edu
FU NIH [P50AA017823, RO1AG043467, RO1MH093473, RO1MH097243]; Janssen
Pharmaceuticals, Inc.; National Institutes of Environmental
Health/National Institutes of Health; [DA16272]
FX This review summarizes a series of talks given at the Neurobiology of
Stress Workshop in Cincinnati, OH from 17-20 June 2014. Dr. Terrence
Deak is currently supported by NIH grants P50AA017823 and RO1AG043467,
and a contract with Janssen Pharmaceuticals, Inc. Dr. Matt Quinn and Dr.
John A. Cidlowski are currently funded by the National Institutes of
Environmental Health/National Institutes of Health. Research presented
by Dr. Nicole C. Victoria and Dr. Anne Z. Murphy was funded by DA16272.
Dr. John F. Sheridan is currently funded by NIH grants RO1MH093473 and
RO1MH097243. Any opinions, findings, and conclusions or recommendations
expressed in this material are those of the author(s) and do not
necessarily reflect the views of the above stated funding agencies. The
authors have no conflicts of interest to declare.
NR 144
TC 7
Z9 7
U1 5
U2 12
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1025-3890
EI 1607-8888
J9 STRESS
JI Stress
PY 2015
VL 18
IS 4
BP 367
EP 380
DI 10.3109/10253890.2015.1053451
PG 14
WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences
SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences &
Neurology
GA DD3KU
UT WOS:000369821900001
PM 26176590
ER
PT J
AU Mustafa, T
Jiang, SZ
Eiden, AM
Weihe, E
Thistlethwaite, I
Eiden, LE
AF Mustafa, Tomris
Jiang, Sunny Zhihong
Eiden, Adrian M.
Weihe, Eberhard
Thistlethwaite, Ian
Eiden, Lee E.
TI Impact of PACAP and PAC1 receptor deficiency on the neurochemical and
behavioral effects of acute and chronic restraint stress in male C57BL/6
mice
SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
LA English
DT Article
DE Acute psychogenic stress; chronic psychogenic stress; HPA axis;
pituitary adenylate cyclase-activating polypeptide; PAC1 receptor;
restraint
ID CYCLASE-ACTIVATING POLYPEPTIDE; STRIA TERMINALIS BNST; HORMONE CRH GENE;
PARAVENTRICULAR NUCLEUS; BED NUCLEUS; CHROMAFFIN CELLS; PEPTIDE PACAP;
EXPRESSION; RATS; CORTICOSTERONE
AB Acute restraint stress (ARS) for 3 h causes corticosterone (CORT) elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP-and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following 7-day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1-deficient mice. However, longer periods of daily restraint (14-21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP-and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of ARS and short-term (<7 days) CRS on the hypothalamo-pituitary-adrenal (HPA) axis, the PAC1 receptor plays a prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia, during long-term (>7 days) CRS.
C1 [Mustafa, Tomris; Jiang, Sunny Zhihong; Thistlethwaite, Ian; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Bldg 49,Room 5A-38, Bethesda, MD 20892 USA.
[Eiden, Adrian M.] NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA.
[Weihe, Eberhard] Univ Marburg, Inst Anat, Marburg, Germany.
RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Bldg 49,Room 5A-38, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
FU National Institute of Health (NIMH) Intramural Research Program
[1ZIAMH002386]; Brain and Behavior Foundation (NARSAD Young Investigator
Award)
FX We acknowledge support from the National Institute of Health (NIMH)
Intramural Research Program (1ZIAMH002386); the Brain and Behavior
Foundation (NARSAD Young Investigator Award to Tomris Mustafa). The
authors declare no conflicts of interest.
NR 29
TC 5
Z9 5
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1025-3890
EI 1607-8888
J9 STRESS
JI Stress
PY 2015
VL 18
IS 4
BP 408
EP 418
DI 10.3109/10253890.2015.1025044
PG 11
WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences
SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences &
Neurology
GA DD3KU
UT WOS:000369821900004
PM 25853791
ER
PT J
AU Klauzinska, M
Bertolette, D
Tippireddy, S
Strizzi, L
Gray, PC
Gonzales, M
Duroux, M
Ruvo, M
Wechselberger, C
Castro, NP
Rangel, MC
Foca, A
Sandomenico, A
Hendrix, MJC
Salomon, D
Cuttitta, F
AF Klauzinska, Malgorzata
Bertolette, Daniel
Tippireddy, Sudhamsh
Strizzi, Luigi
Gray, Peter C.
Gonzales, Monica
Duroux, Meg
Ruvo, Menotti
Wechselberger, Christian
Castro, Nadia P.
Rangel, Maria Cristina
Foca, Annalia
Sandomenico, Annamaria
Hendrix, Mary J. C.
Salomon, David
Cuttitta, Frank
TI Cripto-1: an extracellular protein - connecting the sequestered
biological dots
SO CONNECTIVE TISSUE RESEARCH
LA English
DT Article
DE Autoantibodies; Cripto-1; Cripto-1 detection; drug discovery;
inflammation
ID EPITHELIAL-MESENCHYMAL TRANSITION; CELL-LIKE CHARACTERISTICS;
STEM-CELLS; MAMMARY-GLAND; TGF-BETA; BREAST-CANCER; INFLAMMATION;
EXPRESSION; ADRENOMEDULLIN; SUBPOPULATION
AB Cripto-1 (CR-1) is a multifunctional embryonic protein that is re-expressed during inflammation, wound repair, and malignant transformation. CR-1 can function either as a tethered co-receptor or shed as a free ligand underpinning its flexible role in cell physiology. CR-1 has been shown to mediate cell growth, migration, invasion, and induce epithelial to mesenchymal transition (EMT). The main signaling pathways mediating CR-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways. In addition, there are several naturally occurring binding partner proteins (BPPs) for CR-1 that can either agonize or antagonize its bioactivity. We will review the collective role of CR-1 as an extracellular protein, discuss caveats to consider in developing a quantitation assay, define possible mechanistic avenues applicable for drug discovery, and report on our experimental approaches to overcome these problematic issues.
C1 [Klauzinska, Malgorzata; Bertolette, Daniel; Tippireddy, Sudhamsh; Castro, Nadia P.; Rangel, Maria Cristina; Salomon, David; Cuttitta, Frank] NCI, Tumor Growth Factor Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Strizzi, Luigi] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Stanley Manne Childrens Res Inst,Dept Pathol,Prog, Chicago, IL 60611 USA.
[Gray, Peter C.] Salk Inst Biol Studies, Clayton Fdn, Labs Peptide Biol, La Jolla, CA 92037 USA.
[Gonzales, Monica] NCI, Off Res Operat, Off Director, Ctr Canc Res, Bethesda, MD 20892 USA.
[Duroux, Meg] Aalborg Univ, Dept Hlth Sci & Technol, Biomed Grp, Canc Biol Lab, Aalborg, Denmark.
[Ruvo, Menotti; Sandomenico, Annamaria] Univ Naples Federico II, CIRPeB, Naples, Italy.
[Ruvo, Menotti; Foca, Annalia] Ist Biostrutture & Bioimmagini CRN, Naples, Italy.
[Wechselberger, Christian] Greiner Bioone Diagnost GmbH, Rainbach, Austria.
[Foca, Annalia] Univ Naples Federico II, Dipartimento Farm, Naples, Italy.
[Hendrix, Mary J. C.] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Robert H Lurie Comprehens Canc Ctr,Program Canc B, Stanley Manne Childrens Res Inst,Feinberg Sch Med, Chicago, IL 60611 USA.
RP Klauzinska, M (reprint author), NCI, Tumor Growth Factor Sect, Mouse Canc Genet Program, Ctr Canc Res,Frederick Facil, Bldg 560,Room 12-46,1050 Boyles St, Frederick, MD 21702 USA.
EM malgorzata.klauzinska@nih.gov
RI Cuttitta, Frank/B-4758-2016
NR 54
TC 1
Z9 1
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0300-8207
EI 1607-8438
J9 CONNECT TISSUE RES
JI Connect. Tissue Res.
PY 2015
VL 56
IS 5
SI SI
BP 364
EP 380
DI 10.3109/03008207.2015.1077239
PG 17
WC Cell Biology; Orthopedics
SC Cell Biology; Orthopedics
GA DD3KY
UT WOS:000369822300004
PM 26327334
ER
PT J
AU Arduc, A
Dogan, BA
Bilmez, S
Nasiroglu, NI
Tuna, MM
Isik, S
Berker, D
Guler, S
AF Arduc, Ayse
Dogan, Bercem Aycicek
Bilmez, Sevgi
Nasiroglu, Narin Imga
Tuna, Mazhar Muslum
Isik, Serhat
Berker, Dilek
Guler, Serdar
TI High prevalence of Hashimoto's thyroiditis in patients with polycystic
ovary syndrome: does the imbalance between estradiol and progesterone
play a role?
SO ENDOCRINE RESEARCH
LA English
DT Article
DE Estradiol; Hashimoto's thyroiditis; polycystic ovary syndrome;
progesterone; thyroid autoantibodies
ID BLOOD MONONUCLEAR-CELLS; IMMUNE-SYSTEM; INSULIN-RESISTANCE; WOMEN;
AUTOIMMUNITY; DISEASE; VOLUME; PCOS; INTERLEUKIN-6; MODULATION
AB Objective: Some similar factors, such as genetic susceptibility and subinflammation/autoimmunity, contribute to development of both polycystic ovary syndrome (PCOS) and Hashimoto's thyroiditis (HT), suggesting a potential pathogenic link between the two common disorders. In this study, we investigated the relationship between PCOS and HT, considering the possible effect of PCOS-related hormonal and metabolic factors on thyroid autoimmunity. Methods: Eighty-six reproductive-age women diagnosed with PCOS according to Rotterdam criteria and 60 age-BMI matched control women were included in the study. All subjects had thyroid function tests, thyroid peroxidase anti-body (anti-TPO), thyroglobulin antibody (anti-Tg), LH, FSH, estradiol, progesterone, androgens, fasting glucose, insulin, lipid, homeostasis model assessment insulin resistance (HOMA-IR) levels, thyroid and pelvic ultrasounds. Results: TSH, anti-TPO (p = 0.017), anti-Tg (p = 0.014), LH, DHEAS, testosterone, and HOMA-IR levels were significantly higher and progesterone were lower in PCOS women than in controls. Free T4, free T3, FSH, estradiol levels and thyroid volume were similar between the two groups. A higher percentage of PCOS patients had elevated TSH (26.7 and 5%; p = 0.001), anti-TPO (26.7 and 6.6%; p = 0.002), and anti-Tg (16.2 and 5%; p = 0.039). HT was more common in PCOS patients compared to controls (22.1 and 5%; p = 0.004). Estradiol (p = 0.003) were higher in anti-TPO positive PCOS women than anti-TPO negative ones. Anti-TPO was correlated positively with estradiol, estradiol/progesterone ratio, and TSH. Conclusions: This study demonstrated a higher prevalence of HT, elevated TSH, anti-TPO, and anti-Tg levels in PCOS patients. Increased estrogen and estrogen/progesterone ratio seem to be directly involved in high anti-TPO levels in PCOS patients.
C1 [Arduc, Ayse] NIDDK, NIH, Diabet Endocrine & Obes Branch, Bethesda, MD USA.
[Dogan, Bercem Aycicek; Nasiroglu, Narin Imga; Tuna, Mazhar Muslum; Isik, Serhat; Berker, Dilek] Ankara Numune Training & Res Hosp, Minist Hlth, Dept Endocrinol & Metab, Ankara, Turkey.
[Bilmez, Sevgi] Ankara Numune Training & Res Hosp, Minist Hlth, Dept Internal Med, Ankara, Turkey.
[Guler, Serdar] Hitit Univ, Dept Endocrinol & Metab, Fac Med, Corum, Turkey.
RP Arduc, A (reprint author), 1778 Dawson St, Vienna, VA 22182 USA.
EM ayse_arduc@yahoo.com
NR 46
TC 4
Z9 4
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0743-5800
EI 1532-4206
J9 ENDOCR RES
JI Endocr. Res.
PY 2015
VL 40
IS 4
BP 204
EP 210
DI 10.3109/07435800.2015.1015730
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DD3FJ
UT WOS:000369807200006
PM 25822940
ER
PT S
AU Wells, S
AF Wells, S.
BE Raue, F
TI Medullary Thyroid Carcinoma Biology-Management-Treatment Foreword
SO MEDULLARY THYROID CARCINOMA: BIOLOGY-MANAGEMENT-TREATMENT
SE Recent Results in Cancer Research
LA English
DT Editorial Material; Book Chapter
C1 [Wells, S.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Wells, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0080-0015
BN 978-3-319-22542-5; 978-3-319-22541-8
J9 RECENT RESULTS CANC
JI Rec. Res. Camcer Res.
PY 2015
VL 204
BP V
EP VI
D2 10.1007/978-3-319-22542-5
PG 2
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA BE2OD
UT WOS:000369708900001
PM 26714327
ER
PT B
AU Natrajan, M
Bielekova, B
Franklin, RJM
AF Natrajan, Muktha
Bielekova, Bibiana
Franklin, Robin J. M.
BE David, S
TI Effects of Macrophages and Monocytes in Remyelination of the CNS
SO NEUROINFLAMMATION: NEW INSIGHTS INTO BENEFICIAL AND DETRIMENTAL
FUNCTIONS
LA English
DT Article; Book Chapter
ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
MULTIPLE-SCLEROSIS LESIONS; OLIGODENDROCYTE DIFFERENTIATION; MYELIN
PHAGOCYTOSIS; INDUCED DEMYELINATION; PROGENITOR CELLS; SPINAL-CORD;
INFLAMMATORY RESPONSES; COMPLEMENT RECEPTOR-3
C1 [Natrajan, Muktha; Franklin, Robin J. M.] Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Dept Clin Neurosci, Cambridge, England.
[Bielekova, Bibiana] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Natrajan, M (reprint author), Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Dept Clin Neurosci, Cambridge, England.
NR 85
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
BN 978-1-118-73274-8; 978-1-118-73282-3
PY 2015
BP 205
EP 219
D2 10.1002/9781118732748
PG 15
WC Immunology; Clinical Neurology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA BE2JI
UT WOS:000369409400014
ER
PT S
AU Tokar, EJ
Qu, W
Person, RJ
Ngalame, ON
Waalkes, MP
AF Tokar, Erik J.
Qu, Wei
Person, Rachel J.
Ngalame, Olive N.
Waalkes, Michael P.
BE Roberts, SM
Kehrer, JP
Klotz, LO
TI Oxidative Stress and the Inorganic Carcinogens
SO STUDIES ON EXPERIMENTAL TOXICOLOGY AND PHARMACOLOGY
SE Oxidative Stress in Applied Basic Research and Clinical Practice
LA English
DT Article; Book Chapter
ID INCLUSION-BODY FORMATION; DNA-DAMAGE; METAL CARCINOGENESIS; B6C3F(1)
MICE; LEAD; METALLOTHIONEIN; MECHANISMS; METHYLTRANSFERASE; EXPRESSION;
ARSENICALS
C1 [Tokar, Erik J.; Qu, Wei; Person, Rachel J.; Ngalame, Olive N.; Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Waalkes, MP (reprint author), NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM waalkes@mail.nih.gov
NR 39
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 978-3-319-19096-9; 978-3-319-19095-2
J9 OXID STRESS APPL BAS
JI Oxid. Stress Appl. Basic Res. Clin. Pract.
PY 2015
BP 323
EP 334
DI 10.1007/978-3-319-19096-9_16
D2 10.1007/978-3-319-19096-9
PG 12
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BE2MR
UT WOS:000369643500016
ER
PT S
AU Santosh, KC
Antani, S
Thoma, G
AF Santosh, K. C.
Antani, Sameer
Thoma, George
BE Traina, C
Rodrigues, PP
Kane, B
Marques, PMD
Traina, AJM
TI Stitched Multipanel Biomedical Figure Separation
SO 2015 IEEE 28TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS
(CBMS)
SE IEEE International Symposium on Computer-Based Medical Systems
LA English
DT Proceedings Paper
CT 28th IEEE International Symposium on Computer-Based Medical Systems
(CBMS)
CY JUN 22-25, 2015
CL Univ Sao Paulo, Sao Paulo, BRAZIL
SP IEEE, IEEE Comp Soc, ICMC, SUS, Ministerio Saude, Governo Fed Patria Educadora Brasil, CNPq, Google Brasil, FAPESP
HO Univ Sao Paulo
DE Automation; line segment detection; stitched multipanel figures;
biomedical publications; content-based image retrieval
ID IMAGE RETRIEVAL; FUTURE-DIRECTIONS; TEXT
AB We present a novel technique to separate subpanels from stitched multipanel figures appearing in biomedical research articles. Since such figures may comprise images from different imaging modalities, separating them is a critical first step for effective biomedical content-based image retrieval (CBIR). The method applies local line segment detection based on the gray-level pixel changes. It then applies a line vectorization process that connects prominent broken lines along the subpanel boundaries while eliminating insignificant line segments within the subpanels. We have validated our fully automatic technique on a subset of stitched multipanel biomedical figures extracted from articles within the Open Access subset of PubMed Central repository, and have achieved precision and recall of 81.22% and 85.08%, respectively.
C1 [Santosh, K. C.; Antani, Sameer; Thoma, George] NIH, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Santosh, KC (reprint author), NIH, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM santosh.kc@nih.gov; sameer.antani@nih.gov; george.thoma@nih.gov
NR 23
TC 0
Z9 0
U1 3
U2 3
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA
SN 1063-7125
BN 978-1-4673-6775-2
J9 COMP MED SY
PY 2015
BP 54
EP 59
DI 10.1109/CBMS.2015.51
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA BE2EU
UT WOS:000369099700014
ER
PT S
AU Xue, ZY
You, D
Candemir, S
Jaeger, S
Antani, S
Long, LR
Thoma, GR
AF Xue, Zhiyun
You, Daekeun
Candemir, Sema
Jaeger, Stefan
Antani, Sameer
Long, L. Rodney
Thoma, George R.
BE Traina, C
Rodrigues, PP
Kane, B
Marques, PMD
Traina, AJM
TI Chest X-ray Image View Classification
SO 2015 IEEE 28TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS
(CBMS)
SE IEEE International Symposium on Computer-Based Medical Systems
LA English
DT Proceedings Paper
CT 28th IEEE International Symposium on Computer-Based Medical Systems
(CBMS)
CY JUN 22-25, 2015
CL Univ Sao Paulo, Sao Paulo, BRAZIL
SP IEEE, IEEE Comp Soc, ICMC, SUS, Ministerio Saude, Governo Fed Patria Educadora Brasil, CNPq, Google Brasil, FAPESP
HO Univ Sao Paulo
DE chest radiograph; view classification; contour-based shape feature
ID RADIOGRAPHS
AB The view information of a chest X-ray (CXR), such as frontal or lateral, is valuable in computer aided diagnosis (CAD) of CXRs. For example, it helps for the selection of atlas models for automatic lung segmentation. However, very often, the image header does not provide such information. In this paper, we present a new method for classifying a CXR into two categories: frontal view vs. lateral view. The method consists of three major components: image pre-processing, feature extraction, and classification. The features we selected are image profile, body size ratio, pyramid of histograms of orientation gradients, and our newly developed contour-based shape descriptor. The method was tested on a large (more than 8,200 images) CXR dataset hosted by the National Library of Medicine. The very high classification accuracy (over 99% for 10-fold cross validation) demonstrates the effectiveness of the proposed method.
C1 [Xue, Zhiyun; You, Daekeun; Candemir, Sema; Jaeger, Stefan; Antani, Sameer; Long, L. Rodney; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA.
RP Xue, ZY (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA.
EM xuez@mail.nih.gov; santani@mail.nih.gov; rlong@mail.nih.gov;
gthoma@mail.nih.gov
NR 19
TC 0
Z9 0
U1 1
U2 1
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA
SN 1063-7125
BN 978-1-4673-6775-2
J9 COMP MED SY
PY 2015
BP 66
EP 71
DI 10.1109/CBMS.2015.49
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA BE2EU
UT WOS:000369099700016
ER
PT S
AU Santosh, KC
Vajda, S
Antani, S
Thoma, G
AF Santosh, K. C.
Vajda, Szilard
Antani, Sameer
Thoma, George
BE Traina, C
Rodrigues, PP
Kane, B
Marques, PMD
Traina, AJM
TI Automatic Pulmonary Abnormality Screening using Thoracic Edge Map
SO 2015 IEEE 28TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS
(CBMS)
SE IEEE International Symposium on Computer-Based Medical Systems
LA English
DT Proceedings Paper
CT 28th IEEE International Symposium on Computer-Based Medical Systems
(CBMS)
CY JUN 22-25, 2015
CL Univ Sao Paulo, Sao Paulo, BRAZIL
SP IEEE, IEEE Comp Soc, ICMC, SUS, Ministerio Saude, Governo Fed Patria Educadora Brasil, CNPq, Google Brasil, FAPESP
HO Univ Sao Paulo
ID TUBERCULOSIS
AB We present a novel method for screening pulmonary abnormalities using thoracic edge map in PA chest radiograph (CXR) images. Our particular interest is to aid clinical officers in screening HIV+ populations in resource constrained regions for Tuberculosis (TB). Our work is motivated by the observation that abnormal CXRs tend to exhibit corrupted and/or deformed thoracic edge maps. We study histograms of thoracic edges for all possible orientations of gradients in the range [0, 2 pi) at different numbers of bins and different pyramid levels. We have used two CXR benchmark collections made available by the U.S. National Library of Medicine, and have achieved a maximum abnormality detection accuracy of 85.92% and area under the ROC curve (AUC) of 0.91 at one second per image, on average, which outperforms the reported state-of-the-art.
C1 [Santosh, K. C.; Vajda, Szilard; Antani, Sameer; Thoma, George] NIH, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Santosh, KC (reprint author), NIH, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM santosh.kc@nih.gov; szilard.vajda@nih.gov; sameer.antani@nih.gov;
george.thoma@nih.gov
NR 8
TC 0
Z9 0
U1 1
U2 1
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA
SN 1063-7125
BN 978-1-4673-6775-2
J9 COMP MED SY
PY 2015
BP 360
EP 361
DI 10.1109/CBMS.2015.50
PG 2
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA BE2EU
UT WOS:000369099700076
ER
PT J
AU Altekruse, S
Das, A
Cho, HS
Petkov, V
Yu, MD
AF Altekruse, Sean
Das, Anita
Cho, Hyunsoon
Petkov, Valentina
Yu, Mandi
TI Do US thyroid cancer incidence rates increase with socioeconomic status
among people with health insurance? An observational study using SEER
population-based data
SO BMJ OPEN
LA English
DT Article
DE PUBLIC HEALTH
ID UNITED-STATES; ACCESS; CARE; OVERDIAGNOSIS; EPIDEMIOLOGY; CARCINOMA;
SURVIVAL; REGISTRY; IMPACT; TUMORS
AB Objectives The US thyroid cancer incidence rates are rising while mortality remains stable. Trends are driven by papillary thyroid cancer (PTC), the predominant cancer subtype which has a very good prognosis. We hypothesised that health insurance and high census tract socioeconomic status (SES) are associated with PTC risk.
Design Relationships between thyroid cancer incidence, insurance and census tract SES during 2007-2010 were examined in population-based cancer registries. Cases were stratified by tumour histology, size and demography.
Setting Surveillance, Epidemiology, and End Results (SEER) registries covering 30% of the US population.
Results PTCs accounted for 88% of incident thyroid cancer cases. Small PTCs (2cm) accounted for 60% of cases. Unlike non-PTC cases, the majority of those diagnosed with PTC were <50years of age and had 2cm tumours. Rate ratios (RR) of PTC diagnoses increased monotonically with SES among fully insured cases. The effect was strongest for small PTCs, high-SES versus low-SES quintile RR=2.7, 95% CI 2.6 to 2.9, two-sided trend test p<0.0001. For small PTC cases with insurance, the monotonic increase in incidence rates with rising SES persisted among cases younger than 50years of age (RR=3.3, 95% CI 3.0 to 3.5), women (RR=2.6, 95% CI 2.5 to 2.8) and Caucasians (RR=2.5, 95% CI 2.4 to 2.7). Among the less than fully insured, rates generally decreased with increasing SES.
Conclusions The >2.5-fold increase in risk of PTC diagnosis among insured individuals associated with high SES may be informative with respect to the contemporary issue of PTC overdiagnosis.
C1 [Altekruse, Sean; Das, Anita; Cho, Hyunsoon; Petkov, Valentina; Yu, Mandi] NCI, Div Canc Control & Populat Sci, Surveillance Res Program, Rockville, MD USA.
[Cho, Hyunsoon] Natl Canc Ctr, Div Canc Registrat & Surveillance, Goyang, South Korea.
[Cho, Hyunsoon] Grad Sch Canc Sci & Policy, Dept Canc Control & Policy, Goyang, South Korea.
RP Altekruse, S (reprint author), NCI, Div Canc Control & Populat Sci, Surveillance Res Program, Rockville, MD USA.
EM altekrusesf@mail.nih.gov
NR 34
TC 5
Z9 5
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2015
VL 5
IS 12
AR e009843
DI 10.1136/bmjopen-2015-009843
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DB9MB
UT WOS:000368839100139
PM 26644126
ER
PT J
AU Jonas, WB
Crawford, C
Colloca, L
Kaptchuk, TJ
Moseley, B
Miller, FG
Kriston, L
Linde, K
Meissner, K
AF Jonas, Wayne B.
Crawford, Cindy
Colloca, Luana
Kaptchuk, Ted J.
Moseley, Bruce
Miller, Franklin G.
Kriston, Levente
Linde, Klaus
Meissner, Karin
TI To what extent are surgery and invasive procedures effective beyond a
placebo response? A systematic review with meta-analysis of randomised,
sham controlled trials
SO BMJ OPEN
LA English
DT Review
DE SURGERY; COMPLEMENTARY MEDICINE; INTERNAL MEDICINE
ID GASTROESOPHAGEAL-REFLUX DISEASE; LOW-BACK-PAIN; PERCUTANEOUS MYOCARDIAL
LASER; CONTROLLED MULTICENTER TRIAL; GASTRIC BALLOON DISTENSION;
CONTROLLED CLINICAL-TRIAL; MAMMARY-ARTERY LIGATION; CHRONIC
ABDOMINAL-PAIN; DOUBLE-BLIND TRIAL; SAC SHUNT SURGERY
AB Objectives To assess the quantity and quality of randomised, sham-controlled studies of surgery and invasive procedures and estimate the treatment-specific and non-specific effects of those procedures.
Design Systematic review and meta-analysis.
Data sources We searched PubMed, EMBASE, CINAHL, CENTRAL (Cochrane Library), PILOTS, PsycInfo, DoD Biomedical Research, clinicaltrials.gov, NLM catalog and NIH Grantee Publications Database from their inception through January 2015.
Study selection We included randomised controlled trials of surgery and invasive procedures that penetrated the skin or an orifice and had a parallel sham procedure for comparison.
Data extraction and analysis Three authors independently extracted data and assessed risk of bias. Studies reporting continuous outcomes were pooled and the standardised mean difference (SMD) with 95% CIs was calculated using a random effects model for difference between true and sham groups.
Results 55 studies (3574 patients) were identified meeting inclusion criteria; 39 provided sufficient data for inclusion in the main analysis (2902 patients). The overall SMD of the continuous primary outcome between treatment/sham-control groups was 0.34 (95% CI 0.20 to 0.49; p<0.00001; I-2=67%). The SMD for surgery versus sham surgery was non-significant for pain-related conditions (n=15, SMD=0.13, p=0.08), marginally significant for studies on weight loss (n=10, SMD=0.52, p=0.05) and significant for gastroesophageal reflux disorder (GERD) studies (n=5, SMD=0.65, p<0.001) and for other conditions (n=8, SMD=0.44, p=0.004). Mean improvement in sham groups relative to active treatment was larger in pain-related conditions (78%) and obesity (71%) than in GERD (57%) and other conditions (57%), and was smaller in classical-surgery trials (21%) than in endoscopic trials (73%) and those using percutaneous procedures (64%).
Conclusions The non-specific effects of surgery and other invasive procedures are generally large. Particularly in the field of pain-related conditions, more evidence from randomised placebo-controlled trials is needed to avoid continuation of ineffective treatments.
C1 [Jonas, Wayne B.; Crawford, Cindy] Samueli Inst, Alexandria, VA USA.
[Crawford, Cindy] Univ Maryland, Sch Nursing, Dept Pain & Translat Symptom Sci, Baltimore, MD 21201 USA.
[Colloca, Luana] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA.
[Kaptchuk, Ted J.] Harvard Univ, Med Sch Boston, Beth Israel Deaconess Med Ctr, Program Placebo Studies, Cambridge, MA 02138 USA.
[Moseley, Bruce] Methodist Hosp, Houston, TX 77030 USA.
[Miller, Franklin G.] Natl Inst Hlth, Dept Bioeth, Ctr Clin, Bethesda, MD USA.
[Kriston, Levente] Univ Med Ctr Hamburg Eppendorf, Dept Med Psychol, Hamburg, Germany.
[Linde, Klaus] Tech Univ Munich, Inst Gen Practice, D-80290 Munich, Germany.
[Meissner, Karin] Univ Munich, Inst Med Psychol, D-80539 Munich, Germany.
RP Jonas, WB (reprint author), Samueli Inst, Alexandria, VA USA.
EM wjonas@siib.org
RI Kriston, Levente/D-1713-2013
OI Kriston, Levente/0000-0003-0748-264X
FU US Army Medical Research and Materiel Command [W81XWH-08-1-0615]
FX This work is supported by the US Army Medical Research and Materiel
Command under Award number W81XWH-08-1-0615. The views, opinions and/or
findings contained in this report are those of the author(s) and should
not be construed as an official Department of the Army position, policy
or decision unless so designated by other documentation. The funding
source had no role in the design and conduct of the study, in the
collection, analysis and interpretation of the data, or in the
preparation, review, or approval of the manuscript.
NR 100
TC 6
Z9 6
U1 4
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2015
VL 5
IS 12
AR e009655
DI 10.1136/bmjopen-2015-009655
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DB9MB
UT WOS:000368839100126
PM 26656986
ER
PT J
AU Petkovic, G
Charlesworth, JEG
Kelley, J
Miller, F
Roberts, N
Howick, J
AF Petkovic, Grace
Charlesworth, James E. G.
Kelley, John
Miller, Franklin
Roberts, Nia
Howick, Jeremy
TI Effects of placebos without deception compared with no treatment:
protocol for a systematic review and meta-analysis
SO BMJ OPEN
LA English
DT Review
ID CLINICAL-PRACTICE; NONCONSCIOUS ACTIVATION; CONDITIONED PLACEBO;
INFORMED CONSENT; POWERFUL PLACEBO; ETHICS; TRIAL; ANALGESIA; POWERLESS;
RESPONSES
AB Introduction: Placebos have long provided a robust control for evaluating active pharmacological preparations, but frequently demonstrate a variable therapeutic effect when delivered in double-blinded placebo-controlled trials. Delivery of placebos as treatment alone has been considered unethical, as it has been thought that deception is essential for their effect. However, recent evidence suggests that clinical benefit can be derived from placebos delivered without deception (unblinded/open-label) manner. Here, we present a protocol for the first systematic review and meta-analysis of studies of the effects of non-deceptive placebos compared with no treatment.
Methods and analysis: This protocol will compare the effect of placebos delivered non-deceptively to no treatment. It will also assess the methods of delivery used for non-deceptive placebos. Studies will be sought through relevant database searches and will include those within disease settings and those among healthy controls. To be included, trials must include both non-deceptive (open-label) placebo and no treatment groups. All data extraction and analysis will be conducted by two independent reviewers. The analysis will evaluate any differences in outcome measures between the non-deceptive placebo and no treatment groups. Outcome measures will be the clinically-relevant outcomes detailed in the primary papers. The delivery methods, such as verbal instructions, which may provide positive expectations and outcomes, of non-deceptive placebos will also be assessed. Each study will be comprehensively assessed for bias. Subgroup analyses will identify any discrepancies among heterogeneous data.
Ethics and dissemination: This review does not require ethical approval. The completed review will be widely disseminated by publication and social media where appropriate. This protocol has been registered on PROSPERO (2015: CRD42015023347).
C1 [Petkovic, Grace; Charlesworth, James E. G.; Roberts, Nia; Howick, Jeremy] Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England.
[Kelley, John] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Kelley, John] Endicott Coll, Dept Psychol, Beverly, MA USA.
[Miller, Franklin] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Petkovic, G (reprint author), Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England.
EM grace.petkovic@hmc.ox.ac.uk
NR 47
TC 2
Z9 2
U1 1
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2015
VL 5
IS 11
AR e009428
DI 10.1136/bmjopen-2015-009428
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DB9MK
UT WOS:000368840100130
PM 26610763
ER
PT S
AU Cohen, JI
AF Cohen, Jeffrey I.
BE Munz, C
TI Primary Immunodeficiencies Associated with EBV Disease
SO EPSTEIN BARR VIRUS, VOL 1: ONE HERPES VIRUS: MANY DISEASES
SE Current Topics in Microbiology and Immunology
LA English
DT Review; Book Chapter
ID EPSTEIN-BARR-VIRUS; LINKED LYMPHOPROLIFERATIVE-DISEASE; FAMILIAL
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; NATURAL-KILLER-CELLS; INFECTED
B-CELLS; LOSS-OF-FUNCTION; CD8(+) T-CELLS; XIAP DEFICIENCY; HUMORAL
IMMUNITY; ENCODING GENE
AB Epstein-Barr virus (EBV) infects nearly all humans and usually is asymptomatic, or in the case of adolescents and young adults, it can result in infectious mononucleosis. EBV-infected B cells are controlled primarily by NK cells, iNKT cells, CD4 T cells, and CD8 T cells. While mutations in proteins important for B cell function can affect EBV infection of these cells, these mutations do not result in severe EBV infection. Some genetic disorders affecting T and NK cell function result in failure to control EBV infection, but do not result in increased susceptibility to other virus infections. These include mutations in SH2D1A, BIRC4, ITK, CD27, MAGT1, CORO1A, and LRBA. Since EBV is the only virus that induces proliferation of B cells, the study of these diseases has helped to identify proteins critical for interactions of T and/or NK cells with B cells. Mutations in three genes associated with hemophagocytic lymphohistocytosis, PRF1, STXBP2, and UNC13D, can also predispose to severe chronic active EBV disease. Severe EBV infection can be associated with immunodeficiencies that also predispose to other viral infections and in some cases other bacterial and fungal infections. These include diseases due to mutations in PIK3CD, PIK3R1, CTPS1, STK4, GATA2, MCM4, FCGR3A, CARD11, ATM, and WAS. In addition, patients with severe combined immunodeficiency, which can be due to mutations in a number of different genes, are at high risk for various infections as well as EBV B cell lymphomas. Identification of proteins important for control of EBV may help to identify new targets for immunosuppressive therapies.
C1 [Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, 50 South Dr,MSC 8007, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIH, Med Virol Sect, Infect Dis Lab, 50 South Dr,MSC 8007, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
NR 71
TC 12
Z9 14
U1 4
U2 9
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0070-217X
BN 978-3-319-22822-8; 978-3-319-22821-1
J9 CURR TOP MICROBIOL
JI Curr.Top.Microbiol.Immunol.
PY 2015
VL 390
BP 241
EP 265
DI 10.1007/978-3-319-22822-8_10
D2 10.1007/978-3-319-22822-8
PG 25
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1ZY
UT WOS:000368843200011
PM 26424649
ER
PT S
AU Buchanan, SK
Noinaj, N
AF Buchanan, Susan K.
Noinaj, Nicholas
BE Buchanan, SK
Noinaj, N
TI The BAM Complex Methods and Protocols Preface
SO BAM COMPLEX: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Editorial Material; Book Chapter
C1 [Buchanan, Susan K.] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
[Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.
RP Buchanan, SK (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 3
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2871-2; 978-1-4939-2870-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1329
BP V
EP VI
D2 10.1007/978-1-4939-2871-2
PG 2
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE1RU
UT WOS:000368437400001
ER
PT S
AU Noinaj, N
Kuszak, AJ
Buchanan, SK
AF Noinaj, Nicholas
Kuszak, Adam J.
Buchanan, Susan K.
BE Buchanan, SK
Noinaj, N
TI Heat Modifiability of Outer Membrane Proteins from Gram-Negative
Bacteria
SO BAM COMPLEX: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE BamA; Heat modifiability; OMP; Outer membrane protein; beta-barrel
membrane protein; BAM complex; Protein folding
ID ESCHERICHIA-COLI
AB beta-barrel membrane proteins are somewhat unique in that their folding states can be monitored using semi-native SDS-PAGE methods to determine if they are folded properly or not. This property, which is commonly referred to as heat modifiability, has been used for many years on both purified protein and on whole cells to monitor folded states of proteins of interest. Additionally, heat modifiability assays have proven indispensable in studying the BAM complex and its role in folding and inserting beta-barrel membrane proteins into the outer membrane. Here, we describe the protocol our lab uses for performing the heat modifiability assay in our studies on outer membrane proteins.
C1 [Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.
[Kuszak, Adam J.; Buchanan, Susan K.] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
RP Noinaj, N (reprint author), Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.
FU Intramural NIH HHS [ZIA DK036139-09]; NIAID NIH HHS [K22 AI113078]
NR 5
TC 1
Z9 1
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2871-2; 978-1-4939-2870-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1329
BP 51
EP 56
DI 10.1007/978-1-4939-2871-2_4
D2 10.1007/978-1-4939-2871-2
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE1RU
UT WOS:000368437400005
PM 26427675
ER
PT S
AU Kuszak, AJ
Noinaj, N
Buchanan, SK
AF Kuszak, Adam J.
Noinaj, Nicholas
Buchanan, Susan K.
BE Buchanan, SK
Noinaj, N
TI Methods to Characterize Folding and Function of BamA Cross-Link Mutants
SO BAM COMPLEX: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE BamA; BAM complex; Outer membrane protein; Proteinase K; Disulfide
cross-linking; beta-barrel membrane protein
ID ESCHERICHIA-COLI; BIOGENESIS; MACHINE; COMPLEX
AB The utility of protein engineering, both the mutation and deletion of specific amino acids, to investigate protein structure and function has been demonstrated time and time again, and intermolecular and intramolecular interactions within the BAM complex and its individual components are no exception. Extensive efforts have probed conserved and unique amino acid sequences of the Bam proteins to define their functional roles. This chapter summarizes efforts as applied to the disulfide cross-link mutants of BamA and describes experimental methods used in our studies to determine that lateral opening of the barrel domain is required for function.
C1 [Kuszak, Adam J.; Buchanan, Susan K.] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
[Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.
RP Kuszak, AJ (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
FU Intramural NIH HHS [ZIA DK036139-09]; NIAID NIH HHS [K22 AI113078]
NR 8
TC 0
Z9 0
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2871-2; 978-1-4939-2870-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1329
BP 137
EP 147
DI 10.1007/978-1-4939-2871-2_10
D2 10.1007/978-1-4939-2871-2
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE1RU
UT WOS:000368437400011
PM 26427681
ER
PT S
AU Roman-Hernandez, G
Bernstein, HD
AF Roman-Hernandez, Giselle
Bernstein, Harris D.
BE Buchanan, SK
Noinaj, N
TI An In Vitro Assay for Outer Membrane Protein Assembly by the BAM Complex
SO BAM COMPLEX: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE BAM complex; beta-barrel proteins; Escherichia coli; Membrane proteins;
Molecular chaperones; Protein folding; Protein purification; SurA
ID ESCHERICHIA-COLI; AUTOTRANSPORTER; RECONSTITUTION; BIOGENESIS; EXPORT;
SURA
AB To elucidate the mechanism of a biochemical process it is often essential to reconstitute the reaction in vitro using the minimal set of factors required to drive the reaction to completion. Here, we describe a method to reconstitute the folding and membrane integration of bacterial outer membrane (OM) proteins that have a characteristic beta-barrel structure. In this method the BAM complex, a heteroligomer that catalyzes the membrane integration of beta-barrel proteins, is first purified and inserted into small lipid vesicles. Denatured OM proteins are then assembled and integrated into the vesicles in the presence of a molecular chaperone called SurA.
C1 [Roman-Hernandez, Giselle; Bernstein, Harris D.] Natl Inst Diabet & Digest & Kidney Dis, Genet & Biochem Branch, NIH, Bethesda, MD USA.
RP Roman-Hernandez, G (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Genet & Biochem Branch, NIH, Bethesda, MD USA.
NR 19
TC 0
Z9 0
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2871-2; 978-1-4939-2870-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1329
BP 203
EP 213
DI 10.1007/978-1-4939-2871-2_16
D2 10.1007/978-1-4939-2871-2
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE1RU
UT WOS:000368437400017
PM 26427687
ER
PT S
AU Noinaj, N
Buchanan, SK
AF Noinaj, Nicholas
Buchanan, Susan K.
BE Buchanan, SK
Noinaj, N
TI Summary and Future Directions
SO BAM COMPLEX: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Editorial Material; Book Chapter
DE BamA; OMP; Outer membrane protein; beta-barrel membrane protein; BAM
complex; Protein folding; Lateral opening
AB beta-barrel outer membrane proteins (OMPs) are found in the outer membranes (OMs) of all gram-negative bacteria, yet exactly how they are folded and inserted remains unknown. The last decade has provided a wealth of discovery including the identifi cation of the BAM complex, a multicomponent complex responsible for the biogenesis of all OMPs into the OM. It is anticipated that the next decade will further advance our knowledge of how the BAM complex is able to perform its unique and interesting function.
C1 [Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.
[Buchanan, Susan K.] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
RP Noinaj, N (reprint author), Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.
FU Intramural NIH HHS [ZIA DK036139-09]; NIAID NIH HHS [K22 AI113078]
NR 0
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 978-1-4939-2871-2; 978-1-4939-2870-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1329
BP 279
EP 280
DI 10.1007/978-1-4939-2871-2_22
D2 10.1007/978-1-4939-2871-2
PG 2
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE1RU
UT WOS:000368437400023
PM 26427693
ER
PT J
AU Feltus, FA
Breen, JR
Deng, J
Izard, RS
Konger, CA
Ligon, WB
Preuss, D
Wang, KC
AF Feltus, Frank A.
Breen, Joseph R., III
Deng, Juan
Izard, Ryan S.
Konger, Christopher A.
Ligon, Walter B., III
Preuss, Don
Wang, Kuang-Ching
TI The Widening Gulf between Genomics Data Generation and Consumption: A
Practical Guide to Big Data Transfer Technology
SO BIOINFORMATICS AND BIOLOGY INSIGHTS
LA English
DT Article
DE data life cycle; Big Data; networks; software-defined networking
ID SEQUENCING DATA; CYBERINFRASTRUCTURE; INFRASTRUCTURE; SCIENCE
AB In the last decade, high-throughput DNA sequencing has become a disruptive technology and pushed the life sciences into a distributed ecosystem of sequence data producers and consumers. Given the power of genomics and declining sequencing costs, biology is an emerging "Big Data" discipline that will soon enter the exabyte data range when all subdisciplines are combined. These datasets must be transferred across commercial and research networks in creative ways since sending data without thought can have serious consequences on data processing time frames. Thus, it is imperative that biologists, bioinformaticians, and information technology engineers recalibrate data processing paradigms to fit this emerging reality. This review attempts to provide a snapshot of Big Data transfer across networks, which is often overlooked by many biologists. Specifically, we discuss four key areas: 1) data transfer networks, protocols, and applications; 2) data transfer security including encryption, access, firewalls, and the Science DMZ; 3) data flow control with software-defined networking; and 4) data storage, staging, archiving and access. A primary intention of this article is to orient the biologist in key aspects of the data transfer process in order to frame their genomics-oriented needs to enterprise IT professionals.
C1 [Feltus, Frank A.] Clemson Univ, Dept Biochem & Genet, Clemson, SC USA.
[Breen, Joseph R., III] Univ Utah, Ctr High Performance Comp, Salt Lake City, UT USA.
[Deng, Juan; Izard, Ryan S.; Ligon, Walter B., III; Wang, Kuang-Ching] Clemson Univ, Dept Elect & Comp Engn, Clemson, SC USA.
[Konger, Christopher A.] Clemson Univ, Clemson Comp & Informat Technol, Anderson, SC USA.
[Preuss, Don] NIH, NLM, NCBI, Bethesda, MD 20892 USA.
RP Feltus, FA (reprint author), Clemson Univ, Dept Biochem & Genet, Clemson, SC USA.
EM FFELTUS@clemson.edu
NR 20
TC 4
Z9 4
U1 1
U2 5
PU LIBERTAS ACAD
PI AUCKLAND
PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND
SN 1177-9322
J9 BIOINFORM BIOL INSIG
JI Bioinform. Biol. Insights
PY 2015
VL 9
SU 1
BP 9
EP 19
DI 10.4137/BBI.S28988
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DB5UB
UT WOS:000368578000002
PM 26568680
ER
PT J
AU Han, YX
Gao, SG
Muegge, K
Zhang, W
Zhou, B
AF Han, Yixing
Gao, Shouguo
Muegge, Kathrin
Zhang, Wei
Zhou, Bing
TI Advanced Applications of RNA Sequencing and Challenges
SO BIOINFORMATICS AND BIOLOGY INSIGHTS
LA English
DT Article
DE RNA-seq; data preprocessing; differential gene expression; alternative
splicing; variants detection; pathway analysis; co-expression network;
systems biology
ID GENE-EXPRESSION DATA; ALLELE-SPECIFIC EXPRESSION; SET ENRICHMENT
ANALYSIS; SHORT READ ALIGNMENT; DIFFERENTIAL EXPRESSION;
CANDIDA-ALBICANS; STATISTICAL-METHODS; SPLICE JUNCTIONS; SINGLE-CELL;
COEXPRESSION NETWORKS
AB Next-generation sequencing technologies have revolutionarily advanced sequence-based research with the advantages of high-throughput, high-sensitivity, and high-speed. RNA-seq is now being used widely for uncovering multiple facets of transcriptome to facilitate the biological applications. However, the large-scale data analyses associated with RNA-seq harbors challenges. In this study, we present a detailed overview of the applications of this technology and the challenges that need to be addressed, including data preprocessing, differential gene expression analysis, alternative splicing analysis, variants detection and allele-specific expression, pathway analysis, co-expression network analysis, and applications combining various experimental procedures beyond the achievements that have been made. Specifically, we discuss essential principles of computational methods that are required to meet the key challenges of the RNA-seq data analyses, development of various bioinformatics tools, challenges associated with the RNA-seq applications, and examples that represent the advances made so far in the characterization of the transcriptome.
C1 [Han, Yixing; Muegge, Kathrin] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
[Gao, Shouguo] NHLBI, Bioinformat & Syst Biol Core, NIH, Bethesda, MD 20892 USA.
[Muegge, Kathrin] Frederick Natl Lab, Basic Sci Program, Leidos Biomed Res Inc, Frederick, MD USA.
[Zhang, Wei] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Zhou, Bing] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
RP Han, YX (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
EM yi-xing.han@nih.gov
RI Zhang, Wei/K-4276-2016
OI Zhang, Wei/0000-0002-0942-1245
FU NHGRI NIH HHS [R01 HG004659]; NIEHS NIH HHS [R01 ES014811]; NIGMS NIH
HHS [R01 GM049369, R01 GM052872]
NR 200
TC 12
Z9 12
U1 4
U2 11
PU LIBERTAS ACAD
PI AUCKLAND
PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND
SN 1177-9322
J9 BIOINFORM BIOL INSIG
JI Bioinform. Biol. Insights
PY 2015
VL 9
SU 1
BP 29
EP 46
DI 10.4137/BBI.S28991
PG 18
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DB5UB
UT WOS:000368578000004
PM 26609224
ER
PT S
AU Smith, HE
AF Smith, Harold E.
BE Biron, D
Haspel, G
TI Library Construction for Mutation Identification by Whole-Genome
Sequencing
SO C. ELEGANS: METHODS AND APPLICATIONS, 2ND EDITION
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Sequence variant detection; Polymorphism mapping; NGS library
construction
ID CAENORHABDITIS-ELEGANS; GALAXY
AB Next-generation sequencing provides a rapid and powerful method for mutation identification. Herein is described a workflow for sample preparation to allow the simultaneous mapping and identification of candidate mutations by whole-genome sequencing in Caenorhabditis elegans. The protocol is designed for small numbers of worms to accommodate classes of mutations, such as lethal and sterile alleles, that are difficult to identify by traditional means.
C1 [Smith, Harold E.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA.
RP Smith, HE (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA.
FU Intramural NIH HHS
NR 13
TC 0
Z9 0
U1 2
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2842-2; 978-1-4939-2841-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1327
BP 1
EP 9
DI 10.1007/978-1-4939-2842-2_1
D2 10.1007/978-1-4939-2842-2
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA BE1RT
UT WOS:000368437200002
PM 26423963
ER
PT S
AU Tarca, AL
AF Tarca, Adi Laurentiu
BE Hoeng, J
Peitsch, MC
TI Pathway Analysis and Machine Learning as Tools in Systems Toxicology
SO COMPUTATIONAL SYSTEMS TOXICOLOGY
SE Methods in Pharmacology and Toxicology
LA English
DT Article; Book Chapter
DE Gene set analysis; Pathway analysis; Machine learning; Data-driven
functional homology
ID GENE SET ENRICHMENT; EXPRESSION; NORMALIZATION
AB An important aspect of toxicity testing is the identification of signaling pathways perturbed by biologically active substances or their metabolites that can cause adverse health effects in humans. This chapter describes analysis methods that can use (1) human transcriptomics data to identify perturbed signaling pathways and (2) animal model data to infer the pathway activity in human for the same stimuli. For the former goal, we describe Pathway Analysis with Down-weighting of Overlapping Genes (PADOG) and Pathway Level Analysis of Gene Expression (PLAGE), which have been shown to perform well for pathway prioritization. For the second goal, we describe two strategies that rely on transcriptomic changes induced by a set of training stimuli in both human and animal models to learn how to predict pathway activity in human for new stimuli from similar data in an animal model. One strategy is based on machine learning that maps pathway activity results from animal models to human, and the other strategy works by deriving functional homology between the animal model and human genes so that a gene set analysis method (e.g., PADOG and PLAGE) can be applied to the animal data to identify significantly perturbed pathways in human. In addition to describing the methods and their assumptions and limitations, we illustrate how to apply these methods using the R statistical environment and open-source Bioconductor packages.
C1 [Tarca, Adi Laurentiu] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Tarca, Adi Laurentiu] Wayne State Univ, Bioinformat & Computat Biol Unit, Perinatol Res Branch, NICHD,NIH,DHHS, Bethesda, MD USA.
RP Tarca, AL (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
NR 30
TC 0
Z9 0
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1557-2153
BN 978-1-4939-2778-4; 978-1-4939-2777-7
J9 METHOD PHARMACOL TOX
JI Methods Pharmacol. Toxicol.
PY 2015
BP 209
EP 222
DI 10.1007/978-1-4939-2778-4_9
D2 10.1007/978-1-4939-2778-4
PG 14
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BE1QP
UT WOS:000368400200010
ER
PT B
AU Tsang, KY
Jochems, C
Schlom, J
AF Tsang, Kwong Y.
Jochems, Caroline
Schlom, Jeffrey
BE Ascierto, PA
Stroncek, DF
Wang, E
TI Insights on Peptide Vaccines in Cancer Immunotherapy
SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES
SE Cancer Drug Discovery and Development
LA English
DT Article; Book Chapter
DE Peptide cancer vaccines; Immunotherapy; Combination therapy; Cytokines;
Prime-boost regimen; Checkpoint inhibitors
ID COLONY-STIMULATING FACTOR; T-CELL RESPONSES; PHASE-II TRIAL;
PROSTATE-SPECIFIC ANTIGEN; PULSED DENDRITIC CELLS; HUMAN
CARCINOEMBRYONIC ANTIGEN; MULTIPEPTIDE MELANOMA VACCINE;
MESENCHYMAL-LIKE PHENOTYPE; MYELOID SUPPRESSOR-CELLS; TUMOR-ASSOCIATED
ANTIGEN
AB Human tumor-associated antigens are generally weakly immunogenic and therefore able to escape detection by the immune system. Numerous studies have shown, however, that immune cells infiltrate many tumors, and that these cells are vital for keeping tumor burden in check. Immunotherapy can enhance this process by further stimulating tumor-recognizing cells while decreasing the function of immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells, thereby creating a more immune-activating tumor microenvironment.
Peptide vaccines can stimulate and activate T cells specific to tumor-associated antigens. Because peptides endogenously expressed by tumor cells are often weak immunogens, researchers are investigating various strategies for making them more immunogenic and more potent as vaccines. Here we review multiple strategies for enhancing peptide immunogenicity, including (a) peptides with amino acid substitutions at anchor residues and heteroclitic analogs, (b) multiple variance long peptides, (c) whole protein and 15-mer overlapping peptides, (d) multiple peptides recognizing different tumor-associated antigens, (e) class I and II epitope hybrid vaccines, (f) peptide-pulsed dendritic cells, and (g) combining peptide vaccines with other therapies. While it is unlikely that peptide vaccines alone could significantly affect progressive disease, the combination of these vaccines with the right adjuvants and/or immunomodulatory agents has shown promising results in clinical trials.
C1 [Tsang, Kwong Y.; Jochems, Caroline; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09, Bethesda, MD 20892 USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09, Bethesda, MD 20892 USA.
EM tsangkwo@mail.nih.gov; jochemscm@mail.nih.gov; js141c@nih.gov
NR 190
TC 0
Z9 0
U1 2
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
BN 978-3-319-21167-1; 978-3-319-21166-4
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
BP 1
EP 27
DI 10.1007/978-3-319-21167-1_1
D2 10.1007/978-3-319-21167-1
PG 27
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1UP
UT WOS:000368600900002
ER
PT B
AU Wang, E
Marincola, FM
AF Wang, Ena
Marincola, Francesco M.
BE Ascierto, PA
Stroncek, DF
Wang, E
TI Developments in T Cell Based Cancer Immunotherapies Preface
SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES
SE Cancer Drug Discovery and Development
LA English
DT Editorial Material; Book Chapter
C1 [Wang, Ena] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
[Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Div Translat Med, Doha, Qatar.
RP Wang, E (reprint author), NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
NR 0
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
BN 978-3-319-21167-1; 978-3-319-21166-4
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
BP V
EP VII
D2 10.1007/978-3-319-21167-1
PG 3
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1UP
UT WOS:000368600900001
ER
PT B
AU Berzofsky, JA
Wood, LV
Terabe, M
AF Berzofsky, Jay A.
Wood, Lauren V.
Terabe, Masaki
BE Ascierto, PA
Stroncek, DF
Wang, E
TI Strategies for Improving Vaccines to Elicit T Cells to Treat Cancer
SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES
SE Cancer Drug Discovery and Development
LA English
DT Article; Book Chapter
DE Cancer vaccines; Cancer immunotherapy; Immune regulation; NKT cells;
Epitope enhancement; Cytokines; Checkpoint inhibitors
ID GROWTH-FACTOR-BETA; PROSTATE-SPECIFIC ANTIGEN; COLONY-STIMULATING
FACTOR; LASTING CELLULAR-IMMUNITY; MELANOMA-REACTIVE CTL; HIGH-AVIDITY
CTL; REGULATORY T; NKT CELLS; TUMOR-IMMUNITY; IN-VIVO
AB Cancers have not evolved to be good vaccines. Indeed, most clinically evident cancers have escaped from the immune system. Thus, unlike most existing vaccines, one cannot simply mimic the disease agent to make a successful vaccine, but instead may need to combine several approaches. Our lab has developed a push-pull strategy in which we first improve the immunogenicity of the antigens themselves by modifying the amino acid sequence to improve binding of epitopes to MHC molecules (a process called epitope enhancement). The next step is to "push" the response to improve not only the quantity but also the quality of the immune response, to achieve better avidity, longevity, and type of response, by using combinations of defined molecular adjuvants such as cytokines like IL-15, TLR ligands, and NKT cell agonist antigens. We and others have identified synergistic combinations of these. Then, it is still necessary to overcome negative regulatory mechanisms that cancers elicit to suppress and evade the immune system. These include regulatory cells like Treg cells, myeloid-derived suppressor cells, M2-macrophages, regulatory type II NKT cells, and others, plus regulatory receptors on the T cells themselves such as CTLA-4 and PD-1, and regulatory cytokines like TGF-beta, IL-13 and IL-10. We call this the "pull" in vaccine strategy, removing the brakes to allow vaccines to achieve their maximal potential. Here, we describe preclinical studies to examine each of these elements in cancer vaccines and clinical trials to translate these into patients, including an epitope-enhanced vaccine and blockade of TGF-beta. Overall, the combination of these strategies may allow more effective vaccines to treat established human cancers.
C1 [Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 41 Room D702D,41 Medlars Dr, Bethesda, MD 20892 USA.
[Wood, Lauren V.] NCI, Clin Trials Team, Vaccine Branch,Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Terabe, Masaki] NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch,Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Berzofsky, JA (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 41 Room D702D,41 Medlars Dr, Bethesda, MD 20892 USA.
EM berzofsj@mail.nih.gov; lw51p@nih.gov; terabe@mail.nih.gov
NR 158
TC 0
Z9 0
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
BN 978-3-319-21167-1; 978-3-319-21166-4
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
BP 29
EP 52
DI 10.1007/978-3-319-21167-1_2
D2 10.1007/978-3-319-21167-1
PG 24
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1UP
UT WOS:000368600900003
ER
PT B
AU Stroncek, D
Jin, JJ
David-Ocampo, V
Fellowes, V
Moses, L
Sabatino, M
AF Stroncek, David
Jin, Jianjian
David-Ocampo, Virginia
Fellowes, Vicki
Moses, Larry
Sabatino, Marianna
BE Ascierto, PA
Stroncek, DF
Wang, E
TI Production of Clinical T Cell Therapies
SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES
SE Cancer Drug Discovery and Development
LA English
DT Article; Book Chapter
DE Adoptive cell therapies; Good manufacturing practices; Cell culture;
Cell selection; Tumor infiltrating leukocytes; Genetically engineered T
cells; Cell processing; Chimeric antigen receptor T cells; High affinity
receptor T cells
ID TUMOR-INFILTRATING LYMPHOCYTES; CHIMERIC ANTIGEN RECEPTOR; BOVINE
SERUM-ALBUMIN; ADOPTIVE TRANSFER; RAPID EXPANSION; PRESENTING CELLS;
DENDRITIC CELLS; GENERATION; IMMUNOTHERAPY; ANTIBODIES
AB The improving effectiveness of adoptive T cell therapies has led to their increased clinical application. Most of these adoptive T cell therapies are being produced in small lots in cell therapy centers affiliated with or located within academic health centers. Typically, the cells are produced from autologous or HLA compatible donors and one lot is used for a single patient. As part of early phase clinical trials, the best available methods and devices for the manufacture of clinical grade T cell therapies are described. For most adoptive T cell therapies the starting material is a peripheral blood mononuclear cell (PBMC) product that is collected by apheresis using closed system blood cell separators. Many manufacturing processes require that red blood cells be removed from the PBMCs or that T cells or T cell subsets are isolated. Classically, T cells have been cultured in flasks, but culture in closed systems which reduces the risk of microbial contamination is desirable and bags and bioreactors are often used for T cell culture and expansion. T cell culture involves growth and expansion in media supplemented with serum, cytokines and feeder cells or other artificial stimulators, i.e. anti-CD3/28 beads or K562 cell line. Recently, closed system transduction methods have been developed that can be used to produce genetically engineered T cells. Automated instruments are available to wash and concentrate products. The final product is assessed for the quantity of cells present, purity, sterility and potency. The use of these best practices is allowing for the consistent manufacturing of high quality cellular therapies to support early phase clinical trials.
