FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Moir, S
Fauci, AS
AF Moir, Susan
Fauci, Anthony S.
TI Insights into B cells and HIV-specific B-cell responses in HIV-infected
individuals
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE B cells; HIV; memory; differentiation; immune activation
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-FOLLICULAR-HELPER; ACTIVE ANTIRETROVIRAL
THERAPY; HUMAN MONOCLONAL-ANTIBODIES; CXC CHEMOKINE RECEPTOR-5; CHRONIC
VIRAL-INFECTION; TUMOR-NECROSIS-FACTOR; NEUTRALIZING ANTIBODIES;
LYMPHOID-TISSUE; DISEASE PROGRESSION
AB Human immunodeficiency virus (HIV) disease is associated with dysregulation and dysfunction involving all major lymphocyte populations, including B cells. Such perturbations occur early in the course of infection and are driven in large part by immune activation resulting from ongoing HIV replication leading to bystander effects on B cells. While most of the knowledge regarding immune cell abnormalities in HIV-infected individuals has been gained from studies conducted on the peripheral blood, it is clear that the virus is most active and most damaging in lymphoid tissues. Here, we discuss B-cell perturbations in HIV-infected individuals, focusing on the skewing of B-cell subsets that circulate in the peripheral blood and their counterparts that reside in lymphoid tissues. This review also highlights recent advances in evaluating HIV-specific B-cell responses both in the memory B-cell compartment, as well as in circulating antibody-secreting plasmablasts and the more differentiated plasma cells residing in tissues. Finally, we consider how knowledge gained by investigating B cells in HIV-infected individuals may help inform the development of an effective antibody-based HIV vaccine.
C1 [Moir, Susan; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Moir, S (reprint author), NIH, Bldg 10,Room 6A02,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM smoir@niaid.nih.gov
FU Intramural Research Program of NIAID, NIH
FX This work was funded by the Intramural Research Program of NIAID, NIH.
The authors have no conflicts of interest to disclose.
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUL
PY 2013
VL 254
BP 207
EP 224
DI 10.1111/imr.12067
PG 18
WC Immunology
SC Immunology
GA 164EE
UT WOS:000320390900012
PM 23772622
ER
PT J
AU Mascola, JR
Haynes, BF
AF Mascola, John R.
Haynes, Barton F.
TI HIV-1 neutralizing antibodies: understanding nature's pathways
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE monoclonal antibodies (mAbs); broadly neutralizing antibodies (BNAbs);
unmutated ancestor (UA); B-cell lineages; immune tolerance
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; B-CELL
RESPONSES; RECOMBINANT GLYCOPROTEIN-120 VACCINE; GP120 ENVELOPE
GLYCOPROTEIN; CROSS-CLADE NEUTRALIZATION; 2ND HYPERVARIABLE REGION;
DEFICIENCY SYNDROME AIDS; HTLV-III LAV; SUBTYPE-B
AB The development of an effective vaccine has been hindered by the enormous diversity of human immunodeficiency virus-1 (HIV-1) and its ability to escape a myriad of host immune responses. In addition, conserved vulnerable regions on the HIV-1 envelope glycoprotein are often poorly immunogenic and elicit broadly neutralizing antibody responses (BNAbs) in a minority of HIV-1-infected individuals and only after several years of infection. All of the known BNAbs demonstrate high levels of somatic mutations and often display other unusual traits, such as a long heavy chain complementarity determining region 3 (CDRH3) and autoreactivity that can be limited by host tolerance controls. Nonetheless, the demonstration that HIV-1-infected individuals can make potent BNAbs is encouraging, and recent progress in isolating such antibodies and mapping their immune pathways of development is providing new strategies for vaccination.
C1 [Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Haynes, Barton F.] Duke Univ, Sch Med, Dept Med, Human Vaccine Inst, Durham, NC 27706 USA.
[Haynes, Barton F.] Duke Univ, Sch Med, Dept Immunol, Human Vaccine Inst, Durham, NC USA.
RP Mascola, JR (reprint author), 40 Convent Dr, Bethesda, MD 20892 USA.