C1 [Stroncek, David; Jin, Jianjian; David-Ocampo, Virginia; Fellowes, Vicki; Moses, Larry] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
[Sabatino, Marianna] Kite Pharma Inc, Santa Monica, CA USA.
RP Stroncek, D (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
NR 46
TC 0
Z9 0
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
BN 978-3-319-21167-1; 978-3-319-21166-4
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
BP 129
EP 150
DI 10.1007/978-3-319-21167-1_6
D2 10.1007/978-3-319-21167-1
PG 22
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1UP
UT WOS:000368600900007
ER
PT B
AU Lugli, E
Gattinoni, L
AF Lugli, Enrico
Gattinoni, Luca
BE Ascierto, PA
Stroncek, DF
Wang, E
TI Harnessing Stem Cell-Like Memory T Cells for Adoptive Cell Transfer
Therapy of Cancer
SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES
SE Cancer Drug Discovery and Development
LA English
DT Article; Book Chapter
DE Adoptive T cell therapy; T celldifferentiation; T memory stem cells;
Transcription factors; Immune metabolism; Gene therapy; Reprogramming;
Induced pluripotent stem cells; Small molecules; Homeostatic cytokines
ID TUMOR-INFILTRATING LYMPHOCYTES; VERSUS-HOST-DISEASE; TRANSCRIPTION
FACTOR EOMESODERMIN; METASTATIC MELANOMA PATIENTS; SUPERIOR ANTITUMOR
IMMUNITY; PERIPHERAL-BLOOD CELLS; IN-VIVO PERSISTENCE; EFFECTOR
FUNCTION; DIRECT CONVERSION; DEFINED FACTORS
AB Immunotherapies based on the adoptive transfer of naturally occurring or gene-engineered tumor-reactive T cells can result in durable complete responses in patients with metastatic cancers. Increasing findings from mouse studies and clinical trials indicate that intrinsic properties related to the differentiation state of the transferred T cells are crucial to the success of adoptive immunotherapies. There is now evidence that stem cell-like T cells with enhanced capacity for self-renewal and the ability to derive potent effector T cells might be used to improve persistence and long-term anti-tumor immunity. Here, we describe the molecular, metabolic and cellular aspects of T cell differentiation and their relevance to cancer immunotherapy. We also discuss current efforts and new approaches that might potentiate T cell-based immunotherapies through the modulation of T cell fate and differentiation.
C1 [Lugli, Enrico] Humanitas Clin & Res Ctr, Lab Translat Immunol, Via Alessandro Manzoni 113, Milan, Italy.
[Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Lugli, E (reprint author), Humanitas Clin & Res Ctr, Lab Translat Immunol, Via Alessandro Manzoni 113, Milan, Italy.
EM enrico.lugli@humanitasresearch.it; gattinol@mail.nih.gov
RI Gattinoni, Luca/A-2281-2008
OI Gattinoni, Luca/0000-0003-2239-3282
NR 166
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
BN 978-3-319-21167-1; 978-3-319-21166-4
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
BP 183
EP 209
DI 10.1007/978-3-319-21167-1_8
D2 10.1007/978-3-319-21167-1
PG 27
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1UP
UT WOS:000368600900009
ER
PT B
AU Lee, DW
Wayne, AS
AF Lee, Daniel W.
Wayne, Alan S.
BE Ascierto, PA
Stroncek, DF
Wang, E
TI Chimeric Antigen Receptor (CAR) T Cells
SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES
SE Cancer Drug Discovery and Development
LA English
DT Article; Book Chapter
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ANTITUMOR-ACTIVITY; GENE-THERAPY; ADOPTIVE
IMMUNOTHERAPY; CLINICAL-TRIAL; ADVERSE EVENT; SAFETY SWITCH; SUICIDE
GENE; IN-VIVO; LYMPHOCYTES
AB Recent advances in cellular engineering techniques coupled with modern chimeric antigen receptors (CARs) now permit the efficient targeting and killing of malignant cells using patients' own T cells. Freedom from MHC restriction by relying most commonly on single chain variable fragments of monoclonal antibodies for antigen recognition rather than T cell receptors expands the list of potential targets. Unlike small molecule inhibitors, the targets of CAR T cells are not required to play a critical function in the tumor cell. CAR targets must be extracellular and ideally should have limited expression on normal, vital tissues. By incorporating primary and co-stimulatory domains, CAR T cells possess a substantial proliferative capacity allowing for small cell doses, which reduces the manufacturing burden. This therapeutic approach allows a potent yet customized in vivo response. The potential of CAR T cells to contribute to the overall treatment of cancer is exemplified by the impressive clinical responses with predominantly reversible toxicities seen in early phase clinical trials targeting the B-cell antigen, CD19, in B-lineage
C1 [Lee, Daniel W.] NCI, Ctr Canc Res, Bldg 10 Hatfield CRC,Room 1-3750, Bethesda, MD 20892 USA.
[Wayne, Alan S.] Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA.
RP Lee, DW (reprint author), NCI, Ctr Canc Res, Bldg 10 Hatfield CRC,Room 1-3750, Bethesda, MD 20892 USA.
EM leed3@mail.nih.gov
NR 73
TC 0
Z9 0
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
BN 978-3-319-21167-1; 978-3-319-21166-4
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
BP 259
EP 280
DI 10.1007/978-3-319-21167-1_12
D2 10.1007/978-3-319-21167-1
PG 22
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1UP
UT WOS:000368600900013
ER
PT B
AU Fowler, DH
Halverson, DC
AF Fowler, Daniel H.
Halverson, David C.
BE Ascierto, PA
Stroncek, DF
Wang, E
TI Rapamycin-Resistant T Cells and Pentostatin-Based Immuno-Selective
Conditioning for the Allogeneic T Cell Therapy of Cancer
SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES
SE Cancer Drug Discovery and Development
LA English
DT Article; Book Chapter
DE Reduced-intensity allogeneic stem cell transplantation; Rapamycin;
Pentostatin; Th1/Th2; CD4+T cells; Non-Hodgkin's lymphoma; Graft
rejection; Graft-versus-host disease; Graft-versus-tumor effect;
Co-stimulation
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ANTIGEN-PRESENTING
CELLS; NECROSIS-FACTOR-ALPHA; MEMORY STEM-CELLS; GRAFT-REJECTION;
IN-VIVO; REGULATORY CELLS; MAMMALIAN TARGET; HEMATOLOGIC MALIGNANCIES
AB Allogeneic hematopoietic stem cell transplantation (HSCT) is the most common T cell therapy procedure, yet little is known about how best to harness the graft-versus-tumor (GVT) effect that underlies this curative modality. Importantly, it has proven difficult to clinically dissect GVT effects away from severe GVHD. In this review, we summarize the often times competing roles of key donor and host cellular players in the transplant setting; in particular, it is important to consider the influence of T cells and antigen-presenting-cells (APC) on the fate of host tumor cells. Going forward, it will be critical to evaluate whether anti-tumor effects can be harnessed in the mixed chimeric state, which inherently poses less risk for GVHD. We summarize the history of allogeneic HSCT, with particular attention to its reliance upon myeloablation, which can limit T cell therapy directly by causing conditioning-related toxicity or indirectly through potentiation of GVHD. Novel approaches to the safe and more effective delivery of allogeneic T cell therapy are clearly needed, especially in settings of advanced, chemotherapy refractory malignancy. Our laboratory and clinical trial research has focused on two primary strategies to address these obstacles, namely: (1) minimization of host conditioning intensity through use of pentostatin-based chemotherapy; and (2) adoptive transfer of ex vivo manufactured, rapamycin-resistant allogeneic T cells. Through use of these two approaches, the anti-tumor mechanism of transplantation is dramatically shifted away from chemotherapy and towards immunotherapy, thereby exposing the relative merits and limitations of a given T cell product. Continued advances in allogeneic T cell therapy will rely upon improvements in host conditioning and enhancement of allogeneic T cell products.
C1 [Fowler, Daniel H.; Halverson, David C.] NCI, Expt Transplantat & Immunol Branch, NIH, CRC, 10 Ctr Dr,oom 3-3330, Bethesda, MD 20892 USA.
RP Fowler, DH (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, CRC, 10 Ctr Dr,oom 3-3330, Bethesda, MD 20892 USA.
EM dhfowler@helix.nih.gov; david.halverson@nih.gov
NR 107
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
BN 978-3-319-21167-1; 978-3-319-21166-4
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
BP 281
EP 302
DI 10.1007/978-3-319-21167-1_13
D2 10.1007/978-3-319-21167-1
PG 22
WC Oncology; Immunology
SC Oncology; Immunology
GA BE1UP
UT WOS:000368600900014
ER
PT S
AU Nakajima, K
Gimenez, LED
Gurevich, VV
Wess, J
AF Nakajima, Ken-ichiro
Gimenez, Luis E. Diaz
Gurevich, Vsevolod V.
Wess, Juergen
BE Thiel, G
TI Design and Analysis of an Arrestin-Biased DREADD
SO DESIGNER RECEPTORS EXCLUSIVELY ACTIVATED BY DESIGNER DRUGS
SE Neuromethods
LA English
DT Article; Book Chapter
DE GPCR; Arrestin; DREADD; Transfection; Radioligand binding; FLIPR; BRET
recruitment; Signal transduction
ID PROTEIN-COUPLED RECEPTORS; ENERGY-TRANSFER BRET; 7-TRANSMEMBRANE
RECEPTORS; NONVISUAL ARRESTINS; FLUORESCENT PROTEIN; RENILLA LUCIFERASE;
BINDING; SPECIFICITY; MUTAGENESIS; RESIDUES
AB Muscarinic receptor-based designer G protein-coupled receptors (GPCRs) have emerged as novel pharmacological tools to address key questions regarding GPCR function and biology. These mutant muscarinic receptors are unable to bind acetylcholine (ACh), the endogenous muscarinic receptor ligand, but can be efficiently activated by clozapine-N-oxide (CNO), an otherwise pharmacologically inert compound. These CNO-sensitive designer GPCRs (alternative name: designer receptors exclusively activated by designer drug/DREADDs) have proven highly useful to explore the in vivo roles of distinct G protein signaling pathways in specific cell types or tissues. Like native GPCRs, CNO-activated DREADDs do not only couple to heterotrimeric G proteins but can also recruit proteins of the arrestin family (arrestin-2 and -3). Many studies have shown that arrestins can act as scaffolding proteins to promote signaling through G protein-independent pathways. To develop a novel tool useful for studying the physiological relevance of these arrestin-dependent signaling pathways, we recently described the development of an M-3 muscarinic receptor-based DREADD that is no longer able to couple to G proteins but can recruit arrestins and initiate arrestin-mediated signaling in a CNO-dependent fashion. In this chapter, we provide protocols useful for the pharmacological and functional characterization of this newly developed DREADD. These protocols can be applied more generally to all other members of the DREADD receptor family.
C1 [Nakajima, Ken-ichiro; Wess, Juergen] NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA.
[Gimenez, Luis E. Diaz; Gurevich, Vsevolod V.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
RP Nakajima, K (reprint author), NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA.
RI Gurevich, Vsevolod/A-3236-2008
OI Gurevich, Vsevolod/0000-0002-3950-5351
NR 27
TC 1
Z9 1
U1 1
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 0893-2336
BN 978-1-4939-2944-3; 978-1-4939-2943-6
J9 NEUROMETHODS
JI Neuromethods
PY 2015
VL 108
BP 29
EP 48
DI 10.1007/978-1-4939-2944-3_2
D2 10.1007/978-1-4939-2944-3
PG 20
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA BE1HS
UT WOS:000367915000004
ER
PT S
AU Krashes, M
AF Krashes, Michael
BE Thiel, G
TI Chemogenetic Deconstruction of Feeding Circuits
SO DESIGNER RECEPTORS EXCLUSIVELY ACTIVATED BY DESIGNER DRUGS
SE Neuromethods
LA English
DT Article; Book Chapter
ID PROTEIN-COUPLED RECEPTORS; GLUTAMATE INDUCED LESIONS; CONDITIONAL
EXPRESSION; LATERAL HYPOTHALAMUS; ARCUATE NUCLEUS; NEURAL CIRCUITS;
FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; G(I)-COUPLED RECEPTOR; MAMMALIAN
NEURONS
AB The sensation of hunger and subsequent act of eating for nourishment are the most basic behaviors across all animals. One can trace its rampage through human history by examining how it has shaped our genes, cultures, and landscapes. Yet, despite the shared familiarity of eating, the neural circuits underlying the motivational processes underlying shifts in appetite have remained elusive due to a lack of methods sensitive enough to probe defined subpopulations of brain cells with temporal and spatial precision. Chemogenetics is an innovative neuroscience approach that has recently been applied in order to dissect feeding circuits by allowing for remote, reversible control of specific neural networks. The technique involves the use of exogenously expressed, molecularly evolved G-protein-coupled receptors (GPCRs) in discrete neural populations followed by their unique ligand-dependent activation. These receptors are modified to couple through cellular machinery resulting in either stimulation or inhibition of neural activity. This allows researchers to acutely and explicitly "turn on" and "turn off" a cell type of choice and assess the resulting behavioral output. Here, I describe how these tools have developed over the years and how they have been applied to the deconstruction of central circuits governing feeding. A thorough comprehension of these critical signals and neural pathways will aid in our fight against obesity and the multitude of eating-related disorders.
C1 [Krashes, Michael] NIDDK, Diabet Endocrinol & Obes Branch, Sect Motivat Proc Underlying Appetite, NIH, Bethesda, MD 20892 USA.
RP Krashes, M (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, Sect Motivat Proc Underlying Appetite, NIH, Bethesda, MD 20892 USA.
NR 69
TC 0
Z9 0
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 0893-2336
BN 978-1-4939-2944-3; 978-1-4939-2943-6
J9 NEUROMETHODS
JI Neuromethods
PY 2015
VL 108
BP 61
EP 81
DI 10.1007/978-1-4939-2944-3_4
D2 10.1007/978-1-4939-2944-3
PG 21
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA BE1HS
UT WOS:000367915000006
ER
PT S
AU James, T
Hsieh, ML
Knipling, L
Hinton, D
AF James, Tamara
Hsieh, Meng-Lun
Knipling, Leslie
Hinton, Deborah
BE Leblanc, BP
Rodrigue, S
TI Determining the Architecture of a Protein-DNA Complex by Combining
FeBABE Cleavage Analyses, 3-D Printed Structures, and the ICM Molsoft
Program
SO DNA-PROTEIN INTERACTIONS: PRINCIPLES AND PROTOCOLS, 4TH EDITION
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE 3-D printing; Molsoft; FeBABE; Protein-DNA complex; Structure
ID RNA-POLYMERASE; PROMOTER DNA; MOTA; TRANSCRIPTION; ACTIVATION;
SIGMA(70); BINDING; DOMAIN; SUBUNIT; REGIONS
AB Determining the structure of a protein-DNA complex can be difficult, particularly if the protein does not bind tightly to the DNA, if there are no homologous proteins from which the DNA binding can be inferred, and/or if only portions of the protein can be crystallized. If the protein comprises just a part of a large multi-subunit complex, other complications can arise such as the complex being too large for NMR studies, or it is not possible to obtain the amounts of protein and nucleic acids needed for crystallographic analyses. Here, we describe a technique we used to map the position of an activator protein relative to the DNA within a large transcription complex. We determined the position of the activator on the DNA from data generated using activator proteins that had been conjugated at specific residues with the chemical cleaving reagent, iron bromoacetamidobenzyl-EDTA (FeBABE). These analyses were combined with 3-D models of the available structures of portions of the activator protein and B-form DNA to obtain a 3-D picture of the protein relative to the DNA. Finally, the Molsoft program was used to refine the position, revealing the architecture of the protein-DNA within the transcription complex.
C1 [James, Tamara; Hsieh, Meng-Lun; Knipling, Leslie; Hinton, Deborah] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP James, T (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
NR 16
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 978-1-4939-2877-4; 978-1-4939-2876-7
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1334
BP 29
EP 40
DI 10.1007/978-1-4939-2877-4_3
D2 10.1007/978-1-4939-2877-4
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE1HT
UT WOS:000367915900004
PM 26404142
ER
PT S
AU Clark, DJ
Leblanc, BP
AF Clark, David J.
Leblanc, Benoit P.
BE Leblanc, BP
Rodrigue, S
TI Analysis of DNA Supercoiling Induced by DNA-Protein Interactions
SO DNA-PROTEIN INTERACTIONS: PRINCIPLES AND PROTOCOLS, 4TH EDITION
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE DNA-protein interaction; Supercoiling; Topology; Chloroquine
AB Certain DNA-interacting proteins induce a pronounced bending in the double helix and cause topological stresses that are compensated by the formation of supercoils in DNA. Such supercoils, when forming on a circular plasmid, give rise to a series of topoisomers that run at different speeds during electrophoresis. The number of supercoils introduced in the plasmid can provide information on the protein; it can, for example, help determine the number of nucleosomes that are assembled on the plasmid or indicate whether the DNA-bending activity of a transcription factor is important enough to cause a topological stress. Because a DNA-protein activity can lead to either an overwinding or an underwinding of the helix, supercoiling can occur in either direction. Determining whether a plasmid contains positively or negatively supercoiled DNA is possible, thanks to an agarose gel containing an intercalating agent known to positively supercoil DNA, such as chloroquine. The speed of migration of the topoisomers varies in a characteristic way in the presence and absence of the agent. Topoisomer standards can furthermore be generated to allow the easy evaluation of the number of supercoils induced in a plasmid by a DNA-protein interaction.
C1 [Clark, David J.] Natl Inst Child Hlth & Human Dev NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
[Leblanc, Benoit P.] Univ Sherbrooke, Fac Sci, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada.
RP Clark, DJ (reprint author), Natl Inst Child Hlth & Human Dev NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
NR 8
TC 0
Z9 0
U1 5
U2 6
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2877-4; 978-1-4939-2876-7
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1334
BP 161
EP 172
DI 10.1007/978-1-4939-2877-4_10
D2 10.1007/978-1-4939-2877-4
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE1HT
UT WOS:000367915900011
PM 26404149
ER
PT S
AU Bandettini, PA
AF Bandettini, Peter A.
BE Uludag, K
Ugurbil, K
Berliner, L
TI The Birth of Functional MRI at the Medical College of Wisconsin
SO FMRI: FROM NUCLEAR SPINS TO BRAIN FUNCTIONS
SE Biological Magnetic Resonance
LA English
DT Article; Book Chapter
ID HUMAN BRAIN; SENSORY STIMULATION; OXYGENATION; CONTRAST
C1 [Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
[Bandettini, Peter A.] NIMH, Funct MRI Core Facil, Bethesda, MD 20892 USA.
RP Bandettini, PA (reprint author), NIMH, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
EM bandettp@mail.nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 0192-6020
BN 978-1-4899-7591-1; 978-1-4899-7590-4
J9 BIOL MAGN RESON
JI Biol. Magn. Reson.
PY 2015
VL 30
BP 11
EP 18
DI 10.1007/978-1-4899-7591-1_2
D2 10.1007/978-1-4899-7591-1
PG 8
WC Chemistry, Organic
SC Chemistry
GA BE1LG
UT WOS:000368102000003
ER
PT S
AU Zhu, XH
Du, F
Zhang, NY
Lu, M
Zhang, Y
Liu, X
Lei, H
Zhang, XL
Ugurbil, K
Chen, W
AF Zhu, Xiao-Hong
Du, Fei
Zhang, Nanyin
Lu, Ming
Zhang, Yi
Liu, Xiao
Lei, Hao
Zhang, Xiaoliang
Ugurbil, Kamil
Chen, Wei
BE Uludag, K
Ugurbil, K
Berliner, L
TI Study of Brain Bioenergetics and Function Using In Vivo MRS
SO FMRI: FROM NUCLEAR SPINS TO BRAIN FUNCTIONS
SE Biological Magnetic Resonance
LA English
DT Article; Book Chapter
ID CEREBRAL-BLOOD-FLOW; MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN
VISUAL-CORTEX; MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION;
SATURATION-TRANSFER MEASUREMENTS; CREATINE-KINASE REACTION; INVIVO
NMR-SPECTROSCOPY; OXYGEN METABOLIC-RATE; WHOLE-BODY SYSTEM; ACID CYCLE
FLUX
C1 [Zhu, Xiao-Hong; Lu, Ming; Zhang, Yi; Ugurbil, Kamil; Chen, Wei] Univ Minnesota, Dept Radiol, Ctr Magnet Resonance Res, Sch Med, Minneapolis, MN 55455 USA.
[Du, Fei] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA.
[Zhang, Nanyin] Penn State Univ, Ctr Neural Engn, Dept Bioengn, University Pk, PA 16802 USA.
[Liu, Xiao] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Lei, Hao] Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan, Peoples R China.
[Zhang, Xiaoliang] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
RP Chen, W (reprint author), Univ Minnesota, Dept Radiol, Ctr Magnet Resonance Res, Sch Med, 2021 6th St SE, Minneapolis, MN 55455 USA.
EM wei@cmrr.umn.edu
NR 177
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 0192-6020
BN 978-1-4899-7591-1; 978-1-4899-7590-4
J9 BIOL MAGN RESON
JI Biol. Magn. Reson.
PY 2015
VL 30
BP 819
EP 864
DI 10.1007/978-1-4899-7591-1_28
D2 10.1007/978-1-4899-7591-1
PG 46
WC Chemistry, Organic
SC Chemistry
GA BE1LG
UT WOS:000368102000029
ER
PT S
AU Bandettini, P
Wong, E
AF Bandettini, Peter
Wong, Eric
BE Uludag, K
Ugurbil, K
Berliner, L
TI The Future of Functional MRI
SO FMRI: FROM NUCLEAR SPINS TO BRAIN FUNCTIONS
SE Biological Magnetic Resonance
LA English
DT Article; Book Chapter
ID HUMAN VISUAL-CORTEX; HUMAN BRAIN ACTIVITY; RESONANCE-IMAGING FMRI;
TIME-RESOLVED FMRI; MAGNETIC-RESONANCE; HIGH-FIELD;
OXIDATIVE-METABOLISM; CORTICAL ACTIVATION; TEMPORAL CORTEX; NEURAL
SYSTEM
C1 [Bandettini, Peter] NIMH, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
[Bandettini, Peter] NIMH, Funct MRI Core Facil, Bethesda, MD 20892 USA.
[Wong, Eric] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.
[Bandettini, Peter] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
RP Bandettini, P (reprint author), NIMH, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
EM bandettp@mail.nih.gov
NR 86
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 0192-6020
BN 978-1-4899-7591-1; 978-1-4899-7590-4
J9 BIOL MAGN RESON
JI Biol. Magn. Reson.
PY 2015
VL 30
BP 895
EP 929
DI 10.1007/978-1-4899-7591-1_30
D2 10.1007/978-1-4899-7591-1
PG 35
WC Chemistry, Organic
SC Chemistry
GA BE1LG
UT WOS:000368102000031
ER
PT J
AU Xu, MY
Umbach, DM
Murphy, E
McMahon, F
Shugart, YY
AF Xu, Meng Yuan
Umbach, David M.
Murphy, Eleanor
McMahon, Francis
Shugart, Yin Y.
TI A Novel Mixture Model to Estimate the Time to Drug Effect Onset and Its
Association with Covariates
SO HUMAN HEREDITY
LA English
DT Article
DE Change point; Onset; Mixture model; Expectation-maximization algorithm;
Longitudinal data
ID STAR-ASTERISK-D; MAXIMUM-LIKELIHOOD; EM ALGORITHM; DEPRESSION
AB Objective: Drugs take effect at different times in different individuals. Consequently, researchers seek to examine how the timing of the biological response to drugs may be affected by factors such as gender, genotypes, age, or baseline symptom scores. Methods: Typically, studies measure symptoms immediately after the initiation of drug treatment and then at a sequence of later time points. In this study, we develop a statistical mixture model for analyzing such longitudinal data. Our method estimates the onset of drug effect and assesses the association between the probability distribution of the onset times and possible contributing factors. Our mixture model treats the timing of onset as missing for each individual but restricts it, for simplicity, to two possible onset points, early or late. To estimate the model, we use an expectation-maximization-based approach and provide the general formulas of the variance and covariance matrix for the estimated parameters. Results: We evaluate the model's overall utility and performance via simulation studies. In addition, we illustrate its use by application to longitudinal data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The algorithm identified age and anxiety status as significant factors in affecting the onset distribution of citalopram (Celexa). (C) 2016 S. Karger AG, Basel
C1 [Xu, Meng Yuan; McMahon, Francis; Shugart, Yin Y.] NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20814 USA.
[Umbach, David M.] Natl Inst Environm Hlth Sci Res, Biostat & Computat Biol Branch, Res Triangle Pk, NC USA.
[Murphy, Eleanor] NIMH, Human Genet Branch, Intramural Res Program, NIH, New York, NY USA.
[Murphy, Eleanor] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA.
[Murphy, Eleanor] Res Fdn Mental Hyg, New York, NY USA.
RP Shugart, YY (reprint author), NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bldg 35,Room 3A1000, Bethesda, MD 20814 USA.
EM kay1yao@mail.nih.gov
OI McMahon, Francis/0000-0002-9469-305X
FU Intramural Research Program, National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH) [MH002930-04]; NIMH
[N01MH90003]
FX The authors gratefully acknowledge the support of the Intramural
Research Program, National Institute of Mental Health, National
Institutes of Health (IRP-NIMH-NIH; project No. MH002930-04). Ioline
Henter (NIMH) provided invaluable editorial assistance. Data and
biomaterials from the limited access datasets are obtained from the
NIH-supported STAR*D study. STAR*D focuses on nonpsychotic MDD in adults
seen in outpatient settings. Its primary purpose is to determine which
treatments work best when initial treatments produce no acceptable
response. STAR*D is supported by NIMH Contract No. N01MH90003 to the
University of Texas Southwestern Medical Center. The ClinicalTrials.gov
identifier is NCT00021528.
NR 16
TC 0
Z9 0
U1 0
U2 1
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 2
BP 90
EP 99
DI 10.1159/000440880
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA DB3NJ
UT WOS:000368418100005
PM 26771572
ER
PT J
AU Hansen, KA
Chu, C
Dickinson, A
Pye, B
Weller, JP
Ungerleider, LG
AF Hansen, Kathleen A.
Chu, Carlton
Dickinson, Annelise
Pye, Brandon
Weller, J. Patrick
Ungerleider, Leslie G.
TI Spatial selectivity in the temporoparietal junction, inferior frontal
sulcus, and inferior parietal lobule
SO JOURNAL OF VISION
LA English
DT Article
DE exogenous; stimulus driven; involuntary; attention; spatial
ID RESONANCE-IMAGING FMRI; SURFACE-BASED ANALYSIS; CORTICAL SURFACE;
TOPOGRAPHIC ORGANIZATION; FRONTOPARIETAL NETWORK; COORDINATE SYSTEM;
HUMAN CORTEX; HUMAN BRAIN; ATTENTION; INFORMATION
AB Spatial selectivity, as measured by functional magnetic resonance imaging (fMRI) activity patterns that vary consistently with the location of visual stimuli, has been documented in many human brain regions, notably the occipital visual cortex and the frontal and parietal regions that are active during endogenous, goal-directed attention. We hypothesized that spatial selectivity also exists in regions that are active during exogenous, stimulus-driven attention. To test this hypothesis, we acquired fMRI data while subjects maintained passive fixation. At jittered time intervals, a briefly presented wedge-shaped array of rapidly expanding circles appeared at one of three contralateral or one of three ipsilateral locations. Positive fMRI activations were identified in multiple brain regions commonly associated with exogenous attention, including the temporoparietal junction, the inferior parietal lobule, and the inferior frontal sulcus. These activations were not organized as a map across the cortical surface. However, multivoxel pattern analysis of the fMRI activity correctly classified every pair of stimulus locations, demonstrating that patterns of fMRI activity were correlated with spatial location. These observations held for both contralateral and ipsilateral stimulus pairs as well as for stimuli of different textures (radial checkerboard) and shapes (squares and rings). Permutation testing verified that the obtained accuracies were not due to systematic biases and demonstrated that the findings were statistically significant.
C1 [Hansen, Kathleen A.; Chu, Carlton; Dickinson, Annelise; Pye, Brandon; Weller, J. Patrick; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Ungerleider, LG (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM ungerlel@mail.nih.gov
FU National Institute of Mental Health Intramural Research Program
[93-M-0170]
FX We thank Gang Chen for valuable suggestions. This work was supported by
the National Institute of Mental Health Intramural Research Program
(NCT01087281; Protocol 93-M-0170).
NR 54
TC 0
Z9 0
U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 1534-7362
J9 J VISION
JI J. Vision
PY 2015
VL 15
IS 13
AR 15
DI 10.1167/15.13.15
PG 15
WC Ophthalmology
SC Ophthalmology
GA DB1EQ
UT WOS:000368251200015
PM 26382006
ER
PT S
AU Saveria, T
Duffy, PE
Fried, M
AF Saveria, Tracy
Duffy, Patrick E.
Fried, Michal
BE Vaughan, AM
TI Evaluation of Pregnancy Malaria Vaccine Candidates: The Binding
Inhibition Assay
SO MALARIA VACCINES: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Binding inhibition assay; Plate-based assay; IgG purification; CSA
ID PLASMODIUM-FALCIPARUM; CHONDROITIN SULFATE; ANTIBODIES; PLACENTA
AB The parasite-binding inhibition assay is designed to evaluate the acquisition of naturally acquired functional antibodies that block Plasmodium falciparum binding to endothelial or placental receptors. The assay is also used to assess functional activity by antibodies induced by immunization, for example antibodies raised against pregnancy malaria vaccine candidates like VAR2CSA. Here we describe a plate-based assay to measure the levels of adhesion-blocking antibodies. This assay format can be adapted to any lab that is minimally equipped for short-term parasite culture.
C1 [Saveria, Tracy] Ctr Infect Dis Res, Seattle, WA 98109 USA.
[Duffy, Patrick E.; Fried, Michal] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
RP Saveria, T (reprint author), Ctr Infect Dis Res, Seattle, WA 98109 USA.
FU Intramural NIH HHS
NR 8
TC 2
Z9 2
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 978-1-4939-2815-6; 978-1-4939-2814-9
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1325
BP 231
EP 239
DI 10.1007/978-1-4939-2815-6_19
D2 10.1007/978-1-4939-2815-6
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Immunology
SC Biochemistry & Molecular Biology; Immunology
GA BE1OY
UT WOS:000368336600020
PM 26450393
ER
PT S
AU Bergmann-Leitner, ES
Leitner, WW
AF Bergmann-Leitner, Elke S.
Leitner, Wolfgang W.
BE Vaughan, AM
TI Vaccination Using Gene-Gun Technology
SO MALARIA VACCINES: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE DNA vaccines; Immunization; Gene gun; Particle-mediated epidermal
delivery; Biolistic vaccine
ID IN-VIVO ELECTROPORATION; CIRCUMSPOROZOITE PROTEIN; DNA VACCINES; PLASMID
DNA; PLASMODIUM-FALCIPARUM; BOOST IMMUNIZATION; IMMUNE-RESPONSES;
MALARIA; PROTECTION; IMMUNOGENICITY
AB DNA vaccines against infection with Plasmodium have been highly successful in rodent models of malaria and have shown promise in the very limited number of clinical trials conducted so far. The vaccine platform is highly attractive for numerous reasons, such as low cost and a very favorable safety profile. Gene gun delivery of DNA plasmids drastically reduces the vaccine dose and does not only have the potential to make vaccines more accessible and affordable, but also simplifies (a) the testing of novel antigens as vaccine candidates, (b) the testing of antigen combinations, and (c) the co-delivery of antigens with molecular adjuvants such as cytokines or costimulatory molecules. Described in this chapter are the preparation of the inoculum (i.e., DNA plasmids attached to gold particles, coating to the inside of plastic tubing also referred to as gene gun "bullets"or cartridges), the gene gun vaccination procedure, and the challenge of mice with Plasmodium berghei parasites to test the efficacy of the experimental vaccine.
C1 [Bergmann-Leitner, Elke S.] Walter Reed Army Inst Res, Malaria Vaccine Branch, Silver Spring, MD 20910 USA.
[Leitner, Wolfgang W.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Bergmann-Leitner, ES (reprint author), Walter Reed Army Inst Res, Malaria Vaccine Branch, Silver Spring, MD 20910 USA.
NR 31
TC 0
Z9 0
U1 1
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2815-6; 978-1-4939-2814-9
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1325
BP 289
EP 302
DI 10.1007/978-1-4939-2815-6_22
D2 10.1007/978-1-4939-2815-6
PG 14
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Immunology
SC Biochemistry & Molecular Biology; Immunology
GA BE1OY
UT WOS:000368336600023
PM 26450396
ER
PT J
AU Schindel, DE
Bubela, T
Rosenthal, J
Castle, D
du Plessis, P
Bye, R
AF Schindel, David E.
Bubela, Tania
Rosenthal, Joshua
Castle, David
du Plessis, Pierre
Bye, Robert
CA PMCW
TI The New Age of the Nagoya Protocol
SO NATURE CONSERVATION-BULGARIA
LA English
DT Article
DE Nagoya Protocol; Access and Benefit Sharing; DNA barcoding; medicinal
plants; Convention on Biological Diversity; international agreements
ID DNA BARCODE; IDENTIFICATION; PRODUCTS
AB The entry into force of the Nagoya Protocol of the Convention on Biological Diversity will lead to new legislation and regulations that could change international collaborative research in biology. This article suggests a new approach that researchers can use in negotiating international Access and Benefit Sharing agreements under the Protocol. Research on medicinal plants is used as a case study because it is a domain with many competing stakeholders involving non-commercial and commercial research, as well as national and international commercial markets. We propose a decision-based framework to aid all participants as they negotiate ABS agreements for non-commercial biodiversity research. Our proposed approach promotes transparency and builds trust, reflects the principles in the Convention on Biological Diversity, and respects and protects the interests of biodiversity rich developing countries. This approach is an alternative to often-used adversarial approaches.
C1 [Schindel, David E.] Natl Museum Nat Hist, Smithsonian Inst, Washington, DC 20560 USA.
[Bubela, Tania] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada.
[Rosenthal, Joshua] Fogarty Int Ctr, Div Epidemiol & Populat Studies, Washington, DC USA.
[Castle, David] Univ Victoria, Victoria, BC V8W 2Y2, Canada.
[du Plessis, Pierre] CRIAA SA DC, Windhoek, Namibia.
[Bye, Robert] Univ Nacl Autonoma Mexico, Inst Biol, Mexico City 04510, DF, Mexico.
[PMCW] Mexico City Workshop, Med Plant Barcoding & Nat Hlth Prod Res Moving De, Mexico City, DF, Mexico.
RP Schindel, DE (reprint author), Natl Museum Nat Hist, Smithsonian Inst, Washington, DC 20560 USA.
EM schindeld@si.edu
OI Bubela, Tania/0000-0002-0807-2899
NR 24
TC 2
Z9 2
U1 1
U2 6
PU PENSOFT PUBL
PI SOFIA
PA 12 PROF GEORGI ZLATARSKI ST, SOFIA, 1700, BULGARIA
SN 1314-6947
EI 1314-3301
J9 NAT CONSERV-BULGARIA
JI Nat. Conserv.-Bulgaria
PY 2015
IS 12
BP 43
EP 56
DI 10.3897/natureconservation.12.5412
PG 14
WC Biodiversity Conservation
SC Biodiversity & Conservation
GA CR5SU
UT WOS:000361405100003
ER
PT J
AU Ling, X
Liu, XJ
Zhong, K
Smith, N
Prey, J
Li, FZ
AF Ling, Xiang
Liu, Xiaojun
Zhong, Kai
Smith, Nicholas
Prey, Joshua
Li, Fengzhi
TI FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan
resistance in human tumor xenograft models
SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
LA English
DT Article
DE FL118; irinotecan; topotecan; treatment resistance; antitumor activity;
animal models of human tumor xenografts
ID CELL LUNG-CANCER; CIAP2 SELECTIVE INHIBITOR; P-GLYCOPROTEIN;
MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; TOPOISOMERASE-I; OVARIAN-CANCER;
ACQUIRED-RESISTANCE; CYCLIC-NUCLEOTIDES; 2ND-LINE TREATMENT
AB Irinotecan and topotecan are the only camptothecin analogues approved by the FDA for cancer treatment. However, inherent and/or acquired irinotecan and topotecan resistance is a challenging issue in clinical practice. In this report, we showed that FL118, a novel camptothecin analogue, effectively obliterated human xenograft tumors that acquire irinotecan and topotecan resistance. Consistent with this finding, Pharmacokinetics studies indicated that FL118 rapidly clears from circulation, while effectively accumulating in tumors with a long elimination half-life. Consistent with our previous studies on irinotecan, FL118 exhibited >= 25 fold more effectiveness than topotecan at inhibiting cancer cell growth and colony formation; we further showed that although topotecan can inhibit the expression of survivin, Mcl-1, XIAP or cIAP2, its effectiveness is about 10-100 fold weaker than FL118. Lastly, in contrast to both SN-38 (active metabolite of irinotecan) and topotecan are substrates of the efflux pump proteins P-gp/MDR1 and ABCG2/BCRP, FL118 is not a substrate of P-gp and ABCG2. Consistently, sildenafil, a multiple efflux pump inhibitor, sensitized SN-38 much more than these of the ABCG2-selective inhibitor KO143 in growth inhibition of SW620 and HCT-8 cells. In contrast, both inhibitors showed no effect on FL118 efficacy. Given that both P-gp and ABCG2 express in SW620 and HCT-8 cells and FL118 is not a substrate for P-gp and ABCG2, this suggests that FL118 appears to bypass multiple efflux pump protein-induced resistance, which may contribute to FL118 overcoming irinotecan and topotecan resistance in vivo. These new findings provide renewed perspectives for further development of FL118 for clinical applications.
C1 [Ling, Xiang; Liu, Xiaojun; Li, Fengzhi] Roswell Pk Canc Inst, Dept Pharmacol, Buffalo, NY 14263 USA.
[Ling, Xiang; Liu, Xiaojun; Li, Fengzhi] Roswell Pk Canc Inst, Dept Therapeut, Buffalo, NY 14263 USA.
[Prey, Joshua] Roswell Pk Canc Inst, Pharmacokinet & Pharmacodynam Facil, Buffalo, NY 14263 USA.
[Li, Fengzhi] Roswell Pk Canc Inst, NCI Supported Expt Therapeut Program, Buffalo, NY 14263 USA.
[Ling, Xiang; Zhong, Kai; Smith, Nicholas] Canget BioTekpharma LLC, Buffalo, NY 14203 USA.
RP Li, FZ (reprint author), Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Elm & Carlton Str,CGP L4-301, Buffalo, NY 14263 USA.
EM fengzhi.li@roswellpark.org
FU NIH/NCI [R44CA176937]; NCI [R21CA180764]; US Army Department of Defense
[W81XWH-12-1-0305]; NCI Cancer Center Support Grant [P30CA016056]
FX This work was sponsored in part by grants from NIH/NCI (R44CA176937),
NCI (R21CA180764), US Army Department of Defense (W81XWH-12-1-0305), and
by shared resources supported by NCI Cancer Center Support Grant to
Roswell Park Cancer Institute (P30CA016056). The authors would like to
thank relevant staff scientists including the former PK facility
Director Dr. Jerry Fetterly from the Pharmacokinetics (PK) Facility at
Roswell Park Cancer Institute for their cooperation during development
of FL118 assay and the measurement of FL118 concentration in tumor and
plasma specimen. We would also like to thank our department writing
group for critical review of this manuscript and Mrs. Katherine Plante
for her editorial check of the manuscript before submission.
Additionally, we thank the CRO Absorption System for their service of
the Caco-2 experiment, and the Drug Synthesis and Chemistry Branch,
Developmental Therapeutics Program (DTP), Division of Cancer Treatment
and Diagnosis, National Cancer Institute (NCI) for initially providing
the FL118 drug before we synthesize our own.
NR 56
TC 4
Z9 4
U1 0
U2 2
PU E-CENTURY PUBLISHING CORP
PI MADISON
PA 40 WHITE OAKS LN, MADISON, WI 53711 USA
SN 1943-8141
J9 AM J TRANSL RES
JI Am. J. Transl. Res.
PY 2015
VL 7
IS 10
BP 1765
EP 1781
PG 17
WC Oncology; Medicine, Research & Experimental
SC Oncology; Research & Experimental Medicine
GA DA3BF
UT WOS:000367670200007
PM 26692923
ER
PT J
AU Danforth, DN
Warner, AC
Wangsa, D
Ried, T
Duelli, D
Filie, AC
Prindiville, SA
AF Danforth, David N.
Warner, Andrew C.
Wangsa, Darawalee
Ried, Thomas
Duelli, Dominik
Filie, Armando C.
Prindiville, Sheila A.
TI An Improved Breast Epithelial Sampling Method for Molecular Profiling
and Biomarker Analysis in Women at Risk for Breast Cancer
SO BREAST CANCER-BASIC AND CLINICAL RESEARCH
LA English
DT Article
DE breast cancer; breast ductal epithelium; breast duct sampling; normal
breast epithelium; breast epithelial profiling
ID FINE-NEEDLE-ASPIRATION; GENE MUTATION CARRIERS; DUCTAL LAVAGE FLUID;
PROMOTER HYPERMETHYLATION; NIPPLE; HETEROZYGOSITY; CELLS; PCR;
QUANTIFICATION; METHYLATION
AB BACKGROUND: There is a strong need to define the molecular changes in normal at-risk breast epithelium to identify biomarkers and new targets for breast cancer prevention and to develop a molecular signature for risk assessment. Improved methods of breast epithelial sampling are needed to promote whole-genome molecular profiling, increase ductal epithelial cell yield, and reduce sample cell heterogeneity.
METHODS: We developed an improved method of breast ductal sampling with ductal lavage through a 22-gauge catheter and collection of ductal samples with a microaspirator. Women at normal risk or increased risk for breast cancer were studied. Ductal epithelial samples were analyzed for cytopathologic changes, cellular yield, epithelial cell purity, quality and quantity of DNA and RNA, and use in multiple downstream molecular applications.
RESULTS: We studied 50 subjects, including 40 subjects at normal risk for breast cancer and 37 subjects with non-nipple aspirate fluid-yielding ducts. This method provided multiple 1.0 mL samples of high ductal epithelial cell content (median >= 8 samples per subject of >= 5,000 cells per sample) with 80%-100% epithelial cell purity. Extraction of a single intact ductal sample (fluid and cells) or the separate frozen cellular component provided DNA and RNA for multiple downstream studies, including quantitative reverse transcription-polymerase chain reaction (PCR) for microRNA, quantitative PCR for the human telomerase reverse transcriptase gene, whole-genome DNA amplification, and array comparative genomic hybridization analysis.
CONCLUSION: An improved breast epithelial sampling method has been developed, which should significantly expand the acquisition and biomarker analysis of breast ductal epithelium in women at risk for breast cancer.
C1 [Danforth, David N.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Warner, Andrew C.] Leidos Biomed Res Inc, Pathol Histotechnol Lab, Lab Anim Sci Program, Frederick, MD USA.
[Wangsa, Darawalee; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, Natl Canc Inst, Bethesda, MD 20892 USA.
[Duelli, Dominik] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cellular & Mol Pharmacol, N Chicago, IL USA.
[Filie, Armando C.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Prindiville, Sheila A.] NCI, Off Director, NIH, Bethesda, MD 20892 USA.
RP Danforth, DN (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM david_danforth@nih.gov
NR 34
TC 0
Z9 0
U1 1
U2 1
PU LIBERTAS ACAD
PI AUCKLAND
PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND
SN 1178-2234
J9 BREAST CANCER-BASIC
JI Breast Cancer-Basic Clin. Res.
PY 2015
VL 9
DI 10.4137/BCBCR.S23577
PG 10
WC Oncology
SC Oncology
GA DA6BK
UT WOS:000367886500001
ER
PT J
AU Yang, RH
Beqiri, D
Shen, JB
Redden, JM
Dodge-Kafka, K
Jacobson, KA
Liang, BT
AF Yang, Ronghua
Beqiri, Dardan
Shen, Jian-Bing
Redden, John M.
Dodge-Kafka, Kimberly
Jacobson, Kenneth A.
Liang, Bruce T.
TI P2X4 receptor-eNOS signaling pathway in cardiac myocytes as a novel
protective mechanism in heart failure
SO COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
LA English
DT Review
DE Cardiac myocyte; Cardioprotection; Purines; Heart failure
ID P2X(4) RECEPTORS; PURINERGIC RECEPTORS; MESSENGER-RNA; CARDIOMYOPATHY;
EXPRESSION; ISCHEMIA; RESCUE
AB We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP) to induce a current (mainly Na+) increased the formation of nitric oxide (NO), as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF) with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a new therapy for both ischemic and pressure overloaded HF. (C) 2014 Yang et al. Published by Elsevier B.V. on behalf of the Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
C1 [Yang, Ronghua; Beqiri, Dardan; Shen, Jian-Bing; Redden, John M.; Dodge-Kafka, Kimberly; Liang, Bruce T.] Univ Connecticut, Med Ctr, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06032 USA.
[Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Liang, BT (reprint author), Univ Connecticut, Med Ctr, Calhoun Cardiol Ctr, 263 Farmington Ave,MC3946, Farmington, CT 06032 USA.
EM bliang@uchc.edu
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [ZIA DK031127-08]; NHLBI NIH HHS [R01 HL048225]
NR 19
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2001-0370
J9 COMPUT STRUCT BIOTEC
JI Comp. Struct. Biotechnol. J..
PY 2015
VL 13
BP 1
EP 7
DI 10.1016/j.csbj.2014.11.002
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DA4EJ
UT WOS:000367752600001
PM 25750695
ER
PT J
AU Jones, KR
Kang, EM
AF Jones, Karlie R.
Kang, Elizabeth M.
TI Graft versus host disease: New insights into A(2A) receptor agonist
therapy
SO COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
LA English
DT Review
DE Graft versus host disease; Adenosine; Adenosine A(2A) receptor agonist;
Regulatory T cell; FoxP3; Inflammation
ID REGULATORY T-CELLS; FOXP3 GENE-EXPRESSION; ADENOSINE RECEPTORS; DNA
METHYLATION; ACTIVATION; INFLAMMATION; TOLERANCE; MICE; PREVENTION;
PROTEIN
AB Allogeneic transplantation can cure many disorders, including sickle cell disease, chronic granulomatous disease (CGD), severe combined immunodeficiency (SCID) and many types of cancers. However, there are several associated risks that can result in severe immunological reactions and, in some cases, death. Much of this morbidity is related to graft versus host disease (GVHD) [1]. GVHD is an immune mediated reaction in which donor T cells recognize the host as antigenically foreign, causing donor T cells to expand and attack host tissues. The current method of treating recent transplant patients with immunosuppressants to prevent this reaction has met with only partial success, emphasizing a need for new methods of GVHD treatment and prevention. Recently, a novel strategy has emerged targeting adenosine A(2A) receptors (A(2A)R) through the use of adenosine agonists. These agonists have been shown in vitro to increase the TGF beta-induced generation of FoxP3(+) regulatory T cells (Tregs) and in vivo to improve weight gain and mortality as well as inhibit the release of pro-inflammatory cytokines in GVHD murine models [2,3]. Positive results involving A(2A)R agonists in vitro and in vivo are promising, suggesting that A(2A)R agonists should be a part of the management of clinical GvHD. Jones and Kang. Published by Elsevier B.V. on behalf of the Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
C1 [Jones, Karlie R.; Kang, Elizabeth M.] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
RP Jones, KR (reprint author), NIAID, Lab Host Defenses, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Karlie.sharma@nih.gov
NR 50
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2001-0370
J9 COMPUT STRUCT BIOTEC
JI Comp. Struct. Biotechnol. J..
PY 2015
VL 13
BP 101
EP 105
DI 10.1016/j.csbj.2014.12.003
PG 5
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DA4EJ
UT WOS:000367752600013
PM 25709759
ER
PT J
AU Jacobson, KA
Gao, ZG
Paoletta, S
Kiselev, E
Chakraborty, S
Jayasekara, PS
Balasubramanian, R
Tosh, DK
AF Jacobson, Kenneth A.
Gao, Zhan-Guo
Paoletta, Silvia
Kiselev, Evgeny
Chakraborty, Saibal
Jayasekara, P. Suresh
Balasubramanian, Ramachandran
Tosh, Dilip K.
TI John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y
Receptors
SO COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
LA English
DT Review
DE GPCR; Medicinal chemistry; Purines; X-ray structures; Nucleosides;
Nucleotides; Polypharmacology
ID HUMAN P2Y(12) RECEPTOR; CRYSTAL-STRUCTURE; A(2A) RECEPTOR;
HIGH-AFFINITY; SELECTIVE ANTAGONISTS; INSULIN-SECRETION; AGONISTS;
DERIVATIVES; POTENT; NUCLEOSIDES
AB We establish structure activity relationships of extracellular nucleosides and nucleotides at G protein-coupled receptors (GPCRs), e.g. adenosine receptors (ARs) and P2Y receptors (P2YRs), respectively. We synthesize selective agents for use as pharmacological probes and potential therapeutic agents (e.g. A(3)AR agonists for neuropathic pain). Detailed structural information derived from the X-ray crystallographic structures within these families enables the design of novel ligands, guides modification of known agonists and antagonists, and helps predict polypharmacology. Structures were recently reported for the P2Y(12) receptor (P2Y(12)R), an anti-thrombotic target. Comparison of agonist-bound and antagonist-bound P2Y(12)R indicates unprecedented structural plasticity in the outer portions of the transmembrane (TM) domains and the extracellular loops. Nonphosphate-containing ligands of the P2YRs, such as the selective P2Y(14)R antagonist PPTN, are desired for bioavailability and increased stability. Also, A(2A)AR structures are effectively applied to homology modeling of closely related A(1)AR and A(3)AR, which are not yet crystallized. Conformational constraint of normally flexible ribose with bicyclic analogues increased the ligand selectivity. Comparison of rigid A(3)AR agonist congeners allows the exploration of interaction of specific regions of the nucleoside analogues with the target and off-target GPCRs, such as biogenic amine receptors. Molecular modeling predicts plasticity of the A(3)AR at TM2 to accommodate highly rigidified ligands. Novel fluorescent derivatives of high affinity GPCR ligands are useful tool compounds for characterization of receptors and their oligomeric assemblies. Fluorescent probes are useful for characterization of GPCRs in living cells by flow cytometry and other methods. Thus, 3D knowledge of receptor binding and activation facilitates drug discovery. Jacobson et al. Published by Elsevier B.V. on behalf of the Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
C1 [Jacobson, Kenneth A.; Gao, Zhan-Guo; Paoletta, Silvia; Kiselev, Evgeny; Chakraborty, Saibal; Jayasekara, P. Suresh; Balasubramanian, Ramachandran; Tosh, Dilip K.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDK, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [ZIA DK031116-27, ZIA DK031117-27]; NIDDK NIH HHS
[Z01 DK031117]
NR 74
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2001-0370
J9 COMPUT STRUCT BIOTEC
JI Comp. Struct. Biotechnol. J..
PY 2015
VL 13
BP 286
EP 298
DI 10.1016/j.csbj.2014.10.004
PG 13
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DA4EJ
UT WOS:000367752600035
PM 25973142
ER
PT J
AU Mysliwiec, V
Matsangas, P
Gill, J
Baxter, T
O'Reilly, B
Collen, JF
Roth, BJ
AF Mysliwiec, Vincent
Matsangas, Panagiotis
Gill, Jessica
Baxter, Tristin
O'Reilly, Brian
Collen, Jacob F.
Roth, Bernard J.
TI A Comparative Analysis of Sleep Disordered Breathing in Active Duty
Service Members with and without Combat-Related Posttraumatic Stress
Disorder
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Article
DE obstructive sleep apnea; posttraumatic stress; disorder; depression;
military; combat
ID US MILITARY PERSONNEL; APNEA; PTSD; VETERANS; QUALITY; ADHERENCE; CPAP;
NIGHTMARES; DEPRESSION; INSOMNIA
AB Study Objectives: Posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are frequently co-occurring illnesses. The purpose of this study was to determine whether comorbid PTSD/OSA is associated with increased PTSD symptoms or decreased OSA severity compared to PTSD or OSA alone in recently deployed Active Duty Service Members (ADSM).
Methods: Cross-sectional observational study of ADSM who returned from combat within 24 months. Participants underwent an attended diagnostic polysomnogram and were assessed for PTSD, depression, combat exposure severity, sleepiness, and sleep quality with validated clinical instruments.
Results: Our study included 109 military personnel who returned from a combat deployment within 24 months with a mean age of 34.3 +/- 8.23 and BMI of 30.8 +/- 3.99. Twenty-four participants had PTSD/OSA, 68 had OSA, and 17 had PTSD. Mean PTSD Checklist- Military Version (PCL-M) scores were 62.0 +/- 8.95, 60.5 +/- 4.73, and 32.5 +/- 8.95 in PTSD/OSA, PTSD, and OSA, respectively. The mean AHI was 16.9 +/- 15.0, 18.9 +/- 17.0, and 1.73 +/- 1.3 for those with PTSD/OSA, OSA, and PTSD. PTSD symptoms and OSA severity in military personnel with comorbid PTSD/OSA were not significantly different from those with PTSD or OSA alone. On multivariate analysis, BMI was a significant predictor of OSA (OR, 1.21; 95% CI, 1.04-1.44) and age trended towards significance. Depression, but not OSA severity, was associated with PTSD symptoms. Conclusions: Following recent combat exposure, comorbid PTSD/OSA is not associated with increased PTSD symptoms or decreased severity of OSA. Early evaluation after traumatic exposure for comorbid OSA is indicated in PTSD patients with sleep complaints given the high co-occurrence and adverse clinical implications.
C1 [Mysliwiec, Vincent] 121st Gen Hosp, Med Specialties Clin Unit 15281, Seoul, South Korea.
[Matsangas, Panagiotis] Naval Postgraduate Sch, Dept Operat Res, Monterey, CA USA.
[Gill, Jessica] NINR, NIH, Bethesda, MD 20892 USA.
[Baxter, Tristin; O'Reilly, Brian; Roth, Bernard J.] Madigan Army Med Ctr, Tacoma, WA 98431 USA.
[Collen, Jacob F.] Brooke Army Med Ctr, Jbsa Ft Sam Houston, TX USA.
RP Mysliwiec, V (reprint author), Wilford Hall Ambulatory Surg Ctr, Med Wing 59, Sleep Disorders Ctr, 2200 Berquist Dr,Suite 1, Joint Base Lackland, TX 78236 USA.
EM vincent.mysliwiec.mil@mail.mil
NR 35
TC 1
Z9 1
U1 3
U2 6
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 1550-9389
EI 1550-9397
J9 J CLIN SLEEP MED
JI J. Clin. Sleep Med.
PY 2015
VL 11
IS 12
BP 1393
EP 1401
AR PII jc-00183-15
DI 10.5664/jcsm.5272
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DA1UT
UT WOS:000367581700007
PM 26156954
ER
PT J
AU Zhang, J
Tuo, JS
Wang, ZF
Zhu, AQ
Machalinska, A
Long, Q
AF Zhang, Jun
Tuo, Jingsheng
Wang, Zhoungfeng
Zhu, Aiqin
Machalinska, Anna
Long, Qin
TI Pathogenesis of Common Ocular Diseases
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Editorial Material
C1 [Zhang, Jun] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Zhoungfeng] Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Collaborat Innovat Ctr Brain Sci, Shanghai 200433, Peoples R China.
[Zhu, Aiqin] Qinghai Prov Hosp, Inst Geriatr, Xining, Qinghai, Peoples R China.
[Machalinska, Anna] Pomeranian Med Univ, Dept Ophthalmol, Szczecin, Poland.
[Machalinska, Anna] Pomeranian Med Univ, Dept Histol & Embryol, Szczecin, Poland.
[Long, Qin] Chinese Acad Med Sci, Dept Ophthalmol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China.
[Long, Qin] Peking Union Med Coll, Beijing 100021, Peoples R China.
RP Zhang, J (reprint author), NINDS, Synapt Physiol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM junzhang@ninds.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PY 2015
AR 734527
DI 10.1155/2015/734527
PG 2
WC Medicine, Research & Experimental; Ophthalmology
SC Research & Experimental Medicine; Ophthalmology
GA DA6RB
UT WOS:000367931700001
ER
PT J
AU Gattass, R
Lima, B
Soares, JGM
Ungerleider, LG
AF Gattass, Ricardo
Lima, Bruss
Soares, Juliana G. M.
Ungerleider, Leslie G.
TI Controversies about the visual areas located at the anterior border of
area V2 in primates
SO VISUAL NEUROSCIENCE
LA English
DT Review
DE Visual system; Extrastriate cortex; V3; V4; PO; POd; V6
ID SUPERIOR TEMPORAL SULCUS; MONKEY AOTUS-TRIVIRGATUS; INTER-HEMISPHERIC
CONNECTIONS; VENTRAL EXTRASTRIATE CORTEX; RECEPTIVE-FIELD PROPERTIES;
NEW-WORLD MONKEY; MACAQUE MONKEY; VISUOTOPIC ORGANIZATION;
RHESUS-MONKEY; CEBUS MONKEY
AB Anatomical and electrophysiological studies have provided us with detailed information regarding the extent and topography of the primary (V1) and secondary (V2) visual areas in primates. The consensus about the V1 and V2 maps, however, is in sharp contrast with controversies regarding the organization of the cortical areas lying immediately rostral to V2. In this review, we address the contentious issue of the extent of the third visual area (V3). Specifically, we will argue for the existence of both ventral (V3v) and dorsal (V3d) segments of V3, which are located, respectively, adjacent to the anterior border of ventral and dorsal V2. V3v and V3d would together constitute a single functional area with a complete representation of both upper and lower visual hemifields. Another contentious issue is the organization of the parietal-occipital (PO) area, which also borders the rostral edge of the medial portion of dorsal V2. Different from V1, V2, and V3, which exhibit a topography based on the defined lines of isoeccentricity and isopolar representation, area PO only has a systematic representation of polar angles, with an emphasis on the peripheral visual field (isoeccentricity lines are not well defined). Based on the connectivity patterns of area PO with distinct cytochrome oxidase modules in V2, we propose a subdivision of the dorsal stream of visual information processing into lateral and medial domains. In this model, area PO constitutes the first processing instance of the dorsal-medial stream, coding for the full-field flow of visual cues during navigation. Finally, we compare our findings with those in other species of Old and New World monkeys and argue that larger animals, such as macaque and capuchin monkeys, have similar organizations of the areas rostral to V2, which is different from that in smaller New World monkeys.
C1 [Gattass, Ricardo; Lima, Bruss; Soares, Juliana G. M.] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Cognit Physiol, BR-21941900 Rio de Janeiro, RJ, Brazil.
[Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Gattass, R (reprint author), Univ Fed Rio de Janeiro, IBCCF, Lab Cognit Physiol, Ilha Fundao, Ave Carlos Chagas Filho 373,Room G2-009, BR-21941902 Rio de Janeiro, RJ, Brazil.
EM rgattass@gmail.com
RI Lima, Bruss/I-9164-2016
OI Lima, Bruss/0000-0001-6865-2900
FU CNPq [47.1166/2013-8, 40.0033/2014-3, 55.0003/2011-8]; FAPERJ
[E-26/110.192/2013, E-26/110.905/2013]
FX We wish to thank Marcello G.P. Rosa for his valuable comments on the
manuscript, and Liliane Heringer Motta for her skillful technical
assistance. The research reported here was supported by the CNPq grants
47.1166/2013-8, 40.0033/2014-3 and 55.0003/2011-8 and by FAPERJ grants
E-26/110.192/2013 and E-26/110.905/2013 (to R.G.).
NR 94
TC 0
Z9 0
U1 3
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0952-5238
EI 1469-8714
J9 VISUAL NEUROSCI
JI Visual Neurosci.
PY 2015
VL 32
AR e019
DI 10.1017/S0952523815000188
PG 16
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA DA1RH
UT WOS:000367572700019
PM 26581040
ER
PT J
AU Qian, HH
Ji, R
Gregg, RG
Peachey, NS
AF Qian, Haohua
Ji, Rui
Gregg, Ronald G.
Peachey, Neal S.
TI Identification of a new mutant allele, Grm6(nob7), for complete
congenital stationary night blindness
SO VISUAL NEUROSCIENCE
LA English
DT Article
DE Congenital stationary night blindness; Electroretinogram; Metabotropic
glutamate receptor 6
ID ON-BIPOLAR CELLS; CONE ELECTRORETINOGRAM; MOUSE MODEL; GRM6 GENE;
MGLUR6; TRPM1; MUTATIONS; RESPONSES; TRANSMISSION; COMPONENT
AB Electroretinogram (ERG) studies identified a new mouse line with a normal a-wave but lacking the b-wave component. The ERG phenotype of this new allele, nob7, matched closely that of mouse mutants for Grm6, Lrit3, Trpm1, and Nyx, which encode for proteins expressed in depolarizing bipolar cells (DBCs). To identify the underlying mutation, we first crossed nob7 mice with Grm6(nob3) mutants and measured the ERGs in offspring. All the offspring lacked the b-wave, indicating that nob7 is a new allele for Grm6: Grm6(nob7). Sequence analyses of Grm6(nob7) cDNAs identified a 28 base pair insertion between exons 8 and 9, which would result in a frameshift mutation in the open reading frame that encodes the metabotropic glutamate receptor 6 (Grm6). Sequencing both the cDNA and genomic DNA from exon 8 and intron 8, respectively, from the Grm6(nob7) mouse revealed a G to A transition at the last position in exon 8. This mutation disrupts splicing and the normal exon 8 is extended by 28 base pairs, because splicing occurs 28 base pairs downstream at a cryptic splice donor. Consistent with the impact of the resulting frameshift mutation, there is a loss of mGluR6 protein (encoded by Grm6) from the dendritic tips of DBCs in the Grm6(nob7) retina. These results indicate that Grm6(nob7) is a new model of the complete form of congenital stationary night blindness, a human condition that has been linked to mutations of GRM6
C1 [Qian, Haohua] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA.
[Ji, Rui; Gregg, Ronald G.] Univ Louisville, Dept Biochem & Mol Genet, Louisville, KY 40292 USA.
[Gregg, Ronald G.] Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA.
[Peachey, Neal S.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
[Peachey, Neal S.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA.
[Peachey, Neal S.] Case Western Reserve Univ, Dept Ophthalmol, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
RP Peachey, NS (reprint author), Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM peachen@ccf.org
FU U.S. National Institutes of Health [R21EY021852, R01EY12354]; U.S.
Veterans Administration Medical Research Service; Hope for Vision;
Foundation Fighting Blindness Center; Research to Prevent Blindness
FX We are grateful to Dr. Amy Lee for providing the antibody against
CACNA1F. This research was supported by grants from the U.S. National
Institutes of Health (R21EY021852 to N.S.P. and R.G.G.; R01EY12354 to
R.G.G.), the U.S. Veterans Administration Medical Research Service, Hope
for Vision, a Foundation Fighting Blindness Center Grant to the Cole Eye
Institute, Cleveland Clinic, and unrestricted awards from Research to
Prevent Blindness to the Department of Ophthalmology, Cleveland Clinic
Lerner College of Medicine and to the Department of Ophthalmology &
Visual Sciences, University of Louisville.
NR 30
TC 1
Z9 1
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0952-5238
EI 1469-8714
J9 VISUAL NEUROSCI
JI Visual Neurosci.
PY 2015
VL 32
AR e004
DI 10.1017/S0952523815000012
PG 5
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA DA1RH
UT WOS:000367572700004
PM 26241901
ER
PT S
AU Chan, K
Gordenin, DA
AF Chan, Kin
Gordenin, Dmitry A.
BE Bassler, BL
TI Clusters of Multiple Mutations: Incidence and Molecular Mechanisms
SO ANNUAL REVIEW OF GENETICS, VOL 49
SE Annual Review of Genetics
LA English
DT Review; Book Chapter
DE mutagenesis; cancer; evolution; genome instability; mutation showers;
kataegis
ID BREAK-INDUCED REPLICATION; DNA-POLYMERASE-ZETA; HUMAN CANCERS;
SACCHAROMYCES-CEREVISIAE; SOMATIC HYPERMUTATION; CHRONOCOORDINATE
EVENTS; GENOME EVOLUTION; GENE CONVERSION; TRANSGENIC MICE; APOBEC3
FAMILY
AB It has been long understood that mutation distribution is not completely random across genomic space and in time. Indeed, recent surprising discoveries identified multiple simultaneous mutations occurring in tiny regions within chromosomes while the rest of the genome remains relatively mutation-free. Mechanistic elucidation of these phenomena, called mutation showers, mutation clusters, or kataegis, in parallel with findings of abundant clustered mutagenesis in cancer genomes, is ongoing. So far, the combination of factors most important for clustered mutagenesis is the induction of DNA lesions within unusually long and persistent single-strand DNA intermediates. In addition to being a fascinating phenomenon, clustered mutagenesis also became an indispensable tool for identifying a previously unrecognized major source of mutation in cancer, APOBEC cytidine deaminases. Future research on clustered mutagenesis may shed light onto important mechanistic details of genome maintenance, with potentially profound implications for human health.
C1 [Chan, Kin; Gordenin, Dmitry A.] NIEHS, Mech Genome Dynam Grp, US Dept HHS, NIH, Durham, NC 27709 USA.
RP Gordenin, DA (reprint author), NIEHS, Mech Genome Dynam Grp, US Dept HHS, NIH, Durham, NC 27709 USA.
EM kin.chan@nih.gov; gordenin@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES103266-01]; NIEHS NIH HHS [1K99-ES024424-01];
PHS HHS [Z1AES103266]
NR 140
TC 8
Z9 9
U1 2
U2 10
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0066-4197
BN 978-0-8243-1249-7
J9 ANNU REV GENET
JI Annu. Rev. Genet.
PY 2015
VL 49
BP 243
EP 267
DI 10.1146/annurev-genet-112414-054714
PG 25
WC Genetics & Heredity
SC Genetics & Heredity
GA BE0XC
UT WOS:000367291000011
PM 26631512
ER
PT S
AU Kunkel, TA
Erie, DA
AF Kunkel, Thomas A.
Erie, Dorothy A.
BE Bassler, BL
TI Eukaryotic Mismatch Repair in Relation to DNA Replication
SO ANNUAL REVIEW OF GENETICS, VOL 49
SE Annual Review of Genetics
LA English
DT Review; Book Chapter
DE DNA mismatch repair; replication fidelity; genome instability; mutation
rate; mutator
ID MUTL-ALPHA ENDONUCLEASE; SIMPLE REPETITIVE DNA;
SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; POLYMERASE-DELTA;
RIBONUCLEOTIDE INCORPORATION; MICROSATELLITE INSTABILITY;
SINGLE-MOLECULE; PROTEIN MUTS; IN-VITRO
AB Three processes act in series to accurately replicate the eukaryotic nuclear genome. The major replicative DNA polymerases strongly prevent mismatch formation, occasional mismatches that do form are proofread during replication, and rare mismatches that escape proofreading are corrected by mismatch repair (MMR). This review focuses on MMR in light of increasing knowledge about nuclear DNA replication enzymology and the rate and specificity with which mismatches are generated during leading-and lagging-strand replication. We consider differences in MMR efficiency in relation to mismatch recognition, signaling to direct MMR to the nascent strand, mismatch removal, and the timing of MMR. These studies are refining our understanding of relationships between generating and repairing replication errors to achieve accurate replication of both DNA strands of the nuclear genome.
C1 [Kunkel, Thomas A.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Erie, Dorothy A.] Univ N Carolina, Dept Chem & Curriculum Appl Sci & Engn, Chapel Hill, NC 27599 USA.
RP Kunkel, TA (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov; derie@email.unc.edu
FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES065070, Z01 ES065089]; NIGMS
NIH HHS [R01 GM079480, R01 GM109832]
NR 149
TC 35
Z9 35
U1 8
U2 28
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0066-4197
BN 978-0-8243-1249-7
J9 ANNU REV GENET
JI Annu. Rev. Genet.
PY 2015
VL 49
BP 291
EP 313
DI 10.1146/annurev-genet-112414-054722
PG 23
WC Genetics & Heredity
SC Genetics & Heredity
GA BE0XC
UT WOS:000367291000013
PM 26436461
ER
PT J
AU Ehsani, JP
Haynie, DL
Luthers, C
Perlus, J
Gerber, E
Ouimet, MC
Klauer, SG
Simons-Morton, B
AF Ehsani, Johnathon P.
Haynie, Denise L.
Luthers, Christina
Perlus, Jessannyn
Gerber, Eli
Ouimet, Marie Claude
Klauer, Sheila G.
Simons-Morton, Bruce
TI Teen Drivers' Perceptions of Their Peer Passengers
SO TRANSPORTATION RESEARCH RECORD
LA English
DT Article
ID EXPERIENCE
AB The presence of peer passengers increases the risk of fatal crashes among teenage drivers. Distraction and social influence are the two main factors associated with this increased risk. Teen drivers' perceptions of their peer passengers with regard to distraction and social influence could help inform the understanding of the conditions under which peer passengers increase crash risk or promote safer driving. The purpose of this study was to examine such perceptions. A convenience sample of male and female drivers participated in a semistructured interview process that included questions about their perceptions of the effects of peer passengers on driving. The analysis of the interviews was guided by a grounded theory approach. Teenage drivers were found to be aware of the risk that peer passengers posed. Some described having passengers in the vehicle as distracting and recognized that the level of distraction increased with the number of passengers. Drivers who felt responsible for the safety of their peer passengers described strategies that they used to control the in-vehicle environment. Drivers described driving with passengers as a performance and articulated direct and indirect sources of pressure, gender norms, and the unspoken expectations of their passengers as influences on their driving behavior. The influence of passengers is situation specific and dependent on who the passengers are; passenger influence may be either protective or harmful, according to the circumstances. Some passengers exert direct influence, but often their influence appears more indirect and subtle.
C1 [Ehsani, Johnathon P.; Haynie, Denise L.; Luthers, Christina; Perlus, Jessannyn; Gerber, Eli; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Longueuil, PQ J4K 0A8, Canada.
[Klauer, Sheila G.] Virginia Polytech Inst & State Univ, Virginia Tech, Transportat Inst, Blacksburg, VA 24061 USA.
RP Ehsani, JP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Executive Blvd 7B13, Bethesda, MD 20892 USA.
EM johnathon.ehsani@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development. A complex project such as this cannot succeed without help
from individuals from a variety of backgrounds and capabilities. The
authors thank Suzie Lee and Jennifer Mullen for project management and
data collection and Paula Calabrese for transcribing the interviews.
NR 14
TC 0
Z9 0
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0361-1981
EI 2169-4052
J9 TRANSPORT RES REC
JI Transp. Res. Record
PY 2015
IS 2516
BP 22
EP 26
DI 10.3141/2516-04
PG 5
WC Engineering, Civil; Transportation; Transportation Science & Technology
SC Engineering; Transportation
GA CZ9KA
UT WOS:000367415300005
PM 27346920
ER
PT J
AU Ramos-Murguialday, A
Garcia-Cossio, E
Walter, A
Cho, W
Broetz, D
Bogdan, M
Cohen, LG
Birbaumer, N
AF Ramos-Murguialday, Ander
Garcia-Cossio, Eliana
Walter, Armin
Cho, Woosang
Broetz, Doris
Bogdan, Martin
Cohen, Leonardo G.
Birbaumer, Niels
TI Decoding upper limb residual muscle activity in severe chronic stroke
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID BRAIN-COMPUTER-INTERFACE; PATTERN-RECOGNITION; PROSTHETIC HAND; MOTOR
IMAGERY; RECOVERY; REHABILITATION; SIGNALS; PATIENT; ARM;
NEUROREHABILITATION
AB Objective: Stroke is a leading cause of long-term motor disability. Stroke patients with severe hand weakness do not profit from rehabilitative treatments. Recently, brain-controlled robotics and sequential functional electrical stimulation allowed some improvement. However, for such therapies to succeed, it is required to decode patients' intentions for different arm movements. Here, we evaluated whether residual muscle activity could be used to predict movements from paralyzed joints in severely impaired chronic stroke patients. Methods: Muscle activity was recorded with surface-electromyography (EMG) in 41 patients, with severe hand weakness (Fugl-Meyer Assessment [FMA] hand subscores of 2.93 +/- 2.7), in order to decode their intention to perform six different motions of the affected arm, required for voluntary muscle activity and to control neuroprostheses. Decoding of paretic and nonparetic muscle activity was performed using a feed-forward neural network classifier. The contribution of each muscle to the intended movement was determined. Results: Decoding of up to six arm movements was accurate (>65%) in more than 97% of nonparetic and 46% of paretic muscles. Interpretation: These results demonstrate that some level of neuronal innervation to the paretic muscle remains preserved and can be used to implement neurorehabilitative treatments in 46% of patients with severe paralysis and extensive cortical and/or subcortical lesions. Such decoding may allow these patients for the first time after stroke to control different motions of arm prostheses through muscle-triggered rehabilitative treatments.
C1 [Ramos-Murguialday, Ander; Garcia-Cossio, Eliana; Cho, Woosang; Broetz, Doris; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72076 Tubingen, Germany.
[Ramos-Murguialday, Ander; Garcia-Cossio, Eliana; Cho, Woosang; Broetz, Doris; Birbaumer, Niels] Univ Tubingen, MEG Ctr, D-72076 Tubingen, Germany.
[Ramos-Murguialday, Ander] TECNALIA, San Sebastian 20009, Spain.
[Walter, Armin; Bogdan, Martin] Univ Tubingen, Wilhelm Schickard Inst, Dept Comp Engn, D-72076 Tubingen, Germany.
[Cho, Woosang] DGIST, Daegu 711873, South Korea.
[Bogdan, Martin] Univ Leipzig, Dept Comp Engn, D-04109 Leipzig, Germany.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Birbaumer, Niels] Osped San Camillo, Ist Ricovero & Cura Carattere Sci, I-30126 Venice, Italy.
[Birbaumer, Niels] German Ctr Diabet Res DZD, Tubingen, Germany.
RP Ramos-Murguialday, A (reprint author), Silcherstr 5, D-72076 Tubingen, Germany.
EM ander.ramos@med.uni-tuebingen.de
OI Ramos-Murguialday, Ander/0000-0002-1549-4029
NR 46
TC 3
Z9 3
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD JAN
PY 2015
VL 2
IS 1
BP 1
EP 11
DI 10.1002/acn3.122
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CZ3BL
UT WOS:000366979000001
PM 25642429
ER
PT J
AU Kasukurti, A
Eggleton, CD
Desai, SA
Marr, DWM
AF Kasukurti, A.
Eggleton, C. D.
Desai, S. A.
Marr, D. W. M.
TI FACS-style detection for real-time cell viscoelastic cytometry
SO RSC ADVANCES
LA English
DT Article
ID FREQUENCY ELECTRIC-FIELDS; MICROFLUIDIC SYSTEMS; BLOOD-CELLS;
DEFORMABILITY; DEFORMATION; MECHANICS; CANCER; BAR; ERYTHROCYTES;
BIOMECHANICS
AB Cell mechanical properties have been established as a label-free biophysical marker of cell viability and health; however, real-time methods with significant throughput for accurately and non-destructively measuring these properties remain widely unavailable. Without appropriate labels for use with fluorescence activated cell sorters (FACS), easily implemented real-time technology for tracking cell-level mechanical properties remains a current need. Employing modulated optical forces and enabled by a low-dimensional FACS-style detection method introduced here, we present a viscoelasticity cytometer (VC) capable of real-time and continuous measurements. We demonstrate the utility of this approach by tracking the high-frequency cell physical properties of populations of chemically-modified cells at rates of similar to 1 s(-1) and explain observations within the context of a simple theoretical model.
C1 [Kasukurti, A.; Marr, D. W. M.] Colorado Sch Mines, Dept Chem & Biol Engn, Bethesda, MD 20892 USA.
[Eggleton, C. D.] Univ Maryland Baltimore Cty, Dept Mech Engn, Bethesda, MD USA.
[Desai, S. A.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
RP Marr, DWM (reprint author), Colorado Sch Mines, Dept Chem & Biol Engn, Bethesda, MD 20892 USA.
EM dmarr@mines.edu
FU National Institutes of Health [1R01 AI079347-01]; Intramural Research
Program of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases
FX We acknowledge support from the National Institutes of Health under
grant 1R01 AI079347-01 and the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 40
TC 0
Z9 0
U1 2
U2 7
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2046-2069
J9 RSC ADV
JI RSC Adv.
PY 2015
VL 5
IS 128
BP 105636
EP 105642
DI 10.1039/c5ra24097b
PG 7
WC Chemistry, Multidisciplinary
SC Chemistry
GA CZ2WL
UT WOS:000366965200018
PM 26900453
ER
PT S
AU Brady, RO
AF Brady, Roscoe O.
BE Rosenberg, A
Demeule, B
TI Targeting Glucocerebrosidase to Macrophages for Effective Treatment of
Patients with Gaucher Disease: Setting the Paradigm of a "Fit for
Purpose" Approach to Enzyme Replacement Therapy
SO BIOBETTERS: PROTEIN ENGINEERING TO APPROACH THE CURATIVE
SE AAPS Advances in the Pharmaceutical Sciences Series
LA English
DT Article; Book Chapter
ID PURIFIED GLUCOCEREBROSIDASE; CLEAVING ENZYME; RAT HEPATOCYTES; KUPFFER
CELLS; DEFICIENCY; PHOSPHATIDYLSERINE; PURIFICATION; METABOLISM; TISSUE
C1 [Brady, Roscoe O.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Brady, RO (reprint author), NINDS, NIH, Bldg 10 Room 3D03, Bethesda, MD 20892 USA.
EM bradyr@ninds.nih.gov
NR 26
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 2210-7371
BN 978-1-4939-2543-8; 978-1-4939-2542-1
J9 AAPS ADV PHARM SCI
PY 2015
VL 19
BP 3
EP 8
DI 10.1007/978-1-4939-2543-8_1
D2 10.1007/978-1-4939-2543-8
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA BE0RT
UT WOS:000366803200002
ER
PT B
AU Brainerd, CJ
Reyna, VF
AF Brainerd, Charles J.
Reyna, Valerie F.
BE Raaijmakers, JGW
Criss, AH
Goldstone, RL
Nosofsky, RM
Steyvers, M
TI Memory and Knowledge Memory and Knowledge in Theories of Episodic Memory
SO COGNITIVE MODELING IN PERCEPTION AND MEMORY: A FESTSCHRIFT FOR RICHARD
M. SHIFFRIN
SE Psychology Press Festschrift Series
LA English
DT Proceedings Paper
CT Conference on Cognitive Modeling in Perception and Memory - Festschrift
in Honor of Richard M. Shiffrin
CY MAY, 2012
CL Indiana Univ, Bloomington, IN
HO Indiana Univ
ID FUZZY-TRACE THEORY; COGNITIVE-DEVELOPMENT; RECOGNITION MEMORY; WORKING
MEMORY; FALSE MEMORIES; EVENT MEMORY; MODEL; CHILDREN; INDEPENDENCE;
ABSTRACTION
C1 [Brainerd, Charles J.] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA.
[Brainerd, Charles J.] Cornell Univ, PhD JD Program Law Psychol & Human Dev, Ithaca, NY 14853 USA.
[Brainerd, Charles J.] Assoc Psychol Sci, Washington, DC USA.
[Brainerd, Charles J.] Amer Psychol Assoc, Washington, DC USA.
[Reyna, Valerie F.] Cornell Univ, Human Neurosci Inst, Ithaca, NY 14853 USA.
[Reyna, Valerie F.] Cornell Univ, Magnet Resonance Imaging Facil, Ithaca, NY 14853 USA.
[Reyna, Valerie F.] Amer Assoc Advancement Sci, Washington, DC USA.
[Reyna, Valerie F.] Soc Judgment & Decis Making, Chicago, IL USA.
[Reyna, Valerie F.] Natl Acad Sci, Sci Panels, Washington, DC USA.
[Reyna, Valerie F.] Natl Sci Fdn, Sci Panels, Arlington, VA 22230 USA.
[Reyna, Valerie F.] NIH, Sci Panels, Bethesda, MD USA.
[Reyna, Valerie F.] US FDA, Sci Panels, Rockville, MD 20857 USA.
[Reyna, Valerie F.] MacArthur Fdn, Sci Panels, Chicago, IL USA.
RP Brainerd, CJ (reprint author), Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA.
NR 47
TC 0
Z9 0
U1 1
U2 1
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH ROAD, HOVE BN3 2FA, E SUSSEX, ENGLAND
BN 978-1-315-88558-2; 978-0-415-70938-5
J9 PSYCHOL PR FESTSCHR
PY 2015
BP 173
EP 185
PG 13
WC Psychology, Experimental
SC Psychology
GA BE0SG
UT WOS:000366823800011
ER
PT J
AU Sri, T
Steren, AJ
Stratton, P
AF Sri, Trisha
Steren, Albert J.
Stratton, Pamela
TI Endometrial Cancer: Hidden Pathology in a Patient with Abnormal Uterine
Bleeding and Known Leiomyoma
SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION
LA English
DT Article
DE Leiomyoma; Endometrial cancer; Abnormal uterine bleeding; Focused
ultrasound
ID RISK
AB Uterine leiomyomas and endometrial pathology are both associated with abnormal uterine bleeding. We report a case in which a nulliparous woman with heavy uterine bleeding and leiomyomas had undergone two prior hysteroscopic myomectomies for benign leiomyomas. She was evaluated, but was ineligible for a clinical trial of a novel Magnetic Resonance guided High Intensity Focused Ultrasound (MRg HIFU) device. The 8 cm, prolapsed submucosal leiomyoma hindered endometrial sampling and was inaccessible to HIFU treatment. Preoperatively, neither endometrial sampling nor saline sonohysterography was technically feasible. She underwent hysterectomy, and on histological examination of specimen, stage 1A grade 1 endometrial carcinoma was found on the endometrial side of the prolapsing fibroid. Endometrial pathology is an important consideration in the evaluation of abnormal uterine bleeding, even in women with large prolapsing leiomyoma. (C) 2015 S. Karger AG, Basel
C1 [Sri, Trisha] Epsom & St Helier NHS Trust, London, Surrey, England.
[Steren, Albert J.] Holy Cross Hosp Silver Spring Maryland, Silver Spring, MD USA.
[Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC, Bldg 10,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
EM ps79c@nih.gov
FU Intramural Research Program of the National Institutes of Health
FX Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver
NICHD, Clinical Center, National Institutes of Health, and clinical
trial NCT00837161 and NICHD protocol 13-CH- N054. This study was
supported in part by the Intramural Research Program of the National
Institutes of Health. NIH and Philips Healthcare have a cooperative
research and development agreement.
NR 7
TC 0
Z9 0
U1 2
U2 2
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-7346
EI 1423-002X
J9 GYNECOL OBSTET INVES
JI Gynecol.Obstet.Invest.
PY 2015
VL 80
IS 4
BP 272
EP 275
DI 10.1159/000370002
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CY9RJ
UT WOS:000366743700010
PM 25634727
ER
PT J
AU Park, CY
Zhou, EHH
Tambe, D
Chen, BH
Lavoie, T
Dowell, M
Simeonov, A
Maloney, DJ
Marinkovic, A
Tschumperlin, DJ
Burger, S
Frykenberg, M
Butler, JP
Stamer, WD
Johnson, M
Solway, J
Fredberg, JJ
Krishnan, R
AF Park, Chan Young
Zhou, Enhua H.
Tambe, Dhananjay
Chen, Bohao
Lavoie, Tera
Dowell, Maria
Simeonov, Anton
Maloney, David J.
Marinkovic, Aleksandar
Tschumperlin, Daniel J.
Burger, Stephanie
Frykenberg, Matthew
Butler, James P.
Stamer, W. Daniel
Johnson, Mark
Solway, Julian
Fredberg, Jeffrey J.
Krishnan, Ramaswamy
TI High-throughput screening for modulators of cellular contractile force
SO INTEGRATIVE BIOLOGY
LA English
DT Article
ID AIRWAY SMOOTH-MUSCLE; CONVENTIONAL OUTFLOW FACILITY; DRUG DISCOVERY;
INTRAOCULAR-PRESSURE; ENDOTHELIAL-CELLS; PHYSICAL FORCES; ASTHMA;
BRONCHOCONSTRICTION; RESPONSIVENESS; HYPERTENSION
AB When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signalling intermediates with poorly defined relationships to such a physiological endpoint. Using cellular force as the target, here we report a new screening technology and demonstrate its applications using human airway smooth muscle cells in the context of asthma and Schlemm's canal endothelial cells in the context of glaucoma. This approach identified several drug candidates for both asthma and glaucoma. We attained rates of 1000 compounds per screening day, thus establishing a force-based cellular platform for high-throughput drug discovery.
C1 [Park, Chan Young; Zhou, Enhua H.; Tambe, Dhananjay; Marinkovic, Aleksandar; Tschumperlin, Daniel J.; Burger, Stephanie; Frykenberg, Matthew; Butler, James P.; Fredberg, Jeffrey J.] Harvard Univ, Sch Publ Hlth, Mol & Integrat Physiol Sci, Boston, MA 02115 USA.
[Chen, Bohao; Lavoie, Tera; Dowell, Maria; Solway, Julian] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Stamer, W. Daniel] Duke Univ, Duke Eye Ctr, Durham, NC 27710 USA.
[Johnson, Mark] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA.
[Krishnan, Ramaswamy] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA.
RP Krishnan, R (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, 99 Brookline Ave, Boston, MA 02215 USA.
EM rkrishn2@bidmc.harvard.edu
RI Johnson, Mark/B-6921-2009
FU National Institutes of Health [R01EY019696, R01HL102373, R01HL107561,
P01HL120839, UH2HL123816]
FX The authors are grateful to Dr Reynold Panettieri at University of
Pennsylvania for providing primary HASM cells, to the Institute for
Genomics and Systems Biology at University of Chicago for preparing the
drug plates, and to the Institute of Chemistry and Cell Biology at
Harvard Medical School for technical assistance. We gratefully
acknowledge the critical comments of Emil Millet and Dr Ajit Jadhav and
the support provided by the National Institutes of Health grants
R01EY019696, R01HL102373, R01HL107561, P01HL120839, and UH2HL123816.
NR 59
TC 7
Z9 7
U1 1
U2 4
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1757-9694
EI 1757-9708
J9 INTEGR BIOL-UK
JI Integr. Biol.
PY 2015
VL 7
IS 10
BP 1318
EP 1324
DI 10.1039/c5ib00054h
PG 7
WC Cell Biology
SC Cell Biology
GA CY9HF
UT WOS:000366717300022
PM 25953078
ER
PT J
AU Maggio, M
De Vita, F
Fisichella, A
Lauretani, F
Ticinesi, A
Ceresini, G
Cappola, A
Ferrucci, L
Ceda, GP
AF Maggio, Marcello
De Vita, Francesca
Fisichella, Alberto
Lauretani, Fulvio
Ticinesi, Andrea
Ceresini, Graziano
Cappola, Anne
Ferrucci, Luigi
Ceda, Gian Paolo
TI The Role of the Multiple Hormonal Dysregulation in the Onset of "Anemia
of Aging": Focus on Testosterone, IGF-1, and Thyroid Hormones
SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY
LA English
DT Review
AB Anemia is amultifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is "unexplained." Ageing process is also characterized by a "multiple hormonal dysregulation" with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals.
C1 [Maggio, Marcello; De Vita, Francesca; Fisichella, Alberto; Ticinesi, Andrea; Ceresini, Graziano; Ceda, Gian Paolo] Univ Parma, Sect Geriatr, Dept Clin & Expt Med, I-43126 Parma, Italy.
[Maggio, Marcello; Lauretani, Fulvio; Ceresini, Graziano; Ceda, Gian Paolo] Univ Hosp Parma, Geriatr Rehabil Dept, I-43126 Parma, Italy.
[Cappola, Anne] Univ Penn, Perelman Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21201 USA.
RP Maggio, M (reprint author), Univ Parma, Sect Geriatr, Dept Clin & Expt Med, I-43126 Parma, Italy.
EM marcellomaggio2001@yahoo.it
RI Lauretani, Fulvio/K-5115-2016;
OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian
Paolo/0000-0002-9648-8295; Ticinesi, Andrea/0000-0001-9171-8592
NR 0
TC 1
Z9 1
U1 1
U2 3
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 1687-8337
EI 1687-8345
J9 INT J ENDOCRINOL
JI Int. J. Endocrinol.
PY 2015
AR 292574
DI 10.1155/2015/292574
PG 22
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CZ1FJ
UT WOS:000366851000001
ER
PT S
AU Cheng, J
Shen, DG
Yap, PT
Basser, PJ
AF Cheng, Jian
Shen, Dinggang
Yap, Pew-Thian
Basser, Peter J.
BE Navab, N
Hornegger, J
Wells, WM
Frangi, AF
TI Novel Single and Multiple Shell Uniform Sampling Schemes for Diffusion
MRI Using Spherical Codes
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2015, PT I
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 18th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 05-09, 2015
CL Munich, GERMANY
SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg
AB A good data sampling scheme is important for diffusion MRI acquisition and reconstruction. Diffusion Weighted Imaging (DWI) data is normally acquired on single or multiple shells in q-space. The samples in different shells are typically distributed uniformly, because they should be invariant to the orientation of structures within tissue, or the laboratory coordinate frame. The Electrostatic Energy Minimization (EEM) method, originally proposed for single shell sampling scheme in dMRI by Jones et al., was recently generalized to the multi-shell case, called generalized EEM (GEEM). GEEM has been successfully used in the Human Connectome Project (HCP). Recently, the Spherical Code (SC) concept was proposed to maximize the minimal angle between different samples in single or multiple shells, producing a larger angular separation and better rotational invariance than the GEEM method. In this paper, we propose two novel algorithms based on the SC concept: 1) an efficient incremental constructive method, called Iterative Maximum Overlap Construction (IMOC), to generate a sampling scheme on a discretized sphere; 2) a constrained non-linear optimization (CNLO) method to update a given initial scheme on the continuous sphere. Compared to existing incremental estimation methods, IMOC obtains schemes with much larger separation angles between samples, which are very close to the best known solutions in single shell case. Compared to the existing Riemannian gradient descent method, CNLO is more robust and stable. Experiments demonstrated that the two proposed methods provide larger separation angles and better rotational invariance than the state-of-the-art GEEM and methods based on the SC concept.
C1 [Cheng, Jian; Basser, Peter J.] NIBIB, STBB, PPITS, NICHD, Bethesda, MD 20892 USA.
[Shen, Dinggang; Yap, Pew-Thian] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
[Shen, Dinggang; Yap, Pew-Thian] Univ N Carolina, BRIC, Chapel Hill, NC USA.
RP Cheng, J (reprint author), NIBIB, STBB, PPITS, NICHD, Bethesda, MD 20892 USA.
EM jian.cheng@nih.gov
NR 9
TC 0
Z9 1
U1 2
U2 2
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24553-9; 978-3-319-24552-2
J9 LECT NOTES COMPUT SC
PY 2015
VL 9349
BP 28
EP 36
DI 10.1007/978-3-319-24553-9_4
PG 9
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Computer Science, Theory & Methods;
Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging
GA BE0KQ
UT WOS:000366205700004
ER
PT S
AU Cheng, J
Shen, DG
Yap, PT
Basser, PJ
AF Cheng, Jian
Shen, Dinggang
Yap, Pew-Thian
Basser, Peter J.
BE Navab, N
Hornegger, J
Wells, WM
Frangi, AF
TI Tensorial Spherical Polar Fourier Diffusion MRI with Optimal Dictionary
Learning
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2015, PT I
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 18th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 05-09, 2015
CL Munich, GERMANY
SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg
AB High Angular Resolution Diffusion Imaging (HARDI) can characterize complex white matter micro-structure, avoiding the Gaussian diffusion assumption inherent in Diffusion Tensor Imaging (DTI). However, HARDI methods normally require significantly more signal measurements and a longer scan time than DTI, which limits its clinical utility. By considering sparsity of the diffusion signal, Compressed Sensing (CS) allows robust signal reconstruction from relatively fewer samples, reducing the scanning time. A good dictionary that sparsifies the signal is crucial for CS reconstruction. In this paper, we propose a novel method called Tensorial Spherical Polar Fourier Imaging (TSPFI) to recover continuous diffusion signal and diffusion propagator by representing the diffusion signal using an orthonormal TSPF basis. TSPFI is a generalization of the existing model-based method DTI and the model-free method SPFI. We also propose dictionary learning TSPFI (DL-TSPFI) to learn an even sparser dictionary represented as a linear combination of TSPF basis from continuous mixture of Gaussian signals. The learning process is efficiently performed in a small subspace of SPF coefficients, and the learned dictionary is proved to be sparse for all mixture of Gaussian signals by adaptively setting the tensor in TSPF basis. Then the learned DL-TSPF dictionary is optimally and adaptively applied to different voxels using DTI and a weighted LASSO for CS reconstruction. DL-TSPFI is a generalization of DL-SPFI, by considering general adaptive tensor setting instead of a scale value. The experiments demonstrated that the learned DL-TSPF dictionary has a sparser representation and lower reconstruction Root-Mean-Squared-Error (RMSE) than both the original SPF basis and the DL-SPF dictionary.
C1 [Cheng, Jian; Basser, Peter J.] NICHD, STBB, PPITS, NIBIB, Rockville, MD 20852 USA.
[Shen, Dinggang; Yap, Pew-Thian] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
[Shen, Dinggang; Yap, Pew-Thian] Univ N Carolina, BRIC, Chapel Hill, NC USA.
RP Cheng, J (reprint author), NICHD, STBB, PPITS, NIBIB, Rockville, MD 20852 USA.
EM jian.cheng@nih.gov; pb12q@nih.gov
NR 13
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24553-9; 978-3-319-24552-2
J9 LECT NOTES COMPUT SC
PY 2015
VL 9349
BP 174
EP 182
DI 10.1007/978-3-319-24553-9_22
PG 9
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Computer Science, Theory & Methods;
Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging
GA BE0KQ
UT WOS:000366205700022
ER
PT S
AU Roth, HR
Lu, L
Farag, A
Shin, HC
Liu, JM
Turkbey, EB
Summers, RM
AF Roth, Holger R.
Lu, Le
Farag, Amal
Shin, Hoo-Chang
Liu, Jiamin
Turkbey, Evrim B.
Summers, Ronald M.
BE Navab, N
Hornegger, J
Wells, WM
Frangi, AF
TI DeepOrgan: Multi-level Deep Convolutional Networks for Automated
Pancreas Segmentation
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2015, PT I
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 18th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 05-09, 2015
CL Munich, GERMANY
SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg
ID MULTIORGAN SEGMENTATION; ATLAS
AB Automatic organ segmentation is an important yet challenging problem for medical image analysis. The pancreas is an abdominal organ with very high anatomical variability. This inhibits previous segmentation methods from achieving high accuracies, especially compared to other organs such as the liver, heart or kidneys. In this paper, we present a probabilistic bottom-up approach for pancreas segmentation in abdominal computed tomography (CT) scans, using multi-level deep convolutional networks (ConvNets). We propose and evaluate several variations of deep ConvNets in the context of hierarchical, coarse-tofine classification on image patches and regions, i.e. superpixels. We first present a dense labeling of local image patches via P-ConvNet and nearest neighbor fusion. Then we describe a regional ConvNet (R-1-ConvNet) that samples a set of bounding boxes around each image superpixel at different scales of contexts in a "zoom-out" fashion. Our ConvNets learn to assign class probabilities for each superpixel region of being pancreas. Last, we study a stacked R-2-ConvNet leveraging the joint space of CT intensities and the P-ConvNet dense probability maps. Both 3D Gaussian smoothing and 2D conditional random fields are exploited as structured predictions for post-processing. We evaluate on CT images of 82 patients in 4-fold cross-validation. We achieve a Dice Similarity Coefficient of 83.6+/-6.3% in training and 71.8+/-10.7% in testing.
C1 [Roth, Holger R.; Lu, Le; Farag, Amal; Shin, Hoo-Chang; Liu, Jiamin; Turkbey, Evrim B.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Roth, HR (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
NR 15
TC 11
Z9 11
U1 1
U2 4
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24553-9; 978-3-319-24552-2
J9 LECT NOTES COMPUT SC
PY 2015
VL 9349
BP 556
EP 564
DI 10.1007/978-3-319-24553-9_68
PG 9
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Computer Science, Theory & Methods;
Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging
GA BE0KQ
UT WOS:000366205700068
ER
PT S
AU Seff, A
Lu, L
Barbu, A
Roth, H
Shin, HC
Summers, RM
AF Seff, Ari
Lu, Le
Barbu, Adrian
Roth, Holger
Shin, Hoo-Chang
Summers, Ronald M.
BE Navab, N
Hornegger, J
Wells, WM
Frangi, AF
TI Leveraging Mid-Level Semantic Boundary Cues for Automated Lymph Node
Detection
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2015, PT II
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 18th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 05-09, 2015
CL Munich, GERMANY
SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg
ID CT DATA; SEGMENTATION
AB Histograms of oriented gradients (HOG) are widely employed image descriptors in modern computer-aided diagnosis systems. Built upon a set of local, robust statistics of low-level image gradients, HOG features are usually computed on raw intensity images. In this paper, we explore a learned image transformation scheme for producing higher-level inputs to HOG. Leveraging semantic object boundary cues, our methods compute data-driven image feature maps via a supervised boundary detector. Compared with the raw image map, boundary cues offer mid-level, more object-specific visual responses that can be suited for subsequent HOG encoding. We validate integrations of several image transformation maps with an application of computer-aided detection of lymph nodes on thoracoabdominal CT images. Our experiments demonstrate that semantic boundary cues based HOG descriptors complement and enrich the raw intensity alone. We observe an overall system with substantially improved results (similar to 78% versus 60% recall at 3 FP/volume for two target regions). The proposed system also moderately outperforms the state-of-the-art deep convolutional neural network (CNN) system in the mediastinum region, without relying on data augmentation and requiring significantly fewer training samples.
C1 [Seff, Ari; Lu, Le; Barbu, Adrian; Roth, Holger; Shin, Hoo-Chang; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Seff, A (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
NR 16
TC 1
Z9 1
U1 1
U2 2
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24571-3; 978-3-319-24570-6
J9 LECT NOTES COMPUT SC
PY 2015
VL 9350
BP 53
EP 61
DI 10.1007/978-3-319-24571-3_7
PG 9
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Computer Science, Theory & Methods;
Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging
GA BE0KT
UT WOS:000366206800007
ER
PT S
AU Azizi, S
Imani, F
Zhuang, B
Tahmasebi, A
Kwak, JT
Xu, S
Uniyal, N
Turkbey, B
Choyke, P
Pinto, P
Wood, B
Moradi, M
Mousavi, P
Abolmaesumi, P
AF Azizi, Shekoofeh
Imani, Farhad
Zhuang, Bo
Tahmasebi, Amir
Kwak, Jin Tae
Xu, Sheng
Uniyal, Nishant
Turkbey, Baris
Choyke, Peter
Pinto, Peter
Wood, Bradford
Moradi, Mehdi
Mousavi, Parvin
Abolmaesumi, Purang
BE Navab, N
Hornegger, J
Wells, WM
Frangi, AF
TI Ultrasound-Based Detection of Prostate Cancer Using Automatic Feature
Selection with Deep Belief Networks
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2015, PT II
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 18th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 05-09, 2015
CL Munich, GERMANY
SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg
DE Temporal ultrasound data; deep learning; deep belief network; cancer
diagnosis; prostate cancer; feature selection; classification
ID TISSUE CLASSIFICATION
AB We propose an automatic feature selection framework for analyzing temporal ultrasound signals of prostate tissue. The framework consists of: 1) an unsupervised feature reduction step that uses Deep Belief Network (DBN) on spectral components of the temporal ultrasound data; 2) a supervised fine-tuning step that uses the histopathology of the tissue samples to further optimize the DBN; 3) a Support Vector Machine (SVM) classifier that uses the activation of the DBN as input and outputs a likelihood for the cancer. In leave-one-core-out cross-validation experiments using 35 biopsy cores, an area under the curve of 0.91 is obtained for cancer prediction. Subsequently, an independent group of 36 biopsy cores was used for validation of the model. The results show that the framework can predict 22 out of 23 benign, and all of cancerous cores correctly. We conclude that temporal analysis of ultrasound data can potentially complement multi-parametric Magnetic Resonance Imaging (mp-MRI) by improving the differentiation of benign and cancerous prostate tissue.
C1 [Azizi, Shekoofeh; Imani, Farhad; Zhuang, Bo; Uniyal, Nishant; Abolmaesumi, Purang] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Tahmasebi, Amir] Philips Res North Amer, Briarcliff Manor, NY USA.
[Kwak, Jin Tae; Xu, Sheng] NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter; Pinto, Peter; Wood, Bradford] NCI, Bethesda, MD 20892 USA.
[Moradi, Mehdi] IBM Almaden Res Ctr, San Jose, CA USA.
[Mousavi, Parvin] Queens Univ, Kingston, ON, Canada.
RP Azizi, S (reprint author), Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
NR 12
TC 5
Z9 5
U1 6
U2 9
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24571-3; 978-3-319-24570-6
J9 LECT NOTES COMPUT SC
PY 2015
VL 9350
BP 70
EP 77
DI 10.1007/978-3-319-24571-3_9
PG 8
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Computer Science, Theory & Methods;
Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging
GA BE0KT
UT WOS:000366206800009
ER
PT S
AU Wong, KCL
Tee, M
Chen, M
Bluemke, DA
Summers, RM
Yao, JH
AF Wong, Ken C. L.
Tee, Michael
Chen, Marcus
Bluemke, David A.
Summers, Ronald M.
Yao, Jianhua
BE Navab, N
Hornegger, J
Wells, WM
Frangi, AF
TI Computer-Aided Infarction Identification from Cardiac CT Images: A
Biomechanical Approach with SVM
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2015, PT II
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 18th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 05-09, 2015
CL Munich, GERMANY
SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg
ID DEFORMATION RECOVERY; MOTION; STRAIN; HEART
AB Compared with global measurements such as ejection fraction, regional myocardial deformation can better aid detection of cardiac dysfunction. Although tagged and strain-encoded MR images can provide such regional information, they are uncommon in clinical routine. In contrast, cardiac CT images are more common with lower cost, but only provide motion of cardiac boundaries and additional constraints are required to obtain the myocardial strains. To verify the potential of contrast-enhanced CT images on computer-aided infarction identification, we propose a biomechanical approach combined with the support vector machine (SVM). A biomechanical model is used with deformable image registration to estimate 3D myocardial strains from CT images, and the regional strains and CT image intensities are input to the SVM classifier for regional infarction identification. Cross-validations on ten canine image sequences with artificially induced infarctions showed that the normalized radial and first principal strains were the most discriminative features, with respective classification accuracies of 87 +/- 13% and 84 +/- 10% when used with the normalized CT image intensity.
C1 [Wong, Ken C. L.; Tee, Michael; Bluemke, David A.; Summers, Ronald M.; Yao, Jianhua] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Chen, Marcus] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Tee, Michael] Univ Oxford, Inst Biomed Engn, Oxford, England.
RP Wong, KCL (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
OI Bluemke, David/0000-0002-8323-8086
NR 14
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24571-3; 978-3-319-24570-6
J9 LECT NOTES COMPUT SC
PY 2015
VL 9350
BP 144
EP 151
DI 10.1007/978-3-319-24571-3_18
PG 8
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Computer Science, Theory & Methods;
Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging
GA BE0KT
UT WOS:000366206800018
ER
PT J
AU Berga-Bolanos, R
Zhu, WDS
Steinke, FC
Xue, HH
Sen, JM
AF Berga-Bolanos, Rosa
Zhu, Wandi S.
Steinke, Farrah C.
Xue, Hai-Hui
Sen, Jyoti Misra
TI Cell-autonomous requirement for TCF1 and LEF1 in the development of
Natural Killer T cells
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE TCF1; LEF1; NKT cells
ID DOUBLE-POSITIVE THYMOCYTES; TRANSCRIPTION FACTORS; SELECTION; WNT;
DIFFERENTIATION; HEMATOPOIESIS; SURVIVAL; LINEAGE
AB Natural killer T (NKT) cells develop from common CD4(+) CD8(+) thymocyte precursors. Transcriptional programs that regulate the development of NKT cells in the thymus development remain to be fully delineated. Here, we demonstrate a cell-intrinsic requirement for transcription factors TCF1 and LEF1 for the development of all subsets of NKT cells. Conditional deletion of TCF1 alone results in a substantial reduction in NKT cells. The remaining NKT cells are eliminated when TCF1 and LEF1 are both deleted. These data reveal an essential role for TCF1 and LEF1 in development of NKT cells. Published by Elsevier Ltd.
C1 [Berga-Bolanos, Rosa; Zhu, Wandi S.; Sen, Jyoti Misra] NIA, Immune Cells & Inflammat Sect, NIH, Baltimore, MD 21224 USA.
[Steinke, Farrah C.; Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Interdisciplinary Immunol Grad Program, Iowa City, IA 52242 USA.
[Sen, Jyoti Misra] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA.
RP Sen, JM (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM Jyoti-Sen@nih.gov
FU National Institute on Aging at the National Institutes of Health
FX We thank NIA animal facility and genotyping facility for animal
husbandry and genotyping and the Tetramer Facility of the US National
Institutes of Health for providing PE- and APC-conjugated mouse CD1d
tetramers loaded with glycolipid PBS-57. This research was supported by
the Intramural Research Program of the National Institute on Aging at
the National Institutes of Health.
NR 20
TC 0
Z9 0
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PY 2015
VL 68
IS 2
BP 484
EP 489
DI 10.1016/j.molimm.2015.09.017
PN B
PG 6
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA CZ0AQ
UT WOS:000366767900011
PM 26490636
ER
PT J
AU Chung, HK
Chen, Y
Rao, JN
Liu, L
Xiao, L
Turner, DJ
Yang, PX
Gorospe, M
Wang, JY
AF Chung, Hee Kyoung
Chen, Yu
Rao, Jaladanki N.
Liu, Lan
Xiao, Lan
Turner, Douglas J.
Yang, Peixin
Gorospe, Myriam
Wang, Jian-Ying
TI Transgenic Expression of miR-222 Disrupts Intestinal Epithelial
Regeneration by Targeting Multiple Genes Including Frizzled-7
SO MOLECULAR MEDICINE
LA English
DT Article
ID MESSENGER-RNA TRANSLATION; SCIATIC-NERVE INJURY; CARCINOMA-CELL LINES;
MUCOSAL GROWTH; CANCER CELLS; HOMEOSTASIS; POLYAMINES; MIGRATION;
MICRORNAS; STRESS
AB Defects in intestinal epithelial integrity occur commonly in various pathologies. miR-222 is implicated in many aspects of cellular function and plays an important role in several diseases, but its exact biological function in the intestinal epithelium is underexplored. We generated mice with intestinal epithelial tissue-specific overexpression of miR-222 to investigate the function of miR-222 in intestinal physiology and diseases in vivo. Transgenic expression of miR-222 inhibited mucosal growth and increased susceptibility to apoptosis in the small intestine, thus leading to mucosal atrophy. The miR-222-elevated intestinal epithelium was vulnerable to pathological stress, since local overexpression of miR-222 not only delayed mucosal repair after ischemia/reperfusion-induced injury, but also exacerbated gut barrier dysfunction induced by exposure to cecal ligation and puncture. miR-222 overexpression also decreased expression of the Wnt receptor Frizzled-7 (FZD7), cyclin-dependent kinase 4 and tight junctions in the mucosal tissue. Mechanistically, we identified the Fzd7 messenger ribonucleic acid (mRNA) as a novel target of miR-222 and found that (miR-222/Fzd7 mRNA) association repressed Fzd7 mRNA translation. These results implicate miR-222 as a negative regulator of normal intestinal epithelial regeneration and protection by downregulating expression of multiple genes including the Fzd7. Our findings also suggest a novel role of increased miR-222 in the pathogenesis of mucosal growth inhibition, delayed healing and barrier dysfunction.
C1 [Chung, Hee Kyoung; Chen, Yu; Rao, Jaladanki N.; Liu, Lan; Xiao, Lan; Turner, Douglas J.; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
[Chung, Hee Kyoung; Chen, Yu; Rao, Jaladanki N.; Liu, Lan; Xiao, Lan; Turner, Douglas J.; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
[Yang, Peixin] Univ Maryland, Sch Med, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA.
[Gorospe, Myriam] NIA, Genet Lab, IRP, NIH, Baltimore, MD 21224 USA.
[Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
RP Wang, JY (reprint author), Baltimore Vet Affairs Med Ctr, 112,10 North Greene St, Baltimore, MD 21201 USA.
EM jwang@smail.umaryland.edu
RI Yang, Peixin/G-9036-2016
FU Merit Review Awards from the U.S. Department of Veterans Affairs;
National Institutes of Health [DK57819, DK61972, DK68491]; National
Institute on Aging-Intramural Research Program
FX Funding was provided by Merit Review Awards (to JY Wang, DJ Turner and
JN Rao) from the U.S. Department of Veterans Affairs; grants from the
National Institutes of Health (DK57819, DK61972 and DK68491 to JY Wang);
and the National Institute on Aging-Intramural Research Program (to M
Gorospe). JY Wang is a Senior Research Career Scientist, Biomedical
Laboratory Research and Development Service, U.S. Department of Veterans
Affairs.
NR 43
TC 3
Z9 3
U1 0
U2 4
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 676
EP 687
DI 10.2119/molmed.2015.00147
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CY7NQ
UT WOS:000366595800003
ER
PT J
AU Cortez, KJ
Kottilil, S
AF Cortez, Karoll J.
Kottilil, Shyam
TI Beyond interferon: rationale and prospects for newer treatment paradigms
for chronic hepatitis C
SO THERAPEUTIC ADVANCES IN CHRONIC DISEASE
LA English
DT Review
DE boceprevir; hepatitis C; pegylated interferon; ribavirin; simeprevir;
sofosbuvir; sustained virologic response; telaprevir
ID TREATMENT-NAIVE PATIENTS; GENOTYPE 1 INFECTION; CHRONIC HCV INFECTION;
SOFOSBUVIR PLUS RIBAVIRIN; VIRUS-INFECTION; UNITED-STATES; PEGINTERFERON
ALPHA-2A; PEGYLATED INTERFERON; SIMEPREVIR TMC435; PHASE-2 TRIAL
AB Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-alpha based combination therapy to an all-oral, directly acting antiviral therapy.
C1 [Kottilil, Shyam] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Cortez, Karoll J.] Vet Affairs Med Ctr, Baltimore, MD USA.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11N204, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
NR 51
TC 17
Z9 20
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 2040-6223
EI 2040-6231
J9 THER ADV CHRONIC DIS
JI Ther. Adv. Chronic Dis.
PD JAN
PY 2015
VL 6
IS 1
BP 4
EP 14
DI 10.1177/2040622314551934
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CZ0UL
UT WOS:000366821400001
PM 25553238
ER
PT S
AU Li, Y
Chen, RM
Lee, C
Lin, MY
Lim, H
Bo, Z
Lam, KH
Shung, KK
AF Li, Ying
Chen, Ruimin
Lee, Changyang
Lin, Ming-Yi
Lim, Hae
Bo, Zhang
Lam, Kwok Ho
Shung, K. Kirk
GP IEEE
TI Recent advances in developing biomedical applications of single beam
acoustic tweezers
SO 2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)
SE IEEE International Ultrasonics Symposium
LA English
DT Proceedings Paper
CT IEEE International Ultrasonics Symposium (IUS)
CY OCT 21-24, 2015
CL Taipei, TAIWAN
SP IEEE
DE Single beam acoustic tweezers; in vivo applications; trapping force
calibration
ID RADIATION PRESSURE; FORCE; DNA; MOLECULE
AB The feasibility of single beam acoustic tweezers (SBAT) was first theoretically and experimentally demonstrated in our laboratory. Major efforts have been devoted to fabricate various types of SBATs and explore their applications. In the latest effort, the feasibility of in vivo application of SBAT was demonstrated by trapping microparticles in excised blood vessels in vitro. Besides, a novel method with better accuracy was applied to calibrate the trapping force of SBATs. Those recent advances in SBAT technology will be reported in this article and following by a discussion of potential biomedical applications of SBATs.
C1 [Li, Ying; Chen, Ruimin; Lee, Changyang; Lim, Hae; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Li, Ying; Chen, Ruimin; Lee, Changyang; Lim, Hae; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Lin, Ming-Yi] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
[Bo, Zhang] Tongji Univ, Sch Med, Dept Ultrasound Med, Shanghai East Hosp, Shanghai 200092, Peoples R China.
[Lam, Kwok Ho] Hong Kong Polytech Univ, Dept Elect Engn, Hunghom, Hong Kong, Peoples R China.
RP Li, Y (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
NR 18
TC 0
Z9 0
U1 3
U2 4
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1948-5719
BN 978-1-4799-8182-3
J9 IEEE INT ULTRA SYM
PY 2015
DI 10.1109/ULTSYM.2015.0024
PG 4
WC Engineering, Electrical & Electronic
SC Engineering
GA BE0HK
UT WOS:000366045700013
ER
PT S
AU Shi, W
Anand, A
Sethuraman, S
Huang, SW
Xie, H
Agarwal, H
Yan, P
Azevedo, J
Kruecker, J
Ng, G
Shamdasani, V
Pritchard, W
Karanian, J
Wood, B
AF Shi, William
Anand, Ajay
Sethuraman, Shriram
Huang, Sheng-Wen
Xie, Hua
Agarwal, Harsh
Yan, Pingkun
Azevedo, Jose
Kruecker, Jochen
Ng, Gary
Shamdasani, Vijay
Pritchard, William
Karanian, John
Wood, Bradford
GP IEEE
TI Monitoring of Radiofrequency Ablation with Shear Wave Delay Mapping
SO 2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)
SE IEEE International Ultrasonics Symposium
LA English
DT Proceedings Paper
CT IEEE International Ultrasonics Symposium (IUS)
CY OCT 21-24, 2015
CL Taipei, TAIWAN
SP IEEE
DE ablation monitoring; radiofrequency ablation; shear wave imaging;
stiffness; elasticity; time-to-peak
AB Real-time monitoring of radiofrequency ablation is important to ensure adequate treatment coverage of liver tumors as well as protection of healthy tissues. The high stiffness contrast between ablated and non-treated tissues has led to the use of ultrasound elastography for coagulation zone visualization. A highly sensitive shear wave delay mapping approach was developed for ablation boundary detection, especially, in the presence of a rigid ablation needle. The shear wave technique was evaluated using ex-vivo bovine and porcine liver samples as well as whole livers from sedated live and fresh cadaver pigs. Initial tissue softening was seen ex-vivo for non-perfused livers, but not observed in-vivo for live livers with 'cooling' blood perfusion. The lesion sizes (lateral radii) determined by the shear wave technique were generally in good agreement with those from gross pathology. In addition, T2-weighted MR images were acquired in 3D for direct assessments of ablated tissue volumes. Overall the shear wave technique appears feasible for defining and monitoring the progression of thermal lesion boundary.
C1 [Shi, William; Anand, Ajay; Sethuraman, Shriram; Huang, Sheng-Wen; Xie, Hua; Agarwal, Harsh; Yan, Pingkun; Azevedo, Jose; Kruecker, Jochen] Philips Res North Amer, Cambridge, MA 02141 USA.
[Ng, Gary; Shamdasani, Vijay] Philips Ultrasound, Bothell, WA 98021 USA.
[Pritchard, William; Karanian, John] US FDA, Rockville, MD 20857 USA.
[Wood, Bradford] NIH, Bethesda, MD 20892 USA.
RP Shi, W (reprint author), Philips Res North Amer, Cambridge, MA 02141 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1948-5719
BN 978-1-4799-8182-3
J9 IEEE INT ULTRA SYM
PY 2015
DI 10.1109/ULTSYM.2015.0040
PG 4
WC Engineering, Electrical & Electronic
SC Engineering
GA BE0HK
UT WOS:000366045700412
ER
PT S
AU Tekes, C
Xu, T
Carpenter, TM
Bette, S
Schnakenberg, U
Cowell, D
Freear, S
Kocaturk, O
Lederman, RJ
Degertekin, FL
AF Tekes, Coskun
Xu, Toby
Carpenter, Thomas M.
Bette, Sebastian
Schnakenberg, Uwe
Cowell, David
Freear, Steven
Kocaturk, Ozgur
Lederman, Robert J.
Degertekin, F. Levent
GP IEEE
TI Real-Time Imaging System using a 12-MHz Forward-Looking Catheter with
Single Chip CMUT-on-CMOS Array
SO 2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)
SE IEEE International Ultrasonics Symposium
LA English
DT Proceedings Paper
CT IEEE International Ultrasonics Symposium (IUS)
CY OCT 21-24, 2015
CL Taipei, TAIWAN
SP IEEE
DE Intravascular; ultrasound; intracardiac echocariography; single chip;
real time; CMUT; Forward Looking
ID ECHOCARDIOGRAPHY
AB Forward looking (FL) imaging catheters would be an important tool for several intravascular ultrasound (IVUS) and intracardiac echocardiography (ICE) applications. Single chip capacitive micromachined ultrasonic transducer (CMUT) arrays fabricated on front-end CMOS electronics with simplified electrical interconnect have been previously developed for highly flexible and compact catheters. In this study, we present a custom built real time imaging system utilizing catheters with single chip CMUT-on-CMOS arrays and show initial imaging results. The fabricated array has a dual-ring structure with 64 transmit (Tx) and 56 receive (Rx) elements. The CMUT arrays fit on a 2.1 mm diameter circular region with all the required front-end electronics. The device operates at 12 MHz center frequency and has around 20 V collapse voltage. The single-chip system requires 13 external connections including 4 Rx channels and power lines. The electrical connections to micro cables in the catheter are made from the top side of the chip using polyimide flex tapes. The device is placed on a 6-Fr catheter shaft and secured with a medical grade silicon rubber. For real time data acquisition, we developed a custom design FPGA based imaging platform to generate digital control sequences for the chip and collect RF data from Rx outputs. We performed imaging experiments using wire phantoms immersed in water to test the real time imaging system. The system has the potential to generate images at 32 fps rate with the particular catheter. The overall system is fully functional and shows promising image performance.