EM jmascola@nih.gov
FU Vaccine Research Center, NIAID, NIH; NIH, NIAID Center for HIV/AIDS
Vaccine immunology-Immunogen Design [UM1 AI100645]; Collaboration for
AIDS Vaccine Discovery grants
FX We thank Tony Moody and Rebecca Lynch for their review and suggestions
for this manuscript. Supported by the intramural research program of the
Vaccine Research Center, NIAID, NIH and by the NIH, NIAID Center for
HIV/AIDS Vaccine immunology-Immunogen Design UM1 AI100645 and by
Collaboration for AIDS Vaccine Discovery grants to B. F. H. The authors
have no conflicts of interest to declare.
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUL
PY 2013
VL 254
BP 225
EP 244
DI 10.1111/imr.12075
PG 20
WC Immunology
SC Immunology
GA 164EE
UT WOS:000320390900013
PM 23772623
ER
PT J
AU Martin, MP
Carrington, M
AF Martin, Maureen P.
Carrington, Mary
TI Immunogenetics of HIV disease
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE HLA; KIR; CTL; NK cells; GWAS; host genetic variation
ID IMMUNODEFICIENCY-VIRUS TYPE-1; NATURAL-KILLER-CELLS; CLASS-I MOLECULES;
GENOME-WIDE ASSOCIATION; CD8(+) T-CELLS; EXPOSED UNINFECTED INDIVIDUALS;
HLA-C EXPRESSION; MHC CLASS-I; IMMUNOGLOBULIN-LIKE RECEPTORS; HUMAN
MONOCLONAL-ANTIBODIES
AB Host genetic factors are a major contributing factor to the inter-individual variation observed in response to human immunodeficiency virus (HIV) infection and are linked to resistance to HIV infection among exposed individuals, as well as rate of disease progression and the likelihood of viral transmission. Of the genetic variants that have been shown to affect the natural history of HIV infection, the human leukocyte antigen (HLA) class I genes exhibit the strongest and most consistent association, underscoring a central role for CD8+ T cells in resistance to the virus. HLA proteins play important roles in T-cell-mediated adaptive immunity by presenting immunodominant HIV epitopes to cytotoxic T lymphocytes (CTLs) and CD4+ T cells. Genetic and functional data also indicate a function for HLA in natural killer cell-mediated innate immunity against HIV by interacting with killer cell immunoglobulin-like receptors (KIR). We review the HLA and KIR associations with HIV disease and discuss the mechanisms underlying these associations.
C1 [Martin, Maureen P.; Carrington, Mary] SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, NCI Frederick, Frederick, MD USA.
[Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
RP Carrington, M (reprint author), NCI Frederick, Bldg 560,Rm 21-89B Miller Dr, Frederick, MD 21702 USA.
EM carringm@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This Research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. We
thank Arman Bashirova for helpful comments. The authors have no
conflicts of interest to declare.
NR 207
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U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUL
PY 2013
VL 254
BP 245
EP 264
DI 10.1111/imr.12071
PG 20
WC Immunology
SC Immunology
GA 164EE
UT WOS:000320390900014
PM 23772624
ER
PT J
AU Swaminathan, S
Murray, DD
Kelleher, AD
AF Swaminathan, Sanjay
Murray, Daniel D.
Kelleher, Anthony D.
TI miRNAs and HIV: unforeseen determinants of host-pathogen interaction
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE miRNA; HIV-1; CD4+T cell; monocytes; cytokines; biomarkers
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNA-BINDING PROTEIN; IN-VIVO DELIVERY;
CD4(+) T-CELLS; MESSENGER-RNA; MICRORNA EXPRESSION; CELLULAR MICRORNA;
CIRCULATING MICRORNAS; SILENCING PATHWAY; POLYMERASE-II
AB Our understanding of the complexity of gene regulation has significantly improved in the last decade as the role of small non-coding RNAs, called microRNAs (miRNAs), has been appreciated. These 19-22 nucleotide RNA molecules are critical regulators of mRNA translation and turnover. The miRNAs bind via a protein complex to the 3 untranslated region (3 UTR) of mRNA, ultimately leading to mRNA translational inhibition, degradation, or repression. Although many mechanisms by which human immunodeficiency virus-1 (HIV-1) infection eventually induces catastrophic immune destruction have been elucidated, the important role that miRNAs play in HIV-1 pathogenesis is only now emerging. Accumulating evidence demonstrates that changes to endogenous miRNA levels following infection is important: in maintaining HIV-1 latency in resting CD4+ T cells, potentially affect immune function via changes to cytokines such as interleukin-2 (IL-2) and IL-10 and may predict disease progression. We review the roles that both viral and host miRNAs play in different cell types and disease conditions that are important in HIV-1 infection and discuss how miRNAs affect key immunomodulatory molecules contributing to immune dysfunction. Further, we discuss whether miRNAs may be used as novel biomarkers in serum and the potential to modulate miRNA levels as a unique approach to combating this pathogen.