C1 [Tekes, Coskun; Xu, Toby; Carpenter, Thomas M.; Degertekin, F. Levent] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA.
[Bette, Sebastian; Schnakenberg, Uwe] Rhein Westfal TH Aachen, Inst Mat Elect Engn, Aachen, Germany.
[Cowell, David; Freear, Steven] Univ Leeds, Sch Elect & Elect Engn, Leeds, W Yorkshire, England.
[Kocaturk, Ozgur; Lederman, Robert J.] NIH, Div Intramural Res, Bethesda, MD 20892 USA.
RP Tekes, C (reprint author), Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA.
RI Freear, Steven/D-2356-2016;
OI Freear, Steven/0000-0001-7858-4155; lederman, robert/0000-0003-1202-6673
NR 7
TC 0
Z9 0
U1 1
U2 2
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1948-5719
BN 978-1-4799-8182-3
J9 IEEE INT ULTRA SYM
PY 2015
DI 10.1109/ULTSYM.2015.0521
PG 4
WC Engineering, Electrical & Electronic
SC Engineering
GA BE0HK
UT WOS:000366045700529
ER
PT S
AU Siriborvornratanakul, T
AF Siriborvornratanakul, Thitirat
BE Ho, YS
Sang, J
Ro, YM
Kim, J
Wu, F
TI Color and Active Infrared Vision: Estimate Infrared Vision of Printed
Color Using Bayesian Classifier and K-Nearest Neighbor Regression
SO ADVANCES IN MULTIMEDIA INFORMATION PROCESSING - PCM 2015, PT I
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 16th Pacific-Rim Conference on Multimedia (PCM)
CY SEP 16-18, 2015
CL Gwangju Inst Sci & Technol, Gwangju, SOUTH KOREA
SP Gwangju Inst Sci & Technol, Realist Broadcasting Res Ctr, Gwangju Convent & Visitors Bur
HO Gwangju Inst Sci & Technol
DE Color; Active infrared; Machine learning; Bayesian classification;
K-nearest neighbor regression
AB Speaking of active infrared vision, its inability to see physical colors has long been considered as one major drawback or something everybody has paid no attention to until very recently. Looking at this color blindness from other perspective, we propose an idea of a novel medium whose visibilities in both visible and active infrared light spectrums can be controlled, enabling vision-based techniques to transform everyday printed media into smart, eco-friendly and sustainable monitor-like interactive displays.
To begin with, this paper observes the most important key success procedure regarding the idea-estimating how physical colors should look like when being seen by an active infrared camera. Two alternative methods are proposed and evaluated here. The first one uses Bayesian classifier to find some color-attribute combinations that can precisely classify our sample data. The second alternative relies on simple weighted average and k-nearest neighbor regression in two color models-RGB and CIE L*a* b*. Suggesting by experimental results, the second method is more practical and consistent at different distances. Besides, it shows likelihoods of the model created in this work being able to estimate infrared vision of colors printed on different material.
C1 [Siriborvornratanakul, Thitirat] NIDA, Grad Sch Appl Stat, Bangkok 10240, Thailand.
RP Siriborvornratanakul, T (reprint author), NIDA, Grad Sch Appl Stat, 118 SeriThai Rd, Bangkok 10240, Thailand.
EM thitirat@as.nida.ac.th
NR 14
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-24075-6; 978-3-319-24074-9
J9 LECT NOTES COMPUT SC
PY 2015
VL 9314
BP 518
EP 527
DI 10.1007/978-3-319-24075-6_50
PG 10
WC Computer Science, Artificial Intelligence; Computer Science, Information
Systems; Computer Science, Theory & Methods
SC Computer Science
GA BE0GZ
UT WOS:000366016500050
ER
PT J
AU Ceger, P
Allen, D
Huang, RL
Xia, MH
Casey, W
AF Ceger, Patricia
Allen, David
Huang, Ruili
Xia, Menghang
Casey, Warren
TI Performance of the BG1Luc ER TA Method in a qHTS Format
SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
LA English
DT Article
DE BG1Luc ER TA; quantitative high-throughput screening; Tox21; EDSP
ID ROBOTIC PLATFORM; THROUGHPUT; CHEMICALS; AGONISTS
AB In 2012, the wBG1Luc4E2 estrogen receptor (ER) transactivation (TA) method (BG1Luc ER TA) was accepted by U.S. regulatory agencies and the Organisation for Economic Co-operation and Development to detect substances with ER agonist activity. The method is now part of the Tier 1 testing battery in the Environmental Protection Agency's Endocrine Disruptor Screening Program. The BG1Luc ER TA method uses the BG1 ovarian cell line that endogenously expresses full-length ER (alpha and beta) and is stably transfected with a plasmid containing four estrogen responsive elements upstream of a luciferase reporter gene. To allow increased throughput and testing efficiency, the BG1Luc ER TA ("BG1 manual") method was adapted for quantitative high-throughput screening (BG1 qHTS) in the U.S. Tox21 testing program. The BG1 qHTS test method was used to test approximately 10,000 chemicals three times each, and concentration-response data (n = 15) were analyzed to evaluate test method performance. The balanced accuracy of the BG1 qHTS test method (97%, i.e., 32/33) was determined by comparing results to ER TA performance standards for the BG1 manual method. Concordance between the BG1 manual and qHTS methods was 92% (57/62) when calculated for a larger set of non-reference chemicals tested in both methods. These data demonstrate that the performance of the BG1 qHTS is similar to the currently accepted BG1 manual method, thereby establishing the utility of the BG1 qHTS method for identifying ER active environmental chemicals.
C1 [Ceger, Patricia; Allen, David] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Huang, Ruili; Xia, Menghang] NIH, Natl Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Casey, Warren] NIEHS, Natl Toxicol Program Interagency Ctr Evaluat Alte, Res Triangle Pk, NC 27709 USA.
RP Casey, W (reprint author), NIEHS, NICEATM, POB 12233,Mail Stop K2-16, Res Triangle Pk, NC 27709 USA.
EM warren.casey@nih.gov
FU National Institute of Environmental Health Sciences [N01-ES 35504]; U.S.
Environmental Protection Agency [Y3-HG-7026-03]
FX We thank Dr Xiaoqing Chang of ILS for performing statistical analyses
used in the preparation of this manuscript. This work was supported by
the National Institute of Environmental Health Sciences contract N01-ES
35504 and the U.S. Environmental Protection Agency (Interagency
agreement #Y3-HG-7026-03).
NR 22
TC 1
Z9 1
U1 3
U2 4
PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
PI HEILDEBERG
PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY
SN 1868-596X
EI 1868-8551
J9 ALTEX-ALTERN ANIM EX
JI ALTEX-Altern. Anim. Exp.
PY 2015
VL 32
IS 4
BP 287
EP 296
DI 10.14573/altex.1505121
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CY2EJ
UT WOS:000366221300005
PM 26117232
ER
PT J
AU Madka, V
Mohammed, A
Li, Q
Zhang, YT
Kumar, G
Lightfoot, S
Wu, XR
Steele, V
Kopelovich, L
Rao, CV
AF Madka, Venkateshwar
Mohammed, Altaf
Li, Qian
Zhang, Yuting
Kumar, Gaurav
Lightfoot, Stan
Wu, Xueru
Steele, Vernon
Kopelovich, Levy
Rao, Chinthalapally V.
TI TP53 modulating agent, CP-31398 enhances antitumor effects of ODC
inhibitor in mouse model of urinary bladder transitional cell carcinoma
SO AMERICAN JOURNAL OF CANCER RESEARCH
LA English
DT Article
DE Transitional cell carcinoma; UPII-SV40T; DFMO; CP-31398; ornithine
decarboxylase; polyamines; chemoprevention
ID ORNITHINE-DECARBOXYLASE; P53-STABILIZING AGENT; TOBACCO-SMOKE; P53
MUTATIONS; CANCER-CELLS; MICE; EXPRESSION; DIFLUOROMETHYLORNITHINE;
POLYAMINES; GROWTH
AB Mutations of the tumor suppressor p53 and elevated levels of polyamines are known to play key roles in urothelial tumorigenesis. We investigated the inhibition of polyamines biosynthesis and the restoration of p53 signaling as a possible means of preventing muscle invasive urothelial tumors using DFMO, an ODC-inhibiting agent, and CP-31398 (CP), a p53 stabilizing agent. Transgenic UPII-SV40T male mice at 6weeks age (n=15/group) were fed control diet (AIN-76A) or experimental diets containing DFMO (1000 and 2000 ppm) or 150 ppm CP or both. At 40 weeks of age, all mice were euthanized and urinary bladders were evaluated to determine tumor weight and histopathology. Low-dose DFMO had a moderate significant inhibitory effect on tumor growth (38%, P<0.02) and tumor invasion (23%). High-dose DFMO had a 47% tumor inhibition (P<0.0001) and 40% inhibition tumor invasion. There was no significant difference between 1000 and 2000 ppm doses of DFMO (P>0.05). CP at 150 ppm alone had a strong inhibitory effect on tumor growth by 80% (P<0.0001); however, no effect on tumor invasion was observed. Interestingly, the combination of DFMO (1000 ppm) and CP (150 ppm) led to significant decrease in tumor weight (70%, P<0.0001) and tumor invasion (62.5%; P<0.005). Molecular analysis of the urothelial tumors suggested a modulation of polyamine biosynthesis, proliferation, cell cycle regulators resulting from the use of these agents. These results suggest that targeting two or more pathways could be an effective approach for chemoprevention. A combination of CP and DFMO appears to be a promising strategy for urothelial TCC prevention.
C1 [Madka, Venkateshwar; Mohammed, Altaf; Li, Qian; Zhang, Yuting; Kumar, Gaurav; Lightfoot, Stan; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, Stephenson Canc Ctr,Dept Med,Hematol Oncol Sect, Oklahoma City, OK 73104 USA.
[Wu, Xueru] NYU Med Ctr, Dept Urol, New York, NY 10016 USA.
[Steele, Vernon] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
[Kopelovich, Levy] Cornell Univ, Weill Cornell Med Coll, Ithaca, NY 14853 USA.
RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr OUHSC, Ctr Canc Prevent & Drug Dev, Stephenson Canc Ctr,Dept Med,Hematol Oncol Sect, 975 NE 10th St,BRC Bldg 2,Room 1203, Oklahoma City, OK 73104 USA.
EM cv-rao@ouhsc.edu
FU NIH/NCI [NCI-CN53300]
FX The authors thank the University of Oklahoma Health Sciences Center
Rodent Barrier Facility and Ms. Kathy Kyler for valuable suggestions and
editorial help. This study was funded by NIH/NCI (NCI-CN53300).
NR 50
TC 3
Z9 3
U1 1
U2 1
PU E-CENTURY PUBLISHING CORP
PI MADISON
PA 40 WHITE OAKS LN, MADISON, WI 53711 USA
SN 2156-6976
J9 AM J CANCER RES
JI Am. J. Cancer Res.
PY 2015
VL 5
IS 10
BP 3030
EP +
PG 15
WC Oncology
SC Oncology
GA CX8YE
UT WOS:000365990400008
PM 26693057
ER
PT J
AU Jordan, CE
Anderson, BE
Beyersdorf, AJ
Corr, CA
Dibb, JE
Greenslade, ME
Martin, RF
Moore, RH
Scheuer, E
Shook, MA
Thornhill, KL
Troop, D
Winstead, EL
Ziemba, LD
AF Jordan, C. E.
Anderson, B. E.
Beyersdorf, A. J.
Corr, C. A.
Dibb, J. E.
Greenslade, M. E.
Martin, R. F.
Moore, R. H.
Scheuer, E.
Shook, M. A.
Thornhill, K. L.
Troop, D.
Winstead, E. L.
Ziemba, L. D.
TI Spectral aerosol extinction (SpEx): a new instrument for in situ ambient
aerosol extinction measurements across the UV/visible wavelength range
SO ATMOSPHERIC MEASUREMENT TECHNIQUES
LA English
DT Article
ID SOUTHEASTERN UNITED-STATES; ATMOSPHERIC BROWN CARBON; LIGHT-ABSORPTION;
BLACK CARBON; RADIATIVE PROPERTIES; OPTICAL-PROPERTIES; ANGSTROM
EXPONENT; DESERT DUST; CALIBRATION; COMBUSTION
AB We introduce a new instrument for the measurement of in situ ambient aerosol extinction over the 300700 nm wavelength range, the spectral aerosol extinction (SpEx) instrument. This measurement capability is envisioned to complement existing in situ instrumentation, allowing for simultaneous measurement of the evolution of aerosol optical, chemical, and physical characteristics in the ambient environment. In this work, a detailed description of the instrument is provided along with characterization tests performed in the laboratory. Measured spectra of NO2 and polystyrene latex spheres (PSLs) agreed well with theoretical calculations. Good agreement was also found with simultaneous aerosol extinction measurements at 450, 530, and 630 nm using CAPS PMex instruments in a series of 22 tests including nonabsorbing compounds, dusts, soot, and black and brown carbon analogs. SpEx measurements are expected to help identify the presence of ambient brown carbon due to its 300 nm lower wavelength limit compared to measurements limited to longer UV and visible wavelengths. Extinction spectra obtained with SpEx contain more information than can be conveyed by a simple power law fit (typically represented by Angstrom exponents). Planned future improvements aim to lower detection limits and ruggedize the instrument for mobile operation.
C1 [Jordan, C. E.; Dibb, J. E.; Scheuer, E.] Univ New Hampshire, Inst Study Earth Oceans & Space, Durham, NH 03824 USA.
[Anderson, B. E.; Beyersdorf, A. J.; Corr, C. A.; Martin, R. F.; Moore, R. H.; Shook, M. A.; Thornhill, K. L.; Winstead, E. L.; Ziemba, L. D.] NASA, Langley Res Ctr, Hampton, VA 23665 USA.
[Corr, C. A.] Oak Ridge Associated Univ, Oak Ridge, TN USA.
[Greenslade, M. E.] Univ New Hampshire, Dept Chem, Durham, NH USA.
[Shook, M. A.; Thornhill, K. L.; Winstead, E. L.] Sci Syst & Applicat Inc, Hampton, VA USA.
[Troop, D.] SW Res Inst, Durham, NH USA.
RP Jordan, CE (reprint author), NIA, Hampton, VA 23666 USA.
EM carolyn.jordan@nianet.org
FU NOAA [NA10OAR4590134]
FX The authors thank Kevin Kaye, Tom Wisniewski, John Hair, John Prohaska,
Brian Heikes, Matt Brown, James Hite, and Gao Chen for helpful comments
and suggestions during this project. C. E. Jordan is particularly
grateful to John Daniel for his encouragement and support of this work,
funded by NOAA grant no. NA10OAR4590134.
NR 36
TC 1
Z9 1
U1 3
U2 6
PU COPERNICUS GESELLSCHAFT MBH
PI GOTTINGEN
PA BAHNHOFSALLEE 1E, GOTTINGEN, 37081, GERMANY
SN 1867-1381
EI 1867-8548
J9 ATMOS MEAS TECH
JI Atmos. Meas. Tech.
PY 2015
VL 8
IS 11
BP 4755
EP 4771
DI 10.5194/amt-8-4755-2015
PG 17
WC Meteorology & Atmospheric Sciences
SC Meteorology & Atmospheric Sciences
GA CX8TW
UT WOS:000365978100012
ER
PT S
AU Wang, HS
Lin, JX
Li, P
Skinner, J
Leonard, WJ
Morse, HC
AF Wang, Hongsheng
Lin, Jian-xin
Li, Peng
Skinner, Jeff
Leonard, Warren J.
Morse, Herbert C., III
BA Ghosn, E
BF Ghosn, E
BE Rothstein, TL
Herzenberg, LA
Holodick, NE
TI New insights into heterogeneity of peritoneal B-1a cells
SO B-1 CELL DEVELOPMENT AND FUNCTION
SE Annals of the New York Academy of Sciences
LA English
DT Article; Proceedings Paper
CT Merinoff World Congress - B-1 Cell Development and Function
CY JUN 16-19, 2014
CL Tarrytown, NY
SP Panasonic, Beckman Coulter, Life Sciences, BioLegend, Sony, BD, Cellular Technol Ltd, Genentech
DE B-1a; PC1; IL-10; lymphocyte trafficking
ID LY-1 B-CELLS; NATURAL IMMUNITY; GENE-EXPRESSION; PLASMA BLASTS; MARGINAL
ZONE; MOUSE SPLEEN; BONE-MARROW; B10 CELLS; VH GENE; ANTIGEN
AB Peritoneal B-1a cells are characterized by their expression of CD5 and enrichment for germline-encoded IgM B cell receptors. Early studies showing expression of a diverse array of VDJ sequences among purified B-1a cells provided a molecular basis for understanding the heterogeneity of the B-1a cell repertoire. Antigen-driven positive selection and the identification of B-1a specific progenitors suggest multiple origins of B-1a cells. The introduction of new markers such as PD-L2, CD25, CD73, and PC1 (plasma cell alloantigen 1, also known as ectonucleotide phosphodiesterase/pyrophosphatase 1) further helped to identify phenotypically and functionally distinct B-1a subsets. Among many B-1a subsets defined by these new markers, PC1 is unique in that it subdivides B-1a cells into PC1(hi) and PC1(lo) subpopulations with distinct functions, such as production of natural IgM and gut IgA, response to the pneumococcal antigen PPS-3, secretion of interleukin-10, and support for T helper 1 (T(H)1) cell differentiation. RNA sequencing of these subsets revealed differential expression of genes involved in cellular movement and immune cell trafficking. We will discuss these new insights underlying the heterogeneous nature of the B-1a cell repertoire.
C1 [Wang, Hongsheng; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Lin, Jian-xin; Li, Peng; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Lin, Jian-xin; Li, Peng; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
[Skinner, Jeff] NIAID, Malaria Infect Biol & Immun Unit, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Morse, HC (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM wanghongs@niaid.nih.gov; hmorse@niaid.nih.gov
OI Skinner, Jeff/0000-0001-5697-0442
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute
FX We thank Alfonso Macias for maintaining the mouse colony and Mehrnoosh
Abshari for cell sorting. We also thank the DNA Sequencing and Genomics
Core of the NHLBI for RNA sequencing. All animal studies were performed
under protocols of LIG-16 approved by the National Institute of Allergy
and Infectious Diseases Institutional Care and Use Committee. This study
was supported in part by the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases (HCM) and the National Heart, Lung, and Blood Institute (WJL).
NR 76
TC 2
Z9 2
U1 0
U2 1
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
SN 0077-8923
J9 ANN NY ACAD SCI
JI Ann.NY Acad.Sci.
PY 2015
VL 1362
BP 68
EP 76
DI 10.1111/nyas.12791
PG 9
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA BE0LZ
UT WOS:000366286200010
PM 25988856
ER
PT J
AU Sak, MA
Littrup, PJ
Duric, N
Mullooly, M
Sherman, ME
Gierach, GL
AF Sak, Mark A.
Littrup, Peter J.
Duric, Neb
Mullooly, Maeve
Sherman, Mark E.
Gierach, Gretchen L.
TI Current and future methods for measuring breast density: a brief
comparative review
SO BREAST CANCER MANAGEMENT
LA English
DT Review
DE breast cancer risk; breast density; mammography; ultrasound tomography
ID COMPUTER-AIDED DETECTION; STANDARD MAMMOGRAM FORM; CANCER RISK
PREDICTION; X-RAY ABSORPTIOMETRY; MAGNETIC-RESONANCE; ULTRASOUND
TOMOGRAPHY; TISSUE DENSITY; VISUAL CLASSIFICATION; SCREENING
MAMMOGRAPHY; DIGITAL MAMMOGRAPHY
AB Breast density is one of the strongest predictors of breast cancer risk. Women with the densest breasts are four- to six-times more likely to develop cancer compared with those with the lowest densities. Breast density is generally assessed using mammographic imaging; however, this approach has limitations. Magnetic resonance imaging and ultrasound tomography are some alternative imaging modalities that can aid mammography in patient screening and the measurement of breast density. As breast density becomes more commonly discussed, knowledge of the advantages and limitations of breast density as a marker of risk will become more critical. This review article discusses the relationship between breast density and breast cancer risk, lists the benefits and drawbacks of using multiple different imaging modalities to measure density and briefly discusses how breast density will be applied to aid in breast cancer prevention and treatment.
C1 [Sak, Mark A.; Duric, Neb] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Littrup, Peter J.; Duric, Neb] Delphinus Med Technol, Plymouth, MI 48170 USA.
[Littrup, Peter J.] Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA.
[Mullooly, Maeve; Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Mullooly, Maeve] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Sak, MA (reprint author), Wayne State Univ, Karmanos Canc Inst, 4100 John R St, Detroit, MI 48201 USA.
EM sakm@karmanos.org
NR 103
TC 1
Z9 1
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-1923
EI 1758-1931
J9 BREAST CANCER MANAG
JI Breast Cancer Manag.
PY 2015
VL 4
IS 4
BP 209
EP 221
DI 10.2217/BMT.15.13
PG 13
WC Oncology
SC Oncology
GA CY1QN
UT WOS:000366182600005
ER
PT J
AU Kanemaki, N
Meguro, A
Yamane, T
Takeuchi, M
Okada, E
Iijima, Y
Mizuki, N
AF Kanemaki, Nobuyuki
Meguro, Akira
Yamane, Takahiro
Takeuchi, Masaki
Okada, Eiichi
Iijima, Yasuhito
Mizuki, Nobuhisa
TI Study of association of PAX6 polymorphisms with susceptibility to high
myopia in a Japanese population
SO CLINICAL OPHTHALMOLOGY
LA English
DT Article
DE high myopia; PAX6; association study; polymorphism
ID GENOME-WIDE ASSOCIATION; REFRACTIVE ERROR; EDUCATION INFLUENCES; EXTREME
MYOPIA; HAN CHINESE; GENE; SINGAPORE; STUDENTS; LESSONS; LOCUS
AB Purpose: Many studies have investigated the relationship of paired box 6 (PAX6) gene polymorphisms with the risk of high myopia, but the results across studies remain inconsistent and ambiguous. In the present work, we investigated whether PAX6 polymorphisms are associated with high myopia in a Japanese population.
Methods: A total of 1,585 Japanese patients with high myopia (spherical equivalent [SE] <-9.00 diopters [D]) and 1,011 Japanese healthy controls (SE >=-1.00 D) were recruited. To compare genotype frequencies between cases and controls, we genotyped five single nucleotide polymorphisms in the PAX6 gene that are reportedly associated with high/extreme myopia: rs662702, rs3026393, rs644242, rs3026390, and rs667773.
Results: For rs662702, rs644242, and rs667773, odds ratios (ORs) for their risk alleles tended to increase with the progression of SE and axial length in the additive and recessive models. Of these, rs644242 had the highest OR (2.56) in patients with SE<-15 D in both eyes in the recessive model. On the other hand, for rs3026393 and rs3026390, the ORs for their risk alleles tended to increase according to the progression of SE and axial length in the dominant model. Of the two, rs3026393 had the highest OR (2.32) in patients with SE<-15 D in both eyes in the dominant model. However, no significant associations were identified in this study.
Conclusion: We found that these PAX6 single nucleotide polymorphisms were associated with an increased risk of extreme myopia. Although the results, which are in agreement with some previous studies, did not reach statistical significance, PAX6 single nucleotide polymorphisms may be important risk factors for the development of extreme myopia. Further genetic studies with larger sample sizes and taking into account the degree of myopia are needed to clarify the contribution of PAX6 variants in myopia development.
C1 [Kanemaki, Nobuyuki] Azabu Univ, Vet Teaching Hosp, Sagamihara, Kanagawa, Japan.
[Meguro, Akira; Yamane, Takahiro; Takeuchi, Masaki; Mizuki, Nobuhisa] Yokohama City Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Yokohama, Kanagawa 2360004, Japan.
[Takeuchi, Masaki] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Okada, Eiichi] Okada Eye Clin, Yokohama, Kanagawa, Japan.
[Iijima, Yasuhito] Aoto Eye Clin, Yokohama, Kanagawa, Japan.
RP Meguro, A (reprint author), Yokohama City Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan.
EM akmeguro@yokohama-cu.ac.jp
NR 33
TC 1
Z9 1
U1 0
U2 0
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1177-5483
J9 CLIN OPHTHALMOL
JI Clin. Ophthalmol.
PY 2015
VL 9
BP 2005
EP 2011
DI 10.2147/OPTH.S95167
PG 7
WC Ophthalmology
SC Ophthalmology
GA CY4JS
UT WOS:000366375000001
PM 26604670
ER
PT J
AU Stevens, J
Ou, FS
Truesdale, KP
Zeng, DL
Vaughn, AE
Pratt, C
Ward, DS
AF Stevens, June
Ou, Fang-Shu
Truesdale, Kimberly P.
Zeng, Donglin
Vaughn, Amber E.
Pratt, Charlotte
Ward, Dianne S.
TI A suggested approach for imputation of missing dietary data for young
children in daycare
SO FOOD & NUTRITION RESEARCH
LA English
DT Article
DE nutrition; daycare; children; missing data; methods
ID PRESCHOOL-CHILDREN; ENERGY-INTAKE; MULTIPLE-PASS; RECALL; OVERWEIGHT;
ACCURACY; PRODUCTS; FAMILIES; WEEKDAYS; DESIGN
AB Background: Parent-reported 24-h diet recalls are an accepted method of estimating intake in young children. However, many children eat while at childcare making accurate proxy reports by parents difficult.
Objective: The goal of this study was to demonstrate a method to impute missing weekday lunch and daytime snack nutrient data for daycare children and to explore the concurrent predictive and criterion validity of the method.
Design: Datawere from children aged 2-5 years in theMy Parenting SOS project (n = 308; 870 24-h diet recalls). Mixed models were used to simultaneously predict breakfast, dinner, and evening snacks (B+D+ES); lunch; and daytime snacks for all children after adjusting for age, sex, and body mass index (BMI). From these models, we imputed the missing weekday daycare lunches by interpolation using the mean lunch to B+D+ES [L/(B+D+ES)] ratio among non-daycare children on weekdays and the L/(B+D+ES) ratio for all children on weekends. Daytime snack data were used to impute snacks.
Results: The reported mean (+/- standard deviation) weekday intake was lower for daycare children [725 (+/- 324) kcal] compared to non-daycare children [1,048 (+/- 463) kcal]. Weekend intake for all children was 1,173 (+/- 427) kcal. After imputation, weekday caloric intake for daycare children was 1,230 (+/- 409) kcal. Daily intakes that included imputed data were associated with age and sex but not with BMI.
Conclusion: This work indicates that imputation is a promising method for improving the precision of daily nutrient data from young children.
C1 [Stevens, June; Truesdale, Kimberly P.; Ward, Dianne S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Stevens, June] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Ou, Fang-Shu; Zeng, Donglin] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Vaughn, Amber E.] Univ N Carolina, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC 27599 USA.
[Pratt, Charlotte] NHLBI, Clin Applicat & Prevent Branch, NIH, Bethesda, MD 20892 USA.
RP Stevens, J (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, CB 7461, Chapel Hill, NC 27599 USA.
EM June_Stevens@unc.edu
FU National Heart, Lung, and Blood Institute [5U01HL103561,
U01HL103561-02S1, 1R01HL091093]; National Institutes of Health
[DK056350]; Center for Health Promotion and Disease Prevention, a
Prevention Research Center [U48-DP001944]
FX This project was funded by the National Heart, Lung, and Blood Institute
(5U01HL103561, U01HL103561-02S1, and 1R01HL091093). Support was also
received from the National Institutes of Health through their grant to
the UNC-CH Nutrition Obesity Research Center (DK056350). Data collection
was conducted with the assistance from the Center for Health Promotion
and Disease Prevention, a Prevention Research Center funded through a
cooperative agreement with the Centers for Disease Control and
Prevention (U48-DP001944). Findings and conclusions in this article are
those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
NR 36
TC 0
Z9 0
U1 0
U2 0
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 1654-6628
EI 1654-661X
J9 FOOD NUTR RES
JI Food Nutr. Res.
PY 2015
VL 59
AR 28626
DI 10.3402/fnr.v59.28626
PG 9
WC Food Science & Technology; Nutrition & Dietetics
SC Food Science & Technology; Nutrition & Dietetics
GA CY6LE
UT WOS:000366519700001
PM 26689313
ER
PT J
AU Takaku, M
Grimm, SA
Wade, PA
AF Takaku, Motoki
Grimm, Sara A.
Wade, Paul A.
TI GATA3 in Breast Cancer: Tumor Suppressor or Oncogene?
SO GENE EXPRESSION
LA English
DT Review
DE Oncogene; GATA3; Tumor suppressor; Breast cancer
ID TRANSCRIPTION FACTOR; MOLECULAR PORTRAITS; MAMMARY-GLAND; DNA-BINDING;
DIFFERENTIATION; EXPRESSION; METASTASIS; GENE; IDENTIFICATION;
MORPHOGENESIS
AB GATA3 is a highly conserved, essential transcription factor expressed in a number of tissues, including the mammary gland. GATA3 expression is required for normal development of the mammary gland where it is estimated to be the most abundant transcription factor in luminal epithelial cells. In breast cancer, GATA3 expression is highly correlated with the luminal transcriptional program. Recent genomic analysis of human breast cancers has revealed high-frequency mutation in GATA3 in luminal tumors, suggesting "driver" function(s). Here we discuss mutation of GATA3 in breast cancer and the potential mechanism(s) by which mutation may lead to a growth advantage in cancer.
C1 [Takaku, Motoki; Wade, Paul A.] NIEHS, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC 27709 USA.
[Grimm, Sara A.] NIEHS, Integrated Bioinformat, Res Triangle Pk, NC 27709 USA.
RP Wade, PA (reprint author), NIEHS, 111 TW Alexander Dr,Mail Drop D4-04, Res Triangle Pk, NC 27709 USA.
EM wadep2@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [ES101965];
Japan Society for the Promotion of Science
FX The authors thank the members of the Wade laboratory for many useful
discussions through the course of this work. This work was supported, in
part, by the NIH, National Institute of Environmental Health Sciences
(ES101965 to P.A.W.). M.T. was supported, in part, by a fellowship from
the Japan Society for the Promotion of Science.
NR 32
TC 5
Z9 5
U1 2
U2 7
PU COGNIZANT COMMUNICATION CORP
PI PUTNAM VALLEY
PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA
SN 1052-2166
EI 1555-3884
J9 GENE EXPRESSION
JI Gene Expr.
PY 2015
VL 16
IS 4
BP 163
EP 168
DI 10.3727/105221615X14399878166113
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CY1TV
UT WOS:000366191600002
PM 26637396
ER
PT J
AU Watson, NF
Badr, MS
Belenky, G
Bliwise, DL
Buxton, OM
Buysse, D
Dinges, DF
Gangwisch, J
Grandner, MA
Kushida, C
Malhotra, RK
Martin, JL
Patel, SR
Quan, SF
Tasali, E
Twery, M
Croft, JB
Maher, E
Barrett, JA
Thomas, SM
Heald, JL
AF Watson, Nathaniel F.
Badr, M. Safwan
Belenky, Gregory
Bliwise, Donald L.
Buxton, Orfeu M.
Buysse, Daniel
Dinges, David F.
Gangwisch, James
Grandner, Michael A.
Kushida, Clete
Malhotra, Raman K.
Martin, Jennifer L.
Patel, Sanjay R.
Quan, Stuart F.
Tasali, Esra
Twery, Michael
Croft, Janet B.
Maher, Elise
Barrett, Jerome A.
Thomas, Sherene M.
Heald, Jonathan L.
TI Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus
Statement of the American Academy of Sleep Medicine and Sleep Research
Society
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Article
AB Sleep is essential for optimal health. The American Academy of Sleep Medicine (AASM) and Sleep Research Society (SRS) developed a consensus recommendation for the amount of sleep needed to promote optimal health in adults, using a modified RAND Appropriateness Method process. The recommendation is summarized here. A manuscript detailing the conference proceedings and evidence supporting the final recommendation statement will be published in SLEEP and the Journal of Clinical Sleep Medicine.
C1 [Badr, M. Safwan] Univ Washington, Seattle, WA 98195 USA.
[Badr, M. Safwan] Wayne State Univ, Detroit, MI USA.
[Belenky, Gregory] Washington State Univ, Spokane, WA USA.
[Bliwise, Donald L.] Emory Univ, Atlanta, GA 30322 USA.
[Buxton, Orfeu M.] Penn State Univ, University Pk, PA 16802 USA.
[Buysse, Daniel] Univ Pittsburgh, Pittsburgh, PA USA.
[Dinges, David F.; Grandner, Michael A.] Univ Penn, Philadelphia, PA 19104 USA.
[Gangwisch, James] Columbia Univ, New York, NY USA.
[Kushida, Clete] Stanford Univ, Stanford, CA 94305 USA.
[Malhotra, Raman K.] St Louis Univ, St Louis, MO 63103 USA.
[Martin, Jennifer L.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Patel, Sanjay R.; Quan, Stuart F.] Harvard Univ, Sch Med, Boston, MA USA.
[Tasali, Esra] Univ Chicago, Chicago, IL 60637 USA.
[Twery, Michael] NHLBI, NIH, Bethesda, MD 20892 USA.
[Croft, Janet B.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Maher, Elise] Sleep Disorders Inst, New York, NY USA.
[Barrett, Jerome A.; Thomas, Sherene M.; Heald, Jonathan L.] Amer Acad Sleep Med, Darien, IL USA.
RP Watson, NF (reprint author), 2510 N Frontage Rd, Darien, IL 60561 USA.
EM research@aasmnet.org
OI Patel, Sanjay/0000-0002-9142-5172
FU American Academy of Sleep Medicine and Sleep Research Society; Centers
for Disease Control and Prevention (CDC) [1U50DP004930-01]
FX Funding for this project was provided by the American Academy of Sleep
Medicine and Sleep Research Society, and supported by the cooperative
agreement number 1U50DP004930-01 from the Centers for Disease Control
and Prevention (CDC). Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the CDC.
NR 4
TC 14
Z9 14
U1 1
U2 2
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 1550-9389
EI 1550-9397
J9 J CLIN SLEEP MED
JI J. Clin. Sleep Med.
PY 2015
VL 11
IS 6
BP 591
EP 592
AR PII jc-0X231-15
DI 10.5664/jcsm.4758
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CY3BZ
UT WOS:000366284500001
ER
PT J
AU Rusch, HL
Guardado, P
Baxter, T
Mysliwiec, V
Gill, JM
AF Rusch, Heather L.
Guardado, Pedro
Baxter, Tristin
Mysliwiec, Vincent
Gill, Jessica M.
TI Improved Sleep Quality is Associated with Reductions in Depression and
PTSD Arousal Symptoms and Increases in IGF-1 Concentrations
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Article
DE BDNF; depression; IGF-1; insomnia; military; PTSD; sleep quality; mTBI;
trauma
ID GROWTH-FACTOR-I; TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER;
PSYCHIATRIC-DISORDERS; NEUROTROPHIC FACTOR; CLINICIAN; INSOMNIA;
HOMEOSTASIS; DISTURBANCE; NIGHTMARES
AB Study Objectives: One-third of deployed military personnel will be diagnosed with insomnia, placing them at high risk for comorbid depression, posttraumatic stress disorder (PTSD), and medical conditions. The disruption of trophic factors has been implicated in these comorbid conditions, which can impede postdeployment recovery. This study determined if improved sleep quality is associated with (1) reductions in depression and posttraumatic symptoms, as well as enrichments in health-related quality of life (HRQOL), and (2) changes in plasma concentrations of brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1).
Methods: Forty-four military personnel diagnosed with insomnia underwent clinical evaluations and blood draws at pretreatment and at posttreatment following cognitive behavioral therapy for insomnia and automatic positive airway pressure treatment. Participants were classified as sleep improved (n = 28) or sleep declined (n = 16) based on their change in pretreatment to posttreatment Pittsburgh Sleep Quality Index (PSQI) score. Both groups were compared on outcomes of depression, PTSD, HRQOL, BDNF, and IGF-1.
Results: Paired t-tests of the sleep improved group revealed significant declines in depression (p = 0.005) and posttraumatic arousal (p = 0.006) symptoms, and a significant increase in concentrations of IGF-1 (p = 0.009). The sleep declined group had no relevant change in psychiatric symptoms or trophic factors, and had further declines on five of eight dimensions of HRQOL. Between-group change score differences were significant at p < 0.05.
Conclusions: These findings suggest that interventions, which successfully improve sleep quality, are an effective means to reduce the depression and posttraumatic arousal symptoms common to military personnel, as well as increase protective trophic factors implicated in these conditions.
C1 [Rusch, Heather L.; Guardado, Pedro; Gill, Jessica M.] NINR, NIH, Bethesda, MD 20892 USA.
[Rusch, Heather L.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Baxter, Tristin; Mysliwiec, Vincent] Madigan Army Med Ctr, Tacoma, WA 98431 USA.
RP Rusch, HL (reprint author), 1 Cloister Court,Bldg 60 259, Bethesda, MD 20892 USA.
EM heather.rusch@nih.gov
FU Department of Defense in the Center for Neuroscience and Regenerative
Medicine
FX This was not an industry supported study. The authors have indicated no
financial conflicts of interest. The work was performed at the Madigan
Army Medical Center, Tacoma, WA. Support for this work included funding
from Department of Defense in the Center for Neuroscience and
Regenerative Medicine.
NR 43
TC 8
Z9 8
U1 6
U2 10
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 1550-9389
EI 1550-9397
J9 J CLIN SLEEP MED
JI J. Clin. Sleep Med.
PY 2015
VL 11
IS 6
BP 615
EP 623
AR PII jc-00412-14
DI 10.5664/jcsm.4770
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA CY3BZ
UT WOS:000366284500007
PM 25766717
ER
PT J
AU Watson, NF
Badr, MS
Belenky, G
Bliwise, DL
Buxton, OM
Buysse, D
Dinges, DF
Gangwisch, J
Grandner, MA
Kushida, C
Malhotra, RK
Martin, JL
Patel, SR
Quan, SF
Tasali, E
Twery, M
Croft, JB
Maher, E
Barrett, JA
Thomas, SM
Heald, JL
AF Watson, Nathaniel F.
Badr, M. Safwan
Belenky, Gregory
Bliwise, Donald L.
Buxton, Orfeu M.
Buysse, Daniel
Dinges, David F.
Gangwisch, James
Grandner, Michael A.
Kushida, Clete
Malhotra, Raman K.
Martin, Jennifer L.
Patel, Sanjay R.
Quan, Stuart F.
Tasali, Esra
Twery, Michael
Croft, Janet B.
Maher, Elise
Barrett, Jerome A.
Thomas, Sherene M.
Heald, Jonathan L.
TI Joint Consensus Statement of the American Academy of Sleep Medicine and
Sleep Research Society on the Recommended Amount of Sleep for a Healthy
Adult: Methodology and Discussion
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Article
DE sleep duration; consensus; recommendation; adult; health
ID ALL-CAUSE MORTALITY; SHORT-TERM STABILITY; BODY-MASS INDEX;
GENERAL-POPULATION; YOUNG-ADULTS; INSULIN SENSITIVITY; METABOLIC
SYNDROME; COLORECTAL-CANCER; WAKING ACTIVITIES; BREAST-CANCER
AB The American Academy of Sleep Medicine and Sleep Research Society recently released a Consensus Statement regarding the recommended amount of sleep to promote optimal health in adults. This paper describes the methodology, background literature, voting process, and voting results for the consensus statement. In addition, we address important assumptions and challenges encountered during the consensus process. Finally, we outline future directions that will advance our understanding of sleep need and place sleep duration in the broader context of sleep health.
C1 [Watson, Nathaniel F.] Univ Washington, Seattle, WA 98195 USA.
[Badr, M. Safwan] Wayne State Univ, Detroit, MI USA.
[Belenky, Gregory] Washington State Univ, Spokane, WA USA.
[Bliwise, Donald L.] Emory Univ, Atlanta, GA 30322 USA.
[Buxton, Orfeu M.] Penn State Univ, University Pk, PA 16802 USA.
[Buysse, Daniel] Univ Pittsburgh, Pittsburgh, PA USA.
[Dinges, David F.; Grandner, Michael A.] Univ Penn, Philadelphia, PA 19104 USA.
[Gangwisch, James] Columbia Univ, New York, NY USA.
[Kushida, Clete] Stanford Univ, Stanford, CA 94305 USA.
[Malhotra, Raman K.] St Louis Univ, St Louis, MO 63103 USA.
[Martin, Jennifer L.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Patel, Sanjay R.; Quan, Stuart F.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Tasali, Esra] Univ Chicago, Chicago, IL 60637 USA.
[Twery, Michael] NIH, Natl Heart Lung Blood Inst, Bethesda, MD 20892 USA.
[Croft, Janet B.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Maher, Elise] Sleep Disorders Inst, New York, NY USA.
[Barrett, Jerome A.; Thomas, Sherene M.; Heald, Jonathan L.] Amer Acad Sleep Med, Darien, CT USA.
RP Watson, NF (reprint author), 2510 N Frontage Rd, IL-60561 Darien, Israel.
EM research@aasmnet.org
OI Patel, Sanjay/0000-0002-9142-5172
FU American Academy of Sleep Medicine and Sleep Research Society; Centers
for Disease Control and Prevention (CDC) [1U50DP004930-01]
FX Funding for this project was provided by the American Academy of Sleep
Medicine and Sleep Research Society, and supported by the cooperative
agreement number 1U50DP004930-01 from the Centers for Disease Control
and Prevention (CDC). Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the CDC.
NR 125
TC 10
Z9 10
U1 6
U2 8
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 1550-9389
EI 1550-9397
J9 J CLIN SLEEP MED
JI J. Clin. Sleep Med.
PY 2015
VL 11
IS 8
BP 931
EP 952
AR PII jc-0X367-15
DI 10.5664/jcsm.4950
PG 22
WC Clinical Neurology
SC Neurosciences & Neurology
GA CY3EJ
UT WOS:000366290900014
ER
PT J
AU Rusch, HL
Gill, JM
AF Rusch, Heather L.
Gill, Jessica M.
TI Effect of Acute Sleep Disturbance and Recovery on Insulin-Like Growth
Factor-1 (IGF-1): Possible Connections and Clinical Implications
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Letter
C1 [Rusch, Heather L.; Gill, Jessica M.] NINR, NIH, Bethesda, MD USA.
[Rusch, Heather L.] Henry M Jackson Adv Mil Med, Bethesda, MD USA.
RP Rusch, HL (reprint author), NIH, 1 Cloister Court,Bldg 60,Room 259, Bethesda, MD 20814 USA.
EM heather.rusch@nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 1550-9389
EI 1550-9397
J9 J CLIN SLEEP MED
JI J. Clin. Sleep Med.
PY 2015
VL 11
IS 10
BP 1245
EP 1246
AR PII jc-00361-15
DI 10.5664/jcsm.5108
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CY3FO
UT WOS:000366294100020
PM 26414987
ER
PT S
AU Ambardekar, VV
Stern, ST
AF Ambardekar, Vishakha V.
Stern, Stephan T.
BE Crommelin, DJA
DeVlieger, JSB
TI NBCD Pharmacokinetics and Bioanalytical Methods to Measure Drug Release
SO NON-BIOLOGICAL COMPLEX DRUGS: THE SCIENCE AND THE REGULATORY LANDSCAPE
SE AAPS Advances in the Pharmaceutical Sciences Series
LA English
DT Article; Book Chapter
DE Nanomedicine; Non-biological complex drugs; Pharmacokinetics;
Bioanalytical methods; Drug release methods; Equilibrium dialysis;
Liquid-liquid extraction; Modeling and simulation; Metabolite
pharmacokinetics; Size exclusion chromatography; Solid phase extraction;
Ultracentrifugation; Ultrafiltration
ID PEGYLATED LIPOSOMAL CKD-602; HUMAN-PLASMA; ADVANCED MALIGNANCIES;
UNBOUND PACLITAXEL; DELIVERY-SYSTEMS; SOLID TUMORS; IN-VITRO; PHASE-I;
NANOPARTICLE; DOXORUBICIN
AB A primary regulatory challenge for generics of non-biological complex drugs (NBCDs) (i.e., NBCD similars or nanosimilars) is evaluation of bioequivalence (i.e., pharmacokinetic equivalence). NBCD pharmacokinetics are highly dependent upon drug release kinetics and dynamic tissue distribution, with the simultaneous existence of both NBCD encapsulated (e.g., bound) and unencapsulated (e.g. free) forms of the active pharmaceutical ingredient (API). For this reason, regulators have focused on the importance of evaluation of NBCD drug release, and the pharmacokinetics of both the encapsulated and unencapsulated forms of the API, which is challenging from a bioanalytical perspective. While many separation methods are currently available to evaluate drug release from NBCD formulations and measure encapsulated/unencapsulated forms of the API, including both direct and indirect methods, the most appropriate method for any particular NBCD type ultimately depends upon a combination of existing experience, scientific intuition, and trial and error. Presently, the available separation techniques have arisen from repurposing of small molecule preparatory and protein binding methods, none of which adequately address all concerns, such as the problems of process-induced drug release and accurate determination of unbound drug. This chapter will review the existing regulatory guidance for NBCD generic bioequivalence, as well as methods to evaluate NBCD drug release and pharmacokinetics.
C1 [Ambardekar, Vishakha V.; Stern, Stephan T.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Stern, ST (reprint author), Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM sternstephan@mail.nih.gov
NR 80
TC 5
Z9 5
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 2210-7371
BN 978-3-319-16241-6; 978-3-319-16240-9
J9 AAPS ADV PHARM SCI
PY 2015
VL 20
BP 261
EP 287
DI 10.1007/978-3-319-16241-6_8
D2 10.1007/978-3-319-16241-6
PG 27
WC Multidisciplinary Sciences; Pharmacology & Pharmacy
SC Science & Technology - Other Topics; Pharmacology & Pharmacy
GA BD9KI
UT WOS:000364816500008
ER
PT J
AU Ghosh, AK
Martyr, CD
Kassekert, LA
Nyalapatla, PR
Steffey, M
Agniswamy, J
Wang, YF
Weber, IT
Amano, M
Mitsuya, H
AF Ghosh, Arun K.
Martyr, Cuthbert D.
Kassekert, Luke A.
Nyalapatla, Prasanth R.
Steffey, Melinda
Agniswamy, Johnson
Wang, Yuan-Fang
Weber, Irene T.
Amano, Masayuki
Mitsuya, Hiroaki
TI Design, synthesis, biological evaluation and X-ray structural studies of
HIV-1 protease inhibitors containing substituted fused-tetrahydropyranyl
tetrahydrofuran as P2-ligands
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID RESOLUTION CRYSTAL-STRUCTURES; DRUG-RESISTANT MUTANTS; BIS-THF MOIETIES;
P2 LIGANDS; COMPLEXES; BACKBONE; URETHANES; DARUNAVIR; FACILE; SUITE
AB Design, synthesis, biological and X-ray crystallographic studies of a series of potent HIV-1 protease inhibitors are described. Various polar functionalities have been incorporated on the tetrahydropyranyl-tetrahydrofuran-derived P2 ligand to interact with the backbone atoms in the S2-subsite. The majority of the inhibitors showed very potent enzyme inhibitory and antiviral activity. Two high-resolution X-ray structures of 30b- and 30j-bound HIV-1 protease provide insight into ligand-binding site interactions. In particular, the polar functionalities on the P2-ligand appear to form unique hydrogen bonds with Gly48 amide NH and amide carbonyl groups in the flap region.
C1 [Ghosh, Arun K.; Martyr, Cuthbert D.; Kassekert, Luke A.; Nyalapatla, Prasanth R.; Steffey, Melinda] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.; Martyr, Cuthbert D.; Kassekert, Luke A.; Nyalapatla, Prasanth R.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Steffey, Melinda; Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis, Atlanta, GA 30303 USA.
[Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU National Institutes of Health [GM53386, GM62920]; US Department of
Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38];
Intramural Research Program of Center for Cancer Research, National
Cancer Institute, National Institutes of Health; Ministry of Education,
Culture, Sports, Science, and Technology of Japan; Ministry of Health,
Welfare, and Labor of Japan
FX This research was supported by the National Institutes of Health (Grant
GM53386, AKG and Grant GM62920, ITW). X-ray data were collected at the
Southeast Regional Collaborative Access Team (SER-CAT) beamline 22BM at
the Advanced Photon Source, Argonne National Laboratory. Use of the
Advanced Photon Source was supported by the US Department of Energy,
Basic Energy Sciences, Office of Science, under Contract No.
W-31-109-Eng-38. This work was also supported by the Intramural Research
Program of the Center for Cancer Research, National Cancer Institute,
National Institutes of Health, and in part by a Grant-in-Aid for
Scientific Research (Priority Areas) from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho), a
Grant for Promotion of AIDS Research from the Ministry of Health,
Welfare, and Labor of Japan, and the Grant to the Cooperative Research
Project on Clinical and Epidemiological Studies of Emerging and
Reemerging Infectious Diseases (Renkei Jigyo) of Monbu-Kagakusho. The
authors would like to thank the Purdue University Center for Cancer
Research, which supports the shared NMR and mass spectrometry
facilities. The authors would also like to thank Mr. Steve Scherer
(Purdue University) for his help with the cover page.
NR 38
TC 1
Z9 1
U1 0
U2 4
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
EI 1477-0539
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PY 2015
VL 13
IS 48
BP 11607
EP 11621
DI 10.1039/c5ob01930c
PG 15
WC Chemistry, Organic
SC Chemistry
GA CX9JH
UT WOS:000366021300004
PM 26462551
ER
PT J
AU Lesma, G
Bassanini, I
Bortolozzi, R
Colletto, C
Bai, RL
Hamel, E
Meneghetti, F
Rainoldi, G
Stucchi, M
Sacchetti, A
Silvani, A
Viola, G
AF Lesma, Giordano
Bassanini, Ivan
Bortolozzi, Roberta
Colletto, Chiara
Bai, Ruoli
Hamel, Ernest
Meneghetti, Fiorella
Rainoldi, Giulia
Stucchi, Mattia
Sacchetti, Alessandro
Silvani, Alessandra
Viola, Giampietro
TI Complementary isonitrile-based multicomponent reactions for the
synthesis of diversified cytotoxic hemiasterlin analogues
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID SPONGE PRODUCT HEMIASTERLIN; CATALYZED ALPHA-ARYLATION; TRIPEPTIDE
HEMIASTERLIN; ANTIMICROTUBULE AGENT; TUBULIN INHIBITORS; P-GLYCOPROTEIN;
HTI-286; TALTOBULIN; ALDEHYDES; PEPTIDES
AB A small family of structural analogues of the antimitotic tripeptides, hemiasterlins, have been designed and synthesized as potential inhibitors of tubulin polymerization. The effectiveness of a multicomponent approach was fully demonstrated by applying complementary versions of the isocyanide-based Ugi reaction. Compounds strictly related to the lead natural products, as well as more extensively modified analogues, have been synthesized in a concise and convergent manner. In some cases, biological evaluation provided evidence for strong cytotoxic activity (six human tumor cell lines) and for potent inhibition of tubulin polymerization.
C1 [Lesma, Giordano; Bassanini, Ivan; Colletto, Chiara; Rainoldi, Giulia; Stucchi, Mattia; Silvani, Alessandra] Univ Milan, Dipartimento Chim, I-20133 Milan, Italy.
[Bortolozzi, Roberta; Viola, Giampietro] Univ Padua, Dipartimento Salute Donna & Bambino, I-35128 Padua, Italy.
[Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Canc Treatment & Diag,Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA.
[Meneghetti, Fiorella] Univ Milan, Dipartimento Sci Farmaceut, I-20133 Milan, Italy.
[Sacchetti, Alessandro] Politecn Milan, Dipartimento Chim Mat & Ingn Chim Giulio Natta, I-20133 Milan, Italy.
RP Silvani, A (reprint author), Univ Milan, Dipartimento Chim, Via Golgi 19, I-20133 Milan, Italy.
EM alessandra.silvani@unimi.it; giampietro.viola.1@unipd.it
RI Viola, Giampietro/I-4095-2012; Bortolozzi, Roberta/D-4950-2015; silvani,
alessandra/B-3742-2013; Lesma, Giordano/P-1516-2016;
OI Viola, Giampietro/0000-0001-9329-165X; Bortolozzi,
Roberta/0000-0002-3357-4815; silvani, alessandra/0000-0002-0397-2636;
Lesma, Giordano/0000-0002-3897-0008; BASSANINI,
IVAN/0000-0001-9589-3689; sacchetti, alessandro/0000-0002-4830-0825;
MENEGHETTI, FIORELLA/0000-0002-6511-7360
FU Intramural NIH HHS [Z99 CA999999]
NR 46
TC 2
Z9 2
U1 1
U2 7
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
EI 1477-0539
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PY 2015
VL 13
IS 48
BP 11633
EP 11644
DI 10.1039/c5ob01882j
PG 12
WC Chemistry, Organic
SC Chemistry
GA CX9JH
UT WOS:000366021300006
PM 26467486
ER
PT S
AU Stahl, S
Mueller, F
Pastan, I
Brinkmann, U
AF Stahl, Sebastian
Mueller, Fabian
Pastan, Ira
Brinkmann, Ulrich
BE Verma, RS
TI Factors that Determine Sensitivity and Resistances of Tumor Cells
Towards Antibody-Targeted Protein Toxins
SO RESISTANCE TO IMMUNOTOXINS IN CANCER THERAPY
SE Resistance to Targeted Anti-Cancer Therapeutics
LA English
DT Article; Book Chapter
DE Recombinant immunotoxin; Pseudomonas exotoxin; Diphtheria toxin;
Diphthamide; ADP-ribosylation; Immunogenicity; Biodistribution
ID SEGREGATION GENE CSE1; PHASE-I TRIAL; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22;
PSEUDOMONAS EXOTOXIN-A; HUMAN HOMOLOG; INDUCED APOPTOSIS; CANCER-CELLS;
HEMATOLOGIC MALIGNANCIES; DIPHTHAMIDE BIOSYNTHESIS; MEDIATED APOPTOSIS
AB Recombinant immunotoxins are composed of antibody-derived targeting entities fused to truncated toxins. Pseudomonas toxins inactivate eEF2 by ADP-ribosylation and are potent antitumoral agents in clinical development. The sensitivity of tumor cells towards such fusion proteins, and hence their therapeutic efficacy, is influenced by multiple factors: (i) access to tumor cells, (ii) target antigen binding and internalization, (iii) entry into the cytosol, (iv) enzymatic modification of the intracellular target eEF2, and (v) induction of apoptosis. Parameters that affect these steps and hence modulate sensitivity include: (i) protein stability and immunogenicity, (ii) presence, density and internalization of target antigen, (iii) cellular factors involved in processing, routing or translocation of the toxin, (iv) factors involved in diphthamide synthesis on eEF2, and (v) factors that influence cellular susceptibility towards apoptosis. This chapter describes sensitivity or resistance factors for Pseudomonas exotoxin -derived immunotoxins that were identified experimentally and/or observed in clinical studies.
C1 [Stahl, Sebastian; Brinkmann, Ulrich] Roche Pharma Res & Early Dev pRED, Large Mol Res, Roche Innovat Ctr Penzberg, D-82377 Penzberg, Germany.
[Mueller, Fabian; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Brinkmann, U (reprint author), Roche Pharma Res & Early Dev pRED, Large Mol Res, Roche Innovat Ctr Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany.
EM ulrich.brinkmann@roche.com
NR 70
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2196-5501
BN 978-3-319-17275-0; 978-3-319-17274-3
J9 RESIST TARGET ANTI-C
PY 2015
VL 6
BP 57
EP 73
DI 10.1007/978-3-319-17275-0_3
D2 10.1007/978-3-319-17275-0
PG 17
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA BE0FH
UT WOS:000365949800004
ER
PT S
AU Chung, JY
Hewitt, SM
AF Chung, Joon-Yong
Hewitt, Stephen M.
BE Kurien, BT
Scofield, RH
TI A Well-Based Reverse-Phase Protein Array of Formalin-Fixed
Paraffin-Embedded Tissue
SO WESTERN BLOTTING: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Formalin-fixed; Paraffin-embedded; Tissue lysate; Protein extraction;
Proteomics; Reverse-phase protein array; Electrochemiluminescence
ID EXTRACTION; SECTIONS
AB Biomarkers from tissue-based proteomic studies directly contribute to defining disease states as well as promise to improve early detection or provide for further targeted therapeutics. In the clinical setting, tissue samples are preserved as formalin-fixed paraffin-embedded (FFPE) tissue blocks for histological examination. However, proteomic analysis of FFPE tissue is complicated due to the high level of covalently cross-linked proteins arising from formalin fixation. To address these challenges, we developed well-based reverse-phase protein array (RPPA). This approach is a robust protein isolation methodology (29.44 +/- 7.8 mu g per 1 mm 3 of FFPE tissue) paired with a novel on electrochemiluminescence detection system. Protein samples derived from FFPE tissue by means of laser capture dissection, with as few as 500 shots, demonstrate measurable signal differences for different proteins. The lysates coated to the array plate, dried up and vacuum-sealed, remain stable up to 2 months at room temperature. This methodology is directly applicable to FFPE tissue and presents the direct opportunity of addressing hypothesis within clinical trials and well-annotated clinical tissue repositories.
C1 [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Chung, JY (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU Intramural NIH HHS
NR 15
TC 1
Z9 1
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 978-1-4939-2694-7; 978-1-4939-2693-0
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1312
BP 129
EP 139
DI 10.1007/978-1-4939-2694-7_17
D2 10.1007/978-1-4939-2694-7
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE0GM
UT WOS:000365990800018
PM 26043998
ER
PT S
AU Chung, JY
Hewitt, SM
AF Chung, Joon-Yong
Hewitt, Stephen M.
BE Kurien, BT
Scofield, RH
TI Proteomic Expressional Profiling of a Paraffin-Embedded Tissue by
Multiplex Tissue Immunoblotting
SO WESTERN BLOTTING: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Formalin-fixed; Paraffin-embedded; Tissue; Immunodetection;
Histomorphology; Proteomics; Expressional profiling
ID LASER CAPTURE MICRODISSECTION; ELECTROPHORESIS; MICROARRAYS; PROTEINS;
CANCER
AB In the functional proteome era, the proteomic profiling of clinicopathologic annotated tissues is an essential step for mining and evaluations of candidate biomarkers for disease. Previously, application of routine proteomic methodologies to clinical tissue specimens has provided unsatisfactory results. Multiplex tissue immunoblotting is a method of transferring proteins from a formalin-fixed, paraffin-embedded tissue section to a stack of membranes which can be applied to a conventional immunoblotting method. A single tissue section can be transferred to up to ten membranes, each of which is probed with antibodies and detected with fluorescent tags. By this approach, total protein and target signals can be simultaneously determined on each membrane; hence each antibody is internally normalized. Phosphorylation specific antibodies as well as antibodies that do not readily work well with paraffin-embedded tissue are applicable to the membranes, expanding the menu of antibodies that can be utilized with formalin-fixed tissue. This novel platform can provide quantitative detection retaining histomorphologic detail in clinical samples and has great potential to facilitate discovery and development of new diagnostic assays and therapeutic agents.
C1 [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Chung, JY (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
NR 16
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 978-1-4939-2694-7; 978-1-4939-2693-0
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1312
BP 175
EP 184
DI 10.1007/978-1-4939-2694-7_21
D2 10.1007/978-1-4939-2694-7
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE0GM
UT WOS:000365990800022
PM 26044002
ER
PT S
AU Srinivas, PR
AF Srinivas, Pothur R.
BE Kurien, BT
Scofield, RH
TI Western Blotting Using Microfluidics
SO WESTERN BLOTTING: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Western blot; Microfluidics; Electrophoresis
ID PROTEINS
AB Together with polyacrylamide gel electrophoresis, the western blot has been an invaluable research technique in biological sciences. It continues to serve as an important diagnostic tool in medical laboratories. The procedure, however, involves multiple steps that are often time and resource intensive in addition to being of low throughput. Using advances in microfluidics, Hughes and Herr et al. [1] initially developed a microfluidic western blot approach that significantly optimizes resources and assay times. More recent developments have enabled multiplexing to facilitate probing of multiple proteins.
C1 [Srinivas, Pothur R.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Srinivas, PR (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 1
U2 7
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2694-7; 978-1-4939-2693-0
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1312
BP 469
EP 472
DI 10.1007/978-1-4939-2694-7_48
D2 10.1007/978-1-4939-2694-7
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE0GM
UT WOS:000365990800049
PM 26044029
ER
PT S
AU Miura, N
Kuroda, K
Ueda, M
AF Miura, Natsuko
Kuroda, Kouichi
Ueda, Mitsuyoshi
BE Liu, B
TI Enzyme Evolution by Yeast Cell Surface Engineering
SO YEAST SURFACE DISPLAY: METHODS, PROTOCOLS, AND APPLICATIONS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Yeast cell surface engineering; Protein evolution; In vivo homologous
recombination; Firefly luciferase; Substrate specificity and reactivity
ID RHIZOPUS-ORYZAE LIPASE; CELLULOSE-BINDING DOMAIN; COMBINATORIAL LIBRARY;
SACCHAROMYCES-CEREVISIAE; MOLECULAR DISPLAY; FIREFLY LUCIFERASE;
ORGANIC-SOLVENTS; PROTEIN LIBRARY; ENDOWING YEASTS; SINGLE-CELL
AB Artificial evolution of proteins with the aim of acquiring novel or improved functionality is important for practical applications of the proteins. We have developed yeast cell surface engineering methods (or arming technology) for evolving enzymes. Here, we have described yeast cell surface engineering coupled with in vivo homologous recombination and library screening as a method for the artificial evolution of enzymes such as firefly luciferases. Using this method, novel luciferases with improved substrate specificity and substrate reactivity were engineered.
C1 [Miura, Natsuko; Kuroda, Kouichi; Ueda, Mitsuyoshi] Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Sakyo Ku, Kyoto, Japan.
[Miura, Natsuko] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Miura, N (reprint author), Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Sakyo Ku, Kyoto, Japan.
NR 43
TC 1
Z9 1
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2748-7; 978-1-4939-2747-0
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2015
VL 1319
BP 217
EP 232
DI 10.1007/978-1-4939-2748-7_12
D2 10.1007/978-1-4939-2748-7
PG 16
WC Microbiology
SC Microbiology
GA BE0GJ
UT WOS:000365990000013
PM 26060078
ER
PT J
AU Nee, R
Moon, DS
Jindal, RM
Hurst, FP
Yuan, CM
Agodoa, LY
Abbott, KC
AF Nee, Robert
Moon, Deepti S.
Jindal, Rahul M.
Hurst, Frank P.
Yuan, Christina M.
Agodoa, Lawrence Y.
Abbott, Kevin C.
TI Impact of Poverty and Health Care Insurance on Arteriovenous Fistula Use
among Incident Hemodialysis Patients
SO AMERICAN JOURNAL OF NEPHROLOGY
LA English
DT Article
DE Arteriovenous fistula; End-stage renal disease; Poverty; Racial
disparities; USRDS
ID VASCULAR ACCESS USE; UNITED-STATES; DISPARITIES; CREATION; ESRD;
PLACEMENT; MORTALITY; VETERANS; DISEASE; TRENDS
AB Background: The impact of socioeconomic factors on arteriovenous fistula (AVF) creation in hemodialysis (HD) patients is not well understood. We assessed the association of area and individual-level indicators of poverty and health care insurance on AVF use among incident end-stage renal disease (ESRD) patients initiated on HD. Methods: In this retrospective cohort study using the United States Renal Data System database, we identified 669,206 patients initiated on maintenance HD from January 1, 2007 through December 31, 2012. We assessed the Medicare-Medicaid dual-eligibility status as an indicator of individual-level poverty and ZIP code-level median household income (MHI) data obtained from the 2010 United States Census. We conducted logistic regression of AVF use at start of dialysis as the outcome variable. Results: The proportions of dual-eligible and non-dualeligible patients who initiated HD with an AVF were 12.53 and 16.17%, respectively (p < 0.001). Dual eligibility was associated with significantly lower likelihood of AVF use upon initiation of HD (adjusted odds ratio (aOR) 0.91; 95% CI 0.90-0.93). Patients in the lowest area-level MHI quintile had an aOR of 0.97 (95% CI 0.95-0.99) compared to those in higher quintile levels. However, dual eligibility and area-level MHI were not significant in patients with Veterans Affairs (VA) coverage. Conclusions: Individual-and area-level measures of poverty were independently associated with a lower likelihood of AVF use at the start of HD, the only exception being patients with VA health care benefits. Efforts to improve incident AVF use may require focusing on pre-ESRD care to be successful. (C) 2015 S. Karger AG, Basel
C1 [Nee, Robert; Moon, Deepti S.; Yuan, Christina M.; Abbott, Kevin C.] Walter Reed Natl Mil Med Ctr, Nephrol, Bethesda, MD 20889 USA.
[Jindal, Rahul M.] Uniformed Serv Univ Hlth Sci, Dept Surg & Global Hlth, Bethesda, MD 20814 USA.
[Hurst, Frank P.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Nee, R (reprint author), Walter Reed Natl Mil Med Ctr, Serv Nephrol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM robert.nee.civ@mail.mil
OI Abbott, Kevin/0000-0003-2111-7112
NR 40
TC 1
Z9 1
U1 1
U2 2
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0250-8095
EI 1421-9670
J9 AM J NEPHROL
JI Am. J. Nephrol.
PY 2015
VL 42
IS 4
BP 328
EP 336
DI 10.1159/000441804
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CX4JH
UT WOS:000365665600010
PM 26569600
ER
PT J
AU Khan, RJ
Gebreab, SY
Sims, M
Riestra, P
Xu, RH
Davis, SK
AF Khan, Rumana J.
Gebreab, Samson Y.
Sims, Mario
Riestra, Pia
Xu, Ruihua
Davis, Sharon K.
TI Prevalence, associated factors and heritabilities of metabolic syndrome
and its individual components in African Americans: the Jackson Heart
Study
SO BMJ OPEN
LA English
DT Article
DE Metabolic Syndrome; African Americans; Heritability
ID SYNDROME TRAITS; CARDIOVASCULAR RISK; INSULIN-RESISTANCE;
EUROPEAN-AMERICAN; CENTRAL OBESITY; FAMILY; ADULTS; DISEASE;
HOMOCYSTEINE; ADIPONECTIN
AB Objective Both environmental and genetic factors play important roles in the development of metabolic syndrome (MetS). Studies about its associated factors and genetic contribution in African Americans (AA) are sparse. Our aim was to report the prevalence, associated factors and heritability estimates of MetS and its components in AA men and women.
Participants and setting Data of this cross-sectional study come from a large community-based Jackson Heart Study (JHS). We analysed a total of 5227 participants, of whom 1636 from 281 families were part of a family study subset of JHS.
Methods Participants were classified as having MetS according to the Adult Treatment Panel III criteria. Multiple logistic regression analysis was performed to isolate independently associated factors of MetS (n=5227). Heritability was estimated from the family study subset using variance component methods (n=1636).
Results About 27% of men and 40% of women had MetS. For men, associated factors with having MetS were older age, lower physical activity, higher body mass index, and higher homocysteine and adiponectin levels (p<0.05 for all). For women, in addition to all these, lower education, current smoking and higher stress were also significant (p<0.05 for all). After adjusting for covariates, the heritability of MetS was 32% (p<0.001). Heritability ranged from 14 to 45% among its individual components. Relatively higher heritability was estimated for waist circumference (45%), high density lipoprotein-cholesterol (43%) and triglycerides (42%). Heritability of systolic blood pressure (BP), diastolic BP and fasting blood glucose was 16%, 15% and 14%, respectively.
Conclusions Stress and low education were associated with having MetS in AA women, but not in men. Higher heritability estimates for lipids and waist circumference support the hypothesis of lipid metabolism playing a central role in the development of MetS and encourage additional efforts to identify the underlying susceptibility genes for this syndrome in AA.
C1 [Khan, Rumana J.; Gebreab, Samson Y.; Riestra, Pia; Xu, Ruihua; Davis, Sharon K.] NHGRI, Cardiovasc Sect, Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA.
[Sims, Mario] Univ Mississippi, Med Ctr, Dept Internal Med, Div Hypertens, Jackson, MS 39216 USA.
RP Khan, RJ (reprint author), NHGRI, Cardiovasc Sect, Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA.
EM rumana.khan@nih.gov
FU National Institutes of Health; National Heart, Lung, and Blood Institute
[HHSN2682013000 46C, HHSN2682013000 47C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C]; National Institute on Minority
Health and Health Disparities
FX This research was supported by the Intramural Research Program of the
National Institutes of Health. The Jackson Heart Study is supported by
contracts HHSN2682013000 46C, HHSN2682013000 47C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C from the National Heart, Lung, and
Blood Institute and the National Institute on Minority Health and Health
Disparities.
NR 51
TC 2
Z9 2
U1 1
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2015
VL 5
IS 10
AR e008675
DI 10.1136/bmjopen-2015-008675
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX1PH
UT WOS:000365467600068
PM 26525420
ER
PT J
AU Margolis, L
AF Margolis, L.
TI EXTRACELLULAR VESICLES AND ATHEROSCLEROSIS
SO CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Margolis, L.] NICHHD, NIH, 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 0008-6312
EI 1421-9751
J9 CARDIOLOGY
JI Cardiology
PY 2015
VL 132
SU 1
MA 54
BP 28
EP 28
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CX4KD
UT WOS:000365668000026
ER
PT J
AU Jin, X
Kruth, H
AF Jin, X.
Kruth, H.
TI FUNCTION OF ABCA1 AND ABCG1 IN EXTRACELLULAR CHOLESTEROL DEPOSITION BY
MACROPHAGES
SO CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Jin, X.; Kruth, H.] NHLBI, NIH, Expt Atherosclerosis Sect, 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 0008-6312
EI 1421-9751
J9 CARDIOLOGY
JI Cardiology
PY 2015
VL 132
SU 1
MA 57
BP 31
EP 31
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CX4KD
UT WOS:000365668000029
ER
PT J
AU Myles, IA
Gada, S
AF Myles, Ian A.
Gada, Satyen
TI Allergen Immunotherapy in an HIV+ Patient with Allergic Fungal
Rhinosinusitis
SO CASE REPORTS IN IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BRONCHOPULMONARY ASPERGILLOSIS; SINUSITIS;
TRIAL; ITRACONAZOLE; THERAPY
AB Patients with HIV/AIDS can present with multiple types of fungal rhinosinusitis, fungal balls, granulomatous invasive fungal rhinosinusitis, acute or chronic invasive fungal rhinosinusitis, or allergic fungal rhinosinusitis (AFRS). Given the variable spectrum of immune status and susceptibility to severe infection from opportunistic pathogens it is extremely important that clinicians distinguish aggressive fungal invasive fungal disease from the much milder forms such as AFRS. Here we describe a patient with HIV and AFRS to both remind providers of the importance of ruling out invasive fungal disease and outline the other unique features of fungal sinusitis treatment in the HIV-positive population. Additionally we discuss the evidence for and against use of allergen immunotherapy (AIT) for fungal disease in general, as well as the evidence for AIT in the HIV population.
C1 [Myles, Ian A.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Gada, Satyen] Walter Reed Natl Mil Med Ctr, Allergy Immunol Immunizat Serv, Dept Med, Bethesda, MD 20889 USA.
RP Myles, IA (reprint author), NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,Bldg 33,Room 2W10A, Bethesda, MD 20892 USA.
EM mylesi@niaid.nih.gov
NR 28
TC 2
Z9 2
U1 0
U2 0
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2090-6609
EI 2090-6617
J9 CASE REP IMMUNOL
JI Case Rep. Immunol.
PY 2015
AR 875260
DI 10.1155/2015/875260
PG 5
WC Immunology
SC Immunology
GA CX8VJ
UT WOS:000365982000001
ER
PT J
AU Wang, X
Zeng, Y
Ho, DN
Yin, J
Liu, G
Chen, X
AF Wang, X.
Zeng, Y.
Ho, D. N.
Yin, J.
Liu, G.
Chen, X.
TI Fibroblast Growth Factor-Inducible 14: Multiple Roles in Tumor
Metastasis
SO CURRENT MOLECULAR MEDICINE
LA English
DT Article
DE Fn14; cancer; metastasis; targeted therapy; signal pathway
ID KAPPA-B PATHWAY; CANCER-CELL-MIGRATION; NECROSIS-FACTOR-ALPHA;
SKELETAL-MUSCLE ATROPHY; WEAK INDUCER; TNF-ALPHA; SIGNALING PATHWAY;
EPITHELIAL-CELLS; APOPTOSIS TWEAK; UP-REGULATION
AB Metastasis, the main cause of mortality in cancer patients, is a complex process consisting of several sequential, interlinked, and highly-selective steps. Fibroblast growth factor-inducible 14 (Fn14) is one member of the tumor necrosis factor receptor family, which is influential in controlling cell division, life, and death. The role of Fn14 in tumor metastasis regulation is slowly being unraveled, including roles in the regulation of the epithelial-mesenchymal transition, angiogenesis, cytoskeleton modulation, extracellular matrix degradation and inflammation. This review will focus on recent studies that demonstrate the involvement of Fn14 in tumor progression and will briefly describe various pathways of Fn14-regulated metastasis. Finally, future prospects will be discussed for the potential role of Fn14 as a predictive marker and therapeutic agent for tumor metastasis suppression.
C1 [Wang, X.] Xiamen Univ, Sch Life Sci, Lab Microbial Pharmaceut, Xiamen 361102, Peoples R China.
[Wang, X.; Zeng, Y.; Liu, G.] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China.
[Zeng, Y.; Liu, G.] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.
[Zeng, Y.; Liu, G.] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Peoples R China.
[Ho, D. N.; Chen, X.] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
[Yin, J.] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Liu, G (reprint author), Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.
EM gangliu.cmitm@xmu.edu.cn
FU Major State Basic Research Development Program of China (973 Program)
[2013CB733802, 2014CB744503]; National Natural Science Foundation of
China (NSFC) [81422023, 81101101, 81371596, 51273165]; Program for New
Century Excellent Talents in University [NCET-13-0502]; Key Project of
Chinese Ministry of Education [212149]; Fundamental Research Funds for
the Central Universities, China [2013121039]
FX This work was Project supported by the Major State Basic Research
Development Program of China (973 Program, 2013CB733802 and
2014CB744503), the National Natural Science Foundation of China (NSFC)
(81422023, 81101101, 81371596 and 51273165), the Program for New Century
Excellent Talents in University (NCET-13-0502), the Key Project of
Chinese Ministry of Education (Grant No. 212149), and the Fundamental
Research Funds for the Central Universities, China (Grant No.
2013121039).
NR 157
TC 0
Z9 0
U1 3
U2 12
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5240
EI 1875-5666
J9 CURR MOL MED
JI Curr. Mol. Med.
PY 2015
VL 15
IS 10
BP 892
EP 904
DI 10.2174/1566524016666151123105752
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CX3UO
UT WOS:000365625100002
PM 26592249
ER
PT J
AU de Sousa, RT
Zanetti, MV
Brunoni, AR
Machado-Vieira, R
AF de Sousa, Rafael T.
Zanetti, Marcus V.
Brunoni, Andre R.
Machado-Vieira, Rodrigo
TI Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for
Improved Therapeutics
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Article
DE Antidepressant; antipsychotic; diagnosis treatment; glutamate;
monoamines; major depressive disorder
ID TRANSCRANIAL MAGNETIC STIMULATION; SEROTONIN REUPTAKE INHIBITORS;
PLACEBO-CONTROLLED TRIAL; VAGUS NERVE-STIMULATION; STAR-ASTERISK-D;
RANDOMIZED CONTROLLED-TRIALS; EXTENDED-RELEASE QUETIAPINE; TERM
PSYCHODYNAMIC PSYCHOTHERAPY; COGNITIVE-BEHAVIORAL THERAPY; FAILED
MEDICATION TREATMENTS
AB Major depressive disorder (MDD) is associated with a significant burden and costs to the society. As remission of depressive symptoms is achieved in only one-third of the MDD patients after the first antidepressant trial, unsuccessful treatments contribute largely to the observed suffering and social costs of MDD. The present article provides a summary of the therapeutic strategies that have been tested for treatment-resistant depression (TRD). A computerized search on MedLine/PubMed database from 1975 to September 2014 was performed, using the keywords "treatment-resistant depression", "major depressive disorder", "adjunctive", "refractory" and "augmentation". From the 581 articles retrieved, two authors selected 79 papers. A manual searching further considered relevant articles of the reference lists. The evidence found supports adding or switching to another antidepressant from a different class is an effective strategy in more severe MDD after failure to an initial antidepressant trial. Also, in subjects resistant to two or more classes of antidepressants, some augmentation strategies and antidepressant combinations should be considered, although the overall response and remission rates are relatively low, except for fast acting glutamatergic modulators. The wide range of available treatments for TRD reflects the complexity of MDD, which does not underlie diverse key features of the disorder. Larger and well-designed studies applying dimensional approaches to measure efficacy and effectiveness are warranted.
C1 [de Sousa, Rafael T.; Zanetti, Marcus V.; Brunoni, Andre R.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, Lab Neurosci, LIM27, BR-05508 Sao Paulo, Brazil.
[Zanetti, Marcus V.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo, Brazil.
[Zanetti, Marcus V.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Psychiat Neuroimaging, LIM 21, BR-05508 Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch ETPB, NIH, Bethesda, MD 20892 USA.
RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM27, BR-05508 Sao Paulo, Brazil.
EM machadovieirar@gmail.com
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012;
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Russowsky Brunoni,
Andre/0000-0002-6310-3571
NR 171
TC 1
Z9 1
U1 5
U2 8
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-159X
EI 1875-6190
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PY 2015
VL 13
IS 5
BP 616
EP 635
DI 10.2174/1570159X13666150630173522
PG 20
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA CX3UW
UT WOS:000365625900006
PM 26467411
ER
PT J
AU Siniscalchi, A
Bonci, A
Mercuri, NB
Pirritano, D
Squillace, A
De Sarro, G
Gallelli, L
AF Siniscalchi, Antonio
Bonci, Antonello
Mercuri, Nicola Biagio
Pirritano, Domenico
Squillace, Aida
De Sarro, Giovambattista
Gallelli, Luca
TI The Role of Topiramate in the Management of Cocaine Addiction: A
Possible Therapeutic Option
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Article
DE Cocaine dependence; gamma-aminobutyric acid neurotransmission;
glutamatergic neurotransmission; topiramate
ID ANTIEPILEPTIC DRUGS; CONTROLLED-TRIAL; DOUBLE-BLIND; OPEN-LABEL;
DEPENDENCE; ALCOHOL; MOOD; PAIN
AB Topiramate (TPM) is an antiepileptic drug able to play a role in both neurological and psychiatric disorders. TPM facilitates gamma-aminobutyric acid (GABA) transmission and inhibits glutamatergic transmission (i.e. AMPA/kainate receptors).
Several studies reported that the modulation of GABAergic and glutamatergic synaptic transmission may reduce cocaine reinforcement. Therefore, TPM could be used in the management of cocaine dependence.
C1 [Siniscalchi, Antonio] Annunziata Hosp, Dept Neurol, I-87100 Cosenza, Italy.
[Bonci, Antonello] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Mercuri, Nicola Biagio] Univ Roma Tor Vergata, IRCCS Fdn S Lucia, Rome, Italy.
[Mercuri, Nicola Biagio] Univ Roma Tor Vergata, Dept Neurophysiopathol, Rome, Italy.
[Pirritano, Domenico] Diagnost Ctr Igea SRL, Catanzaro, Italy.
[Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca] Univ Catanzaro, Clin Pharmacol & Pharmacovigilance Unit, Chair Pharmacol, Dept Hlth Sci,Sch Med,Mater Domini Univ Hosp, Catanzaro, Italy.
RP Siniscalchi, A (reprint author), Annunziata Hosp, Dept Neurol, Via F Migliori 1, I-87100 Cosenza, Italy.
EM anto.siniscalchi@libero.it
NR 35
TC 1
Z9 1
U1 1
U2 4
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-159X
EI 1875-6190
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PY 2015
VL 13
IS 6
BP 815
EP 818
DI 10.2174/1570159X13666150729222643
PG 4
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA CX3VA
UT WOS:000365626400009
PM 26630959
ER
PT J
AU Dastgheyb, SS
Otto, M
AF Dastgheyb, Sana S.
Otto, Michael
TI Staphylococcal adaptation to diverse physiologic niches: an overview of
transcriptomic and phenotypic changes in different biological
environments
SO FUTURE MICROBIOLOGY
LA English
DT Review
DE gene expression; host-pathogen interaction; niche adaptation;
staphylococci
ID AUREUS NASAL COLONIZATION; ACCESSORY GENE REGULATOR; PHENOL-SOLUBLE
MODULINS; POLYSACCHARIDE INTERCELLULAR ADHESIN; URINARY-TRACT-INFECTION;
PEPTIDE-SENSING SYSTEM; SYNOVIAL-FLUID; BIOFILM FORMATION; ANTIMICROBIAL
PEPTIDES; VIRULENCE FACTORS
AB Host niches can differ strongly regarding, for example, oxygen tension, pH or nutrient availability. Staphylococcus aureus and other staphylococci are common colonizers of human epithelia as well as important human pathogens. The phenotypes that they show in different host environments, and the corresponding bacterial transcriptomes and proteomes, are currently under intense investigation. In this review, we examine the available literature describing staphylococcal phenotypes, such as expression of virulence factors, gross morphologic characteristics and growth patterns, in various physiological environments. Going forward, these studies will help researchers and clinicians to form an enhanced and more detailed picture of the interactions existing between the host and staphylococci as some of its most frequent colonizers and invaders.
C1 [Dastgheyb, Sana S.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Bacteriol, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Bacteriol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Dastgheyb, Sana/0000-0001-8275-1614; Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases, The National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, The National
Institutes of Health. The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 153
TC 4
Z9 5
U1 1
U2 6
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0913
EI 1746-0921
J9 FUTURE MICROBIOL
JI Future Microbiol.
PY 2015
VL 10
IS 12
BP 1981
EP 1995
DI 10.2217/fmb.15.116
PG 15
WC Microbiology
SC Microbiology
GA CX5MS
UT WOS:000365746600008
PM 26584249
ER
PT J
AU Goodman, M
Fletcher, RH
Doria-Rose, VP
Jensen, CD
Zebrowski, AM
Becerra, TA
Quinn, VP
Zauber, AG
Corley, DA
Doubeni, CA
AF Goodman, Michael
Fletcher, Robert H.
Doria-Rose, V. Paul
Jensen, Christopher D.
Zebrowski, Alexis M.
Becerra, Tracy A.
Quinn, Virginia P.
Zauber, Ann G.
Corley, Douglas A.
Doubeni, Chyke A.
TI Observational methods to assess the effectiveness of screening
colonoscopy in reducing right colon cancer mortality risk: SCOLAR
SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
LA English
DT Article
DE cancer screening; case-control study; colorectal cancer; selection bias
ID ADENOMA DETECTION RATE; FECAL-OCCULT-BLOOD; COLORECTAL-CANCER; BETHESDA
GUIDELINES; BOWEL MOVEMENT; RECTAL-CANCER; DEATH; ENDOSCOPY; COHORT;
CONSTIPATION
AB Aims: Screening colonoscopy's effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)'. Methods: SCOLAR is a nested case-control study based on two large integrated health systems. This affords access to a large, well-defined historical cohort linked to integrated data on cancer outcomes, patient eligibility, test indications and important confounders. Results: We found electronic data adequate for excluding ineligible patients (except family history), but not the detailed information needed for test indication assignment. Conclusion: The lessons of SCOLAR's design and implementation may be useful for future studies seeking to evaluate the effectiveness of screening tests in community settings.
C1 [Goodman, Michael] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Populat Hlth, Boston, MA 02115 USA.
[Doria-Rose, V. Paul] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Jensen, Christopher D.; Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Zebrowski, Alexis M.; Doubeni, Chyke A.] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA.
[Becerra, Tracy A.; Quinn, Virginia P.] Kaiser Permanente, Dept Res & Evaluat, Pasadena, CA 91107 USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
RP Doubeni, CA (reprint author), Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA.
EM chyke.doubeni@uphs.upenn.edu
OI Doria-Rose, Vincent/0000-0002-8802-5143
FU National Cancer Institute at the US NIH [U01 CA151736]
FX The study was supported by a grant from the National Cancer Institute at
the US NIH (# U01 CA151736). The authors have no other relevant
affiliations or financial involvement with any organization or entity
with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those
disclosed.
NR 48
TC 2
Z9 2
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 2042-6305
EI 2042-6313
J9 J COMP EFFECT RES
JI J. Comp. Eff. Res.
PY 2015
VL 4
IS 6
BP 541
EP 551
DI 10.2217/cer.15.39
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CX5OH
UT WOS:000365751000002
PM 26201973
ER
PT J
AU Friedman, EL
Chawla, N
Morris, PT
Castro, KM
Carrigan, AC
Das, IP
Clauser, SB
AF Friedman, Eliot L.
Chawla, Neetu
Morris, Paul T.
Castro, Kathleen M.
Carrigan, Angela C.
Das, Irene Prabhu
Clauser, Steven B.
TI Assessing the Development of Multidisciplinary Care: Experience of the
National Cancer Institute Community Cancer Centers Program
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
ID BREAST-CANCER; TEAMS; QUALITY
AB Purpose: The National Cancer Institute Community Cancer Centers Program (NCCCP) began in 2007 with a goal of expanding cancer research and delivering quality care in communities. The NCCCP Quality of Care (QoC) Subcommittee was charged with developing and improving the quality of multidisciplinary care. An assessment tool with nine key elements relevant to MDC structure and operations was developed.
Methods: Fourteen NCCCP sites reported multidisciplinary care assessments for lung, breast, and colorectal cancer in June 2010, June 2011, and June 2012 using an online reporting tool. Each site evaluated their level of maturity (level 1 = no multidisciplinary care, level 5 = highly integrated multidisciplinary care) in nine elements integral to multidisciplinary care. Thematic analysis of open-ended qualitative responses was also conducted.
Results: The proportion of sites that reported level 3 or greater on the assessment tool was tabulated at each time point. For all tumor types, sites that reached this level increased in six elements: case planning, clinical trials, integration of care coordination, physician engagement, quality improvement, and treatment team integration. Factors that enabled improvement included increasing organizational support, ensuring appropriate physician participation, increasing patient navigation, increasing participation in national quality initiatives, targeting genetics referrals, engaging primary care providers, and integrating clinical trial staff.
Conclusions: Maturation of multidisciplinary care reflected focused work of the NCCCP QoC Subcommittee. Working group efforts in patient navigation, genetics, and physician conditions of participation were evident in improved multidisciplinary care performance for three common malignancies. This work provides a blueprint for health systems that wish to incorporate prospective multidisciplinary care into their cancer programs.
C1 [Friedman, Eliot L.] Lehigh Valley Hlth Network, Allentown, PA 18105 USA.
NCI, Rockville, MD USA.
Frederick Natl Lab Canc Res, Frederick, MD USA.
Queens Med Ctr, Honolulu, HI USA.
RP Friedman, EL (reprint author), Lehigh Valley Hlth Network, 1240 S Cedar Crest Blvd,Suite 411, Allentown, PA 18105 USA.
EM Eliot_L.Friedman@lvhn.org
NR 22
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD JAN
PY 2015
VL 11
IS 1
BP E36
EP E43
DI 10.1200/JOP.2014.001535
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CW9ZW
UT WOS:000365357700005
PM 25336082
ER
PT J
AU Chalmers, NI
Oh, K
Hughes, CV
Pradhan, N
Kanasi, E
Ehrlich, Y
Dewhirst, FE
Tanner, ACR
AF Chalmers, Natalia I.
Oh, Kevin
Hughes, Christopher V.
Pradhan, Nooruddin
Kanasi, Eleni
Ehrlich, Ygal
Dewhirst, Floyd E.
Tanner, Anne C. R.
TI Pulp and plaque microbiotas of children with severe early childhood
caries
SO JOURNAL OF ORAL MICROBIOLOGY
LA English
DT Article
DE 16S rRNA; culture; Streptococcus mutans; Parascardovia
ID DENTAL-CARIES; PRIMARY TEETH; ORAL-HEALTH; ENDODONTIC INFECTIONS;
MOLECULAR ANALYSIS; NECROTIC PULPS; BACTERIA; LESIONS; MICROFLORA;
DISPARITIES
AB Background and objective: Bacterial invasion into pulps of primary teeth can lead to infection and premature tooth loss in children. This pilot study aimed to explore whether the microbiota of carious exposures of dental pulps resembles that of carious dentin or that of infected root canals.
Design: Children with severe early childhood caries were studied. Children were consented and extent of caries, plaque, and gingivitis measured. Bacteria were sampled from carious lesion biofilms and vital carious exposures of pulps, and processed by anaerobic culture. Isolates were characterized from partial sequences of the 16S rRNA gene and identified by comparison with taxa in the Human Oral Microbiome Database (http://www.HOMD.org). The microbiotas of carious lesions and dental pulps were compared using univariate and multivariate approaches.
Results: The microbiota of cariously exposed pulps was similar in composition to that of carious lesion biofilms except that fewer species/taxa were identified from pulps. The major taxa identified belonged to the phyla Firmicutes (mainly streptococci) and Actinobacteria (mainly Actinomyces species). Actinomyces and Selenomonas species were associated with carious lesions whereas Veillonella species, particularly Veillonella dispar was associated with pulps. Other bacteria detected in pulps included Streptococcus mutans, Parascardovia denticolens, Bifidobacterium longum, and several Lactobacillus and Actinomyces species. By principal, component analysis pulp microbiotas grouped together, whereas those in caries biofilms were widely dispersed.
Conclusions: We conclude that the microbiota of cariously exposed vital primary pulps is composed of a subset of species associated with carious lesions. Vital primary pulps had a dominant Firmicutes and Actinobacteria microbiota which contrasts with reports of endodontic infections which can harbor a gram-negative microbiota. The microbiota of exposed primary pulps may provide insight into bacterial species at the forefront of caries invasion in dentinal lesions that can invade into the pulp and the nature of species that need suppressing for successful pulp therapy.
C1 [Chalmers, Natalia I.] NIDCR, NIH, Bethesda, MD USA.
[Chalmers, Natalia I.; Kanasi, Eleni; Dewhirst, Floyd E.; Tanner, Anne C. R.] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA.
[Oh, Kevin; Dewhirst, Floyd E.; Tanner, Anne C. R.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Hughes, Christopher V.; Kanasi, Eleni] Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA.
[Pradhan, Nooruddin] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA.
[Ehrlich, Ygal] Indiana Univ, Sch Dent, Indianapolis, IN USA.
RP Tanner, ACR (reprint author), Forsyth Inst, Dept Microbiol, 245 First St, Cambridge, MA 02142 USA.
EM annetanner@forsyth.org
FU NIDCR at the National Institutes of Health [DE-015847, DE016937,
T32-DE-007327]
FX This study was performed with grants from NIDCR at the National
Institutes of Health DE-015847, DE016937, and T32-DE-007327.
NR 37
TC 6
Z9 6
U1 3
U2 9
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2000-2297
J9 J ORAL MICROBIOL
JI J. Oral Microbiology
PY 2015
VL 7
AR 25951
DI 10.3402/jom.v7.25951
PG 8
WC Microbiology
SC Microbiology
GA CX4UM
UT WOS:000365695800001
PM 25651832
ER
PT J
AU Fan, J
He, NY
He, QJ
Liu, Y
Ma, Y
Fu, X
Liu, YJ
Huang, P
Chen, XY
AF Fan, Jing
He, Nongyue
He, Qianjun
Liu, Yi
Ma, Ying
Fu, Xiao
Liu, Yijing
Huang, Peng
Chen, Xiaoyuan
TI A novel self-assembled sandwich nanomedicine for NIR-responsive release
of NO
SO NANOSCALE
LA English
DT Article
ID NITRIC-OXIDE DELIVERY; GRAPHENE OXIDE; RESISTANCE; EFFICIENT; CANCER;
MULTIPLICATION; NANOPARTICLES; DOXORUBICIN; GENERATION; EXCITATION
AB A novel sandwich nanomedicine (GO-BNN6) for near-infrared (NIR) light responsive release of nitric oxide (NO) has been constructed by self-assembly of graphene oxide (GO) nanosheets and a NO donor BNN6 through the pi-pi stacking interaction. The GO-BNN6 nanomedicine has an extraordinarily high drug loading capacity (1.2 mg BNN6 per mg GO), good thermal stability, and high NIR responsiveness. The NO release from GO-BNN6 can be easily triggered and effectively controlled by adjusting the switching, irradiation time and power density of NIR laser. The intracellular NIR-responsive release of NO from the GO-BNN6 nanomedicine causes a remarkable anti-cancer effect.
C1 [Fan, Jing; He, Nongyue] Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China.
[Fan, Jing] Nanxishan Hosp Guangxi Zhuang Nationality Autonom, Clin Lab, Guilin 541002, Guangxi, Peoples R China.
[Fan, Jing; Liu, Yi; Ma, Ying; Fu, Xiao; Liu, Yijing; Huang, Peng; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
[He, Qianjun] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Guangdong, Peoples R China.
RP He, NY (reprint author), Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China.
EM nyhe1958@163.com; Nanoflower@126.com; shawn.chen@nih.gov
RI Liu, Yijing/D-6666-2016; Huang, Peng/R-2480-2016; HE,
QIANJUN/M-2642-2013
OI Huang, Peng/0000-0003-3651-7813; HE, QIANJUN/0000-0003-0689-8838
FU Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering; National Institutes of Health; National Key Program
for Developing Basic Research of China [2014CB744501]; NSFC [61271056,
61471168, 61527806]; China Scholarship Council [201406090085]
FX We thank financial support from the Intramural Research Program,
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health, the National Key Program for Developing Basic
Research of China (no. 2014CB744501), the NSFC (no. 61271056, 61471168
and 61527806), and the State Scholarship Fund from China Scholarship
Council (no. 201406090085).
NR 30
TC 23
Z9 23
U1 19
U2 61
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-3364
EI 2040-3372
J9 NANOSCALE
JI Nanoscale
PY 2015
VL 7
IS 47
BP 20055
EP 20062
DI 10.1039/c5nr06630a
PG 8
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA CX2MJ
UT WOS:000365530700024
PM 26568270
ER
PT B
AU Murai, J
Pommier, Y
AF Murai, Junko
Pommier, Yves
BE Curtin, NJ
Sharma, RA
TI Classification of PARP Inhibitors Based on PARP Trapping and Catalytic
Inhibition, and Rationale for Combinations with Topoisomerase I
Inhibitors and Alkylating Agents
SO PARP INHIBITORS FOR CANCER THERAPY
SE Cancer Drug Discovery and Development
LA English
DT Article; Book Chapter
DE PARP inhibitor; Topoisomerase; Camptothecin; PARP trapping; PARP-DNA
complex; Synthetic lethal; Veliparib; Niraparib; Olaparib; Rucaparib;
Talazoparib
ID TYROSYL-DNA PHOSPHODIESTERASE; DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE)
POLYMERASE; CANCER-CELLS; ANTICANCER THERAPY; MAMMALIAN-CELLS; DAMAGE
REPAIR; TDP1; ASSOCIATION; ABT-888
AB All PARP inhibitors in clinical development (veliparib, olaparib, niraparib, rucaparib, talazoparib) are potent submicromolar competitive NAD(+) inhibitors for PARP1 and PARP2, thereby blocking PARylation reactions [i.e. formation of poly(ADPribose) polymers]. In addition, PARP trapping, which determines the anticancer activity of PARP inhibitors as single agents, is drug-specific, and PARP inhibitors can be ranked according to their PARP trapping potency: Talazoparib >> niraparib approximate to olaparib approximate to rucaparib > veliparib. The highly synergistic effects of PARP inhibitors in combination with alkylating agent (temozolomide or methyl methanesulfonate, MMS) and topoisomerase I (Top1) inhibitors (camptothecins and indenoisoquinolines) are well documented. Both classes of drugs induce DNA single-strand breaks sensed by PARP. Yet, the molecular mechanisms of synergy are different. For alkylating agents (temozolomide and MMS), both PARP trapping and PARylation inhibition account for the synergy, whereas for Top1 inhibitors, there is no involvement of PARP trapping and it is PARylation inhibition that deters the coupling of PARP with the repair enzyme, tyrosyl-DNA phosphodiesterase TDP1. In this chapter, we will review the differences between PARP inhibitors and the rationale for choosing among different PARP inhibitors in combination with alkylating agents or Top1 inhibitors.
C1 [Murai, Junko; Pommier, Yves] NCI, Dev Therapeut Branch, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
NR 50
TC 3
Z9 3
U1 1
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
BN 978-3-319-14151-0; 978-3-319-14150-3
J9 CANCER DRUG DISCOV D
JI Canc. Drug. Disc. Dev.
PY 2015
VL 83
BP 261
EP 274
DI 10.1007/978-3-319-14151-0_10
D2 10.1007/978-3-319-14151-0
PG 14
WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy
GA BD9UZ
UT WOS:000365493100011
ER
PT J
AU Vance, TM
Azabdaftari, G
Pop, EA
Lee, SG
Su, LJ
Fontham, ETH
Bensen, JT
Steck, SE
Arab, L
Mohler, JL
Chen, MH
Koo, SI
Chun, OK
AF Vance, Terrence M.
Azabdaftari, Gissou
Pop, Elena A.
Lee, Sang Gil
Su, L. Joseph
Fontham, Elizabeth T. H.
Bensen, Jeannette T.
Steck, Susan E.
Arab, Lenore
Mohler, James L.
Chen, Ming-Hui
Koo, Sung I.
Chun, Ock K.
TI Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score,
Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants
SO PROSTATE CANCER
LA English
DT Article
ID OXIDATIVE STRESS; CANCER CELLS; RISK; EXPRESSION; CAPACITY; DISEASE
AB Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher's exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.
C1 [Vance, Terrence M.; Lee, Sang Gil; Koo, Sung I.; Chun, Ock K.] Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA.
[Azabdaftari, Gissou; Pop, Elena A.; Mohler, James L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA.
[Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA 70112 USA.
[Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA.
[Steck, Susan E.] Univ S Carolina, Canc Prevent & Control Program, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
RP Chun, OK (reprint author), Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA.
EM ock.chun@uconn.edu
NR 26
TC 3
Z9 3
U1 1
U2 1
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2090-3111
EI 2090-312X
J9 PROSTATE CANCER
JI Prostate Cancer
PY 2015
AR 728046
DI 10.1155/2015/728046
PG 8
WC Oncology
SC Oncology
GA CX8WF
UT WOS:000365984400001
ER
PT J
AU Wei, L
Hao, J
Lacher, RK
Abbott, T
Chung, L
Colangelo, CM
Kaffman, A
AF Wei, Lan
Hao, Jin
Lacher, Richard K.
Abbott, Thomas
Chung, Lisa
Colangelo, Christopher M.
Kaffman, Arie
TI Early-Life Stress Perturbs Key Cellular Programs in the Developing Mouse
Hippocampus
SO DEVELOPMENTAL NEUROSCIENCE
LA English
DT Article
DE Early-life stress; Hippocampus; Liquid chromatography multiple reaction
monitoring mass spectrometry; Neurodevelopment; Proteomics; Synaptosomes
ID ANTERIOR CINGULATE CORTEX; CORPUS-CALLOSUM; SPINE DENSITY; CHILDHOOD
MALTREATMENT; MATERNAL SEPARATION; PYRAMIDAL NEURONS; RAT HIPPOCAMPUS;
MICE; NEUROFILAMENTS; NEGLECT
AB Conflicting reports are available with regard to the effects of childhood abuse and neglect on hippocampal function in children. While earlier imaging studies and some animal work have suggested that the effects of early-life stress (ELS) manifest only in adulthood, more recent studies have documented impaired hippocampal function in maltreated children and adolescents. Additional work using animal modes is needed to clarify the effects of ELS on hippocampal development. In this regard, genomic, proteomic, and molecular tools uniquely available in the mouse make it a particularly attractive model system to study this issue. However, very little work has been done so far to characterize the effects of ELS on hippocampal development in the mouse. To address this issue, we examined the effects of brief daily separation (BDS), a mouse model of ELS that impairs hippocampal-dependent memory in adulthood, on hippocampal development in 28-day-old juvenile mice. This age was chosen because it corresponds to the developmental period in which human imaging studies have revealed abnormal hippocampal development in maltreated children. Exposure to BDS caused a significant decrease in the total protein content of synaptosomes harvested from the hippocampus of 28-day-old male and female mice, suggesting that BDS impairs normal synaptic development in the juvenile hippocampus. Using a novel liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM) assay, We found decreased expression of many synaptic proteins, as well as proteins involved in axonal growth, myelination, and mitochondrial activity. Golgi staining in 28-day-old BDS mice showed an increase in the number of immature and abnormally shaped spines and a decrease in the number of mature spines in CA1 neurons, consistent with defects in synaptic maturation and synaptic pruning at this age. In 14-day-old pups, BDS deceased the expression of proteins involved in axonal growth and myelination, but did not affect the total protein content of synaptosomes harvested from the hippocampus, or protein levels of other synaptic markers. These results add two important findings to previous work in the field. First, our findings demonstrate that in 28-day-old juvenile mice, BDS impairs synaptic maturation and reduces the expression of proteins that are necessary for axonal growth, myelination, and mitochondrial function. Second, the results suggest a sequential model in which BDS impairs normal axonal growth and myelination before it disrupts synaptic maturation in the juvenile hippocampus. (C) 2015 S. Karger AG, Basel
C1 [Wei, Lan; Hao, Jin; Lacher, Richard K.; Kaffman, Arie] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA.
[Abbott, Thomas; Chung, Lisa; Colangelo, Christopher M.] Yale Univ, Yale NIDA Neuroprote Ctr, New Haven, CT 06511 USA.
[Abbott, Thomas; Chung, Lisa; Colangelo, Christopher M.] Yale Univ, WM Keck Fdn Biotechnol Resource Lab, New Haven, CT 06511 USA.
[Colangelo, Christopher M.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06511 USA.
RP Kaffman, A (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St,Suite 901, New Haven, CT 06511 USA.
EM arie.kaffman@yale.edu
FU NIMH [R21MH098181, R01MH100078]; DANA foundation Program in Brain and
Immuno-Imagine; Clinical Neuroscience Division of the VA National Center
for PTSD
FX We thank Jean-Christophe Delpech and Evelyn Cumberbatch for helpful
comments on the manuscript. This work was supported by NIMH R21MH098181,
NIMH R01MH100078, DANA foundation Program in Brain and Immuno-Imagine
2011, and the Clinical Neuroscience Division of the VA National Center
for PTSD.
NR 58
TC 3
Z9 3
U1 4
U2 6
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-5866
EI 1421-9859
J9 DEV NEUROSCI-BASEL
JI Dev. Neurosci.
PY 2015
VL 37
IS 6
BP 476
EP 488
DI 10.1159/000430861
PG 13
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA CW6YR
UT WOS:000365144900002
PM 26068561
ER
PT J
AU Pellom, ST
Dudimah, DF
Thounaojam, MC
Sayers, TJ
Shanker, A
AF Pellom, Samuel Troy, Jr.
Dudimah, Duafalia Fred
Thounaojam, Menaka Chanu
Sayers, Thomas Joseph
Shanker, Anil
TI Modulatory effects of bortezomib on host immune cell functions
SO IMMUNOTHERAPY
LA English
DT Review
DE B cells; bortezomib; chemokine; cytokine; dendritic cells; immunity;
inflammation; ligands; lymphocyte receptors; NK cells; T cells
ID PROTEASOME INHIBITOR BORTEZOMIB; MULTIPLE-MYELOMA CELLS;
NATURAL-KILLER-CELLS; NF-KAPPA-B; CD4(+) T-CELLS; DENDRITIC CELLS;
TUMOR-CELLS; MEDIATED CYTOTOXICITY; CANCER-CELLS; 6-SULFO LACNAC
AB Bortezomib is an inhibitor of the ubiquitin-proteasome proteolytic pathway responsible for intracellular protein turnover. Cellular proteins controlled by this pathway represent a diverse group of potential therapeutic targets, particularly in cancer cells, which exploit this proteasomal pathway to promote their growth and diminish apoptosis. Along with inhibiting the proteasome and thus sensitizing tumor cells to apoptosis, bortezomib may also have multiple effects on the host immune responses. This review summarizes the effects that bortezomib may play on immune cell subsets in various disease states in modifying lymphocyte receptors, ligands, the expression of various cytokines and chemokines and their downstream signaling. We also propose steps that can be taken to refine combinatorial strategies that include bortezomib to improve current immunotherapeutic approaches.
C1 [Pellom, Samuel Troy, Jr.; Dudimah, Duafalia Fred; Thounaojam, Menaka Chanu; Shanker, Anil] Meharry Med Coll, Sch Med, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
[Pellom, Samuel Troy, Jr.; Shanker, Anil] Meharry Med Coll, Sch Grad Studies & Res, Nashville, TN 37208 USA.
[Pellom, Samuel Troy, Jr.] Meharry Med Coll, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37208 USA.
[Sayers, Thomas Joseph] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Sayers, Thomas Joseph] Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA.
[Shanker, Anil] Vanderbilt Univ, Host Tumor Interact Res Program, Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN 37232 USA.
RP Shanker, A (reprint author), Meharry Med Coll, Sch Med, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
EM ashanker@mmc.edu
FU NIH [U54 CA163069, P50 CA 090949, SC1 CA182843, U54 MD007593, R01
CA175370, T32 5T32HL007737, R25 GM059994]; National Cancer Institute,
NIH [N01-CO-12400, HHSN261200800001E]; Intramural Research Program of
NIH, Frederick National Lab, Center for Cancer Research
FX A Shanker has been supported by NIH grants U54 CA163069, P50 CA 090949,
SC1 CA182843, U54 MD007593 and R01 CA175370. ST Pellom is supported by
NIH training grants T32 5T32HL007737 and R25 GM059994. TJ Sayers has
been funded in whole or in part with federal funds from the National
Cancer Institute, NIH, under contracts N01-CO-12400 and
HHSN261200800001E. This Research was also supported (in part) by the
Intramural Research Program of NIH, Frederick National Lab, Center for
Cancer Research. The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 72
TC 6
Z9 6
U1 0
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
EI 1750-7448
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PY 2015
VL 7
IS 9
BP 1011
EP 1022
DI 10.2217/imt.15.66
PG 12
WC Immunology
SC Immunology
GA CW7HL
UT WOS:000365168700009
PM 26325610
ER
PT J
AU Yang, D
Bustin, M
Oppenheim, JJ
AF Yang, De
Bustin, Michael
Oppenheim, Joost J.
TI Harnessing the alarmin HMGN1 for anticancer therapy
SO IMMUNOTHERAPY
LA English
DT Editorial Material
DE alarmin; antitumor immunity; cancer therapy; chromatin modification;
dendritic cell; gene regulation; G protein-coupled receptor; HMGN1; HMG
protein; TLR4
ID CHROMOSOMAL-PROTEIN HMGN1; CANCER; CHROMATIN
AB "HMGN1, as a booster of antitumor immunity, can potentially be used in combination with agents aimed at reverting the immune suppressive microenvironment of tumors, checkpoint inhibitors or conventional cancer therapeutic regimens of surgery, chemotherapy and/or radiation therapy."
C1 [Yang, De; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 20892 USA.
[Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM oppenhej@mail.nih.gov
RI Bustin, Michael/G-6155-2015
NR 15
TC 0
Z9 0
U1 1
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
EI 1750-7448
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PY 2015
VL 7
IS 11
BP 1129
EP 1131
DI 10.2217/imt.15.76
PG 3
WC Immunology
SC Immunology
GA CW7HR
UT WOS:000365169400002
PM 26567750
ER
PT J
AU Zhang, DF
Tu, E
Kasagi, S
Zanvit, P
Chen, QM
Chen, WJ
AF Zhang, Dunfang
Tu, Eric
Kasagi, Shimpei
Zanvit, Peter
Chen, Qianming
Chen, WanJun
TI Manipulating regulatory T cells: a promising strategy to treat
autoimmunity
SO IMMUNOTHERAPY
LA English
DT Review
DE antigen-specific Treg; autoantigen; autoimmune disease; cell apoptosis;
IL-2; immunotherapy; TGF-beta; Treg
ID IMMUNOLOGICAL SELF-TOLERANCE; ANTIGEN-SPECIFIC SUPPRESSION;
TRANSCRIPTION FACTOR FOXP3; LOW-DOSE INTERLEUKIN-2; TNF-ALPHA THERAPY;
TGF-BETA; DENDRITIC CELLS; IN-VIVO; CUTTING EDGE; RHEUMATOID-ARTHRITIS
AB CD4(+)CD25(+)Foxp3(+)regulatory T cells (Treg cells) are extremely important in maintaining immune tolerance. Manipulation of Treg cells, especially autoantigen-specific Treg cells is a promising approach for treatments of autoimmune disease since Treg cells may provide the advantage of antigen specificity without overall immune suppression. However, the clinical application of Treg cells has long been limited due to low numbers of Treg cells and the difficulty in identifying their antigen specificity. In this review, we summarize studies that demonstrate regression of autoimmune diseases using Treg cells as therapeutics. We also discuss approaches to generate polyclonal and autoantigen-specific Treg cells in vitro and in vivo. We also discuss our recent study that describes a novel approach of generating autoantigen-specific Treg cells in vivo and restoring immune tolerance by two steps apoptosis-antigen therapy.
C1 [Zhang, Dunfang; Tu, Eric; Kasagi, Shimpei; Zanvit, Peter; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Zhang, Dunfang; Chen, Qianming] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China.
RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA.
EM wchen@mail.nih.gov
FU Intramural Research Program of NIH, National Institute of Dental and
Craniofacial Research, USA; 111 Project of MOE ISTCPC [2012DFA31370];
National Nature Science Foundation of China [81321002]
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Dental and Craniofacial Research, USA. This work
was also supported by the 111 Project of MOE & ISTCPC (2012DFA31370) and
the National Nature Science Foundation of China (document no.:
81321002). The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript apart from those disclosed.
NR 86
TC 4
Z9 4
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
EI 1750-7448
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PY 2015
VL 7
IS 11
BP 1201
EP 1211
DI 10.2217/imt.15.79
PG 11
WC Immunology
SC Immunology
GA CW7HR
UT WOS:000365169400009
PM 26568117
ER
PT J
AU Ossoli, A
Lucca, F
Boscutti, G
Remaley, AT
Calabresi, L
AF Ossoli, Alice
Lucca, Fabio
Boscutti, Giuliano
Remaley, Alan T.
Calabresi, Laura
TI Familial LCAT deficiency: from pathology to enzyme replacement therapy
SO CLINICAL LIPIDOLOGY
LA English
DT Review
DE enzyme replacement therapy; HDL; LCAT deficiency; lecithin: cholesterol
acyltransferase; lipoproteins
ID LECITHIN-CHOLESTEROL ACYLTRANSFERASE; HIGH-DENSITY-LIPOPROTEIN;
CARDIOVASCULAR-DISEASE; METABOLISM; ATHEROSCLEROSIS; PATIENT; PROFILE;
MANAGEMENT; OXIDATION; INFUSION
AB Lecithin: cholesterol acyltransferase (LCAT) synthesizes most of the plasma cholesteryl esters, and plays a major role in HDL metabolism. Mutations in the LCAT gene cause two syndromes, familial LCAT deficiency and fish-eye disease, both characterized by severe alterations in plasma lipoprotein profile. Renal disease is the major cause of morbidity and mortality in familial LCAT deficiency cases, but an established therapy is not currently available. The present therapy of LCAT deficiency is mainly aimed at correcting the dyslipidemia associated with the disease and at delaying evolution of chronic nephropathy. LCAT deficiency represents a candidate disease for enzyme replacement therapy. In vitro and in vivo studies proved the efficacy of recombinant human LCAT in correcting dyslipidemia, and recombinant human LCAT is presently under development.
C1 [Ossoli, Alice; Lucca, Fabio; Calabresi, Laura] Univ Milan, Dipartimento Sci Farmacol & Biomol, Ctr Grossi Paoletti, Milan, Italy.
[Boscutti, Giuliano] Azienda Osped Univ Osped Riuniti Trieste, Div Nephrol, Trieste, Italy.
[Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Calabresi, L (reprint author), Univ Milan, Dipartimento Sci Farmacol & Biomol, Ctr Grossi Paoletti, Milan, Italy.
EM laura.calabresi@unimi.it
RI Ossoli, Alice/K-5917-2016
OI Ossoli, Alice/0000-0002-9902-252X
FU MedImmune
FX L. Calabresi is a consultant to MedImmune and received a research grant.
AT Remaley received a CRADA research grant from MedImmune to work on
recombinant LCAT. The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 46
TC 0
Z9 0
U1 0
U2 4
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-4299
EI 1758-4302
J9 CLIN LIPIDOL
JI Clin. Lipidol.
PY 2015
VL 10
IS 5
BP 405
EP 413
DI 10.2217/clp.15.34
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CW4KI
UT WOS:000364959800005
ER
PT J
AU Demberg, T
Robert-Guroff, M
AF Demberg, Thorsten
Robert-Guroff, Marjorie
TI B-Cells and the Use of Non-Human Primates for Evaluation of HIV Vaccine
Candidates
SO CURRENT HIV RESEARCH
LA English
DT Article
DE B cell development; B cell dysfunction; B cell maturation; HIV;
non-human primate model; SIV; vaccine development
ID SIMIAN IMMUNODEFICIENCY VIRUS; T FOLLICULAR HELPER; BROADLY NEUTRALIZING
ANTIBODIES; CLASS-SWITCH RECOMBINATION; INFECTED RHESUS-MONKEYS;
SECRETING PLASMA-CELLS; MEMORY B; GERMINAL CENTER; BONE-MARROW; MARGINAL
ZONE
AB The RV144 clinical trial in Thailand associated vaccine-induced antibodies with protective efficacy, leading to a focus in HIV vaccine research on protective antibody induction. This has necessitated greater understanding of B cell biology in humans as well as non-human primates (NHP), the principle animal model for pre-clinical HIV/SIV vaccine research. This review covers development and maturation of NHP B cells within the framework of current knowledge of human and murine B cells. Identification of many NHP B cell subpopulations is now possible, although consensus is lacking in some cases, and better distinction of some populations is still needed. Elucidation of mechanisms that control germinal center maintenance, selection of B cells into the memory cell pool, and differentiation of B cells into long-lived plasma cells remains critical for improving vaccine design. B cell dysfunction occurs during both HIV and SIV infection. Whether the processes leading to this impairment are identical in humans and NHP is not known. Uncovering the mechanisms involved could lead to improved treatment regimens. The SIV/NHP model effectively mimics HIV infection of people, but key differences between NHP and humans in antibody characteristics such as glycosylation and structure may lead to unexpected outcomes in pre-clinical studies. Important new areas for investigation include the role of B cell cytokines in the immune system and the impact of the microbiome on B cell development and maturation. Enhanced knowledge of B cells in NHP as well as humans should enable improved vaccine design, leading to induction of potent, long-lasting protective antibodies.
C1 [Demberg, Thorsten; Robert-Guroff, Marjorie] NCI, Sect Immune Biol Retroviral Infect, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, CCR, NIH, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 245
TC 0
Z9 0
U1 4
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-162X
EI 1873-4251
J9 CURR HIV RES
JI Curr. HIV Res.
PY 2015
VL 13
IS 6
BP 462
EP 478
DI 10.2174/1570162X13666150724095339
PG 17
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA CW5NG
UT WOS:000365041800002
PM 26206458
ER
PT J
AU Raza-Iqbal, S
Tanaka, T
Anai, M
Inagaki, T
Matsumura, Y
Ikeda, K
Taguchi, A
Gonzalez, FJ
Sakai, J
Kodama, T
AF Raza-Iqbal, Sana
Tanaka, Toshiya
Anai, Motonobu
Inagaki, Takeshi
Matsumura, Yoshihiro
Ikeda, Kaori
Taguchi, Akashi
Gonzalez, Frank J.
Sakai, Juro
Kodama, Tatsuhiko
TI Transcriptome Analysis of K-877 (a Novel Selective PPAR alpha Modulator
(SPPARM alpha))-Regulated Genes in Primary Human Hepatocytes and the
Mouse Liver
SO JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
LA English
DT Article
DE Transcriptome; SPPARM alpha; Species difference
ID ACTIVATED RECEPTOR-ALPHA; REVERSE CHOLESTEROL TRANSPORT; MANNOSE-BINDING
LECTIN; FATTY-ACID OXIDATION; ACYL-COA; LIPID-METABOLISM; PEROXISOME
PROLIFERATORS; AMINOPEPTIDASE-A; FACTOR CREBH; COENZYME-A
AB Aim: Selective PPAR alpha modulators (SPPARM alpha) are under development for use as next-generation lipid lowering drugs. In the current study, to predict the pharmacological and toxicological effects of a novel SPPARMa K-877, comprehensive transcriptome analyses of K-877-treated primary human hepatocytes and mouse liver tissue were carried out.
Methods: Total RNA was extracted from the K-877 treated primary human hepatocytes and mouse liver and adopted to the transcriptome analysis. Using a cluster analysis, commonly and species specifically regulated genes were identified. Also, the profile of genes regulated by K-877 and fenofibrate were compared to examine the influence of different SPPARMa on the liver gene expression.