C1 [Swaminathan, Sanjay] Sci Applicat Int Corp SAIC Frederick Inc, Lab Human Retrovirol, Appl & Dev Res Directorate ADD, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Murray, Daniel D.; Kelleher, Anthony D.] St Vincents Ctr Appl Med Res, Immunovirol Lab, Darlinghurst, NSW 2010, Australia.
[Murray, Daniel D.; Kelleher, Anthony D.] Univ New S Wales, Kirby Inst, Kensington, NSW 2033, Australia.
RP Kelleher, AD (reprint author), St Vincents Ctr Appl Med Res, Immunovirol Lab, Kirby Inst, 405 Liverpool St, Darlinghurst, NSW 2010, Australia.
EM t.kelleher@amr.org.au
OI Swaminathan, Sanjay/0000-0001-5315-6445
FU Australian Government Department of Health and Ageing; National Health
and Medical Research Council; Australian Postgraduate Research
Scholarship
FX This study was supported by the Australian Government Department of
Health and Ageing, the National Health and Medical Research Council via
a Program Grant, Project Grants, and a practitioner fellowship (to A. D.
K.) and an Australian Postgraduate Research Scholarship (to D. M.). The
authors report no conflicts of interest.
NR 123
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U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUL
PY 2013
VL 254
BP 265
EP 280
DI 10.1111/imr.12077
PG 16
WC Immunology
SC Immunology
GA 164EE
UT WOS:000320390900015
PM 23772625
ER
PT J
AU Klatt, NR
Chomont, N
Douek, DC
Deeks, SG
AF Klatt, Nichole R.
Chomont, Nicolas
Douek, Daniel C.
Deeks, Steven G.
TI Immune activation and HIV persistence: implications for curative
approaches to HIV infection
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE AIDS; immunodeficiency diseases; cell activation; cell differentiation;
cell proliferation; inflammation
ID ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS
TYPE-1; PLASMACYTOID DENDRITIC CELLS; TISSUE FACTOR EXPRESSION; INNATE
LYMPHOID-CELLS; CHRONIC SIV INFECTION; NATURAL-KILLER-CELL; MICROBIAL
TRANSLOCATION; VIRAL REPLICATION
AB Despite complete or near-complete suppression of human immunodeficiency virus (HIV) replication with combination antiretroviral therapy, both HIV and chronic inflammation/immune dysfunction persist indefinitely. Untangling the association between the virus and the host immune environment during therapy might lead to novel interventions aimed at either curing the infection or preventing the development of inflammation-associated end-organ disease. Chronic inflammation and immune dysfunction might lead to HIV persistence by causing virus production, generating new target cells, enabling infecting of activated and resting target cells, altering the migration patterns of susceptible target cells, increasing the proliferation of infected cells, and preventing normal HIV-specific clearance mechanisms from function. Chronic HIV production or replication might contribute to persistent inflammation and immune dysfunction. The rapidly evolving data on these issues strongly suggest that a vicious cycle might exist in which HIV persistence causes inflammation that in turn contributes to HIV persistence.
C1 [Klatt, Nichole R.] Univ Washington, Dept Pharmaceut, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
[Chomont, Nicolas] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA.
[Douek, Daniel C.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94110 USA.
RP Deeks, SG (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, San Francisco Gen Hosp, Bldg 80,1001 Potrero Ave, San Francisco, CA 94110 USA.
EM sdeeks@php.ucsf.edu
FU National Institute of Allergy and Infectious Diseases [R01 AI087145, K24
AI069994]; DARE: Delaney AIDS Research Enterprise (DARE) [U19AI096109];
American Foundation for AIDS Research (amfAR); Intramural Program of the
National Institute of Allergy and Infectious Diseases
FX This work was supported by grants from the National Institute of Allergy
and Infectious Diseases (R01 AI087145, K24 AI069994), the DARE: Delaney
AIDS Research Enterprise (DARE; U19AI096109), the American Foundation
for AIDS Research (amfAR), and the Intramural Program of the National
Institute of Allergy and Infectious Diseases. The authors have no
conflicts of interest to declare.
NR 238
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUL
PY 2013
VL 254
BP 326
EP 342
DI 10.1111/imr.12065
PG 17
WC Immunology
SC Immunology
GA 164EE
UT WOS:000320390900019
PM 23772629
ER
PT J
AU Wilson, EMP
Sereti, I
AF Wilson, Eleanor M. P.
Sereti, Irini
TI Immune restoration after antiretroviral therapy: the pitfalls of hasty
or incomplete repairs
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE IRIS; monocytes; macrophages; AIDS; T cells; cytokines
ID RECONSTITUTION INFLAMMATORY SYNDROME; HUMAN-IMMUNODEFICIENCY-VIRUS;
T-CELL RECOVERY; CHRONIC HIV-INFECTION; SUSTAINED VIROLOGICAL
SUPPRESSION; RANDOMIZED CONTROLLED-TRIAL; LYMPHOID-TISSUE STRUCTURE;
WHITE-NOSE SYNDROME; RISK-FACTORS; HIV-1-INFECTED PATIENTS
AB Antiretroviral therapy (ART) is a life-saving intervention in human immunodeficiency virus (HIV) infection. Immune restoration after ART dramatically reduces the incidence and severity of opportunistic diseases and death. On some occasions, immune restoration may be erratic, leading to acute inflammatory responses (known as immune reconstitution inflammatory syndrome) shortly after ART initiation, or incomplete, with residual inflammation despite chronic treatment, leading to non-infectious morbidity and mortality. We propose that ART may not always restore the perfect balance of innate and adaptive immunity in strategic milieus, predisposing HIV-infected persons to complications of acute or chronic inflammation. The best current strategy for fully successful immune restoration is early antiretroviral therapy, which can prevent acquired immunodeficiency syndrome (AIDS)-associated events, restrict cell subset imbalances and dysfunction, while preserving structural integrity of lymphoid tissues. Future HIV research should capitalize on innovative techniques and move beyond the static study of T-cell subsets in peripheral blood or isolated tissues. Improved targeted therapeutic strategies could stem from a better understanding of how HIV perturbs the environmental niches and the mobility and trafficking of cells that affect the dynamic cell-to-cell interactions and determine the outcome of innate and adaptive immune responses.
C1 [Wilson, Eleanor M. P.; Sereti, Irini] NIAID, HIV Pathogenesis Unit, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), 10 Ctr Dr,Bldg 10,Room 11B-07A, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
OI Wilson, Eleanor/0000-0002-4855-514X
FU NIAID/NIH
FX This study was supported by the Intramural Research Program of
NIAID/NIH. The authors have no conflicts of interest to declare.
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUL
PY 2013
VL 254
BP 343
EP 354
DI 10.1111/imr.12064
PG 12
WC Immunology
SC Immunology
GA 164EE
UT WOS:000320390900020
PM 23772630
ER
PT J
AU Ittiprasert, W
Miller, A
Su, XZ
Mu, JB
Bhusudsawang, G
Ukoskit, K
Knight, M
AF Ittiprasert, Wannaporn
Miller, Andre
Su, Xin-zhuan
Mu, Jianbing
Bhusudsawang, Ganlayarat
Ukoskit, Kitipat
Knight, Matty
TI Identification and characterisation of functional expressed sequence
tags-derived simple sequence repeat (eSSR) markers for genetic linkage
mapping of Schistosoma mansoni juvenile resistance and susceptibility
loci in Biomphalaria glabrata
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Expressed sequence tags; Genetic linkage mapping; Resistance;
Susceptibility; Biomphalaria glabrata; Schistosoma mansoni
ID FIBRINOGEN-RELATED PROTEINS; SNAIL HOST; INFECTION; HEMOCYTES; GENOME;
COMPATIBILITY; CONSTRUCTION; INVERTEBRATE; MODEL; BURST
AB Biomphalaria glabrata susceptibility to Schistosoma mansoni has a strong genetic component, offering the possibility for investigating host-parasite interactions at the molecular level, perhaps leading to novel control approaches. The identification, mapping and molecular characterisation of genes that influence the outcome of parasitic infection in the intermediate snail host is, therefore, seen as fundamental to the control of schistosomiasis. To better understand the evolutionary processes driving disease resistance/susceptibility phenotypes, we previously identified polymorphic random amplification of polymorphic DNA and genomic simple sequence repeats from B. glabrata. In the present study we identified