Results: Consequently, a cell-based transactivation assay showed that K-877 activates PPARa with much greater potency and selectivity than fenofibric acid, the active metabolite of clinically used fenofibrate. K-877 upregulates the expression of several fatty acid beta-oxidative genes in human hepatocytes and the mouse liver. Almost all genes up-or downregulated by K-877 treatment in the mouse liver were also regulated by fenofibrate treatment. In contrast, the K-877-regulated genes in the mouse liver were not affected by K-877 treatment in the Ppara-null mouse liver. Depending on the species, the peroxisomal biogenesis-related gene expression was robustly induced in the K-877-treated mouse liver, but not human hepatocytes, thus suggesting that the clinical dose of K-877 may not induce peroxisome proliferation or liver toxicity in humans. Notably, K-877 significantly induces the expression of clinically beneficial target genes (VLDLR, FGF21, ABCA1, MBL2, ENPEP) in human hepatocytes.
Conclusion: These results indicate that changes in the gene expression induced by K-877 treatment are mainly mediated through PPARa activation. K-877 regulates the hepatic gene expression as a SPPARMa and thus may improve dyslipidemia as well as metabolic disorders, such as metabolic syndrome and type 2 diabetes, without untoward side effects.
C1 [Raza-Iqbal, Sana; Tanaka, Toshiya; Anai, Motonobu; Taguchi, Akashi; Kodama, Tatsuhiko] Univ Tokyo, RCAST, LSBM, Tokyo 1538904, Japan.
[Tanaka, Toshiya; Inagaki, Takeshi; Ikeda, Kaori; Sakai, Juro] Univ Tokyo, Fac Med, Ctr Dis Biol & Integrat Med, Translat Syst Biol & Med Initiat, Tokyo 1538904, Japan.
[Inagaki, Takeshi; Matsumura, Yoshihiro; Sakai, Juro] Univ Tokyo, RCAST, Div Metab Med, Tokyo 1538904, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kodama, T (reprint author), Univ Tokyo, RCAST, LSBM, Meguro Ku, Komaba 4-6-1, Tokyo 1538904, Japan.
EM kodama@lsbm.org
FU Translational Systems Biology and Medicine Initiative from the Ministry
of Education, Culture, Sports, Science and Technology of Japan
FX This work was supported by a grant for Translational Systems Biology and
Medicine Initiative from the Ministry of Education, Culture, Sports,
Science and Technology of Japan.
NR 59
TC 4
Z9 4
U1 2
U2 6
PU JAPAN ATHEROSCLEROSIS SOC
PI TOKYO
PA NICHINAI-KAIKAN B1, 3-28-8 HONGO BUNKYO-KU, TOKYO, 113-0033, JAPAN
SN 1340-3478
EI 1880-3873
J9 J ATHEROSCLER THROMB
JI J. Atheroscler. Thromb.
PY 2015
VL 22
IS 8
BP 754
EP 772
PG 19
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CW7LJ
UT WOS:000365179900004
PM 26040752
ER
PT J
AU Ainsztein, AM
Brooks, PJ
Dugan, VG
Ganguly, A
Guo, M
Howcroft, TK
Kelley, CA
Kuo, LS
Labosky, PA
Lenzi, R
Mckie, GA
Mohla, S
Procaccini, D
Reilly, M
Satterlee, JS
Srinivas, PR
Church, ES
Sutherland, M
Tagle, DA
Tucker, JM
Venkatachalam, S
AF Ainsztein, Alexandra M.
Brooks, Philip J.
Dugan, Vivien G.
Ganguly, Aniruddha
Guo, Max
Howcroft, T. Kevin
Kelley, Christine A.
Kuo, Lillian S.
Labosky, Patricia A.
Lenzi, Rebecca
Mckie, George A.
Mohla, Suresh
Procaccini, Dena
Reilly, Matthew
Satterlee, John S.
Srinivas, Pothur R.
Church, Elizabeth Stansell
Sutherland, Margaret
Tagle, Danilo A.
Tucker, Jessica M.
Venkatachalam, Sundar
TI The NIH Extracellular RNA Communication Consortium
SO JOURNAL OF EXTRACELLULAR VESICLES
LA English
DT Article
DE ERCC; exRNA; extracellular RNA
AB The Extracellular RNA (exRNA) Communication Consortium, funded as an initiative of the NIH Common Fund, represents a consortium of investigators assembled to address the critical issues in the exRNA research arena. The overarching goal is to generate a multi-component community resource for sharing fundamental scientific discoveries, protocols, and innovative tools and technologies. The key initiatives include (a) generating a reference catalogue of exRNAs present in body fluids of normal healthy individuals that would facilitate disease diagnosis and therapies, (b) defining the fundamental principles of exRNA biogenesis, distribution, uptake, and function, as well as development of molecular tools, technologies, and imaging modalities to enable these studies, (c) identifying exRNA biomarkers of disease, (d) demonstrating clinical utility of exRNAs as therapeutic agents and developing scalable technologies required for these studies, and (e) developing a community resource, the exRNA Atlas, to provide the scientific community access to exRNA data, standardized exRNA protocols, and other useful tools and technologies generated by funded investigators.
C1 [Ainsztein, Alexandra M.] NIGMS, Div Cell Biol & Biophys, Bethesda, MD USA.
[Brooks, Philip J.] Natl Ctr Adv Translat Sci NCATS, Div Clin Innovat, Bethesda, MD USA.
[Dugan, Vivien G.] NIAID, Off Genom & Adv Technol, Div Microbiol & Infect Dis, Rockville, MD USA.
[Ganguly, Aniruddha] NCI, Canc Diag Program, Div Canc Treatment & Diag, Rockville, MD 20850 USA.
[Guo, Max] NIA, Genet & Cell Biol Branch, Div Aging Biol, Bethesda, MD 20892 USA.
[Howcroft, T. Kevin] NCI, Div Canc Biol, Canc Immunol & Hematol Branch, Rockville, MD 20850 USA.
[Kelley, Christine A.] NIBIB, Div Discovery Sci & Technol, Bethesda, MD USA.
[Kuo, Lillian S.; Tagle, Danilo A.] Natl Ctr Adv Translat Sci NCATS, Bethesda, MD USA.
[Labosky, Patricia A.; Lenzi, Rebecca] NIH, Off Strateg Coordinat, Div Program Coordinat Planning & Strateg Initiat, Bethesda, MD 20892 USA.
[Mckie, George A.] NEI, Ocular Infect Inflammat & Immunol, Rockville, MD USA.
[Mohla, Suresh] NCI, Div Canc Biol, Tumor Biol & Metastasis Branch TBMB, Rockville, MD 20850 USA.
[Procaccini, Dena; Satterlee, John S.] NIDA, Rockville, MD USA.
[Reilly, Matthew] NIAAA, Div Neurosci & Behav, Rockville, MD 20852 USA.
[Srinivas, Pothur R.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Church, Elizabeth Stansell] NIAID, Pathogenesis & Basic Res Branch, Div Aids, Rockville, MD USA.
[Sutherland, Margaret] NINDS, Neurodegenerat Cluster, Rockville, MD USA.
[Tucker, Jessica M.] NIBIB, Bethesda, MD USA.
[Venkatachalam, Sundar] Natl Inst Dent & Craniofacial Res NIDCR, Integrat Biol & Infect Dis Branch, Bethesda, MD USA.
RP Howcroft, TK (reprint author), NCI, Div Canc Biol, Canc Immunol & Hematol Branch, 9609 Med Ctr Dr,Room 6W560, Rockville, MD 20850 USA.
EM howcrofk@mail.nih.gov
NR 0
TC 3
Z9 3
U1 0
U2 0
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2001-3078
J9 J EXTRACELL VESICLES
JI J. Extracell. Vesicles
PY 2015
VL 4
SI SI
AR 27493
DI 10.3402/jev.v4.27493
PG 6
WC Cell Biology
SC Cell Biology
GA CW5ZW
UT WOS:000365077100002
PM 26320938
ER
PT J
AU Eitan, E
Zhang, S
Witwer, KW
Mattson, MP
AF Eitan, Erez
Zhang, Shi
Witwer, Kenneth W.
Mattson, Mark P.
TI Extracellular vesicle-depleted fetal bovine and human sera have reduced
capacity to support cell growth
SO JOURNAL OF EXTRACELLULAR VESICLES
LA English
DT Article
DE fetal bovine serum; exosomes; proliferation; cultured cells; cell death;
endoplasmic reticulum stress
ID EXOSOMES; CULTURE; MICROSCOPY; LIPIDOMICS; PLASMA
AB Background: Fetal bovine serum (FBS) is the most widely used serum supplement for mammalian cell culture. It supports cell growth by providing nutrients, growth signals, and protection from stress. Attempts to develop serum-free media that support cell expansion to the same extent as serum-supplemented media have not yet succeeded, suggesting that FBS contains one or more as-yet-undefined growth factors. One potential vehicle for the delivery of growth factors from serum to cultured cells is extracellular vesicles (EVs).
Methods: EV-depleted FBS and human serum were generated by 120,000g centrifugation, and its cell growth-supporting activity was measured. Isolated EVs from FBS were quantified and characterized by nanoparticle tracking analysis, electron microscopy, and protein assay. EV internalization into cells was quantified using fluorescent plate reader analysis and microscopy.
Results: Most cell types cultured with EV-depleted FBS showed a reduced growth rate but not an increased sensitivity to the DNA-damaging agent etoposide and the endoplasmic reticulum stress-inducing chemical tunicamycin. Supplying cells with isolated FBS-derived EVs enhanced their growth. FBS-derived EVs were internalized by mouse and human cells wherein 65 +/- 26% of them interacted with the lysosomes. EV-depleted human serum also exhibited reduced cell growth-promoting activity.
Conclusions: EVs play a role in the cell growth and survival-promoting effects of FBS and human serum. Thus, it is important to take the effect of EV depletion under consideration when planning EV extraction experiments and while attempting to develop serum-free media that support rapid cell expansion. In addition, these findings suggest roles for circulating EVs in supporting cell growth and survival in vivo.
C1 [Eitan, Erez; Zhang, Shi; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Witwer, Kenneth W.] Johns Hopkins Univ, Sch Med, Inst NanoBioTechnol, Dept Mol & Comparat Pathol, Baltimore, MD USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Mattson, MP (reprint author), NIH, Biomed Res Ctr, Room 5C214,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mark.mattson@nih.gov
RI Witwer, Kenneth/G-1626-2013
OI Witwer, Kenneth/0000-0003-1664-4233
NR 27
TC 13
Z9 13
U1 1
U2 3
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2001-3078
J9 J EXTRACELL VESICLES
JI J. Extracell. Vesicles
PY 2015
VL 4
AR 26373
DI 10.3402/jev.v4.26373
PG 10
WC Cell Biology
SC Cell Biology
GA CW5YU
UT WOS:000365074000001
PM 25819213
ER
PT J
AU Laurent, LC
Abdel-Mageed, AB
Adelson, PD
Arango, J
Balaj, L
Breakefield, X
Carlson, E
Carter, BS
Majem, B
Chen, CC
Cocucci, E
Danielson, K
Courtright, A
Das, S
Abd Elmageed, ZY
Enderle, D
Ezrin, A
Ferrer, M
Freedman, J
Galas, D
Gandhi, R
Huentelman, MJ
Van Keuren-Jensen, K
Kalani, Y
Kim, Y
Krichevsky, AM
Lai, C
Lal-Nag, M
Laurent, CD
Leonardo, T
Li, F
Malenica, I
Mondal, D
Nejad, P
Patel, T
Raffai, RL
Rubio, R
Skog, J
Spetzler, R
Sun, J
Tanriverdi, K
Vickers, K
Wang, L
Wang, YY
Wei, ZY
Weiner, HL
Wong, D
Yan, IK
Yeri, A
Gould, S
AF Laurent, Louise C.
Abdel-Mageed, Asim B.
Adelson, P. David
Arango, Jorge
Balaj, Leonora
Breakefield, Xandra
Carlson, Elizabeth
Carter, Bob S.
Majem, Blanca
Chen, Clark C.
Cocucci, Emanuele
Danielson, Kirsty
Courtright, Amanda
Das, Saumya
Abd Elmageed, Zakaria Y.
Enderle, Daniel
Ezrin, Alan
Ferrer, Marc
Freedman, Jane
Galas, David
Gandhi, Roopali
Huentelman, Matthew J.
Van Keuren-Jensen, Kendall
Kalani, Yashar
Kim, Yong
Krichevsky, Anna M.
Lai, Charles
Lal-Nag, Madhu
Laurent, Clara D.
Leonardo, Trevor
Li, Feng
Malenica, Ivana
Mondal, Debasis
Nejad, Parham
Patel, Tushar
Raffai, Robert L.
Rubio, Renee
Skog, Johan
Spetzler, Robert
Sun, Jie
Tanriverdi, Kahraman
Vickers, Kasey
Wang, Liang
Wang, Yaoyu
Wei, Zhiyun
Weiner, Howard L.
Wong, David
Yan, Irene K.
Yeri, Ashish
Gould, Stephen
TI Meeting report: discussions and preliminary findings on extracellular
RNA measurement methods from laboratories in the NIH Extracellular RNA
Communication Consortium
SO JOURNAL OF EXTRACELLULAR VESICLES
LA English
DT Article
DE extracellular RNA; extracellular vesicles; exosomes; microvesicles; RNA
sequencing
ID HIGH-DENSITY-LIPOPROTEINS; PROSTATE-CANCER; BREAST-CANCER; CIRCULATING
MICRORNAS; POLYETHYLENE-GLYCOL; CEREBROSPINAL-FLUID; SEQUENCING METHODS;
EXOSOME ISOLATION; GENE-EXPRESSION; RECIPIENT CELLS
AB Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.
C1 [Laurent, Louise C.] Univ Calif San Diego, Dept Reprod Med, Div Maternal Fetal Med, San Diego, CA 92103 USA.
[Laurent, Louise C.] Sanford Consortium Regenerat Med,San Diego, San Diego, CA USA.
[Abdel-Mageed, Asim B.; Abd Elmageed, Zakaria Y.] Tulane Univ, Sch Med, Dept Urol, New Orleans, LA 70112 USA.
[Adelson, P. David; Arango, Jorge] Phoenix Childrens Hosp, Phoenix, AZ USA.
[Balaj, Leonora; Breakefield, Xandra; Lai, Charles] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Balaj, Leonora; Breakefield, Xandra; Lai, Charles] Harvard Univ, Sch Med, Program Neurosci, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Breakefield, Xandra] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Carlson, Elizabeth; Courtright, Amanda; Van Keuren-Jensen, Kendall; Malenica, Ivana; Yeri, Ashish] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA.
[Carter, Bob S.; Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, Ctr Theoret & Appl Neurooncol, San Diego, CA 92103 USA.
[Majem, Blanca; Kim, Yong; Li, Feng; Sun, Jie; Wong, David] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA.
[Cocucci, Emanuele] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
[Danielson, Kirsty; Das, Saumya; Laurent, Clara D.; Leonardo, Trevor] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
[Enderle, Daniel] Exosome Diagnost GmbH, Martinsried, Germany.
[Ezrin, Alan] NXPharmaGen, Miami, FL USA.
[Ferrer, Marc; Lal-Nag, Madhu] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci NCATS, Bethesda, MD 20892 USA.
[Freedman, Jane; Tanriverdi, Kahraman] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Galas, David] Pacific Northwest Diabet Res Inst, Seattle, WA USA.
[Galas, David] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Sur Alzette, Luxembourg.
[Gandhi, Roopali; Nejad, Parham; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Neurol Dis, Boston, MA 02115 USA.
[Huentelman, Matthew J.] TGen, Phoenix, AZ USA.
[Kalani, Yashar; Raffai, Robert L.] Barrow Neurol Inst, Phoenix, AZ USA.
[Krichevsky, Anna M.; Wei, Zhiyun] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Mondal, Debasis] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA.
[Patel, Tushar] Mayo Clin Florida, Dept Transplantat, Jacksonville, FL USA.
[Patel, Tushar; Yan, Irene K.] Mayo Clin Florida, Dept Canc Biol, Jacksonville, FL USA.
[Spetzler, Robert] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Spetzler, Robert] Dept Vet Affairs, San Francisco, CA USA.
[Rubio, Renee; Wang, Yaoyu] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA.
[Skog, Johan] Exosome Diagnost, Cambridge, MA USA.
[Vickers, Kasey] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN USA.
[Vickers, Kasey] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN USA.
[Wang, Liang] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA.
[Gould, Stephen] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA.
RP Laurent, LC (reprint author), Univ Calif San Diego, Sanford Consortium Regenerat Med, 2880 Torrey Pines Scen Dr, La Jolla, CA 92093 USA.
EM llaurent@ucsd.edu
FU NCATS NIH HHS [UH2 TR000931, UH2 TR000884, UH2 TR000890, UH2 TR000891,
UH2 TR000901, UH2 TR000906, UH2 TR000921, UH2 TR000923, UH2 TR000928,
UH3 TR000884, UH3 TR000901, UH3 TR000923, UH3 TR000931]; NCI NIH HHS
[P01 CA069246, U19 CA179512, U19 CA179514, U19 CA179563]; NHLBI NIH HHS
[P01 HL116263, R01 HL128996, U01 HL126494, U01 HL126496]; NIDA NIH HHS
[U54 DA036134]
NR 100
TC 11
Z9 11
U1 3
U2 8
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2001-3078
J9 J EXTRACELL VESICLES
JI J. Extracell. Vesicles
PY 2015
VL 4
SI SI
AR 26533
DI 10.3402/jev.v4.26533
PG 18
WC Cell Biology
SC Cell Biology
GA CW5ZW
UT WOS:000365077100001
PM 26320937
ER
PT B
AU Good, BJ
Grayman, JH
Good, MJD
AF Good, Byron J.
Grayman, Jesse Hession
Good, Maly-Jo DelVecchio
BE Abramowitz, S
PanterBrick, C
TI Humanitarianism and "Mobile Sovereignty" in Strong State Settings:
Reflections on Medical Humanitarianism in Aceh, Indonesia
SO MEDICAL HUMANITARIANISM: ETHNOGRAPHIES OF PRACTICE
SE Pennsylvania Studies in Human Rights
LA English
DT Article; Book Chapter
ID HUMAN-RIGHTS; GOVERNANCE; PROGRAMS; CONFLICT; TSUNAMI
C1 [Good, Byron J.] Harvard Univ, Sch Med, Med Anthropol, Cambridge, MA 02138 USA.
[Good, Byron J.] Harvard Univ, Sch Med, Dept Social Med, Cambridge, MA 02138 USA.
[Good, Byron J.] Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA.
[Good, Byron J.] Dept Social Med, Programs Global Mental Hlth, Boston, MA USA.
[Good, Byron J.] Int Mental Hlth Training Program, Cape Town, South Africa.
[Good, Byron J.] NIMH, Training Program, Culture & Mental Hlth Serv, Bethesda, MD USA.
[Grayman, Jesse Hession] Univ Auckland, Sch Social Sci, Auckland 1, New Zealand.
RP Good, BJ (reprint author), Harvard Univ, Sch Med, Med Anthropol, Cambridge, MA 02138 USA.
NR 30
TC 0
Z9 0
U1 0
U2 0
PU UNIV PENNSYLVANIA PRESS
PI PHILADELPHIA
PA 3905 SPRUCE STREET, PHILADELPHIA, PA 19104 USA
BN 978-0-8122-4732-9
J9 PA STUD HUM RIGHTS
PY 2015
BP 155
EP 175
D2 10.9783/9780812291698
PG 21
WC Anthropology; Health Policy & Services
SC Anthropology; Health Care Sciences & Services
GA BD7RK
UT WOS:000363491300009
ER
PT J
AU Sun, X
Chen, YW
Wu, NJ
Kang, CS
Song, HA
Jin, SN
Fu, Y
Bryant, H
Frank, JA
Chong, HS
AF Sun, Xiang
Chen, Yunwei
Wu, Ningjie
Kang, Chi Soo
Song, Hyun A.
Jin, Shengnan
Fu, Yao
Bryant, Henry, Jr.
Frank, Joseph A.
Chong, Hyun-Soon
TI Application of aziridinium ring opening for preparation of optically
active diamine and triamine analogues: highly efficient synthesis and
evaluation of DTPA-based MRI contrast enhancement agents
SO RSC ADVANCES
LA English
DT Article
ID DIETHYLENETRIAMINEPENTAACETIC ACID; COMPLEXES; ANGIOGENESIS; STABILITY;
BACKBONE; DYNAMICS; LIGANDS
AB Ring opening of aziridinium ions with nitrogen nucleophiles was applied to the highly efficient synthesis of optically active vicinal diamines and diethylene triamine pentaacetic acid (DTPA) analogues as potential magnetic resonance imaging (MRI) contrast enhancement agents. The synthetic method features a column-free isolation of the regiospecific and stereospecific nucleophilic substitution products of enantiomerically enriched aziridinium ions in excellent yield.
C1 [Sun, Xiang; Chen, Yunwei; Wu, Ningjie; Kang, Chi Soo; Song, Hyun A.; Jin, Shengnan; Fu, Yao; Chong, Hyun-Soon] IIT, Dept Biol & Chem Sci, Dept Chem, Chicago, IL 60616 USA.
[Bryant, Henry, Jr.; Frank, Joseph A.] NIH, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA.
RP Chong, HS (reprint author), IIT, Dept Biol & Chem Sci, Dept Chem, 3101 S Dearborn St,LS 182, Chicago, IL 60616 USA.
EM Chong@iit.edu
FU National Institutes of Health [2R01CA112503]
FX This work was partly supported by National Institutes of Health
(2R01CA112503 to H. S. Chong).
NR 27
TC 0
Z9 0
U1 0
U2 1
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2046-2069
J9 RSC ADV
JI RSC Adv.
PY 2015
VL 5
IS 115
BP 94571
EP 94581
DI 10.1039/c5ra11306g
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA CW3QK
UT WOS:000364906600007
PM 26989478
ER
PT S
AU Chen, F
Wang, SL
Fang, JW
AF Chen, Fang
Wang, Shulin
Fang, Jianwen
BE Huang, DS
Han, K
TI Spectral Clustering of High-Dimensional Data via k-Nearest Neighbor
Based Sparse Representation Coefficients
SO ADVANCED INTELLIGENT COMPUTING THEORIES AND APPLICATIONS, ICIC 2015, PT
III
SE Lecture Notes in Artificial Intelligence
LA English
DT Proceedings Paper
CT 11th International Conference on Intelligent Computing (ICIC)
CY AUG 20-23, 2015
CL Fuzhou, PEOPLES R CHINA
SP Int Neural Network Soc, Natl Sci Fdn China
DE Spectral clustering; Affinity matrix; k-nearest neighbor; Sparse
representation; Cosine similarity; Gene expression profiling
ID CLASSIFICATION; RECOGNITION; PREDICTION
AB Recently, subspace clustering has achieved promising clustering quality by performing spectral clustering over an affinity graph. It is a key to construct a robust affinity matrix in graph-oriented subspace clustering. Sparse representation can represent each object as a sparse linear combination of other objects and has been used to cluster high-dimensional data. However, all the coefficients are trusted blindly to construct the affinity matrix which may suffer from noise and decrease the clustering performance. We propose to construct the affinity matrix via k-nearest neighbor (KNN) based sparse representation coefficient vectors for clustering high-dimensional data. For each data object, the sparse representation coefficient vector is computed by sparse representation theory and KNN algorithm is used to find the k nearest neighbors. Instead of using all the coefficients to construct the affinity matrix directly, we update each coefficient vector by remaining the k coefficients of the k neighbors unchanged and set the other coefficients to zero. Experiments on six gene expression profiling (GEP) datasets prove that the proposed algorithm can construct better affinity matrices and result in higher performance for clustering high-dimensional data.
C1 [Chen, Fang; Wang, Shulin] Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China.
[Fang, Jianwen] NCI, 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
NR 19
TC 0
Z9 0
U1 2
U2 5
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0302-9743
BN 978-3-319-22053-6; 978-3-319-22052-9
J9 LECT NOTES ARTIF INT
PY 2015
VL 9227
BP 363
EP 374
DI 10.1007/978-3-319-22053-6_40
PG 12
WC Computer Science, Artificial Intelligence; Computer Science, Information
Systems; Computer Science, Interdisciplinary Applications; Robotics
SC Computer Science; Robotics
GA BD9IE
UT WOS:000364716700040
ER
PT S
AU Yarmolinsky, M
Hoess, R
AF Yarmolinsky, Michael
Hoess, Ronald
BE Enquist, LW
TI The Legacy of Nat Sternberg: The Genesis of Cre-lox Technology
SO Annual Review of Virology, Vol 2
SE Annual Review of Virology
LA English
DT Article; Book Chapter
DE bacteriophage P1; plasmid; site-specific recombination; chromosome
segregation; genetic engineering
ID SITE-SPECIFIC RECOMBINATION; ESCHERICHIA-COLI CHROMOSOME; XERCD-DIF
RECOMBINATION; INTEGRASE FAMILY; FUNCTIONAL LIMITS; BACTERIOPHAGE-P1;
DNA; P1; FTSK; SYSTEM
AB Cre-lox of bacteriophage P1 has become one of the most widely used tools for genetic engineering in eukaryotes. The origins of this tool date to more than 30 years ago when Nat L. Sternberg discovered the recombinase, Cre, and its specific locus of crossover, lox, while studying the maintenance of bacteriophage P1 as a stable plasmid. Recombinations mediated by Cre assist in cyclization of the DNA of infecting phage and in resolution of prophage multimers created by generalized recombination. Early in vitro work demonstrated that, although it shares similarities with the well-characterized bacteriophage. integration, Cre-lox is in many ways far simpler in its requirements for carrying out recombination. These features would prove critical for its development as a powerful and versatile tool in genetic engineering. We review the history of the discovery and characterization of Cre-lox and touch upon the present direction of Cre-lox research.
C1 [Yarmolinsky, Michael] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Yarmolinsky, M (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM myarmo@helix.nih.gov; hoessr@earthlink.net
FU Intramural NIH HHS
NR 50
TC 2
Z9 2
U1 1
U2 6
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 2327-056X
BN 978-0-8243-3402-4
J9 ANN REV VIROL
PY 2015
VL 2
BP 25
EP 40
DI 10.1146/annurev-virology-100114-054930
PG 16
WC Virology
SC Virology
GA BD8WH
UT WOS:000364397900002
PM 26958905
ER
PT S
AU Xu, WQ
Eiden, MV
AF Xu, Wenqin
Eiden, Maribeth V.
BE Enquist, LW
TI Koala Retroviruses: Evolution and Disease Dynamics
SO ANNUAL REVIEW OF VIROLOGY, VOL 2
SE Annual Review of Virology
LA English
DT Article; Book Chapter
DE Phascolarctos cinereus; SLC20A1; SLC19A2; provirus; epizoonosis;
endogenous retrovirus
ID PORCINE ENDOGENOUS RETROVIRUS; PHASCOLARCTOS-CINEREUS; C VIRUSES;
MUS-CERVICOLOR; LEUKEMIA VIRUSES; MURINE; DIVERSITY; KORV;
IDENTIFICATION; CONSERVATION
AB A retroviral etiology for malignant neoplasias in koalas has long been suspected. Evidence for retroviral involvement was bolstered in 2000 by the isolation of a koala retrovirus (KoRV), now termed KoRV-A. KoRV-A is an endogenous retrovirus-a retrovirus that infects germ cells-a feature that makes it a permanent resident of the koala genome. KoRV-A lacks the genetic diversity of an exogenous retrovirus, a quality associated with the ability of a retrovirus to cause neoplasias. In 2013, a second KoRV isolate, KoRV-B, was obtained from koalas with lymphomas in the Los Angeles Zoo. Unlike KoRV-A, which is present in the genomes of all koalas in the United States, KoRV-B is restricted in its distribution and is associated with host pathology (neoplastic disease). Here, our current understanding of the evolution of endogenous and exogenous KoRVs, and the relationship between them, is reviewed to build a perspective on the future impact of these viruses on koala sustainability.
C1 [Xu, Wenqin; Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
RP Xu, WQ (reprint author), NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
EM eidenm@mail.nih.gov
FU Intramural NIH HHS; PHS HHS [1ZIAMH002592]
NR 58
TC 1
Z9 1
U1 2
U2 12
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 2327-056X
BN 978-0-8243-3402-4
J9 ANNU REV VIROL
PY 2015
VL 2
BP 119
EP 134
DI 10.1146/annurev-virology-100114-055056
PG 16
WC Virology
SC Virology
GA BD8WH
UT WOS:000364397900006
PM 26958909
ER
PT J
AU Gopinath, C
Nathar, TJ
Ghosh, A
Hickstein, DD
Nelson, EJR
AF Gopinath, Chitra
Nathar, Trupti Job
Ghosh, Arkasubhra
Hickstein, Dennis Durand
Nelson, Everette Jacob Remington
TI Contemporary Animal Models For Human Gene Therapy Applications
SO CURRENT GENE THERAPY
LA English
DT Article
DE Animal models; Gene therapy; Genetic diseases; Viral vectors; Humanized
mice; Clinical trials
ID LEUKOCYTE ADHESION DEFICIENCY; LEBER CONGENITAL AMAUROSIS; SPINAL
MUSCULAR-ATROPHY; ONE-STEP GENERATION; SEVERE COMBINED IMMUNODEFICIENCY;
ZINC-FINGER NUCLEASES; KNOCKOUT MOUSE MODEL; PHASE-I TRIAL; LENTIVIRAL
VECTOR; RETINITIS-PIGMENTOSA
AB Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.
C1 [Gopinath, Chitra; Nathar, Trupti Job; Nelson, Everette Jacob Remington] VIT Univ, Sch Biosci & Technol, Gene Therapy Lab, Div Biomed Sci, Vellore 632014, Tamil Nadu, India.
[Ghosh, Arkasubhra] Narayana Nethralaya, GROW Lab, Mol Signaling & Gene Therapy, Bangalore 560099, Karnataka, India.
[Hickstein, Dennis Durand] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Nelson, EJR (reprint author), VIT Univ, Sch Biosci & Technol, Gene Therapy Lab, SMV 124A, Vellore 632014, Tamil Nadu, India.
EM everette.nelson@vit.ac.in
FU Department of Biotechnology, Ministry of Science and Technology,
Government of India
FX Award of Ramalingaswami Fellowship by the Department of Biotechnology,
Ministry of Science and Technology, Government of India to the senior
author (E.J.R.N) is gratefully acknowledged.
NR 135
TC 1
Z9 1
U1 1
U2 5
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5232
EI 1875-5631
J9 CURR GENE THER
JI Curr. Gene Ther.
PY 2015
VL 15
IS 6
BP 531
EP 540
DI 10.2174/1566523215666150929110424
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CV8VO
UT WOS:000364566400001
PM 26415576
ER
PT S
AU Zhang, XY
Ambale-Venkatesh, B
Bluemke, DA
Cowan, BR
Finn, JP
Hundley, WG
Kadish, AH
Lee, DC
Lima, JAC
Suinesiaputra, A
Young, AA
Medrano-Gracia, P
AF Zhang, Xingyu
Ambale-Venkatesh, Bharath
Bluemke, David A.
Cowan, Brett R.
Finn, J. Paul
Hundley, William G.
Kadish, Alan H.
Lee, Daniel C.
Lima, Joao A. C.
Suinesiaputra, Avan
Young, Alistair A.
Medrano-Gracia, Pau
BE VanAssen, H
Bovendeerd, P
Delhaas, T
TI Orthogonal Shape Modes Describing Clinical Indices of Remodeling
SO FUNCTIONAL IMAGING AND MODELING OF THE HEART (FIMH 2015)
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 8th International Conference on Functional Imaging and Modeling of the
Heart(FIMH)
CY JUN 25-27, 2015
CL Maastricht, NETHERLANDS
SP Maastricht Univ, Eindhoven Univ Technol
DE Cardiac remodeling; Magnetic resonance imaging; Principal component
analysis
ID LEFT-VENTRICULAR GEOMETRY; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS;
SPHERICITY; SURVIVAL; DESIGN; VOLUME; RISK
AB Quantification of the left ventricle (LV) shape changes (remodeling) is of great importance for therapeutic management of myocardial infarction. Orthogonal shape modes derived from principal component analysis (PCA) often do not describe clinical remodeling indices. We developed a method for deriving orthogonal shape modes directly from any set of clinical indices. Cardiac magnetic resonance images of 1,991 asymptomatic volunteers from the MESA study (age 44-84, mean age 62, 52 % women) and 300 patients with myocardial infarction from the DETERMINE study (age 31-86, mean age 63, 20 % women) were obtained from the Cardiac Atlas Project. Clinical indices of LV size, sphericity, wall thickness and apical conicity were calculated. For each index, cases outside two standard deviations of the mean, but within one standard deviation for all other indices, were chosen as a representative subgroup. Orthogonal modes were defined sequentially, using the first principal component of each subgroup. At each step, the contribution of the previous mode was removed mathematically from the shape description, similar to Gram-Schmidt orthogonalization. Correlation analysis and logistic regression were performed to show the effectiveness of these features to characterize remodeling due to myocardial infarction.
C1 [Zhang, Xingyu; Cowan, Brett R.; Suinesiaputra, Avan; Young, Alistair A.; Medrano-Gracia, Pau] Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand.
[Ambale-Venkatesh, Bharath; Lima, Joao A. C.] Johns Hopkins Univ, Donald W Reynolds Cardiovasc Clin Res Ctr, Baltimore, MD USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Finn, J. Paul] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA.
[Kadish, Alan H.; Lee, Daniel C.] Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA.
[Hundley, William G.] Cardiol Sect, Winston Salem, NC USA.
RP Zhang, XY (reprint author), Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand.
EM zha238@aucklanduni.ac.nz
RI Ambale Venkatesh, Bharath/F-4941-2016;
OI Ambale Venkatesh, Bharath/0000-0002-2330-2373; Bluemke,
David/0000-0002-8323-8086; Medrano-Gracia, Pau/0000-0002-6255-4864
NR 18
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0302-9743
BN 978-3-319-20309-6; 978-3-319-20308-9
J9 LECT NOTES COMPUT SC
PY 2015
VL 9126
BP 273
EP 281
DI 10.1007/978-3-319-20309-6_32
PG 9
WC Computer Science, Artificial Intelligence; Computer Science, Theory &
Methods; Mathematical & Computational Biology; Radiology, Nuclear
Medicine & Medical Imaging
SC Computer Science; Mathematical & Computational Biology; Radiology,
Nuclear Medicine & Medical Imaging
GA BD9ER
UT WOS:000364538500032
ER
PT J
AU Treadwell, EL
Wiley, K
Word, B
Melchior, W
Tolleson, WH
Gopee, N
Hammons, G
Lyn-Cook, BD
AF Treadwell, Edward L.
Wiley, Kenneth
Word, Beverly
Melchior, William
Tolleson, William H.
Gopee, Neera
Hammons, George
Lyn-Cook, Beverly D.
TI Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus
Erythematosus: The Role of the Extrapituitary Prolactin Promoter
Polymorphism at-1149G/T
SO JOURNAL OF IMMUNOLOGY RESEARCH
LA English
DT Article
ID PATHOGENESIS
AB Systemic lupus erythematosus (SLE) has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA), and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a -1149G/T functional single-nucleotide polymorphism (SNP) (rs1341239) in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the -1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p = 0.0001) in peripheral blood mononuclear cells (PBMCs). Lower levels of DHEA in serum were demonstrated in lupus patients (p = 0.001); those with the -1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI). Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p = 0.0001) and TNF-alpha (p = 0.042). This study suggests that the -1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.
C1 [Treadwell, Edward L.] E Carolina Univ, Brody Sch Med, Greenville, NC 27834 USA.
[Wiley, Kenneth] NHGRI, Bethesda, MD 20892 USA.
[Word, Beverly; Melchior, William; Tolleson, William H.; Gopee, Neera; Hammons, George; Lyn-Cook, Beverly D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Lyn-Cook, BD (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM beverly.lyn-cook@fda.hhs.gov
NR 32
TC 0
Z9 0
U1 1
U2 3
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA
SN 2314-8861
EI 2314-7156
J9 J IMMUNOL RES
JI J Immunol. Res.
PY 2015
AR 435658
DI 10.1155/2015/435658
PG 10
WC Immunology
SC Immunology
GA CW0YA
UT WOS:000364714900001
ER
PT J
AU Xu, XH
Jin, T
AF Xu, Xuehua
Jin, Tian
TI The Novel Functions of the PLC/PKC/PKD Signaling Axis in G
Protein-Coupled Receptor-Mediated Chemotaxis of Neutrophils
SO JOURNAL OF IMMUNOLOGY RESEARCH
LA English
DT Review
ID PHOSPHOLIPASE-C-GAMMA; PKC-DELTA; STRUCTURAL INSIGHTS; ADENYLYL-CYCLASE;
CELL POLARITY; NADPH OXIDASE; BETA-II; ACTIVATION; ROLES;
PHOSPHORYLATION
AB Chemotaxis, a directional cell migration guided by extracellular chemoattractant gradients, plays an essential role in the recruitment of neutrophils to sites of inflammation. Chemotaxis is mediated by the G protein-coupled receptor (GPCR) signaling pathway. Extracellular stimuli trigger activation of the PLC/PKC/PKD signaling axis, which controls several signaling pathways. Here, we concentrate on the novel functions of PLC/PKC/PKD signaling in GPCR-mediated chemotaxis of neutrophils.
C1 [Xu, Xuehua; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Xu, XH (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM xxu@niaid.nih.gov
FU Intramural Research Program of the NIH, NIAID
FX The authors thank Joseph Brzostowski for his critical reading. The
authors would like to thank all members of the Chemotaxis Signal
Section, LIG/NIAID/NIH. This research was supported by the Intramural
Research Program of the NIH, NIAID.
NR 68
TC 0
Z9 0
U1 1
U2 1
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA
SN 2314-8861
EI 2314-7156
J9 J IMMUNOL RES
JI J Immunol. Res.
PY 2015
AR 817604
DI 10.1155/2015/817604
PG 10
WC Immunology
SC Immunology
GA CW0YO
UT WOS:000364716400001
ER
PT B
AU Ramchandani, VA
Slattum, PW
Patkar, AA
Wu, LT
Lee, JC
Mohanty, M
Coe, M
Li, TK
AF Ramchandani, Vijay A.
Slattum, Patricia W.
Patkar, Ashwin A.
Wu, Li-Tzy
Lee, Jonathan C.
Mohanty, Maitreyee
Coe, Marion
Li, Ting-Kai
BE Crome, I
Wu, LT
Rao, R
Crome, P
TI PSYCHOPHARMACOLOGY AND THE CONSEQUENCES OF ALCOHOL AND DRUG INTERACTIONS
SO Substance Use and Older People
SE Addiction Press Series
LA English
DT Article; Book Chapter
ID NATIONAL EPIDEMIOLOGIC SURVEY; CORONARY-HEART-DISEASE;
CENTRAL-NERVOUS-SYSTEM; AT-RISK DRINKING; OLDER-ADULTS; THERAPEUTIC
CONSIDERATIONS; CLINICAL PHARMACOKINETICS; CARDIOVASCULAR HEALTH;
ETHANOL-METABOLISM; ELDERLY ADULTS
C1 [Ramchandani, Vijay A.; Coe, Marion] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Slattum, Patricia W.] Virginia Commonwealth Univ, Geriatr Pharmacotherapy Program, Richmond, VA USA.
[Slattum, Patricia W.; Mohanty, Maitreyee] Virginia Commonwealth Univ, Pharmacotherapy & Outcomes Sci, Richmond, VA USA.
[Patkar, Ashwin A.] Duke Univ, Med Ctr, Sch Med, Duke Addict Program, Durham, NC 27710 USA.
[Patkar, Ashwin A.] Duke Univ, Med Ctr, Sch Med, Ctr Addict Behav & Change, Durham, NC 27710 USA.
[Patkar, Ashwin A.] Duke Univ, Med Ctr, Sch Med, Dept Psychiat & Behav Sci,Dept Community & Family, Durham, NC 27710 USA.
[Wu, Li-Tzy; Li, Ting-Kai] Duke Univ, Med Ctr, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
[Lee, Jonathan C.] Farley Ctr, Williamsburg, VA USA.
[Lee, Jonathan C.] E Carolina Univ, Brody Sch Med, Dept Psychiat Med, Greenville, NC 27858 USA.
RP Ramchandani, VA (reprint author), NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 92
TC 3
Z9 3
U1 0
U2 2
PU JOHN WILEY & SONS
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND
BN 978-1-118-43096-5; 978-1-119-97538-0
J9 ADDICT PRESS SER
PY 2015
BP 149
EP 170
PG 22
WC Substance Abuse; Geriatrics & Gerontology
SC Substance Abuse; Geriatrics & Gerontology
GA BD6YY
UT WOS:000362748700014
ER
PT B
AU Hingson, R
Li, TK
AF Hingson, Ralph
Li, Ting-Kai
BE Crome, I
Wu, LT
Rao, R
Crome, P
TI PROPOSALS FOR ALCOHOL-RELATED POLICY DEVELOPMENT IN THE UNITED STATES
SO Substance Use and Older People
SE Addiction Press Series
LA English
DT Article; Book Chapter
ID VEHICLE COLLISION INVOLVEMENT; SERVICES TASK-FORCE; OLDER-ADULTS; CRASH
INVOLVEMENT; CATARACT-SURGERY; SELF-REGULATION; PRIMARY-CARE; MORTALITY;
DRIVERS; INTERVENTIONS
C1 [Hingson, Ralph] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
[Li, Ting-Kai] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med, Durham, NC USA.
RP Hingson, R (reprint author), NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
NR 36
TC 0
Z9 0
U1 1
U2 1
PU JOHN WILEY & SONS
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND
BN 978-1-118-43096-5; 978-1-119-97538-0
J9 ADDICT PRESS SER
PY 2015
BP 364
EP 371
PG 8
WC Substance Abuse; Geriatrics & Gerontology
SC Substance Abuse; Geriatrics & Gerontology
GA BD6YY
UT WOS:000362748700027
ER
PT S
AU Reed, CE
Fenton, SE
AF Reed, Casey E.
Fenton, Suzanne E.
BE DeWitt, JC
TI Effects of PFOA on Endocrine-Related Systems
SO TOXICOLOGICAL EFFECTS OF PERFLUOROALKYL AND POLYFLUOROALKYL SUBSTANCES
SE Molecular and Integrative Toxicology
LA English
DT Article; Book Chapter
DE PFOA; Mammary gland; Thyroid; Endocrine disruptor; Puberty; Lactation;
Fertility
ID PERFLUOROOCTANOIC ACID PFOA; MAMMARY-GLAND DEVELOPMENT; HUMAN SEMEN
QUALITY; CORD BLOOD-SAMPLES; MID-OHIO VALLEY; PERFLUORINATED COMPOUNDS;
PERFLUOROALKYL SUBSTANCES; POLYFLUOROALKYL CHEMICALS; REPRODUCTIVE
HORMONES; NORWEGIAN MOTHER
AB Perfluorooctanoic acid (PFOA) is an 8-carbon fully fluorinated chemical that has reported effects on endocrine-related systems in rodents, humans, and other species. Numerous endocrine organs may be targets for PFOA, including the brain, thyroid, pancreas, adipose tissue, ovary, uterus, testes, and breast. Developmental exposure effects have been reported on behavior, serum thyroid and gonadal steroid profiles, breast epithelial growth, and metabolic end points, such as serum insulin, leptin, and triglyceride levels and weight gain. Many of these PFOA-induced effects have been reported in two or more species. The mechanisms for these numerous effects are poorly understood and deserve further investigation to define the pathways that should be avoided as PFOA-replacement products enter the market.
C1 [Reed, Casey E.; Fenton, Suzanne E.] NIEHS, Natl Toxicol Program NTP Lab, Div NTP, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
RP Fenton, SE (reprint author), NIEHS, Natl Toxicol Program NTP Lab, Div NTP, NIH,DHHS, 111 TW Alexander Dr,Bldg 101,MD E1-08, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
NR 83
TC 1
Z9 1
U1 1
U2 6
PU SPRINGER-VERLAG LONDON LTD
PI GODALMING
PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY,
ENGLAND
SN 2168-4219
BN 978-3-319-15518-0; 978-3-319-15517-3
J9 MOLEC INTEGR TOXICOL
PY 2015
BP 249
EP 264
DI 10.1007/978-3-319-15518-0_11
D2 10.1007/978-3-319-15518-0
PG 16
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BD9KE
UT WOS:000364811700012
ER
PT S
AU Rooney, AA
Boyles, AL
Walker, VR
AF Rooney, Andrew A.
Boyles, Abee L.
Walker, Vickie R.
BE DeWitt, JC
TI Systematic Review, An Illustration of Increased Transparency in a
Framework for Evaluating Immunotoxicity Associated with PFOA and PFOS
Exposure
SO TOXICOLOGICAL EFFECTS OF PERFLUOROALKYL AND POLYFLUOROALKYL SUBSTANCES
SE Molecular and Integrative Toxicology
LA English
DT Article; Book Chapter
DE Systematic review; Perfluorinated chemicals; Immunotoxicity; Risk of
bias; Hazard identification; PFOA; PFOS
ID ENVIRONMENTAL-HEALTH SCIENCE; PERFLUORINATED COMPOUNDS; PERFLUOROOCTANE
SULFONATE; IN-VITRO; SEA OTTERS; MICE; CYTOKINE; OUTCOMES; TYPE-1; RISK
AB Background: Systematic review methodologies were first developed to assess the efficacy of health care interventions, but these approaches can be adapted to evaluations of environmental health questions such as immunotoxicity associated with PFOA and PFOS exposure. This structured approach provides objectivity and transparency to the process of collecting, synthesizing, and reaching conclusions based on the scientific evidence available.
Objectives: To outline the process of systematic review and evidence integration and demonstrate each step by following a single research question from start to finish. The example systematic review will evaluate the evidence that PFOA and PFOS exposure are associated with immunotoxicity using a subset of the available evidence to illustrate concepts, not to develop hazard identification conclusions.
Methods: The Office of Health Assessment and Translation (OHAT) Approach to evaluating the scientific evidence for immunotoxicity of PFOA and PFOS is detailed in a protocol that is laid out in seven steps: scoping and problem formulation, search for and select studies for inclusion, extract data from studies, assess quality of individual studies, rate confidence in the body of evidence, translate confidence ratings into level of evidence, and integrate evidence to develop hazard identification conclusions incorporating human, animal, and mechanistic evidence.
Results and Discussion: Eligibility criteria for identifying important exposures and outcomes were presented as the basis for assembling the relevant studies for evaluating whether or not PFOA or PFOS exposure is associated with immunotoxicity (human, n= 18; animal, n=80: and mechanistic/in vitro assays, n= 19). A tool for assessing study quality in terms of risk of bias or internal validity was tailored to the research question particularly for evaluating PFC exposure and assessing immunological outcomes. An example of an evidence profile is provided to illustrate the basis for confidence ratings using a hypothetical set of studies of PFOS and functional antibody response. Finally, a discussion is presented on how the hazard identification conclusions would be reached and interpreted by integrating the human, animal, and mechanistic evidence.
Conclusion: The OHAT Approach to hazard identification of health effects of PFCs is illustrated with a case study on PFOA/PFOS and immunotoxicity. Communication of the evaluation process is enhanced by using objective, reproducible methods that transparently document scientific judgments and the scientific basis for hazard identification conclusions.
C1 [Rooney, Andrew A.; Boyles, Abee L.; Walker, Vickie R.] NIEHS, Off Hlth Assessment & Translat, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Rooney, AA (reprint author), NIEHS, Off Hlth Assessment & Translat, Div Natl Toxicol Program, NIH, POB 12233,Mail Drop K2-04, Res Triangle Pk, NC 27709 USA.
EM Andrew.Rooney@nih.gov
NR 62
TC 0
Z9 0
U1 2
U2 4
PU SPRINGER-VERLAG LONDON LTD
PI GODALMING
PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY,
ENGLAND
SN 2168-4219
BN 978-3-319-15518-0; 978-3-319-15517-3
J9 MOLEC INTEGR TOXICOL
PY 2015
BP 419
EP 449
DI 10.1007/978-3-319-15518-0_16
D2 10.1007/978-3-319-15518-0
PG 31
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BD9KE
UT WOS:000364811700017
ER
PT S
AU Moayeri, M
Leppla, SH
Vrentas, C
Pomerantsev, AP
Liu, SH
AF Moayeri, Mahtab
Leppla, Stephen H.
Vrentas, Catherine
Pomerantsev, Andrei P.
Liu, Shihui
BE Gottesman, S
TI Anthrax Pathogenesis
SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 69
SE Annual Review of Microbiology
LA English
DT Review; Book Chapter
DE anthrax toxins; protective antigen; lethal factor; edema factor
ID SMALL-MOLECULE INHIBITORS; TOXIN PROTECTIVE ANTIGEN; ACTIN-BASED
MOTILITY; CAPILLARY MORPHOGENESIS PROTEIN-2; BACILLUS-ANTHRACIS;
LETHAL-TOXIN; EDEMA FACTOR; INHALATION ANTHRAX; IN-VIVO; DENDRITIC CELLS
AB Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and) an antiphagocytic polyglutamic capsule. These are encoded by two large plasmids. the former by pXO1 and the latter by pXO2. The expression of both is controlled by the bicarbonate-responsive transcriptional regulator, AtxA. The anthrax toxins are three polypeptides protective antigen (PA), lethal factor (11), and edema factor (EF)-that come together in binary combinations to form lethal toxin and edema toxin. PA binds to cellular receptors to translocate LF (a protease) and EF (an adenylate cyclase) into cells. The toxins alter cell signaling pathways in the host to interfere with innate immune responses in early stages of infection and to induce vascular collapse at late stages. This review focuses on the role of anthrax toxins in pathogenesis. Other virulence determinants, as well as vaccines and therapeutics, are briefly discussed.
C1 [Moayeri, Mahtab; Leppla, Stephen H.; Vrentas, Catherine; Pomerantsev, Andrei P.; Liu, Shihui] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moayeri, M (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mmoayeri@niaid.nih.gov; sleppla@niaid.nih.gov;
catherine.vrentas@gmail.com; apomerantsev@niaid.nih.gov;
shliu@niaid.nih.gov
FU Intramural NIH HHS
NR 275
TC 20
Z9 20
U1 15
U2 41
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0066-4227
BN 978-0-8243-1169-8
J9 ANNU REV MICROBIOL
JI Annu. Rev. Microbiol.
PY 2015
VL 69
BP 185
EP 208
DI 10.1146/annurev-micro-091014-104523
PG 24
WC Microbiology
SC Microbiology
GA BD7UR
UT WOS:000363614100010
PM 26195305
ER
PT S
AU Galletta, BJ
Rusan, NM
AF Galletta, Brian J.
Rusan, Nasser M.
BE Basto, R
Oegema, K
TI A yeast two-hybrid approach for probing protein-protein interactions at
the centrosome
SO CENTROSOME & CENTRIOLE
SE Methods in Cell Biology
LA English
DT Review; Book Chapter
ID C-ELEGANS; PERICENTRIOLAR MATERIAL; INTERACTION MAP;
SACCHAROMYCES-CEREVISIAE; CENTRIOLE DUPLICATION; MOLECULAR DISSECTION;
STRUCTURE PREDICTION; MITOTIC SPINDLE; SPB DUPLICATION; 9-FOLD SYMMETRY
AB As a large, nonmembrane bound organelle, the centrosome must rely heavily on protein-protein interactions to assemble itself in the cytoplasm and perform its functions as a microtubule-organizing center. Therefore, to understand how this organelle is built and functions, one must understand the proteineprotein interactions made by each centrosome protein. Unfortunately, the highly interconnected nature of the centrosome, combined with its predicted unstructured, coil-rich proteins, has made the use of many standard approaches to studying proteineprotein interactions very challenging. The yeast-two hybrid (Y2H) system is well suited for studying the centrosome and is an important complement to other biochemical approaches. In this chapter we describe how to carry out a directed Y2H screen to identify the direct interactions between a given centrosome protein and a library of others. Specifically, we detail using a bioinformatics-based approach (structure prediction programs) to subdivide proteins and screen for interactions using an array-based Y2H approach. We also describe how to use the interaction information garnered from this screen to generate mutations to disrupt specific interactions using mutagenic-PCR and a "reverse" Y2H screen. Finally, we discuss how information from such a screen can be integrated into existing models of centrosome assembly and how it can initiate and guide extensive in vitro and in vivo experimentation to test these models.
C1 [Galletta, Brian J.; Rusan, Nasser M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Galletta, BJ (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM brian.galletta@nih.gov
RI Rusan, Nasser/P-3511-2016
FU Intramural NIH HHS [ZIA HL006104-05]; NHLBI NIH HHS [ZIA HL006104]; PHS
HHS [1ZIAHL006104]
NR 77
TC 3
Z9 3
U1 1
U2 9
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-679X
BN 978-0-12-802638-0; 978-0-12-802449-2
J9 METHOD CELL BIOL
JI Methods Cell Biol.
PY 2015
VL 129
BP 251
EP 277
DI 10.1016/bs.mcb.2015.03.012
PG 27
WC Cell Biology
SC Cell Biology
GA BD8HD
UT WOS:000363929300015
PM 26175443
ER
PT J
AU Migueles, SA
Mendoza, D
Zimmerman, MG
Martins, KM
Toulmin, SA
Kelly, EP
Peterson, BA
Johnson, SA
Galson, E
Poropatich, KO
Patamawenu, A
Imamichi, H
Ober, A
Rehm, CA
Jones, S
Hallahan, CW
Follmann, DA
Connors, M
AF Migueles, Stephen A.
Mendoza, Daniel
Zimmerman, Matthew G.
Martins, Kelly M.
Toulmin, Sushila A.
Kelly, Elizabeth P.
Peterson, Bennett A.
Johnson, Sarah A.
Galson, Eric
Poropatich, Kate O.
Patamawenu, Andy
Imamichi, Hiromi
Ober, Alexander
Rehm, Catherine A.
Jones, Sara
Hallahan, Claire W.
Follmann, Dean A.
Connors, Mark
TI CD8(+) T-cell Cytotoxic Capacity Associated with Human Immunodeficiency
Virus-1 Control Can Be Mediated through Various Epitopes and Human
Leukocyte Antigen Types
SO EBIOMEDICINE
LA English
DT Article
DE Long-term nonprogressors/elite controllers; Immune control; CD8(+) T
cells; Cytotoxic capacity; Epitope specificity
ID VIRAL REPLICATION CAPACITY; LONG-TERM NONPROGRESSORS; HIV-1 INFECTION;
IMMUNE CONTROL; LYMPHOCYTE EPITOPES; ELITE SUPPRESSORS; ESCAPE;
RESPONSES; PROLIFERATION; REVERSION
AB Understanding natural immunologic control over Human Immunodeficiency Virus (HIV)-1 replication, as occurs in rare long-term nonprogressors/elite controllers (LTNP/EC), should inform the design of efficacious HIV vaccines and immunotherapies. Durable control in LTNP/EC is likely mediated by highly functional virus-specific CD8(+) T-cells. Protective Human Leukocyte Antigen (HLA) class I alleles, like B* 27 and B* 57, are present in most, but not all LTNP/EC, providing an opportunity to investigate features shared by their HIV-specific immune responses. To better understand the contribution of epitope targeting and conservation to immune control, we compared the CD8(+) T-cell specificity and function of B* 27/57(neg) LTNP/EC (n = 23), B* 27/57(pos) LTNP/EC (n = 23) and B* 27/57(neg) progressors (n= 13). Fine mapping revealed 11 previously unreported immunodominant responses. Although B* 27/57(neg) LTNP/EC did not target more highly conserved epitopes, their CD8(+) T-cell cytotoxic capacity was significantly higher than progressors. Similar to B* 27/57(pos) LTNP/EC, this superior cytotoxicity was mediated by preferential expansion of immunodominant responses and lysis through the predicted HLA. These findings suggest that increased CD8(+) T-cell cytotoxic capacity is a common mechanism of control in most LTNP/EC regardless of HLA type. They also suggest that potent cytotoxicity can be mediated through various epitopes and HLA molecules and could, in theory, be induced in most people. Published by Elsevier B.V.
C1 [Migueles, Stephen A.; Mendoza, Daniel; Zimmerman, Matthew G.; Martins, Kelly M.; Toulmin, Sushila A.; Kelly, Elizabeth P.; Peterson, Bennett A.; Johnson, Sarah A.; Galson, Eric; Poropatich, Kate O.; Patamawenu, Andy; Imamichi, Hiromi; Ober, Alexander; Rehm, Catherine A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Jones, Sara] Leidos Biomed Res Inc, Clin Monitoring Res Program, Frederick, MD USA.
[Hallahan, Claire W.; Follmann, Dean A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-07,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mconnors@niaid.nih.gov
OI Mendoza, Daniel/0000-0002-6362-0771
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; PHS
HHS [HHSN261200800001E]
NR 57
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD JAN
PY 2015
VL 2
IS 1
BP 46
EP 58
DI 10.1016/j.ebiom.2014.12.009
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA CV3JZ
UT WOS:000364156800012
PM 26137533
ER
PT J
AU Suomi, SJ
AF Suomi, Stephen J.
TI Behavioural, Biological, and Epigenetic Consequences of Early Social
Experience in Rhesus Monkeys
SO FOLIA PRIMATOLOGICA
LA English
DT Meeting Abstract
C1 [Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Poolesville, MD USA.
EM suomis@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0015-5713
EI 1421-9980
J9 FOLIA PRIMATOL
JI Folia Primatol.
PY 2015
VL 86
IS 4
BP 367
EP 368
PG 2
WC Zoology
SC Zoology
GA CV0QD
UT WOS:000363955000229
ER
PT J
AU Conejero-Goldberg, C
Hyde, TM
Chen, SF
Herman, MM
Kleinman, JE
Davies, P
Goldberg, TE
AF Conejero-Goldberg, Concepcion
Hyde, Thomas M.
Chen, Shufen
Herman, Mary M.
Kleinman, Joel E.
Davies, Peter
Goldberg, Terry E.
TI Cortical Transcriptional Profiles in APOE4 Carriers with Alzheimer's
Disease: Patterns of Protection and Degeneration
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Article
DE Alzheimer's disease; APOE; gene expression; human brain; microarray
ID PERISYNAPTIC EXTRACELLULAR-MATRIX; GENE-EXPRESSION; CELL-DEATH;
MICROARRAY ANALYSIS; OXIDATIVE STRESS; BRAIN; DNA; NEUROPATHOLOGY
AB Transcriptional profiling of postmortem Alzheimer's disease (AD) brain tissue has yielded important insights into disease. We recently described a novel approach to understand transcriptional changes in AD designed to identify both neurosusceptibility and intrinsic neuroprotective factors in young non-AD E4 carriers. Here we extend our work to APOE4 related AD itself. In temporal cortex (BA 21), a region known to be vulnerable to AD pathology, we identified over 1400 transcripts that differed between APOE4 controls and APOE4 carriers diagnosed with AD. Results from somatosensory cortex (BA 1/2/3), a region relatively preserved in AD differed strikingly from temporal cortex in that differences were far fewer (37 vs. 1492). We also conducted another set of contrasts involving APOE3 AD cases and APOE4 AD cases to better understand what transcriptional differences were dependent on genotype, but independent of disease status and found 6 transcripts to differ. We also conducted detailed pathway analyses in BA 1/2/3 and found significant transcriptional upregulations in pro-survival gene networks (e.g., TNF and NFkB). In summary, our results indicate that many of the molecular changes identified in the brains of patients with AD reflect the non-specific consequences of neurodegeneration, rather than causative processes. Additionally, the molecular signatures specific to somatosensory cortex may make it uniquely resistant to AD pathology and thereby could provide important leads for treatment.
C1 [Conejero-Goldberg, Concepcion; Chen, Shufen; Davies, Peter; Goldberg, Terry E.] Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, Manhasset, NY 11030 USA.
[Hyde, Thomas M.; Kleinman, Joel E.] Lieber Inst Brain Dev, Neuropathol Sect, Baltimore, MD USA.
[Herman, Mary M.] NIMH, Neuropathol Sect, GCAP, IRP,NIH, Bethesda, MD 20892 USA.
RP Conejero-Goldberg, C (reprint author), Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, 350 Community Dr, Manhasset, NY 11030 USA.
EM cgoldber@nshs.edu
FU Litwin-Zucker Research Center for the Study of Alzheimer's Disease
FX This work was supported by the Litwin-Zucker Research Center for the
Study of Alzheimer's Disease.
NR 26
TC 1
Z9 1
U1 0
U2 1
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 1387-2877
EI 1875-8908
J9 J ALZHEIMERS DIS
JI J. Alzheimers Dis.
PY 2015
VL 48
IS 4
BP 969
EP 978
DI 10.3233/JAD-150345
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CU9LZ
UT WOS:000363867300009
PM 26444771
ER
PT J
AU Binukumar, BK
Shukla, V
Amin, ND
Bhaskar, M
Skuntz, S
Steiner, J
Winkler, D
Pelech, SL
Pant, HC
AF Binukumar, B. K.
Shukla, Varsha
Amin, Niranjana D.
Bhaskar, Manju
Skuntz, Suzanne
Steiner, Joseph
Winkler, Dirk
Pelech, Steven L.
Pant, Harish C.
TI Analysis of the Inhibitory Elements in the p5 Peptide Fragment of the
CDK5 Activator, p35, CDKR1 Protein
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Article
DE Alzheimer's disease; CDK5 activator protein 35; cyclin-dependent kinase
5; phosphorylation
ID CYCLIN-DEPENDENT KINASE-5; ALZHEIMERS-DISEASE; ROSCOVITINE;
NEURODEGENERATION; PHOSPHORYLATION
AB Besides the hallmark pathology of amyloid plaques and neurofibrillary tangles, it is well documented that cyclin-dependent kinase 5 (CDK5), a critical neuronal protein kinase in nervous system development, function, and survival, when deregulated and hyperactivated induces Alzheimer's disease (AD) and amyotrophic lateral sclerosis and Parkinson's disease-like phenotypes in mice. In a recent study, we demonstrated that p5, a small, truncated fragment of 24 amino acid residues derived from the CDK5 activator protein 35 (NCK5A, p35), selectively inhibited deregulated CDK5 hyperactivity and ameliorated AD phenotypes in model mice. In this study, we identified the most inhibitory elements in the p5 peptide fragment. Each amino acid residue in p5 was systematically replaced with its homologous residues that may still be able to functionally substitute. The effects of these p5 peptide analogs were studied on the phosphotransferase activities of CDK5/p35, CDK5/p25, ERK1, and GSK3 beta. The mimetic p5 peptide (A/V substitution at the C-terminus of the peptide) in the sequence, KNAFYERALSIINLMTSKMVQINV (p5-MT) was the most effective inhibitor of CDK5 kinase activity of 79 tested mimetic peptides including the original p5 peptide, KEAFWDRCLSVINLMSSKMLQINA (p5-WT). Replacement of the residues in C-terminus end of the peptide affected CDK5 phosphotransferase activity most significantly. These peptides were strong inhibitors of CDK5, but not the related proline-directed kinases, ERK1 and GSK3 beta.
C1 [Binukumar, B. K.; Shukla, Varsha; Amin, Niranjana D.; Bhaskar, Manju; Skuntz, Suzanne; Steiner, Joseph; Pant, Harish C.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Winkler, Dirk; Pelech, Steven L.] Univ British Columbia, Kinexus Bioinformat Corp, Vancouver, BC V5Z 1M9, Canada.
[Winkler, Dirk; Pelech, Steven L.] Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 1W5, Canada.
RP Pant, HC (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Neuronal Cytoskeletal Prot Regulat Sect, NIH, Bethesda, MD 20892 USA.
EM PantH@ninds.nih.gov
FU intramural research program of the U.S. National Institutes of Health
(NIH), NINDS
FX The authors thank Dr. Philip Grant for helpful discussions. This work
was supported by the intramural research program of the U.S. National
Institutes of Health (NIH), NINDS.
NR 21
TC 1
Z9 1
U1 2
U2 2
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 1387-2877
EI 1875-8908
J9 J ALZHEIMERS DIS
JI J. Alzheimers Dis.
PY 2015
VL 48
IS 4
BP 1009
EP 1017
DI 10.3233/JAD-150412
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA CU9LZ
UT WOS:000363867300013
PM 26444778
ER
PT J
AU Mensah, GA
Norrving, B
Feigin, VL
AF Mensah, George A.
Norrving, Bo
Feigin, Valery L.
TI The Global Burden of Stroke
SO NEUROEPIDEMIOLOGY
LA English
DT Editorial Material
C1 [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden.
[Feigin, Valery L.] Auckland Univ Technol, Fac Hlth & Environm Studies, Natl Inst Stroke & Appl Neurosci, Sch Rehabil & Occupat Studies,Sch Publ Hlth & Psy, Auckland, New Zealand.
RP Mensah, GA (reprint author), NHLBI, NIH, IOD, 31 Ctr Dr MSC 2486, Bethesda, MD 20892 USA.
EM george.mensah@nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 9
TC 3
Z9 3
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 143
EP 145
DI 10.1159/000441082
PG 3
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500001
PM 26505979
ER
PT J
AU Truelsen, T
Krarup, LH
Iversen, HK
Mensah, GA
Feigin, VL
Sposato, LA
Naghavi, M
AF Truelsen, Thomas
Krarup, Lars-Henrik
Iversen, Helle K.
Mensah, George A.
Feigin, Valery L.
Sposato, Luciano A.
Naghavi, Mohsen
TI Causes of Death Data in the Global Burden of Disease Estimates for
Ischemic and Hemorrhagic Stroke
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Stroke; Cerebrovascular diseases; Epidemiology; Ischemic stroke;
Hemorrhagic stroke
ID PUBLIC-HEALTH UTILITY; HEART-DISEASE; MORTALITY; VALIDITY; TRENDS
AB Background: Stroke mortality estimates in the Global Burden of Disease (GBD) study are based on routine mortality statistics and redistribution of ill-defined codes that cannot be a cause of death, the so-called 'garbage codes' (GCs). This study describes the contribution of these codes to stroke mortality estimates. Methods: All available mortality data were compiled and non-specific cause codes were redistributed based on literature review and statistical methods. Ill-defined codes were redistributed to their specific cause of disease by age, sex, country and year. The reassignment was done based on the International Classification of Diseases and the pathology behind each code by checking multiple causes of death and literature review. Results: Unspecified stroke and primary and secondary hypertension are leading contributing 'GCs' to stroke mortality estimates for hemorrhagic stroke (HS) and ischemic stroke (IS). There were marked differences in the fraction of death assigned to IS and HS for unspecified stroke and hypertension between GBD regions and between age groups. Conclusions: A large proportion of stroke fatalities are derived from the redistribution of 'unspecified stroke' and 'hypertension' with marked regional differences. Future advancements in stroke certification, data collections and statistical analyses may improve the estimation of the global stroke burden. (C) 2015 S. Karger AG, Basel
C1 [Truelsen, Thomas; Krarup, Lars-Henrik; Iversen, Helle K.] Univ Copenhagen, Rigshosp, Dept Neurol, DK-2100 Copenhagen O, Denmark.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Naghavi, Mohsen] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Sposato, Luciano A.] Univ Western Ontario, Dept Clin Neurol Sci, London Hlth Sci Ctr, London, ON, Canada.
[Feigin, Valery L.] Auckland Univ Technol, Fac Hlth & Environm Sci, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
RP Truelsen, T (reprint author), Univ Copenhagen, Rigshosp, Dept Neurol, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark.
EM thomas.clement.truelsen@regionh.dk
FU Intramural NIH HHS [Z99 HL999999]
NR 16
TC 7
Z9 7
U1 5
U2 7
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 152
EP 160
DI 10.1159/000441084
PG 9
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500003
PM 26505189
ER
PT J
AU Feigin, VL
Krishnamurthi, RV
Parmar, P
Norrving, B
Mensah, GA
Bennett, DA
Barker-Collo, S
Moran, AE
Sacco, RL
Truelsen, T
Davis, S
Pandian, JD
Naghavi, M
Forouzanfar, MH
Nguyen, G
Johnson, CO
Vos, T
Meretoja, A
Murray, CJL
Roth, GA
AF Feigin, Valery L.
Krishnamurthi, Rita V.
Parmar, Priya
Norrving, Bo
Mensah, George A.
Bennett, Derrick A.
Barker-Collo, Suzanne
Moran, Andrew E.
Sacco, Ralph L.
Truelsen, Thomas
Davis, Stephen
Pandian, Jeyaraj Durai
Naghavi, Mohsen
Forouzanfar, Mohammad H.
Nguyen, Grant
Johnson, Catherine O.
Vos, Theo
Meretoja, Atte
Murray, Christopher J. L.
Roth, Gregory A.
CA GBD 2013 Writing Grp
GBD 2013 Stroke Panel Experts Grp
TI Update on the Global Burden of Ischemic and Hemorrhagic Stroke in
1990-2013: The GBD 2013 Study
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Stroke; Ischemic stroke; Hemorrhagic stroke; Global burden; GBD 2013
ID SYSTEMATIC ANALYSIS; REGIONAL BURDEN; DISEASE; HYPERTENSION; COUNTRIES;
MULTIMORBIDITY; PREVALENCE; COMMUNITY; MORTALITY; HEALTH
AB Background: Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. Objectives: This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. Methodology: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). Results: In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. Conclusion: Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority. (C) 2015 S. Karger AG, Basel
C1 [Feigin, Valery L.; Krishnamurthi, Rita V.; Parmar, Priya] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
[Barker-Collo, Suzanne] Univ Auckland, Sch Psychol, Clin Training Programme, Auckland 1, New Zealand.
[Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden.
[Bennett, Derrick A.] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.
[Bennett, Derrick A.] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
[Truelsen, Thomas] Univ Copenhagen, Rigshosp, Dept Neurol, DK-2100 Copenhagen, Denmark.
[Davis, Stephen] Univ Melbourne, Translat Neurosci, Parkville, Vic 3052, Australia.
[Meretoja, Atte] Univ Melbourne, Royal Melbourne Hosp L4C, Parkville, Vic 3052, Australia.
[Pandian, Jeyaraj Durai] Christian Med Coll & Hosp, Dept Neurol, Ludhiana, Punjab, India.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Moran, Andrew E.] Columbia Univ, Div Gen Med, New York, NY USA.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[Naghavi, Mohsen; Forouzanfar, Mohammad H.; Vos, Theo; Murray, Christopher J. L.] Univ Washington, Sch Med & Publ Hlth, Dept Global Hlth, Seattle, WA 98195 USA.
[Nguyen, Grant; Johnson, Catherine O.] Univ Washington, Sch Med & Publ Hlth, Dept Global Hlth, Seattle, WA 98195 USA.
[Nguyen, Grant; Johnson, Catherine O.; Roth, Gregory A.] Univ Washington, Sch Med, Inst Hlth Metr & Evaluat, Seattle, WA USA.
[Roth, Gregory A.] Univ Washington, Sch Med, Div Cardiol, Seattle, WA USA.
RP Feigin, VL (reprint author), AUT Univ, NISAN, AUT North Shore Campus,AA254 90 Akoranga Dr, Auckland 0627, New Zealand.
EM valery.feigin@aut.ac.nz
RI Kravchenko, Michael/B-2596-2012; Varakin, Yuriy/C-8634-2012; Hankey,
Graeme /H-4968-2014; Rajagopalan, Vasanthan/G-8733-2015; Piradov,
Mikhail/B-4407-2012; Lotufo, Paulo/A-9843-2008; Dokova,
Klara/N-2448-2016;
OI Kravchenko, Michael/0000-0001-5187-5518; Hankey, Graeme
/0000-0002-6044-7328; Rajagopalan, Vasanthan/0000-0002-7524-8487;
Piradov, Mikhail/0000-0002-6055-8335; Lotufo, Paulo/0000-0002-4856-8450;
Vlassov, Valentin/0000-0003-2845-2992; Vlassov,
Vasiliy/0000-0001-5203-549X; Prabhakaran, Dorairaj/0000-0002-3172-834X;
Catala-Lopez, Ferran/0000-0002-3833-9312; Norheim, Ole
F./0000-0002-5748-5956
FU Bill and Melinda Gates Foundation
FX This study was funded by the Bill and Melinda Gates Foundation. The
sponsor of the study had no role in the study design, data collection,
data analysis, data interpretation or writing of the report. The Writing
and GBD 2013 Global Analysis Group had access to all data sources and
has responsibility for the content of the report and the decision to
submit for publication.
NR 22
TC 49
Z9 50
U1 13
U2 25
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 161
EP 176
DI 10.1159/000441085
PG 16
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500004
PM 26505981
ER
PT J
AU Krishnamurthi, RV
deVeber, G
Feigin, VL
Barker-Collo, S
Fullerton, H
Mackay, MT
O'Callahan, F
Lindsay, MP
Kolk, A
Lo, W
Shah, P
Linds, A
Jones, K
Parmar, P
Taylor, S
Norrving, B
Mensah, GA
Moran, AE
Naghavi, M
Forouzanfar, MH
Nguyen, G
Johnson, CO
Vos, T
Murray, CJL
Roth, GA
AF Krishnamurthi, Rita V.
deVeber, Gabrielle
Feigin, Valery L.
Barker-Collo, Suzanne
Fullerton, Heather
Mackay, Mark T.
O'Callahan, Finbar
Lindsay, M. Patrice
Kolk, Anneli
Lo, Warren
Shah, Priyanka
Linds, Alexandra
Jones, Kelly
Parmar, Priya
Taylor, Steve
Norrving, Bo
Mensah, George A.
Moran, Andrew E.
Naghavi, Mohsen
Forouzanfar, Mohammed H.
Nguyen, Grant
Johnson, Catherine O.
Vos, Theo
Murray, Christopher J. L.
Roth, Gregory A.
CA GBD 2013 Stroke Panel Experts Grp
TI Stroke Prevalence, Mortality and Disability-Adjusted Life Years in
Children and Youth Aged 0-19 Years: Data from the Global and Regional
Burden of Stroke 2013
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Childhood stroke; Stroke epidemiology; Prevalence; Deaths;
Disability-adjusted life years
ID ARTERIAL ISCHEMIC-STROKE; PEDIATRIC STROKE; RISK-FACTORS; CHILDHOOD
STROKE; CEREBROVASCULAR-DISEASE; HEMORRHAGIC STROKE; CLINICAL-FEATURES;
SAUDI CHILDREN; CASE-FATALITY; EPIDEMIOLOGY
AB Background: There is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management. Objectives: To estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013. Conclusions: Globally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries.
There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care. (C) 2015 S. Karger AG, Basel
C1 [Krishnamurthi, Rita V.; Feigin, Valery L.; Jones, Kelly; Parmar, Priya] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Auckland 0627, New Zealand.
[Barker-Collo, Suzanne] Univ Auckland, Sch Psychol, Auckland 1, New Zealand.
[Taylor, Steve] Auckland Univ Technol, Dept Biostat & Epidemiol, Auckland 0627, New Zealand.
[deVeber, Gabrielle; Shah, Priyanka; Linds, Alexandra] Univ Toronto, Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada.
[Lindsay, M. Patrice] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Mackay, Mark T.] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia.
[O'Callahan, Finbar] UCL, Inst Child Hlth, London, England.
[Kolk, Anneli] Tartu Univ Hosp, Dept Neurol & Neurorehabil, Childrens Clin, Tartu, Estonia.
[Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden.
[Fullerton, Heather] Univ Calif San Francisco, Benioff Childrens Hosp, San Francisco, CA 94143 USA.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Lo, Warren] Nationwide Childrens Hosp, Columbus, OH USA.
[Moran, Andrew E.] Columbia Univ, Div Gen Med, New York, NY USA.
[Naghavi, Mohsen; Forouzanfar, Mohammed H.; Vos, Theo; Murray, Christopher J. L.] Univ Washington, Dept Global Hlth, Sch Med & Publ Hlth, Seattle, WA 98195 USA.
[Nguyen, Grant; Johnson, Catherine O.; Roth, Gregory A.] Univ Washington, Sch Med, Inst Hlth Metr & Evaluat, Seattle, WA USA.
[Roth, Gregory A.] Univ Washington, Sch Med, Div Cardiol, Seattle, WA USA.
RP Krishnamurthi, RV (reprint author), Auckland Univ Technol, 90 Akoranga Dr, Auckland 0627, New Zealand.
EM rita.krishnamurthi@aut.ac.nz
RI Hankey, Graeme /H-4968-2014; Rajagopalan, Vasanthan/G-8733-2015;
Piradov, Mikhail/B-4407-2012; Lo, Warren/E-3531-2011; Dokova,
Klara/N-2448-2016; Kravchenko, Michael/B-2596-2012; Varakin,
Yuriy/C-8634-2012; Lotufo, Paulo/A-9843-2008;
OI Hankey, Graeme /0000-0002-6044-7328; Norheim, Ole
F./0000-0002-5748-5956; Rajagopalan, Vasanthan/0000-0002-7524-8487;
Piradov, Mikhail/0000-0002-6055-8335; Kravchenko,
Michael/0000-0001-5187-5518; Lotufo, Paulo/0000-0002-4856-8450; Vlassov,
Valentin/0000-0003-2845-2992; Prabhakaran, Dorairaj/0000-0002-3172-834X;
Catala-Lopez, Ferran/0000-0002-3833-9312
FU Bill and Melinda Gates Foundation
FX The study was funded by the Bill and Melinda Gates Foundation. The
sponsor of the study had no role in the study design, data collection,
data analysis, data interpretation or writing of the report. The writing
group and GBD 2013 core analysts had access to all data sources and has
responsibility for the content of the report and the decision to submit
for publication.
NR 44
TC 7
Z9 7
U1 2
U2 11
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 177
EP 189
DI 10.1159/000441087
PG 13
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500005
PM 26505982
ER
PT J
AU Krishnamurthi, RV
Moran, AE
Feigin, VL
Barker-Collo, S
Norrving, B
Mensah, GA
Taylor, S
Naghavi, M
Forouzanfar, MH
Nguyen, G
Johnson, CO
Vos, T
Murray, CJL
Roth, GA
AF Krishnamurthi, Rita V.
Moran, Andrew E.
Feigin, Valery L.
Barker-Collo, Suzanne
Norrving, Bo
Mensah, George A.
Taylor, Steve
Naghavi, Mohsen
Forouzanfar, Mohammed H.
Nguyen, Grant
Johnson, Catherine O.
Vos, Theo
Murray, Christopher J. L.
Roth, Gregory A.
CA GBD 2013 Stroke Panel Experts Grp
TI Stroke Prevalence, Mortality and Disability-Adjusted Life Years in
Adults Aged 20-64 Years in 1990-2013: Data from the Global Burden of
Disease 2013 Study
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Stroke; Ischemic; Hemorrhagic; Young adult; Global trends; Prevalence;
Deaths; DALYs
ID TRANSIENT ISCHEMIC ATTACK; YOUNG FABRY PATIENTS; RISK-FACTORS; REGISTRY;
TRENDS; THROMBOLYSIS; ETIOLOGY; QUALITY; CARE
AB Background: Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working individuals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. Objectives: This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. Conclusions: Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world.
A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities. (C) 2015 S. Karger AG, Basel
C1 [Krishnamurthi, Rita V.; Feigin, Valery L.] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
[Taylor, Steve] Auckland Univ Technol, Dept Biostat & Epidemiol, Auckland, New Zealand.
[Barker-Collo, Suzanne] Univ Auckland, Sch Psychol, Auckland 1, New Zealand.
[Norrving, Bo] Lund Univ, Dept Clin Sci, Lund, Sweden.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Moran, Andrew E.] Columbia Univ, Div Gen Med, New York, NY USA.
[Naghavi, Mohsen; Forouzanfar, Mohammed H.; Vos, Theo; Murray, Christopher J. L.] Univ Washington, Dept Global Hlth, Sch Med & Publ Hlth, Seattle, WA 98195 USA.
[Nguyen, Grant; Johnson, Catherine O.; GBD 2013 Stroke Panel Experts Grp] Univ Washington, Sch Med, Inst Hlth Metr & Evaluat, Seattle, WA USA.
[Roth, Gregory A.] Univ Washington, Sch Med, Div Cardiol, Seattle, WA USA.
RP Krishnamurthi, RV (reprint author), Auckland Univ Technol, 90 Akoranga Dr,Northcote 0627, Auckland, New Zealand.
EM rita.krishnamurthi@aut.ac.nz
RI Hankey, Graeme /H-4968-2014; Rajagopalan, Vasanthan/G-8733-2015;
Piradov, Mikhail/B-4407-2012; Dokova, Klara/N-2448-2016; Kravchenko,
Michael/B-2596-2012; Varakin, Yuriy/C-8634-2012; Lotufo,
Paulo/A-9843-2008;
OI Hankey, Graeme /0000-0002-6044-7328; Rajagopalan,
Vasanthan/0000-0002-7524-8487; Piradov, Mikhail/0000-0002-6055-8335;
Kravchenko, Michael/0000-0001-5187-5518; Lotufo,
Paulo/0000-0002-4856-8450; Vlassov, Valentin/0000-0003-2845-2992;
Prabhakaran, Dorairaj/0000-0002-3172-834X; Catala-Lopez,
Ferran/0000-0002-3833-9312; Norheim, Ole F./0000-0002-5748-5956
FU Bill and Melinda Gates Foundation
FX This study was funded by the Bill and Melinda Gates Foundation. The
sponsor of the study had no role in the study design, data collection,
data analysis, data interpretation or writing of the report. The Writing
and GBD 2013 Global Analysis Group had access to all data sources and
was responsible for the content of the report and the decision to submit
for publication.
NR 31
TC 17
Z9 18
U1 4
U2 8
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 190
EP 202
DI 10.1159/000441098
PG 13
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500006
PM 26505983
ER
PT J
AU Barker-Collo, S
Bennett, DA
Krishnamurthi, RV
Parmar, P
Feigin, VL
Naghavi, M
Forouzanfar, MH
Johnson, CO
Nguyen, G
Mensah, GA
Vos, T
Murray, CJL
Roth, GA
AF Barker-Collo, Suzanne
Bennett, Derrick A.
Krishnamurthi, Rita V.
Parmar, Priya
Feigin, Valery L.
Naghavi, Mohsen
Forouzanfar, Mohammed H.
Johnson, Catherine O.
Nguyen, Grant
Mensah, George A.
Vos, Theo
Murray, Christopher J. L.
Roth, Gregory A.
CA GBD 2013 Writing Grp
GBD 2013 Stroke Panel Experts Grp
TI Sex Differences in Stroke Incidence, Prevalence, Mortality and
Disability-Adjusted Life Years: Results from the Global Burden of
Disease Study 2013
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Sex differences; Stroke; Epidemiology; Burden; Global
ID INTRACEREBRAL HEMORRHAGE; CARDIOVASCULAR-DISEASE; GENDER-DIFFERENCES;
CASE-FATALITY; RISK-FACTORS; CLINICAL PRESENTATION; SYSTEMATIC ANALYSIS;
POPULATION; TRENDS; WOMEN
AB Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time. Methods: Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed. Findings: In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women. Changes in global HS incidence were not statistically significant for males (1990 = 65.31 (95% UI 61.63-69.0), 2013 = 64.89 (95% UI 59.82-68.85)), but was significant for females (1990 = 64.892 (95% UI 59.82-68.85), 2013 = 45.48 (95% UI 42.427-48.53)). The number of DALYs related to IS rose from 1990 (male = 16.62 (95% UI 13.27-19.62), female = 17.53 (95% UI 14.08-20.33)) to 2013 (male = 25.22 (95% UI 20.57-29.13), female = 22.21 (95% UI 17.71-25.50)). The number of DALYs associated with HS also rose steadily and was higher than DALYs for IS at each time point (male 1990 = 29.91 (95% UI 25.66-34.54), male 2013 = 37.27 (95% UI 32.29-45.12); female 1990 = 26.05 (95% UI 21.70-30.90), female 2013 = 28.18 (95% UI 23.68-33.80)). Interpretation: Globally, men continue to have a higher incidence of IS than women while significant sex differences in the incidence of HS were not observed. The total health loss due to stroke as measured by DALYs was similar for men and women for both stroke sub-types in 2013, with HS higher than IS. Both IS and HS DALYs show an increasing trend for both men and women since 1990, which is statistically significant only for IS among men. Ongoing monitoring of sex differences in the burden of stroke will be needed to determine if disease rates among men and women continue to diverge. Sex disparities related to stroke will have important clinical and policy implications that can guide funding and resource allocation for national, regional and global health programs. (C) 2015 S. Karger AG, Basel
C1 [Barker-Collo, Suzanne] Univ Auckland, Sch Psychol, Auckland 1, New Zealand.
[Krishnamurthi, Rita V.; Parmar, Priya; Feigin, Valery L.] AUT Univ, Natl Inst Stroke & Appl Neurosci, Fac Hlth & Environm Studies, Auckland, New Zealand.
[Bennett, Derrick A.] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.
[Bennett, Derrick A.] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
[Naghavi, Mohsen; Vos, Theo; Murray, Christopher J. L.] Univ Washington, Sch Med & Publ Hlth, Dept Global Hlth, Seattle, WA 98195 USA.
[Forouzanfar, Mohammed H.; Johnson, Catherine O.; Nguyen, Grant; Roth, Gregory A.] Univ Washington, Sch Med, Inst Hlth Metr & Evaluat, Seattle, WA USA.
[Roth, Gregory A.] Univ Washington, Sch Med, Div Cardiol, Seattle, WA USA.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci &, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Barker-Collo, S (reprint author), Univ Auckland, Sch Psychol, Level 6,10 Symonds St,Private Bag 92019, Auckland 1, New Zealand.
EM s.barker-collo@auckland.ac.nz
RI Hankey, Graeme /H-4968-2014; Rajagopalan, Vasanthan/G-8733-2015;
Piradov, Mikhail/B-4407-2012; Dokova, Klara/N-2448-2016; Kravchenko,
Michael/B-2596-2012; Varakin, Yuriy/C-8634-2012; Lotufo,
Paulo/A-9843-2008;
OI Hankey, Graeme /0000-0002-6044-7328; Prabhakaran,
Dorairaj/0000-0002-3172-834X; Catala-Lopez, Ferran/0000-0002-3833-9312;
Rajagopalan, Vasanthan/0000-0002-7524-8487; Piradov,
Mikhail/0000-0002-6055-8335; Kravchenko, Michael/0000-0001-5187-5518;
Lotufo, Paulo/0000-0002-4856-8450; Vlassov,
Valentin/0000-0003-2845-2992; Vlassov, Vasiliy/0000-0001-5203-549X;
Norheim, Ole F./0000-0002-5748-5956
FU Department of Health [RP-PG-0407-10184]; Intramural NIH HHS [Z99
HL999999]; NCATS NIH HHS [UL1 TR001079]
NR 61
TC 17
Z9 17
U1 5
U2 11
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 203
EP 214
DI 10.1159/000441103
PG 12
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500007
PM 26505984
ER
PT J
AU Norrving, B
Davis, SM
Feigin, VL
Mensah, GA
Sacco, RL
Varghese, C
AF Norrving, Bo
Davis, Stephen M.
Feigin, Valery L.
Mensah, George A.
Sacco, Ralph L.
Varghese, Cherian
TI Stroke Prevention Worldwide - What Could Make It Work?
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Stroke; Epidemiology; Prevention; Public health
ID GLOBAL BURDEN; CARDIOVASCULAR-DISEASE; HEMORRHAGIC STROKE; REGIONAL
BURDEN; RISK-FACTORS; GUIDELINES; COUNTRIES; TRENDS; AGE
AB The global burden of stroke is of continual major importance for global health. The present report addresses some of the core principles that could make stroke prevention work. The prevention of stroke shares many common features with other non-communicable diseases (NCDs); stroke prevention should therefore be part of the joint actions on NCD led by the WHO and member states. Stroke prevention is an integral part of both the 2011 UN declaration on actions on NCDs and the UN Post-2015 Sustainable Developmental Goals. Stroke prevention requires an intersectoral approach, with important responsibilities on the part of governmental bodies, non-government organizations and the health sector as well as communities, industries and individuals. Although official development assistance will need to be provided for the lowest income countries, financing will need to be raised for most countries by reallocation of resources within the country. Stroke is a prototype NCD in that there is overwhelming scientific evidence that with actions taken to reduce risk factors, the risk of stroke can be substantially reduced. Prevention of stroke will also have beneficial effects on cognitive decline and dementia. As most strokes do not lead to death, stroke statistics should not only focus on mortality, but also on disability and quality of life. All preventive actions should start early in life and continue during the life cycle. Prevention of stroke is a complex medical and a political issue with many challenges. Upscaling of efforts to prevent stroke are urgently needed in all regions, and the opportunity to act is now. (C) 2015 S. Karger AG, Basel
C1 [Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol, SE-22185 Lund, Sweden.
[Davis, Stephen M.] Royal Melbourne Hosp, Melbourne Brain Ctr, Parkville, Vic 3050, Australia.
[Davis, Stephen M.] Univ Melbourne, Parkville, Vic 3052, Australia.
[Feigin, Valery L.] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Fac Hlth & Environm Studies, Auckland, New Zealand.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Sacco, Ralph L.] Univ Miami, Jackson Mem Hosp, Evelyn McKnight Brain Inst, Miami, FL 33136 USA.
[Sacco, Ralph L.] Univ Miami, Neurol Epidemiol & Human Genet, Miami, FL 33136 USA.
[Varghese, Cherian] WHO, Management Noncommunicable Dis, CH-1211 Geneva, Switzerland.
RP Norrving, B (reprint author), Lund Univ, Dept Clin Sci, Neurol, SE-22185 Lund, Sweden.
EM Bo.norrving@med.lu.se
FU Intramural NIH HHS [Z99 HL999999]
NR 15
TC 8
Z9 8
U1 4
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 215
EP 220
DI 10.1159/000441104
PG 6
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500008
PM 26505459
ER
PT J
AU Mensah, GA
Sacco, RL
Vickrey, BG
Sampson, UKA
Waddy, S
Ovbiagele, B
Pandian, JD
Norrving, B
Feigin, VL
AF Mensah, George A.
Sacco, Ralph L.
Vickrey, Barbara G.
Sampson, Uchechukwu K. A.
Waddy, Salina
Ovbiagele, Bruce
Pandian, Jeyaraj Durai
Norrving, Bo
Feigin, Valery L.
TI From Data to Action: Neuroepidemiology Informs Implementation Research
for Global Stroke Prevention and Treatment
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Comparative effectiveness research; Pragmatic trials; Developing
country; Health inequities; Implementation research; Neuroepidemiology;
Stroke epidemiology; Health policy development
ID NORTHERN MANHATTAN STROKE; COMMON DATA ELEMENTS; SUB-SAHARAN AFRICA;
RISK-FACTORS; NEUROLOGICAL DISORDERS; ISCHEMIC-STROKE;
GUIDELINES-STROKE; MEDICARE BENEFICIARIES; MYOCARDIAL-INFARCTION;
SYSTEMATIC ANALYSIS
AB As a scientific field of study, neuroepidemiology encompasses more than just the descriptive study of the frequency, distribution, determinants and outcomes of neurologic diseases in populations. It also includes experimental aspects that span the full spectrum of clinical and population science research. As such, neuroepidemiology has a strong potential to inform implementation research for global stroke prevention and treatment. This review begins with an overview of the progress that has been made in descriptive and experimental neuroepidemiology over the past quarter century with emphasis on standards for evidence generation, critical appraisal of that evidence and impact on clinical and public health practice at the national, regional and global levels. Specific advances made in high-income countries as well as in low- and middle-income countries are presented. Gaps in implementation as well as evidence gaps in stroke research, stroke burden, clinical outcomes and disparities between developed and developing countries are then described. The continuing need for high quality neuroepidemiologic data in low- and middle-income countries is highlighted. Additionally, persisting disparities in stroke burden and care by sex, race, ethnicity, income and socioeconomic status are discussed. The crucial role that national stroke registries have played in neuroepidemiologic research is also addressed. Opportunities presented by new directions in comparative effectiveness and implementation research are discussed as avenues for turning neuroepidemiological insights into action to maximize health impact and to guide further biomedical research on neurological diseases. (C) 2015 S. Karger AG, Basel
C1 [Mensah, George A.; Sampson, Uchechukwu K. A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.; Sampson, Uchechukwu K. A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Evelyn McKnight Brain Inst, Miami, FL 33136 USA.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Evelyn McKnight Brain Inst, Miami, FL 33136 USA.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Human Genom, Evelyn McKnight Brain Inst, Miami, FL 33136 USA.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurosurg, Evelyn McKnight Brain Inst, Miami, FL 33136 USA.
[Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Waddy, Salina] NINDS, NIH, Rockville, MD USA.
[Ovbiagele, Bruce] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA.
[Pandian, Jeyaraj Durai] Christian Med Coll & Hosp, Dept Neurol, Ludhiana, Punjab, India.
[Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden.
[Feigin, Valery L.] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Sch Rehabil & Occupat Studies, Sch Publ Hlth & Psychosocial Studies,Fac Hlth & E, Auckland, New Zealand.
RP Mensah, GA (reprint author), NHLBI, NIH, IOD, 31 Ctr Dr MSC 2486, Bethesda, MD 20892 USA.
EM george.mensah@nih.gov
FU Intramural NIH HHS [Z99 HL999999]; NINDS NIH HHS [U54 NS081764]
NR 74
TC 1
Z9 1
U1 3
U2 5
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 221
EP 229
DI 10.1159/000441105
PG 9
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500009
PM 26505615
ER
PT J
AU Feigin, VL
Mensah, GA
Norrving, B
Murray, CJL
Roth, GA
AF Feigin, Valery L.
Mensah, George A.
Norrving, Bo
Murray, Christopher J. L.
Roth, Gregory A.
CA GBD 2013 Stroke Panel Experts Grp
TI Atlas of the Global Burden of Stroke (1990-2013): The GBD 2013 Study
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Stroke; Atlas; Burden; GBD 2013
AB Background: World mapping is an important tool to visualize stroke burden and its trends in various regions and countries. Objectives: To show geographic patterns of incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke and hemorrhagic stroke in the world for 1990-2013. Methodology: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated following the general approach of the Global Burden of Disease (GBD) 2010 with several important improvements in methods. Data were updated for mortality (through April 2014) and stroke incidence, prevalence, case fatality and severity through 2013. Death was estimated using an ensemble modeling approach. A new software package, DisMod-MR 2.0, was used as part of a custom modeling process to estimate YLDs. All rates were age-standardized to new GBD estimates of global population. All estimates have been computed with 95% uncertainty intervals. Results: Age-standardized incidence, mortality, prevalence and DALYs/YLDs declined over the period from 1990 to 2013. However, the absolute number of people affected by stroke has substantially increased across all countries in the world over the same time period, suggesting that the global stroke burden continues to increase. There were significant geographical (country and regional) differences in stroke burden in the world, with the majority of the burden borne by low- and middle-income countries. Conclusions: Global burden of stroke has continued to increase in spite of dramatic declines in age-standardized incidence, prevalence, mortality rates and disability. Population growth and aging have played an important role in the observed increase in stroke burden. (C) 2015 S. Karger AG, Basel
C1 [Feigin, Valery L.] Auckland Univ Technol, FAAN, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
[Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden.
[Murray, Christopher J. L.; Roth, Gregory A.] Univ Washington, Sch Med, Inst Hlth Metr & Evaluat, Seattle, WA USA.
[Murray, Christopher J. L.; Roth, Gregory A.] Univ Washington, Sch Med, Div Cardiol, Seattle, WA USA.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Feigin, VL (reprint author), AUT Univ, AUT North Shore Campus,AA254,90 Akoranga Dr, Auckland 1142, New Zealand.
EM valery.feigin@aut.ac.nz
RI Hankey, Graeme /H-4968-2014; Rajagopalan, Vasanthan/G-8733-2015;
Piradov, Mikhail/B-4407-2012; Dokova, Klara/N-2448-2016; Kravchenko,
Michael/B-2596-2012; Varakin, Yuriy/C-8634-2012; Lotufo,
Paulo/A-9843-2008;
OI Hankey, Graeme /0000-0002-6044-7328; Rajagopalan,
Vasanthan/0000-0002-7524-8487; Piradov, Mikhail/0000-0002-6055-8335;
Kravchenko, Michael/0000-0001-5187-5518; Lotufo,
Paulo/0000-0002-4856-8450; Vlassov, Valentin/0000-0003-2845-2992;
Vlassov, Vasiliy/0000-0001-5203-549X; Catala-Lopez,
Ferran/0000-0002-3833-9312; Norheim, Ole F./0000-0002-5748-5956;
Prabhakaran, Dorairaj/0000-0002-3172-834X
FU Bill and Melinda Gates Foundation
FX This study was funded by the Bill and Melinda Gates Foundation. The
sponsor of the study had no role in the study design, data collection,
data analysis, data interpretation or writing of the report. The GBD
2013 Core investigators had access to all data sources and were
responsible for the content of the report and the decision to submit for
publication.
NR 0
TC 21
Z9 23
U1 3
U2 5
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
EI 1423-0208
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2015
VL 45
IS 3
BP 230
EP 236
DI 10.1159/000441106
PG 7
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA CV4FE
UT WOS:000364221500010
PM 26505985
ER
PT J
AU Seminowicz, DA
Ceko, M
AF Seminowicz, David A.
Ceko, Marta
TI Can we exploit cognitive brain networks to treat chronic pain?
SO PAIN MANAGEMENT
LA English
DT Editorial Material
DE attention; cognition; conflict; default mode network; dorsolateral
prefrontal cortex; extrinsic mode network; fMRI; gray matter;
intervention task
ID LOW-BACK-PAIN; FUNCTIONAL CONNECTIVITY; FIBROMYALGIA; PERFORMANCE;
CORTEX
C1 [Seminowicz, David A.] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA.
[Ceko, Marta] NIH, Natl Ctr Complementary & Integrat Hlth, Bethesda, MD 20892 USA.
RP Seminowicz, DA (reprint author), Univ Maryland, Sch Dent, Dept Neural & Pain Sci, 650 W Baltimore St,8 South, Baltimore, MD 21201 USA.
EM dseminowicz@umaryland.edu
OI CEKO, MARTA/0000-0001-8679-8145
FU NCCIH NIH HHS [R01AT007176]; NIDCR NIH HHS [R21DE023964]
NR 20
TC 0
Z9 0
U1 4
U2 7
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-1869
EI 1758-1877
J9 PAIN MANAG
JI Pain Manag.
PY 2015
VL 5
IS 6
BP 399
EP 402
DI 10.2217/pmt.15.44
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA CV3LK
UT WOS:000364160500001
PM 26399153
ER
PT J
AU Ajiro, M
Jia, R
Wang, RH
Deng, CX
Zheng, ZM
AF Ajiro, Masahiko
Jia, Rong
Wang, Rui-Hong
Deng, Chu-Xia
Zheng, Zhi-Ming
TI Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs
in Mouse Littermates
SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
LA English
DT Article
DE Srsf3; shRNAs; transgenic mouse
ID SPLICING FACTOR SRP20; RNA INTERFERENCE; MAMMALIAN-CELLS; CANCER CELLS;
SUPPRESSION; EXPRESSION; SYSTEM; INDUCTION
AB Gene silencing techniques are widely used to control gene expression and have potential for RNAi-based therapeutics. In this report, transgenic mouse lines were created for conditional knockdown of Srsf3 (SRp20) expression in liver and mammary gland tissues by expressing Srsf3-specific shRNAs driven by a U6 promoter. Although a small portion of the transgenic mouse littermates were found to produce siRNAs in the targeted tissues, most of the transgenic littermates at two months of age failed to display a knockdown phenotype of Srsf3 expression in their liver and mammary gland tissues where an abundant level of Srsf3 siRNAs remained. We saw only one of four mice with liver/mammary gland expressing Srsf3 siRNA displayed a suppressed level of Srsf3 protein, but not the mRNA. Data indicate that the host resistance to a gene-specific siRNA targeting an essential gene transcript can be developed in animals, presumably as a physiological necessity to cope with the hostile perturbation.
C1 [Ajiro, Masahiko; Jia, Rong; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Wang, Rui-Hong; Deng, Chu-Xia] NCI, Genet Dev & Dis Branch, NIDDK, NIH, Bethesda, MD 20892 USA.
[Jia, Rong] Wuhan Univ, Sch Stomatol, Wuhan 430072, Hubei, Peoples R China.
[Wang, Rui-Hong; Deng, Chu-Xia] Univ Macau, Fac Hlth Sci, Macau, Macau, Peoples R China.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM zhengt@exchange.nih.gov
RI deng, chuxia/N-6713-2016
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; National Institute of Diabetes, Digestive
and Kidney Diseases, NIH
FX We thank Haiyan Lu in NIDDK transgenic Core for her performance of
oocyte pro-nuclear injection. This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, and National Institute of Diabetes,
Digestive and Kidney Diseases, NIH.
NR 26
TC 0
Z9 0
U1 0
U2 2
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1449-2288
J9 INT J BIOL SCI
JI Int. J. Biol. Sci.
PY 2015
VL 11
IS 11
BP 1248
EP 1256
DI 10.7150/ijbs.13011
PG 9
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA CU6XD
UT WOS:000363677500001
PM 26435690
ER
PT J
AU Gross, R
Zheng, L
La Rosa, A
Sun, X
Rosenkranz, SL
Cardoso, SW
Ssali, F
Camp, R
Godfrey, C
Cohn, SE
Robbins, GK
Chisada, A
Wallis, CL
Reynolds, NR
Lu, D
Safren, SA
Hosey, L
Severe, P
Collier, AC
AF Gross, Robert
Zheng, Lu
La Rosa, Alberto
Sun, Xin
Rosenkranz, Susan L.
Cardoso, Sandra Wagner
Ssali, Francis
Camp, Rob
Godfrey, Catherine
Cohn, Susan E.
Robbins, Gregory K.
Chisada, Anthony
Wallis, Carole L.
Reynolds, Nancy R.
Lu, Darlene
Safren, Steven A.
Hosey, Lara
Severe, Patrice
Collier, Ann C.
CA ACTG 5234 Team
TI Partner-based adherence intervention for second-line antiretroviral
therapy (ACTG A5234): a multinational randomised trial
SO LANCET HIV
LA English
DT Article
ID SUB-SAHARAN AFRICA; CLINICAL-TRIALS; METAANALYSIS; FAILURE; RESISTANCE;
OUTCOMES; USERS
AB Background Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefit patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modified directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom first-line therapy had failed.
Methods We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom first-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1: 1), via computer-generated randomisation, to receive partner-based modified directly observed therapy or standard of care. Randomisation was stratified by screening HIV RNA concentration (<= 10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confirmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569.
Findings Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modified directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modified directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25.1% (95% CI 17.7-32.4) in the modified directly observed therapy group and 17.3% (10.8-23.7) in the standard-of-care group, for a weighted difference in standard of care versus modified directly observed therapy of -6.6% (95% CI -16.5% to 3.2%; p=0.19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modified directly observed therapy group and n=15 in the standard-of-care group).
Interpretation Partner-based training with modified directly observed therapy had no effect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting.
C1 [Gross, Robert] Univ Penn, Perelman Sch Med, Med Infect Dis & Epidemiol, Philadelphia, PA 19104 USA.
[Zheng, Lu; Sun, Xin; Rosenkranz, Susan L.; Lu, Darlene] Harvard Univ, Sch Publ Hlth, Biostat, Boston, MA 02115 USA.
[La Rosa, Alberto] Asociac Civil IMPACTA Salud & Educ, Lima, Peru.
[Cardoso, Sandra Wagner] Fiocruz MS, BR-21045900 Rio De Janeiro, Brazil.
[Ssali, Francis] Joint Clin Res Ctr, Kampala, Uganda.
[Camp, Rob] EUPATI, Barcelona, Spain.
[Godfrey, Catherine] NIAID, Bethesda, MD 20892 USA.
[Cohn, Susan E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Robbins, Gregory K.; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Robbins, Gregory K.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA.
[Chisada, Anthony] Univ Zimbabwe, Harare, Zimbabwe.
[Wallis, Carole L.] Lancet Labs, Johannesburg, South Africa.
[Reynolds, Nancy R.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA.
[Hosey, Lara] Social & Sci Syst, Silver Spring, MD USA.
[Severe, Patrice] GHESKIO, Port Au Prince, Haiti.
[Collier, Ann C.] Univ Washington, Seattle, WA 98195 USA.
RP Gross, R (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
EM grossr@mail.med.upenn.edu
FU National Institute of Allergy and Infectious Diseases [UM1AI068636,
UM1AI069434, UM1AI069481, UM1AI068634, U01-AI069467]; National Institute
of Mental Health, National Institute of Dental and Craniofacial
Research; AIDS Clinical Trials Group Clinical Trials Unit [ACTG CTU]
grant [AI 069421]; ACTG CTU grant [U01-A1069501, UM 1AI069436, AI069463,
2UM1AI069438-08, AI069438, 7UMIA1069455, 2UMIAI069456-08, AI069476]
FX The project was supported by award numbers UM1AI068636, UM1AI069434,
UM1AI069481, UM1AI068634, and U01-AI069467 from the National Institute
of Allergy and Infectious Diseases and supported by National Institute
of Mental Health, National Institute of Dental and Craniofacial
Research. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institute of Allergy and Infectious Diseases or the National Institutes
of Health. Abbott Laboratories and Gilead Pharmaceuticals provided the
study drugs. We thank the study participants for their contributions and
acknowledge the following individual sites' grant support, study team
members, and site personnel: Valerie Francois and Samuel Pierre (Les
Centres GHESKIO clinical research site 30022, AIDS Clinical Trials Group
Clinical Trials Unit [ACTG CTU] grant AI 069421), Michael Ssemmanda and
Haspha Nassolo (Joint Clinical Research Centre clinical research site
12401, ACTG CTU grant U01-A1069501), Wadzanai Samaneka and James G Hakim
(Parirenyatwa clinical research site 30313, ACTG CTU grant UM
1AI069436), Mohammed Rassool and Pauline Vunandlala (Wits HIV clinical
research site 11101, ACTG CTU grant AI069463), Jorge Sanchez and Fanny
Rosas (Barranco clinical research site 11301, ACTG CTU grant
2UM1AI069438-08), Rosa Infante (San Miguel clinical research site 11302,
ACTG CTU grant AI069438), Elizabeth Stringer and Margaret Kasaro
(Kalingalinga Clinic clinical research site 12801, ACTG CTU grant
7UMIA1069455), Mpho Shakes Raesi and Lesedi Tirelo (Gaborone
Prevention/Treatment Trials clinical research site 12701, ACTG CTU grant
2UMIAI069456-08 and Catalog of Federal Domestic Assistance grant
93.865), and Brenda Hoagland and Isabel Tavares (Instituto de Pesquisa
Clinica Evandro Chagas clinical research site 12101, ACTG CTU grant
AI069476).
NR 28
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 2352-3018
J9 LANCET HIV
JI Lancet HIV
PD JAN
PY 2015
VL 2
IS 1
BP E12
EP E19
DI 10.1016/S2352-3018(14)00007-1
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CU8KP
UT WOS:000363791600008
PM 25664336
ER
PT J
AU Fu, JW
Ma, GD
Mai, H
Luo, XD
Yin, JW
Chen, Q
Lin, ZX
Tao, H
Li, Y
Cui, LL
Li, Z
Lin, JD
Zhao, B
Li, KS
AF Fu, Jiawu
Ma, Guoda
Mai, Hui
Luo, Xudong
Yin, Jingwen
Chen, Qing
Lin, Zhixiong
Tao, Hua
Li, You
Cui, Lili
Li, Zheng
Lin, Juda
Zhao, Bin
Li, Keshen
TI Association study of sepiapterin reductase gene promoter polymorphisms
with schizophrenia in a Han Chinese population
SO NEUROPSYCHIATRIC DISEASE AND TREATMENT
LA English
DT Article
DE schizophrenia; sepiapterin reductase; polymorphisms; Han Chinese
population; transcriptional activity
ID TRANSCRIPTION FACTOR; PARKINSONS-DISEASE; EXPRESSION; DOPAMINE; SP1;
DEFICIENCY; SEROTONIN; DISORDER; ESTROGEN; PATHWAY
AB Sepiapterin reductase participates in the biosynthesis of tetrahydrobiopterin, which plays very important roles in the pathogenesis of schizophrenia via dysregulation of neurotransmitter systems. Here, two single nucleotide polymorphisms (rs1876487 and rs2421095) in the promoter region of SPR were genotyped in 941 schizophrenic patients and 944 controls in a Han Chinese population using the SNaPshot technique. No significant differences were found in the distribution of alleles or genotypes of the two single nucleotide polymorphisms (SNPs) between schizophrenic patients and controls (all P>0.05). Likewise, no haplotype was found to be associated with schizophrenia. However, sex-stratified analysis revealed that the frequencies of the A allele of rs1876487 and the A-A (rs2421095-rs1876487) haplotype were all significantly different between schizophrenia and controls in females (P=0.040 and P=0.033, respectively), but not in males. Additionally, luciferase reporter gene assays revealed that the A-A haplotype had significantly higher SPR transcriptional activity compared with the A-C haplotype in SH-SY5Y cells. Our data indicate that the two SNPs do not influence the risk of schizophrenia when using the total sample, but the A allele of rs1876487 and the A-A haplotype may contribute to protective roles for schizophrenia in females.
C1 [Fu, Jiawu; Ma, Guoda; Mai, Hui; Tao, Hua; Li, You; Cui, Lili; Zhao, Bin; Li, Keshen] Guangdong Med Univ, Inst Neurol, Affiliated Hosp, Zhanjiang 524001, Guangdong, Peoples R China.
[Luo, Xudong; Yin, Jingwen; Chen, Qing; Lin, Zhixiong; Lin, Juda] Guangdong Med Univ, Dept Psychiat, Affiliated Hosp, Zhanjiang 524001, Guangdong, Peoples R China.
[Li, Zheng] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA.
RP Zhao, B (reprint author), Guangdong Med Univ, Inst Neurol, Affiliated Hosp, Zhanjiang 524001, Guangdong, Peoples R China.
EM binzhaoe@163.com; likeshen1971@126.com
OI Cui, Lili/0000-0003-0273-2531; Cui, Lili/0000-0003-2150-3857
FU US-China Biomedical Collaborative Research Program [81261120404];
National Nature Science Foundation of China [31171219, 81271213,
81070878, 81271214, 81471294]; Science and Technology Innovation Fund of
Guangdong Medical University [STIF 201101, M2014047]
FX This work was supported by funding from the US-China Biomedical
Collaborative Research Program (grant number 81261120404), the National
Nature Science Foundation of China (grant numbers 31171219, 81271213,
81070878, and 81271214, and 81471294), and the Science and Technology
Innovation Fund of Guangdong Medical University (numbers STIF 201101 and
M2014047).
NR 26
TC 0
Z9 0
U1 0
U2 0
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1178-2021
J9 NEUROPSYCH DIS TREAT
JI Neuropsychiatr. Dis. Treat.
PY 2015
VL 11
BP 2793
EP 2799
DI 10.2147/NDT.S92986
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CU8HS
UT WOS:000363783200001
PM 26604763
ER
PT J
AU Zhang, F
Cao, JB
Chen, X
Yang, K
Zhu, L
Fu, GF
Huang, XL
Chen, XY
AF Zhang, Fan
Cao, Jianbo
Chen, Xiao
Yang, Kai
Zhu, Lei
Fu, Guifeng
Huang, Xinglu
Chen, Xiaoyuan
TI Noninvasive Dynamic Imaging of Tumor Early Response to
Nanoparticle-mediated Photothermal Therapy
SO THERANOSTICS
LA English
DT Article
DE Photothermal therapy; nanoparticles; magnetic resonance imaging; tumor
blood vessels
ID DIFFUSION-WEIGHTED MRI; REDUCED GRAPHENE OXIDE; NANOGRAPHENE OXIDE;
THERMAL ABLATION; BLOOD-FLOW; HYPERTHERMIA; TISSUE; LASER;
NANOCOMPOSITES; ULTRASOUND
AB In spite of rapidly increasing interest in the use of nanoparticle-mediated photothermal therapy (PTT) for treatment of different types of tumors, very little is known on early treatment-related changes in tumor response. Using graphene oxide (GO) as a model nanoparticle (NP), in this study, we tracked the changes in tumors after GO NP-mediated PTT by magnetic resonance imaging (MRI) and quantitatively identified MRI multiple parameters to assess the dynamic changes of MRI signal in tumor at different heating levels and duration. We found a time- and temperature-dependent dynamic change of the MRI signal intensity in intratumor microenvironment prior to any morphological change of tumor, mainly due to quick and effective eradication of tumor blood vessels. Based on the distribution of GO particles, we also demonstrated that NP-medited PTT caused heterogeneous thermal injury of tumor. Overall, these new findings provide not only a clinical-related method for non-invasive early tracking, identifying, and monitoring treatment response of NP-mediated PTT but also show a new vision for better understanding mechanisms of NP-mediated PTT.
C1 [Zhang, Fan; Cao, Jianbo; Zhu, Lei; Fu, Guifeng] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361005, Fujian, Peoples R China.
[Zhang, Fan; Cao, Jianbo; Zhu, Lei; Fu, Guifeng] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Fujian, Peoples R China.
[Chen, Xiao] Xinjiang Med Univ, Dept Pathol, Urumqi 830011, Xinjiang, Peoples R China.
[Yang, Kai] Soochow Univ, Inst Funct Nano & Soft Mat Lab FUNSOM, Jiangsu Key Lab Carbon Based Funct Mat & Devices, Suzhou 215123, Jiangsu, Peoples R China.
[Huang, Xinglu; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Zhang, F (reprint author), Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361005, Fujian, Peoples R China.
EM sailfmri@hotmail.com; xhuang33@jhmi.edu; shawn.chen@nih.gov
RI Zhu, Lei/P-9786-2016
OI Zhu, Lei/0000-0002-1820-4795
FU National Science Foundation of China (NSFC) [81201086, 81471655,
81301256]; intramural research program, National Institute of Biomedical
Imaging and Bioengineering, National Institutes of Health
FX The authors thank Rebecca Zhang (Molecular and Cellular Biology at the
Johns Hopkins University) for proof editing of this manuscript. This
work was supported by the National Science Foundation of China (NSFC)
(81201086, 81471655and 81301256), and the intramural research program,
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health.
NR 36
TC 5
Z9 5
U1 3
U2 15
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2015
VL 5
IS 12
BP 1444
EP 1455
DI 10.7150/thno.13398
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CU6XJ
UT WOS:000363678100011
PM 26681988
ER
PT B
AU Zerbe, MJ
DelliCarpini, DF
AF Zerbe, Michael J.
DelliCarpini, Dominic F.
BE Giberson, G
Nugent, J
Ostergaard, L
TI WRITING AS AN ART AND PROFESSION AT YORK COLLEGE
SO WRITING MAJORS: EIGHTEEN PROGRAM PROFILES
LA English
DT Article; Book Chapter
C1 [Zerbe, Michael J.] York Coll Penn, English & Humanities, York, PA 17403 USA.
[Zerbe, Michael J.] York Coll Penn, York, PA USA.
[Zerbe, Michael J.] York Coll Penn, Profess Writing Major, York, PA USA.
[Zerbe, Michael J.] York Coll Penn, FYC Program, York, PA USA.
[Zerbe, Michael J.] NCI, Bethesda, MD 20892 USA.
[DelliCarpini, Dominic F.] York Coll Penn, Acad Affairs, York, PA USA.
[DelliCarpini, Dominic F.] York Coll Penn, Writing Studies, York, PA USA.
[DelliCarpini, Dominic F.] York Coll Penn, Writing Program, York, PA USA.
[DelliCarpini, Dominic F.] Council Writing Program Administrators, Execut Board, New York, NY USA.
RP Zerbe, MJ (reprint author), York Coll Penn, English & Humanities, York, PA 17403 USA.
NR 12
TC 0
Z9 0
U1 0
U2 0
PU UTAH STATE UNIV PRESS
PI LOGAN
PA UTAH STATE UNIV, LOGAN, UTAH 84322 USA
BN 978-0-87421-971-5; 978-0-87421-972-2
PY 2015
BP 119
EP 133
DI 10.7330/9780874219722.c010
D2 10.7330/9780874219722
PG 15
WC Education & Educational Research
SC Education & Educational Research
GA BD5WE
UT WOS:000361837700012
ER
PT J
AU Sarkar, D
Jung, MK
Wang, HJ
AF Sarkar, Dipak
Jung, M. Katherine
Wang, H. Joe
TI Alcohol and the Immune System
SO ALCOHOL RESEARCH-CURRENT REVIEWS
LA English
DT Editorial Material
C1 [Sarkar, Dipak] Rutgers State Univ, Dept Anim Sci, New Brunswick, NJ 08903 USA.
[Sarkar, Dipak] Rutgers State Univ, Endocrine Program, New Brunswick, NJ 08903 USA.
[Jung, M. Katherine; Wang, H. Joe] NIAAA, Div Metab & Hlth Effects, Rockville, MD 20852 USA.
RP Sarkar, D (reprint author), Rutgers State Univ, Dept Anim Sci, New Brunswick, NJ 08903 USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
PU NATL INST ALCOHOL ABUSE ALCOHOLISM
PI ROCKVILLE
PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA
SN 1535-7414
EI 1930-0573
J9 ALCOHOL RES-CURR REV
JI Alcohol Res.-Curr. Rev.
PY 2015
VL 37
IS 2
BP 153
EP 155
PG 3
WC Substance Abuse
SC Substance Abuse
GA CU0RH
UT WOS:000363225900001
ER
PT J
AU Vaisman, BL
Vishnyakova, TG
Freeman, LA
Amar, MJ
Demosky, SJ
Liu, CY
Stonik, JA
Sampson, ML
Pryor, M
Bocharov, AV
Eggerman, TL
Patterson, AP
Remaley, AT
AF Vaisman, Boris L.
Vishnyakova, Tatyana G.
Freeman, Lita A.
Amar, Marcelo J.
Demosky, Stephen J.
Liu, Chengyu
Stonik, John A.
Sampson, Maureen L.
Pryor, Milton
Bocharov, Alexander V.
Eggerman, Thomas L.
Patterson, Amy P.
Remaley, Alan T.
TI Endothelial Expression of Scavenger Receptor Class B, Type I Protects
against Development of Atherosclerosis in Mice
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; MARROW-DERIVED CELLS; SR-BI; TRANSGENIC MICE;
PERIPHERAL-TISSUES; LESION DEVELOPMENT; HDL METABOLISM; DEFICIENT MICE;
TRANSPORT; CHOLESTEROL
AB The role of scavenger receptor class B, type I (SR-BI) in endothelial cells (EC) was examined in several novel transgenic mouse models expressing SR-BI in endothelium of mice with normal C57Bl6/N, apoE-KO, or Scarb1-KO backgrounds. Mice were also created expressing SR-BI exclusively in endothelium and liver. Endothelial expression of the Tie2-Scarb1 transgene had no significant effect on plasma lipoprotein levels in mice on a normal chow diet but on an atherogenic diet, significantly decreased plasma cholesterol levels, increased plasma HDL cholesterol (HDL-C) levels, and protected mice against atherosclerosis. In 8-month-old apoE-KO mice fed a normal chow diet, the Tie2-Scarb1 transgene decreased aortic lesions by 24%. Mice expressing SR-BI only in EC and liver had a 1.5 +/- 0.1-fold increase in plasma cholesterol compared to mice synthesizing SR-BI only in liver. This elevation was due mostly to increased HDL-C. In EC culture studies, SR-BI was found to be present in both basolateral and apical membranes but greater cellular uptake of cholesterol from HDL was found in the basolateral compartment. In summary, enhanced expression of SR-BI in EC resulted in a less atherogenic lipoprotein profile and decreased atherosclerosis, suggesting a possible role for endothelial SR-BI in the flux of cholesterol across EC.
C1 [Vaisman, Boris L.; Freeman, Lita A.; Amar, Marcelo J.; Demosky, Stephen J.; Stonik, John A.; Pryor, Milton; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Vishnyakova, Tatyana G.; Bocharov, Alexander V.; Eggerman, Thomas L.; Patterson, Amy P.] NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Core, NIH, Bethesda, MD 20892 USA.
[Sampson, Maureen L.] NIH, Dept Lab Med, NIH, Bethesda, MD 20892 USA.
RP Vaisman, BL (reprint author), NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA.
EM borisv@mail.nih.gov
FU Intramural Division of NHLBI, NIH
FX The authors would like to thank Dr. Thomas N. Sato for providing the
pSPTg.T2FpAXK plasmid, Dr. Christian Combs and Dr. Daniela Malide, The
Light Microscopy Core, and Dr. Zu-Xi Yu, the Pathology Core, for help in
immunofluorescent confocal and immunohistological microscopy analysis.
Research for this study was supported by funds from the Intramural
Division of NHLBI, NIH.
NR 46
TC 1
Z9 1
U1 1
U2 2
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PY 2015
AR 607120
DI 10.1155/2015/607120
PG 13
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA CT9QZ
UT WOS:000363153000001
ER
PT J
AU Neychev, V
Steinberg, SM
Cottle-Delisle, C
Merkel, R
Nilubol, N
Yao, JH
Meltzer, P
Pacak, K
Marx, S
Kebebew, E
AF Neychev, Vladimir
Steinberg, Seth M.
Cottle-Delisle, Candice
Merkel, Roxanne
Nilubol, Naris
Yao, Jianhua
Meltzer, Paul
Pacak, Karel
Marx, Stephen
Kebebew, Electron
TI Mutation-targeted therapy with sunitinib or everolimus in patients with
advanced low-grade or intermediate-grade neuroendocrine tumours of the
gastrointestinal tract and pancreas with or without cytoreductive
surgery: protocol for a phase II clinical trial
SO BMJ OPEN
LA English
DT Article
ID ENDOCRINE TUMORS; PROGNOSTIC-FACTORS; RAD001 EVEROLIMUS; UNITED-STATES;
GROWTH-FACTOR; MTOR PATHWAY; MANAGEMENT; DIAGNOSIS; EXPRESSION;
METASTASES
AB Introduction: Finding the optimal management strategy for patients with advanced, metastatic neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas is a work in progress. Sunitinib and everolimus are currently approved for the treatment of progressive, unresectable, locally advanced or metastatic low-grade or intermediate-grade pancreatic NETs. However, mutation-targeted therapy with sunitinib or everolimus has not been studied in this patient population.
Methods and analysis: This prospective, open-label phase II clinical trial was designed to determine if mutation-targeting therapy with sunitinib or everolimus for patients with advanced low-grade or intermediate-grade NETs is more effective than historically expected results with progression-free survival (PFS) as the primary end point. Patients >= 18 years of age with progressive, low-grade or intermediate-grade locally advanced or metastatic NETs are eligible for this study. Patients will undergo tumour biopsy (if they are not a surgical candidate) for tumour genotyping. Patients will be assigned to sunitininb or everolimus based on somatic/germline mutations profile. Patients who have disease progression on either sunitinib or everolimus will crossover to the other drug. Treatment will continue until disease progression, unacceptable toxicity, or consent to withdrawal. Using the proposed criteria, 44 patients will be accrued within each treatment group during a 48-month period (a total of 88 patients for the 2 treatments), and followed for up to an additional 12 months (a total of 60 months from entry of the first patient) to achieve 80% power in order to test whether there is an improvement in PFS compared to historically expected results, with a 0.10 a level one-sided significance test.
Ethics and dissemination: The study protocol was approved by the institutional review board of the National Cancer Institute (NCI-IRB Number 15C0040; IRIS Reference Number 339636). The results will be published in a peer-reviewed journal and shared with the worldwide medical community.
C1 [Neychev, Vladimir; Cottle-Delisle, Candice; Merkel, Roxanne; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Yao, Jianhua] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Meltzer, Paul] NIH, Mol Genet Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Marx, Stephen] Natl Inst Diabet & Digest & Kidney Dis, Genet & Endocrinol Sect, Bethesda, MD USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD, USA
FX This work is supported by the intramural research programme of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD, USA. Sunitinib and evrolimus are by
Pfizer Inc, and Novartis Pharmaceuticals Corporation, respectively.
NR 46
TC 6
Z9 6
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2015
VL 5
IS 5
AR e008248
DI 10.1136/bmjopen-2015-008248
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA CU4CG
UT WOS:000363473200046
PM 25991462
ER
PT J
AU Dasgeb, B
Morris, MA
Mehregan, D
Siegel, EL
AF Dasgeb, Bahar
Morris, Michael A.
Mehregan, Darius
Siegel, Eliot L.
TI Quantified ultrasound elastography in the assessment of cutaneous
carcinoma
SO BRITISH JOURNAL OF RADIOLOGY
LA English
DT Article
ID SHEAR-WAVE ELASTOGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; NONPIGMENTED SKIN
TUMORS; PRIMARY-CARE PHYSICIANS; INVASIVE BREAST-CANCER; VASCULAR
STRUCTURES; MELANOMA; DERMOSCOPY; DIAGNOSIS; DERMATOLOGISTS
AB Objective: To evaluate the feasibility of high-frequency ultrasound and ultrasound elastography (USE) in discriminating benign from malignant skin lesions in a prospective cohort study and to introduce the use of a "strain ratio" for evaluation of skin lesions.
Methods: A commercial ultrasound system with a 14-MHz transducer was used to visualize skin lesions requiring biopsy on clinical evaluation. Anatomic ultrasound and USE imaging of the skin lesions was performed using 2- to 4-mm gel stand-off pads. A region of interest was manually selected over the area of each lesion with the lowest strain. The concept of a strain ratio of the compressibility of the normal skin at the corresponding layer to that of the least compressible region of a lesion in question was created and applied. This ratio was subsequently correlated with blind histopathological evaluation for malignancy.
Results: 55 patients were included in the study with a total of 67 lesions evaluated. 29 lesions were malignant and 38 benign. All malignant lesions had strain ratios >= 3.9. All benign lesions had strain ratios <= 3.0. A diagnostic value between 3.0 and 3.9 would result in 100% sensitivity and specificity in the characterization of these lesions as malignant.
Conclusion: This pilot study demonstrated that USE plus strain ratio appears to be a promising modality in providing diagnostic determination between cancerous and benign primary solitary skin lesions prior to biopsy.
Advances in knowledge: This is the first reported study applying an original mathematical elastographic ratio, or strain ratio, to evaluate primary solitary skin lesions.
C1 [Dasgeb, Bahar] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10021 USA.
[Dasgeb, Bahar] NIH, Analyt & Stochast Biomed Phys Sect, Bethesda, MD 20892 USA.
[Morris, Michael A.; Siegel, Eliot L.] Univ Maryland, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA.
[Morris, Michael A.] Mercy Med Ctr, Dept Internal Med, Baltimore, MD USA.
[Mehregan, Darius] Wayne State Univ, Dept Dermatol, Dearborn, MI USA.
[Mehregan, Darius] Pinkus Dermatopathol Labs, Monroe, MI USA.
[Siegel, Eliot L.] Baltimore Vet Affairs Med Ctr, Dept Diagnost Radiol & Nucl Med, Baltimore, MD USA.
RP Dasgeb, B (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, 1275 York Ave, New York, NY 10021 USA.
EM dasgebb@mskcc.org
FU University of Maryland Office of Student Research
FX The authors wish to acknowledge Hitachi Medical America, Ohio, and
Hitachi Medical Corporation, Tokyo, Japan, for loaning their Hi Vision
Ultrasound Elastography unit for the duration of this project. The
authors would also like to acknowledge Brigitte Pocta, Joan Liebmann,
PhD and Nancy Knight, PhD, for their assistance with editing. Finally,
the authors wish to acknowledge the University of Maryland Office of
Student Research for supporting this research.
NR 51
TC 1
Z9 1
U1 0
U2 0
PU BRITISH INST RADIOLOGY
PI LONDON
PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND
SN 0007-1285
EI 1748-880X
J9 BRIT J RADIOL
JI Br. J. Radiol.
PY 2015
VL 88
IS 1054
AR 20150344
DI 10.1259/bjr.20150344
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CU1XN
UT WOS:000363315800022
PM 26268142
ER
PT S
AU Palena, C
Hamilton, DH
AF Palena, Claudia
Hamilton, Duane H.
BE Wang, XY
Fisher, PB
TI Immune Targeting of Tumor Epithelial-Mesenchymal Transition via
Brachyury-Based Vaccines
SO IMMUNOTHERAPY OF CANCER
SE Advances in Cancer Research
LA English
DT Review; Book Chapter
ID TRANSCRIPTION FACTOR BRACHYURY; THERAPEUTIC CANCER VACCINES; EGFR
INHIBITOR RESISTANCE; CELL-CYCLE PROGRESSION; HUMAN CARCINOMA-CELLS;
E-CADHERIN EXPRESSION; STEM-CELLS; PROSTATE-CANCER; AUTOPHAGY INDUCTION;
CERVICAL-CANCER
AB As a manifestation of their inherent plasticity, carcinoma cells undergo profound phenotypic changes during progression toward metastasis. One such phenotypic modulation is the epithelial-mesenchymal transition (EMT), an embryonically relevant process that can be reinstated by tumor cells, resulting in the acquisition of metastatic propensity, stem-like cell properties, and resistance to a variety of anticancer therapies, including chemotherapy, radiation, and some small-molecule targeted therapies. Targeting of the EMT is emerging as a novel intervention against tumor progression. This review focuses on the potential use of cancer vaccine strategies targeting tumor cells that exhibit mesenchymal-like features, with an emphasis on the current status of development of vaccine platforms directed against the T-box transcription factor brachyury, a novel cancer target involved in tumor EMT, stemness, and resistance to therapies. Also presented is a summary of potential mechanisms of resistance to immune-mediated attack driven by EMT and the development of novel combinatorial strategies based on the use of agents that alleviate tumor EMT for an optimized targeting of plastic tumor cells that are responsible for tumor recurrence and the establishment of therapeutic refractoriness.
C1 [Palena, Claudia; Hamilton, Duane H.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Palena, C (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM palenac@mail.nih.gov; hamiltondh@mail.nih.gov
NR 110
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0065-230X
BN 978-0-12-802554-3; 978-0-12-802316-7
J9 ADV CANCER RES
JI Adv.Cancer Res.
PY 2015
VL 128
BP 69
EP 93
DI 10.1016/bs.acr.2015.04.001
PG 25
WC Oncology; Immunology
SC Oncology; Immunology
GA BD7PY
UT WOS:000363451000003
PM 26216630
ER
PT J
AU Chen, SD
Shen, DF
Popp, NA
Ogilvy, AJ
Tuo, JS
Abu-Asab, M
Xie, T
Chan, CC
AF Chen, Shida
Shen, Defen
Popp, Nicholas A.
Ogilvy, Alexander J.
Tuo, Jingsheng
Abu-Asab, Mones
Xie, Ting
Chan, Chi-Chao
TI Responses of Multipotent Retinal Stem Cells to IL-1 beta, IL-18, or
IL-17
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; T-CELLS; NLRP3 INFLAMMASOME; FAMILY CYTOKINES;
INNATE IL-17; CRUCIAL ROLE; INTERLEUKIN-17; EXPRESSION; DEATH;
NECROPTOSIS
AB Purpose. To investigate how multipotent retinal stem cells (RSCs) isolated from mice respond to the proinflammatory signaling molecules, IL-1 beta, IL-18, and IL-17A. Materials and Methods. RSCs were cultured in a specific culture medium and were treated with these cytokines. Cell viability was detected by MTT assay; ultrastructure was evaluated by transmission electron microscopy; expression of IL-17rc and proapoptotic proteins was detected by immunocytochemistry and expression of Il-6 and Il-17a was detected by quantitative RT-PCR. As a comparison, primary mouse retinal pigment epithelium (RPE) cells were also treated with IL-1 beta, IL-18, or IL-17A and analyzed for the expression of Il-6 and Il-17rc. Results. Treatment with IL-1 beta, IL-18, or IL-17A decreased RSC viability in a dose-dependent fashion and led to damage in cellular ultrastructure including pyroptotic and/or necroptotic cells. IL-1 beta and IL-18 could induce proapoptotic protein expression. All treatments induced significantly higher expression of Il-6 and Il-17rc in both cells. However, neither IL-1 beta nor IL-18 could induce Il-17a expression in RSCs. Conclusions. IL-1 beta, IL-18, and IL-17A induce retinal cell death via pyroptosis/necroptosis and apoptosis. They also provoke proinflammatory responses in RSCs. Though IL-1 beta and IL-18 could not induce Il-17a expression in RSCs, they both increase Il-17rc expression, which may mediate the effect of Il-17a.
C1 [Chen, Shida; Shen, Defen; Popp, Nicholas A.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Shida] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China.
[Ogilvy, Alexander J.; Abu-Asab, Mones] NEI, Histol Core, NIH, Bethesda, MD 20892 USA.
[Xie, Ting] Stowers Inst Med Res, Kansas City, MO 64110 USA.
[Xie, Ting] Univ Kansas, Sch Med, Dept Anat & Cell Biol, Kansas City, KS 66160 USA.
RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
FU NEI
FX This research received the NEI intramural research fund. The authors
would like to thank Dr. Chun Gao of the Biological Imaging Core, NEI,
who helped them with the confocal experiments.
NR 37
TC 0
Z9 0
U1 0
U2 0
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PY 2015
AR 369312
DI 10.1155/2015/369312
PG 9
WC Medicine, Research & Experimental; Ophthalmology
SC Research & Experimental Medicine; Ophthalmology
GA CT9TI
UT WOS:000363159100001
ER
PT S
AU Hejtmancik, JF
Nickerson, JM
AF Hejtmancik, J. Fielding
Nickerson, John M.
BE Hejtmancik, JF
Nickerson, JM
TI Overview of the Visual System
SO MOLECULAR BIOLOGY OF EYE DISEASE
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
AB This introduction provides an overview of the retina, in which we survey the fundus, layers of the retina, retinal cell types, visual transduction cascade, vitamin A cycle, neuronal wiring of the retina, and blood supply of the retina.
C1 [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Nickerson, John M.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
RP Nickerson, JM (reprint author), Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
EM litjn@emory.edu
NR 0
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1877-1173
BN 978-0-12-801267-3; 978-0-12-801059-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 134
BP 1
EP 4
DI 10.1016/bs.pmbts.2015.05.006
PG 4
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA BD7MP
UT WOS:000363312000002
PM 26310145
ER
PT S
AU Hejtmancik, JF
Nickerson, JM
AF Hejtmancik, J. Fielding
Nickerson, John M.
BE Hejtmancik, JF
Nickerson, JM
TI PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE Molecular
Biology of Eye Disease PREFACE
SO MOLECULAR BIOLOGY OF EYE DISEASE
SE Progress in Molecular Biology and Translational Science
LA English
DT Editorial Material; Book Chapter
C1 [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Nickerson, John M.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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 978-0-12-801267-3; 978-0-12-801059-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 134
BP XIX
EP XX
PG 2
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA BD7MP
UT WOS:000363312000001
PM 26310176
ER
PT S
AU Hejtmancik, JF
Shiels, A
AF Hejtmancik, J. Fielding
Shiels, Alan
BE Hejtmancik, JF
Nickerson, JM
TI Overview of the Lens
SO MOLECULAR BIOLOGY OF EYE DISEASE
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
ID AGE-RELATED-CHANGES; ALPHA-B-CRYSTALLIN; HUMAN EYE LENS; DEAMIDATION
DESTABILIZES; REFRACTIVE-INDEX; LIGHT-SCATTERING; NUCLEAR CATARACT;
GENE-EXPRESSION; MESSENGER-RNA; A-CRYSTALLIN
AB In order to accomplish its function of transmitting and focusing light, the crystalline lens of the vertebrate eye has evolved a unique cellular structure and protein complement. These distinct adaptations have provided a rich source of scientific discovery ranging from biochemistry and genetics to optics and physics. In addition, because of these adaptations, lens cells persist for the lifetime of an organism, providing an excellent model of the aging process. The chapters dealing with the lens will demonstrate how the different aspects of lens biology and biochemistry combine in this singular refractive organ to accomplish its critical role in the visual system.
C1 [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Shiels, Alan] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
RP Shiels, A (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
EM Shiels@vision.wustl.edu
NR 79
TC 0
Z9 0
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 1877-1173
BN 978-0-12-801267-3; 978-0-12-801059-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 134
BP 119
EP 127
DI 10.1016/bs.pmbts.2015.04.006
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA BD7MP
UT WOS:000363312000010
PM 26310153
ER
PT S
AU Hejtmancik, JF
Riazuddin, SA
McGreal, R
Liu, W
Cvekl, A
Shiels, A
AF Hejtmancik, J. Fielding
Riazuddin, S. Amer
McGreal, Rebecca
Liu, Wei
Cvekl, Ales
Shiels, Alan
BE Hejtmancik, JF
Nickerson, JM
TI Lens Biology and Biochemistry
SO MOLECULAR BIOLOGY OF EYE DISEASE
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
ID ALPHA-B-CRYSTALLIN; HEAT-SHOCK-PROTEIN; EPITHELIAL-CELL APOPTOSIS;
CHAPERONE-LIKE ACTIVITY; BETA-GAMMA-CRYSTALLIN; FIBRILLARY ACIDIC
PROTEIN; GLUTATHIONE REDOX CYCLE; TRAIL-INDUCED APOPTOSIS;
ACTIN-FILAMENT BUNDLES; GAP-JUNCTION PROTEIN
AB The primary function of the lens resides in its transparency and ability to focus light on the retina. These require both that the lens cells contain high concentrations of densely packed lens crystallins to maintain a refractive index constant over distances approximating the wavelength of the light to be transmitted, and a specific arrangement of anterior epithelial cells and arcuate fiber cells lacking organelles in the nucleus to avoid blocking transmission of light. Because cells in the lens nucleus have shed their organelles, lens crystallins have to last for the lifetime of the organism, and are specifically adapted to this function. The lens crystallins comprise two major families: the beta gamma-crystallins are among the most stable proteins known and the alpha-crystallins, which have a chaperone-like function. Other proteins and metabolic activities of the lens are primarily organized to protect the crystallins from damage over time and to maintain homeostasis of the lens cells. Membrane protein channels maintain osmotic and ionic balance across the lens, while the lens cytoskeleton provides for the specific shape of the lens cells, especially the fiber cells of the nucleus. Perhaps most importantly, a large part of the metabolic activity in the lens is directed toward maintaining a reduced state, which shelters the lens crystallins and other cellular components from damage from UV light and oxidative stress. Finally, the energy requirements of the lens are met largely by glycolysis and the pentose phosphate pathway, perhaps in response to the avascular nature of the lens. Together, all these systems cooperate to maintain lens transparency over time.
C1 [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[McGreal, Rebecca; Liu, Wei; Cvekl, Ales] Albert Einstein Coll Med, Dept Genet & Ophthalmol, Bronx, NY 10467 USA.
[McGreal, Rebecca; Liu, Wei; Cvekl, Ales] Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10467 USA.
[Shiels, Alan] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
RP Shiels, A (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
EM Shiels@vision.wustl.edu
NR 245
TC 2
Z9 2
U1 0
U2 6
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1877-1173
BN 978-0-12-801267-3; 978-0-12-801059-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 134
BP 169
EP 201
DI 10.1016/bs.pmbts.2015.04.007
PG 33
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA BD7MP
UT WOS:000363312000012
PM 26310155
ER
PT S
AU Shiels, A
Hejtmancik, JF
AF Shiels, Alan
Hejtmancik, J. Fielding
BE Hejtmancik, JF
Nickerson, JM
TI Molecular Genetics of Cataract
SO MOLECULAR BIOLOGY OF EYE DISEASE
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
ID AGE-RELATED CATARACT; DNA-REPAIR GENES; RECESSIVE CONGENITAL CATARACTS;
HAN CHINESE POPULATION; NANCE-HORAN SYNDROME; PEDIATRIC CATARACT;
CORTICAL CATARACT; NUCLEAR CATARACT; JIANGSU EYE; OCULAR LENS
AB Lens opacities or cataract(s) represent a universally important cause of visual impairment and blindness. Typically, cataract is acquired with aging as a complex disorder involving environmental and genetic risk factors. Cataract may also be inherited with an early onset either in association with other ocular and/or systemic abnormalities or as an isolated lens phenotype. Here we briefly review recent advances in gene discovery for inherited and age-related forms of cataract that are providing new insights into lens development and aging.
C1 [Shiels, Alan] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
[Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Shiels, A (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
EM Shiels@vision.wustl.edu
FU NEI NIH HHS [EY012284, EY02687]
NR 73
TC 6
Z9 6
U1 2
U2 6
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1877-1173
BN 978-0-12-801267-3; 978-0-12-801059-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 134
BP 203
EP 218
DI 10.1016/bs.pmbts.2015.05.004
PG 16
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA BD7MP
UT WOS:000363312000013
PM 26310156
ER
PT S
AU Wright, CB
Redmond, TM
Nickerson, JM
AF Wright, Charles B.
Redmond, T. Michael
Nickerson, John M.
BE Hejtmancik, JF
Nickerson, JM
TI A History of the Classical Visual Cycle
SO MOLECULAR BIOLOGY OF EYE DISEASE
SE Progress in Molecular Biology and Translational Science
LA English
DT Review; Book Chapter
ID LEBER CONGENITAL AMAUROSIS; RETINAL-PIGMENT EPITHELIUM; RPE65
MESSENGER-RNA; ISOMEROHYDROLASE ACTIVITY; VITAMIN-A; IN-VITRO; MEMBRANE
ASSOCIATION; RETINITIS-PIGMENTOSA; MICROSOMAL PROTEIN; BINDING PROTEINS
AB The visual cycle, the biochemical process by which the light-sensitive isomer of vitamin A is continually recycled, is crucial to vision in a healthy eye. More than 150 years of research into this remarkable biochemical process has given invaluable understanding in debilitating visual diseases that impact thousands of individuals worldwide, many of them children. The visual cycle spans photoreceptor cells in the retina and the underlying retinal pigment epithelium (RPE) and requires a protein called RPE65 for its function. In many ways, RPE65 is the capstone to the cyclical processing of vitamin A in the eye, and the discovery of this retinol isomerase helped fill a critical gap in the understanding of retinoid processing in vision. This chapter will focus on the history of visual cycle research, from the first experiments well over a century ago to the discovery of RPE65. Because of the undeniable importance of RPE65 in the visual cycle, this chapter will also focus on the protein structure and mechanism by which it converts light-insensitive all-trans-vitamin A to light-sensitive 11-cis-vitamin A for continued visual function. Finally, this chapter will briefly discuss RPE65 and its known disease associations in the clinical setting. Thanks to the efforts of researchers for well over a century in studying the visual cycle, the medical community is now poised to make significant gains in the treatment of blindness.
C1 [Wright, Charles B.] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
[Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Nickerson, John M.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
RP Wright, CB (reprint author), Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
EM wright.charles@uky.edu
NR 74
TC 3
Z9 4
U1 2
U2 8
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1877-1173
BN 978-0-12-801267-3; 978-0-12-801059-4
J9 PROG MOL BIOL TRANSL
JI Prog. Molec. Biol. Transl. Sci.
PY 2015
VL 134
BP 433
EP 448
DI 10.1016/bs.pmbts.2015.06.009
PG 16
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA BD7MP
UT WOS:000363312000026
PM 26310169
ER
PT J
AU Choi, CH
Chung, JY
Cho, H
Kitano, H
Chang, E
Ylaya, K
Chung, EJ
Kim, JH
Hewitt, SM
AF Choi, Chel Hun
Chung, Joon-Yong
Cho, Hanbyoul
Kitano, Haruhisa
Chang, Eileen
Ylaya, Kris
Chung, Eun Joo
Kim, Jae-Hoon
Hewitt, Stephen M.
TI Prognostic Significance of AMP-Dependent Kinase Alpha Expression in
Cervical Cancer
SO PATHOBIOLOGY
LA English
DT Article
DE AMP-activated protein kinase; Carcinogenesis; Cervical neoplasms;
Disease-free survival
ID ACTIVATED PROTEIN-KINASE; TUMOR-SUPPRESSOR; CELL-GROWTH; BREAST-CANCER;
METFORMIN; ENERGY; METABOLISM; REGULATOR; SURVIVAL; IMPACT
AB Objectives: Cervical cancer is one of the most common gynecological malignancies worldwide, and its association with the AMP-activated protein kinase (AMPK) is still unknown. We aimed to investigate the clinical correlation between AMPK expression and cervical cancer. Methods: The expression of AMPK alpha 1, AMPK alpha 2 and phosphorylated AMPK alpha (p-AMPK alpha) was determined immunohistochemically in 524 formalin-fixed, paraffin-embedded malignant and premalignant cervical tissues. Subsequently, associations with clinicopathological characteristics and patient survival were assessed. Results: AMPK alpha 2 expression was observed in the cytoplasm and nucleus, while expression of AMPK alpha 1 and p-AMPK alpha was mainly observed in the cytoplasm. p-AMPK alpha expression increased during the normal-to-tumor transition of cervical carcinoma (p < 0.001), but, once cancer developed, the expression of AMPK alpha 2 and p-AMPK alpha decreased in large-sized tumors when compared to smaller tumors (36 vs. 68%, p = 0.004 and 39 vs. 64%, p = 0.029, respectively). Notably, AMPK alpha 2 expression was significantly associated with better disease-free survival (HR 0.29, 95% CI 0.10-0.86, p = 0.026). Conclusion: The AMPK alpha 2 isoform showed potential as a favorable prognostic marker in cervical cancer. Therefore, additional studies are necessary to further clarify the complex contribution of AMPK isoforms and of phosphorylation status to cervical cancer progression and prognosis. (C) 2015 S. Karger AG, Basel
C1 [Choi, Chel Hun; Chung, Joon-Yong; Kitano, Haruhisa; Chang, Eileen; Ylaya, Kris; Hewitt, Stephen M.] NCI, Expt Pathol Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Chung, Eun Joo] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Choi, Chel Hun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea.
[Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul 135720, South Korea.
[Kitano, Haruhisa] Shiga Univ Med Sci, Dept Thorac Surg, Otsu, Shiga 52021, Japan.
RP Kim, JH (reprint author), Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, 146-92 Dogok Dong, Seoul 135720, South Korea.
EM jaehoonkim@yuhs.ac; genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute, Center for
Cancer Research.
NR 38
TC 5
Z9 5
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1015-2008
EI 1423-0291
J9 PATHOBIOLOGY
JI Pathobiology
PY 2015
VL 82
IS 5
BP 203
EP 211
DI 10.1159/000434726
PG 9
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA CT8VJ
UT WOS:000363094700003
PM 26337566
ER
PT S
AU Chen, PW
Jian, XY
Luo, RB
Randazzo, PA
AF Chen, Pei-Wen
Jian, Xiaoying
Luo, Ruibai
Randazzo, Paul A.
BE Guo, W
TI Simple in vitro assay of Arf GAPs and preparation of Arf proteins as
substrates
SO SORTING AND RECYCLING ENDOSOMES
SE Methods in Cell Biology
LA English
DT Review; Book Chapter
ID GTPASE-ACTIVATING PROTEINS; ADP-RIBOSYLATION FACTOR; BINDING-PROTEINS;
PH DOMAIN; FAMILY; TERMINUS; NOMENCLATURE; REGULATORS; ROLES
AB Defining the interaction of Arf GAPs with specific Arfs is important for understanding their functions in the endocytic system. Cell-based approaches have been valuable for identifying Arfs and Arf GAPs active in the endocytic compartment; however, the cell-based assays have some limitations in establishing relationships among the Arfs and ArfGAPs. Here we describe a simple in vitro assay that will provide a means for comparing Arfs as substrates and serve to complement cell-based studies.
C1 [Chen, Pei-Wen; Jian, Xiaoying; Luo, Ruibai; Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
FU Intramural NIH HHS
NR 25
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-679X
BN 978-0-12-802871-1; 978-0-12-802829-2
J9 METHOD CELL BIOL
JI Methods Cell Biol.
PY 2015
VL 130
BP 69
EP 80
DI 10.1016/bs.mcb.2015.03.021
PG 12
WC Cell Biology
SC Cell Biology
GA BD7NG
UT WOS:000363330300007
PM 26360029
ER
PT S
AU Dutta, D
Donaldson, JG
AF Dutta, Dipannita
Donaldson, Julie G.
BE Guo, W
TI Rab and Arf G proteins in endosomal trafficking
SO SORTING AND RECYCLING ENDOSOMES
SE Methods in Cell Biology
LA English
DT Review; Book Chapter
ID INDEPENDENT ENDOCYTOSIS; CLATHRIN; PHOSPHOINOSITIDES; BIOGENESIS;
ACTIVATION; PATHWAY; CELL
AB Endocytosis is a fundamental process that cells use to remove receptors, extracellular material, plasma membrane proteins and lipids from the cell surface. After entry into cells, the cargo proteins are subsequently trafficked to late endosomes and lysosomes for degradation, to the Golgi complex, or to recycling endosomes for return to the plasma membrane. Small G proteins in the Rab and Arf family are present on endosomes and coordinate the trafficking of cargo proteins. Here we describe some basic experimental approaches to begin to study the endosomal trafficking of a given cell surface protein.
C1 [Dutta, Dipannita; Donaldson, Julie G.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Donaldson, JG (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM donaldsonj@helix.nih.gov
NR 19
TC 3
Z9 3
U1 5
U2 6
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-679X
BN 978-0-12-802871-1; 978-0-12-802829-2
J9 METHOD CELL BIOL
JI Methods Cell Biol.
PY 2015
VL 130
BP 127
EP 138
DI 10.1016/bs.mcb.2015.04.004
PG 12
WC Cell Biology
SC Cell Biology
GA BD7NG
UT WOS:000363330300010
PM 26360032
ER
PT J
AU Nani, RR
Kelley, JA
Ivanic, J
Schnermann, MJ
AF Nani, Roger R.
Kelley, James A.
Ivanic, Joseph
Schnermann, Martin J.
TI Reactive species involved in the regioselective photooxidation of
heptamethine cyanines
SO CHEMICAL SCIENCE
LA English
DT Article
ID FOCK PERTURBATION-THEORY; SINGLET OXYGEN; ELECTRONIC-STRUCTURE;
OPEN-SHELL; IMPROVED PHOTOSTABILITY; INDUCED DECOMPOSITION; ORGANIC
FLUOROPHORES; SYMMETRY-BREAKING; POLYMETHINE DYES; MECHANISM
AB Heptamethine cyanines are important near-IR fluorophores used in many fluorescence applications. Despite this utility, these molecules are susceptible to light-promoted reactions (photobleaching) involving photochemically generated reactive oxygen species (ROS). Here, we have sought to define key chemical aspects of this nearly inescapable process. Near-IR photolysis of a model heptamethine cyanine leads to the regioselective oxidative cleavage of the characteristic polyene. We report the first quantitative analysis of the major reaction pathway following either photolysis or exposure to candidate ROS. These studies clearly indicate that only singlet oxygen (O-1(2)), and not other feasible ROS, recapitulates the direct photolysis pathway. Computational studies were employed to investigate the regioselectivity of the oxidative cleavage process, and the theoretical ratio is comparable to observed experimental values. These results provide a more complete picture of heptamethine cyanine photooxidation, and provide insight for the design of improved compounds for future applications.
C1 [Nani, Roger R.; Kelley, James A.; Schnermann, Martin J.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Ivanic, Joseph] Frederick Natl Lab Canc Res, DSITP, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
RP Ivanic, J (reprint author), Frederick Natl Lab Canc Res, DSITP, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
EM joseph.ivanic@nih.gov; martin.schnermann@nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the National
Institutes of Health; Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E and by the Intramural Research Program of
the National Institutes of Health, Center for Cancer Research, and the
National Cancer Institute, National Institutes of Health. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 61
TC 9
Z9 9
U1 6
U2 13
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2041-6520
EI 2041-6539
J9 CHEM SCI
JI Chem. Sci.
PY 2015
VL 6
IS 11
BP 6556
EP 6563
DI 10.1039/c5sc02396c
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA CT7EP
UT WOS:000362977000066
PM 26508998
ER
PT J
AU Bond, LM
Sellers, JR
McKerracher, L
AF Bond, Lisa M.
Sellers, James R.
McKerracher, Lisa
TI Rho kinase as a target for cerebral vascular disorders
SO FUTURE MEDICINAL CHEMISTRY
LA English
DT Review
ID BLOOD-BRAIN-BARRIER; ANEURYSMAL SUBARACHNOID HEMORRHAGE; INTRACRANIAL
BERRY ANEURYSMS; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS;
ABDOMINAL-AORTIC-ANEURYSM; CELL-CELL JUNCTIONS; BINDING PROTEIN RHO;
DOUBLE-BLIND TRIAL; CAVERNOUS MALFORMATIONS
AB The development of novel pharmaceutical treatments for disorders of the cerebral vasculature is a serious unmet medical need. These vascular disorders are typified by a disruption in the delicate Rho signaling equilibrium within the blood vessel wall. In particular, Rho kinase overactivation in the smooth muscle and endothelial layers of the vessel wall results in cytoskeletal modifications that lead to reduced vascular integrity and abnormal vascular growth. Rho kinase is thus a promising target for the treatment of cerebral vascular disorders. Indeed, preclinical studies indicate that Rho kinase inhibition may reduce the formation/growth/rupture of both intracranial aneurysms and cerebral cavernous malformations.
C1 [Bond, Lisa M.; McKerracher, Lisa] BioAxone BioSci Inc, Cambridge, MA 02142 USA.
[Bond, Lisa M.; Sellers, James R.] NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA.
RP McKerracher, L (reprint author), BioAxone BioSci Inc, 10 Rogers St,Suite 101,Kendall Sq, Cambridge, MA 02142 USA.
EM lmck@bioaxonebio.com
FU National Heart Lung and Blood Institute Intramural Program at the
National Institutes of Health [HL001786]
FX BioAxone BioSciences, Inc. owns the intellectual property for Cethrin
and BA-1049 and is actively engaged in the development of Rho
signaling-based treatments for neurological conditions. L McKerracher is
the inventor of Cethrin and the Founder and CEO of BioAxone BioSciences.
L Bond is the Senior Director of Clinical and Regulatory Affairs at
BioAxone. L McKerracher and L Bond thus have commercial and proprietary
interests in Cethrin and BA-1049 and in the investigation of Rho pathway
modulation for neurological disorders. J Sellers is funded by the
National Heart Lung and Blood Institute Intramural Program at the
National Institutes of Health (HL001786). The authors have no other
relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the
subject matter or materials discussed in the manuscript apart from those
disclosed.
NR 175
TC 1
Z9 1
U1 0
U2 2
PU FUTURE SCI LTD
PI LONDON
PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND
SN 1756-8919
EI 1756-8927
J9 FUTURE MED CHEM
JI Future Med. Chem.
PY 2015
VL 7
IS 8
BP 1039
EP 1053
DI 10.4155/FMC.15.45
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CT5ZR
UT WOS:000362890300007
PM 26062400
ER
PT J
AU Kennedy, AE
Qadirl, XV
Lane, CA
Dorak, MT
AF Kennedy, Amy E.
Qadirl, Ximena V.
Lane, Crystal A.
Dorak, Mehmet Tevfik
TI A SURVEY OF CANCER SOMATIC MUTATIONS IN THE HLA REGION
SO HUMAN IMMUNOLOGY
LA English
DT Meeting Abstract
CT 41st Annual Meeting of the
American-Society-for-Histocompatibility-and-Immunogenetics (ASHI)
CY SEP 28-OCT 02, 2015
CL Savannah, GA
SP Amer Soc Histocompatibil & Immunogenet
C1 [Kennedy, Amy E.; Qadirl, Ximena V.; Lane, Crystal A.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
[Dorak, Mehmet Tevfik] Liverpool Hope Univ, Liverpool, Merseyside, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
EI 1879-1166
J9 HUM IMMUNOL
JI Hum. Immunol.
PY 2015
VL 76
SU 1
MA OR41
BP 33
EP 33
PG 1
WC Immunology
SC Immunology
GA CT7NH
UT WOS:000363001300042
ER
PT J
AU Gao, XJ
Tang, MZ
Martin, P
Zeng, Y
Carrington, M
AF Gao, Xiaojiang
Tang, Minzhong
Martin, Pat
Zeng, Yi
Carrington, Mary
TI COMPOUND HLA/KIR GENOTYPES INFLUENCE RISK OF NASOPHARYNGEAL CARCINOMA
(NPC) IN A SOUTHERN CHINESE COHORT.
SO HUMAN IMMUNOLOGY
LA English
DT Meeting Abstract
CT 41st Annual Meeting of the
American-Society-for-Histocompatibility-and-Immunogenetics (ASHI)
CY SEP 28-OCT 02, 2015
CL Savannah, GA
SP Amer Soc Histocompatibil & Immunogenet
C1 [Gao, Xiaojiang; Martin, Pat; Carrington, Mary] NCI, Frederick, MD 21701 USA.
[Tang, Minzhong; Zeng, Yi] Beijing Univ Technol, Beijing, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
EI 1879-1166
J9 HUM IMMUNOL
JI Hum. Immunol.
PY 2015
VL 76
SU 1
MA P019
BP 52
EP 52
PG 1
WC Immunology
SC Immunology
GA CT7NH
UT WOS:000363001300065
ER
PT J
AU Tang, MZ
Zheng, YM
Cai, YL
Gao, XJ
Carrington, M
Peng, T
AF Tang, Minzhong
Zheng, Yuming
Cai, Yonglin
Gao, Xiaojiang
Carrington, Mary
Peng, Tao
TI GENETIC ASSOCIATION BETWEEN HLA CLASS I ALLELES AND HEPATITIS B
VIRUS-RELATED HEPATOCELLULAR CARCINOMA IN A SOUTHERN CHINESE POPULATION
SO HUMAN IMMUNOLOGY
LA English
DT Meeting Abstract
CT 41st Annual Meeting of the
American-Society-for-Histocompatibility-and-Immunogenetics (ASHI)
CY SEP 28-OCT 02, 2015
CL Savannah, GA
SP Amer Soc Histocompatibil & Immunogenet
C1 [Tang, Minzhong; Zheng, Yuming; Cai, Yonglin] Wuzhou Red Cross Hosp, Wuzhou, Peoples R China.
[Gao, Xiaojiang; Carrington, Mary] NCI, Frederick, MD 21701 USA.
[Peng, Tao] Guangxi Med Univ, Affiliated Hosp 1, Nanning, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
EI 1879-1166
J9 HUM IMMUNOL
JI Hum. Immunol.
PY 2015
VL 76
SU 1
MA P062
BP 80
EP 80
PG 1
WC Immunology
SC Immunology
GA CT7NH
UT WOS:000363001300107
ER
PT J
AU Kennedy, AE
Mustafi, S
Singh, S
Konidari, I
McCauley, JL
Barbieri, A
Dorak, MT
AF Kennedy, Amy E.
Mustafi, Sushmita
Singh, Sandeep
Konidari, Ioanna
McCauley, Jacob L.
Barbieri, Alejandro
Dorak, Mehmet Tevfik
TI A CATALOG OF HLA REGION SNPS WITH FUNCTIONAL ANNOTATIONS, DISEASE
ASSOCIATIONS AND CORRELATIONS WITH HLA TYPES.
SO HUMAN IMMUNOLOGY
LA English
DT Meeting Abstract
CT 41st Annual Meeting of the
American-Society-for-Histocompatibility-and-Immunogenetics (ASHI)
CY SEP 28-OCT 02, 2015
CL Savannah, GA
SP Amer Soc Histocompatibil & Immunogenet
C1 [Kennedy, Amy E.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
[Mustafi, Sushmita; Barbieri, Alejandro] Florida Int Univ, Biomol Sci Inst, Miami, FL 33199 USA.
[Singh, Sandeep] Robert Stempel Coll Publ Hlth & Social Work, Environm & Occupat Hlth, Miami, FL USA.
[Konidari, Ioanna; McCauley, Jacob L.] Univ Miami, Dept Human Genet, Hussman Inst Human Genom, Miami, FL USA.
[Dorak, Mehmet Tevfik] Liverpool Hope Univ, Liverpool, Merseyside, England.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
EI 1879-1166
J9 HUM IMMUNOL
JI Hum. Immunol.
PY 2015
VL 76
SU 1
MA P121
BP 122
EP 122
PG 1
WC Immunology
SC Immunology
GA CT7NH
UT WOS:000363001300166
ER
PT J
AU Karnati, HK
Panigrahi, MK
Gutti, RK
Greig, NH
Tamargo, IA
AF Karnati, Hanuma Kumar
Panigrahi, Manas Kumar
Gutti, Ravi Kumar
Greig, Nigel H.
Tamargo, Ian A.
TI miRNAs: Key Players in Neurodegenerative Disorders and Epilepsy
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Review
DE Alzheimer's disease; amyotrophic lateral sclerosis; epilepsy;
Huntington's disease; miRNAs; neurodegenerative disorders; Parkinson's
disease
ID TEMPORAL-LOBE EPILEPSY; AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID PRECURSOR
PROTEIN; ALZHEIMERS-DISEASE BRAIN; TRANSCRIPTION FACTOR SP1; IMMATURE
RAT MODEL; ALPHA-SYNUCLEIN EXPRESSION; MESSENGER-RNA EXPRESSION;
MESENCHYMAL STEM-CELLS; HUNTINGTONS-DISEASE
AB MicroRNAs (miRNAs) are endogenous, similar to 22 nucleotide, non-coding RNA molecules that function as posttranscriptional regulators of gene expression. miRNA dysregulation has been observed in cancer and in neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and the neurological disorder, epilepsy. Neuronal degradation and death are important hallmarks of neurodegenerative disorders. Additionally, abnormalities in metabolism, synapsis and axonal transport have been associated with Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. A number of recently published studies have demonstrated the importance of miRNAs in the nervous system and have contributed to the growing body of evidence on miRNA dysregulation in neurological disorders. Knowledge of the expressions and activities of such miRNAs may aid in the development of novel therapeutics. In this review, we discuss the significance of miRNA dysregulation in the development of neurodegenerative disorders and the use of miRNAs as targets for therapeutic intervention.
C1 [Karnati, Hanuma Kumar; Gutti, Ravi Kumar] Univ Hyderabad, Sch Life Sci, Dept Biochem, Hyderabad 500134, Telangana, India.
[Panigrahi, Manas Kumar] KIMS, Dept Neurosurg, Hyderabad, Telangana, India.
[Greig, Nigel H.; Tamargo, Ian A.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Tamargo, IA (reprint author), NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
EM hanumabio@gmail.com; ian.tamargo@nih.gov
OI Gutti, Ravi/0000-0002-0912-5796
FU University of Hyderabad; Krishna Institute of Medical Sciences (KIMS),
Hyderabad, India; Intramural Research Program of the National Institute
on Aging (NHG, IAT), Baltimore, MD, USA
FX This work was supported in part by the University of Hyderabad and the
Krishna Institute of Medical Sciences (KIMS), Hyderabad, India, and by
the Intramural Research Program of the National Institute on Aging (NHG,
IAT), Baltimore, MD, USA.
NR 186
TC 3
Z9 4
U1 1
U2 9
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 1387-2877
EI 1875-8908
J9 J ALZHEIMERS DIS
JI J. Alzheimers Dis.
PY 2015
VL 48
IS 3
BP 563
EP 580
DI 10.3233/JAD-150395
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA CT6YE
UT WOS:000362958800001
PM 26402105
ER
PT J
AU McBride, CM
Abrams, LR
Koehly, LM
AF McBride, Colleen M.
Abrams, Leah R.
Koehly, Laura M.
TI Using a Historical Lens to Envision the Next Generation of Genomic
Translation Research
SO PUBLIC HEALTH GENOMICS
LA English
DT Article
DE Genomics; Health promotion; Translational research; Epistemology;
Meta-narratives; Pivotal events
ID MANAGED CARE ORGANIZATION; BREAST-CANCER; PUBLIC-HEALTH; PERSONALIZED
MEDICINE; GENETIC INFORMATION; HIGH-RISK; EDUCATION; CHILDREN; DISEASE;
IMPACT
AB Background: The past 20 years have witnessed successive and exponential advances in genomic discovery and technology, with a broad scientific imperative pushing for continual advancements. The most consistent critique of these advances is that they have vastly outpaced translation of new knowledge into improvements in public health and medicine. Methods: We employ a historical and epistemological analysis to characterize how prevailing scientific meta-narratives have shaped the pace and priorities of research applying genomics to health promotion. We use four 'pivotal events' - the genetic characterization of Down syndrome, the launch of the Human Genome Research Project, the discovery of BRCA1, and the emergence of direct-to-consumer genetic testing - to illustrate how these scientific meta-narratives have inhibited genomic translation research. Results: The notion that discovery should precede translation research has over-focused translation research on the latest genetic testing platform. The idea that genetic-related research has an exceptional potential for public harm has encouraged research on worst case scenarios. The perceived competition between genetics and social determinants of health has discouraged a unified research agenda to move genomic translation forward. Conclusion: We make a case for creating new scientific meta-narratives in which discovery and translation research agendas are envisioned as an interdependent enterprise. (C) 2015 S. Karger AG, Basel
C1 [McBride, Colleen M.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Abrams, Leah R.; Koehly, Laura M.] NHGRI, Bethesda, MD 20892 USA.
RP McBride, CM (reprint author), Emory Univ, Rollins Sch Publ Hlth, SPH Behav Sci 8r Hlth Educ, 1518 Clifton Rd NE Mailstop 1518-002-5AA, Atlanta, GA 30322 USA.
EM Colleen.marie.mcbride@emory.edu
NR 84
TC 1
Z9 1
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1662-4246
EI 1662-8063
J9 PUBLIC HEALTH GENOM
JI Pub. Health Genomics
PY 2015
VL 18
IS 5
BP 272
EP 282
DI 10.1159/000435832
PG 11
WC Genetics & Heredity; Public, Environmental & Occupational Health
SC Genetics & Heredity; Public, Environmental & Occupational Health
GA CT7MZ
UT WOS:000363000200003
PM 26226840
ER
PT J
AU Medoff, ZM
Colloca, L
AF Medoff, Zev M.
Colloca, Luana
TI Placebo analgesia: understanding the mechanisms
SO PAIN MANAGEMENT
LA English
DT Article
DE conditioning; expectations; genetic variants; learning; placebo
predictors; social observation
ID DISPOSITIONAL OPTIMISM; NOCEBO RESPONSES; OPIOID ACTIVITY; SOCIAL
ANXIETY; SPINAL-CORD; PAIN; EXPECTATION; PERSONALITY; ACTIVATION;
POLYMORPHISMS
AB Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo analgesic effects. Distinct psychological traits can modulate expectations of analgesia, which facilitate brain pain control mechanisms involved in pain reduction. Many studies have highlighted the importance and clinical relevance of these responses. Gaining deeper understanding of these pain modulatory mechanisms has important implications for personalizing patient pain management.
C1 [Medoff, Zev M.] NIMH, NIH, Bethesda, MD 20892 USA.
[Colloca, Luana] Univ Maryland, Sch Nursing, Ctr Adv Chron Pain Res, Dept Pain & Translat Symptom Sci, Baltimore, MD 21201 USA.
[Colloca, Luana] Univ Maryland, Dept Anesthesiol, Sch Med, Baltimore, MD 21201 USA.
RP Colloca, L (reprint author), Univ Maryland, Sch Nursing, Ctr Adv Chron Pain Res, Dept Pain & Translat Symptom Sci, Baltimore, MD 21201 USA.
EM colloca@son.umaryland.edu
FU Intramural NIH HHS [Z99 MH999999]
NR 57
TC 3
Z9 3
U1 1
U2 9
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-1869
EI 1758-1877
J9 PAIN MANAG
JI Pain Manag.
PY 2015
VL 5
IS 2
BP 89
EP 96
DI 10.2217/PMT.15.3
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CT2XM
UT WOS:000362669100006
PM 25806903
ER
PT J
AU Marceglia, S
Fontelo, P
Rossi, E
Ackerman, MJ
AF Marceglia, S.
Fontelo, P.
Rossi, E.
Ackerman, M. J.
TI A Standards-Based Architecture Proposal for Integrating Patient mHealth
Apps to Electronic Health Record Systems
SO APPLIED CLINICAL INFORMATICS
LA English
DT Article
DE Mobile health; delivery of health; heart failure
ID SELF-MANAGEMENT; CARE; METAANALYSIS; INFORMATION; ENGAGEMENT
AB Background: Mobile health Applications (mHealth Apps) are opening the way to patients' responsible and active involvement with their own healthcare management. However, apart from Apps allowing patient's access to their electronic health records (EHRs), mHealth Apps are currently developed as dedicated "island systems".
Objective: Although much work has been done on patient's access to EHRs, transfer of information from mHealth Apps to EHR systems is still low. This study proposes a standards-based architecture that can be adopted by mHealth Apps to exchange information with EHRs to support better quality of care.
Methods: Following the definition of requirements for the EHR/mHealth App information exchange recently proposed, and after reviewing current standards, we designed the architecture for EHR/mHealth App integration. Then, as a case study, we modeled a system based on the proposed architecture aimed to support home monitoring for congestive heart failure patients. We simulated such process using, on the EHR side, OpenMRS, an open source longitudinal EHR and, on the mHealth App side, the iOS platform.
Results: The integration architecture was based on the bi-directional exchange of standard documents (clinical document architecture rel2-CDA2). In the process, the clinician "prescribes" the home monitoring procedures by creating a CDA2 prescription in the EHR that is sent, encrypted and de-identified, to the mHealth App to create the monitoring calendar. At the scheduled time, the App alerts the patient to start the monitoring. After the measurements are done, the App generates a structured CDA2-compliant monitoring report and sends it to the EHR, thus avoiding local storage.
Conclusions: The proposed architecture, even if validated only in a simulation environment, represents a step forward in the integration of personal mHealth Apps into the larger health-IT ecosystem, allowing the bi-directional data exchange between patients and healthcare professionals, supporting the patient's engagement in self-management and self-care.
C1 [Marceglia, S.; Fontelo, P.; Ackerman, M. J.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20994 USA.
[Marceglia, S.] Fdn IRCCS CaGranda Osped Maggiore Policlin, Ctr Neurostimulat Neurotechnol & Movement Disorde, Milan, Italy.
[Rossi, E.] Politecn Milan, Dipartimento Elettron Informaz & Bioingn, eHealthLAB, I-20133 Milan, Italy.
RP Marceglia, S (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20994 USA.
EM sara.marceglia@nih.gov
NR 35
TC 2
Z9 2
U1 5
U2 12
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 1869-0327
J9 APPL CLIN INFORM
JI Appl. Clin. Inform.
PY 2015
VL 6
IS 3
BP 488
EP 505
DI 10.4338/ACI-2014-12-RA-0115
PG 18
WC Medical Informatics
SC Medical Informatics
GA CS7KU
UT WOS:000362263300006
PM 26448794
ER
PT J
AU Schlichting, JA
Soliman, AS
Schairer, C
Harford, JB
Hablas, A
Ramadan, M
Seifeldin, I
Merajver, SD
AF Schlichting, Jennifer A.
Soliman, Amr S.
Schairer, Catherine
Harford, Joe B.
Hablas, Ahmed
Ramadan, Mohamed
Seifeldin, Ibrahim
Merajver, Sofia D.
TI Breast Cancer by Age at Diagnosis in the Gharbiah, Egypt,
Population-Based Registry Compared to the United States Surveillance,
Epidemiology, and End Results Program, 2004-2008
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Article
ID BODY-MASS INDEX; YOUNG-WOMEN; CLINICOPATHOLOGICAL FEATURES; ARAB
POPULATIONS; TUNISIA; PROGNOSIS; MENARCHE; BIOLOGY; RISK
AB Objective. Although breast cancers (BCs) in young women often display more aggressive features, younger women are generally not screened for early detection. It is important to understand the characteristics of young onset breast cancer to increase awareness in this population. This analysis includes all ages, with emphasis placed on younger onset BC in Egypt as compared to the United States. Methods. BC cases in the Gharbiah cancer registry (GCR), Egypt, were compared to those in the Surveillance, Epidemiology, and End Results (SEER) database. This analysis included 3,819 cases from the GCR and 273,019 from SEER diagnosed 2004-2008. Results. GCR cases were diagnosed at later stages, with <5% diagnosed at Stage I and 12% diagnosed at Stage IV. 48% of all SEER cases were diagnosed at Stage I, dropping to 30% among those <= 40. Significant differences in age, tumor grade, hormone receptor status, histology, and stage exist between GCR and SEER BCs. After adjustment, GCR cases were nearly 45 times more likely to be diagnosed at stage III and 16 times more likely to be diagnosed at stage IV than SEER cases. Conclusions. Future research should examine ways to increase literacy about early detection and prompt therapy in young cases.
C1 [Schlichting, Jennifer A.; Merajver, Sofia D.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Soliman, Amr S.] Univ Nebraska Med Ctr, Dept Epidemiol, Omaha, NE 68198 USA.
[Schairer, Catherine] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Harford, Joe B.] NCI, Ctr Global Hlth, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hablas, Ahmed; Ramadan, Mohamed; Seifeldin, Ibrahim] Tanta Canc Ctr, Tanta 31111, Gharbiah, Egypt.
[Merajver, Sofia D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
RP Soliman, AS (reprint author), Univ Nebraska Med Ctr, Dept Epidemiol, Omaha, NE 68198 USA.
EM amr.soliman@unmc.edu
FU Cancer Epidemiology Education in Special Populations (CEESP) Program
from the National Cancer Institute [R25CA112383]; Avon Foundation;
Breast Cancer Research Foundation
FX The authors thank Ms. Melanie Wells and Ms. Lynne Le for providing
editorial expertise. Dr. Jennifer A. Schlichting was supported in part
by the Cancer Epidemiology Education in Special Populations (CEESP)
Program: Grant no. R25CA112383 from the National Cancer Institute.
Authors acknowledge research support from the Avon Foundation (Amr S.
Soliman, Sofia D. Merajver) and the Breast Cancer Research Foundation
(Sofia D. Merajver).
NR 46
TC 1
Z9 1
U1 2
U2 2
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PY 2015
AR 381574
DI 10.1155/2015/381574
PG 9
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA CT3WV
UT WOS:000362738500001
ER
PT J
AU Tomoyose, K
Okada, Y
Sumioka, T
Miyajima, M
Flanders, KC
Shirai, K
Morii, T
Reinach, PS
Yamanaka, O
Saika, S
AF Tomoyose, Katsuo
Okada, Yuka
Sumioka, Takayoshi
Miyajima, Masayasu
Flanders, Kathleen C.
Shirai, Kumi
Morii, Tomoya
Reinach, Peter S.
Yamanaka, Osamu
Saika, Shizuya
TI Suppression of In Vivo Neovascularization by the Loss of TRPV1 in Mouse
Cornea
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INFLAMMATORY CYTOKINE RELEASE; EPITHELIAL-CELLS; INHIBITS ANGIOGENESIS;
CAPSAICIN RECEPTOR; KAPPA-B; MICE; CHANNELS; ACTIVATION; TISSUE;
BEVACIZUMAB
AB To investigate the effects of loss of transient receptor potential vanilloid receptor 1 (TRPV1) on the development of neovascularization in corneal stroma in mice. Blocking TRPV1 receptor did not affect VEGF-dependent neovascularization in cell culture. Lacking TRPV1 inhibited neovascularization in corneal stroma following cauterization. Immunohistochemistry showed that immunoreactivity for active form of TGF beta 1 and VEGF was detected in subepithelial stroma at the site of cauterization in both genotypes of mice, but the immunoreactivity seemed less marked in mice lacking TRPV1. mRNA expression of VEGF and TGF beta 1 in a mouse cornea was suppressed by the loss of TRPV1. TRPV1 gene ablation did not affect invasion of neutrophils and macrophage in a cauterized mouse cornea. Blocking TRPV1 signal does not affect angiogenic effects by HUVECs in vitro. TRPV1 signal is, however, involved in expression of angiogenic growth factors in a cauterized mouse cornea and is required for neovascularization in the corneal stroma in vivo.
C1 [Tomoyose, Katsuo; Okada, Yuka; Sumioka, Takayoshi; Shirai, Kumi; Morii, Tomoya; Yamanaka, Osamu; Saika, Shizuya] Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan.
[Miyajima, Masayasu] Wakayama Med Univ, Lab Anim Ctr, Wakayama 6410012, Japan.
[Flanders, Kathleen C.] NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA.
[Reinach, Peter S.] Wenzhou Med Univ, Sch Ophthalmol & Optometry, Wenzhou, Peoples R China.
RP Okada, Y (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan.
EM yokada@wakayama-med.ac.jp
FU Ministry of Education, Science, Sports and Culture of Japan [C40433362,
C21592241, C19592036]
FX This study was supported by grant from the Ministry of Education,
Science, Sports and Culture of Japan (C40433362 to Takayoshi Sumioka,
C21592241 to Yuka Okada, and C19592036 to Shizuya Saika).
NR 35
TC 0
Z9 0
U1 1
U2 1
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PY 2015
AR 706404
DI 10.1155/2015/706404
PG 9
WC Medicine, Research & Experimental; Ophthalmology
SC Research & Experimental Medicine; Ophthalmology
GA CT4BR
UT WOS:000362751400001
ER
EF