and characterised polymorphic expressed simple sequence repeats markers (Bg-eSSR) from existing B. glabrata expressed sequence tags. Using these markers, and with previously identified genomic simple sequence repeats, genetic linkage mapping for parasite refractory and susceptibility phenotypes, the first known for B. glabrata, was initiated. Data mining of 54,309 expressed sequence tag, produced 660 expressed simple sequence repeats of which dinucleotide motifs (TA)(n) were the most common (37.88%), followed by trinucleotide (29.55%), mononucleotide (18.64%) and tetranucleotide (10.15%). Penta- and hexanucleotide motifs represented <3% of the Bg-eSSRs identified. While the majority (71%) of Bg-eSSRs were monomorphic between resistant and susceptible snails, several were, however, useful for the construction of a genetic linkage map based on their inheritance in segregating F2 progeny snails derived from crossing juvenile BS-90 and. NMRI snails. Polymorphic Bg-eSSRs assorted into six linkage groups at a logarithm of odds score of 3. Interestingly, the heritability of four markers (Prim1_910, Prim1_771, Prim6_1024 and Prim7_823) with juvenile snail resistance were, by t-test, significant (P < 0.05) while an allelic marker, Prim24_524, showed linkage with the juvenile snail susceptibility phenotype. On the basis of our results it is possible that the gene(s) controlling juvenile resistance and susceptibility to S. mansoni infection in B. glabrata are not only on the same linkage group but lie within a short distance (42 cM) of each other. (C) 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Ittiprasert, Wannaporn; Miller, Andre; Knight, Matty] Biomed Res Inst, Rockville, MD 20852 USA.
[Su, Xin-zhuan; Mu, Jianbing] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Bhusudsawang, Ganlayarat; Ukoskit, Kitipat] Thammasat Univ, Fac Sci & Technol, Pathum Thani, Thailand.
RP Knight, M (reprint author), Biomed Res Inst, 12111 Parklawn Dr, Rockville, MD 20852 USA.
EM matty_knight@gwu.edu
OI Su, Xinzhuan/0000-0003-3246-3248
FU National Institute of Allergy and Infectious Diseases, National
Institute of Health, USA [R01-AI063480]; Intramural Research Program of
the Division of Intramural Research at the National Institute of Allergy
and Infectious Diseases, National Institute of Health
FX This work was supported by a grant from the National Institute of
Allergy and Infectious Diseases, National Institute of Health, USA,
R01-AI063480 and the Intramural Research Program of the Division of
Intramural Research at the National Institute of Allergy and Infectious
Diseases, National Institute of Health. We are grateful to Ms Frances
Barnes for technical support and to Dr. Fred Lewis for his helpful
editing of the manuscript. We also thank Drs. Nithya Raghavan and Peter
FitzGerald for their guidance with the determination of SSR sequences
for B. glabrata in GenBank.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-7519
J9 INT J PARASITOL
JI Int. J. Parasit.
PD JUL
PY 2013
VL 43
IS 8
BP 669
EP 677
DI 10.1016/j.ijpara.2013.03.007
PG 9
WC Parasitology
SC Parasitology
GA 175MA
UT WOS:000321233600007
PM 23643514
ER
PT J
AU Kaur, G
Behrsing, H
Parchment, RE
Millin, MD
Teicher, BA
AF Kaur, Gurmeet
Behrsing, Holger
Parchment, Ralph E.
Millin, Myrtle Davis
Teicher, Beverly A.
TI Analyses of the combination of 6-MP and dasatinib in cell culture
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE 6-mercaptopurine; dasatinib; combination index; isobologram; response
surface
ID DRUG-COMBINATION; IN-VITRO; INVITRO CULTIVATION; EXPERIMENTAL-DESIGN;
BREAST CARCINOMA; HUMAN TUMORS; LUNG-CANCER; LINES; MODEL; P53
AB A major tenet of cancer therapeutics is that combinations of anticancer agents with different mechanisms of action and different toxicities may be effective treatment regimens. Evaluation of additivity/synergy in cell culture may be used to identify drug combination opportunities and to assess risk of additive/synergistic toxicity. The combination of 6-mercaptopurine and dasatinib was assessed for additivity/synergy using the combination index (CI) method and a response surface method in six human tumor cell lines including MCF-7 and MDA-MB-468 breast cancer, NCI-H23 and NCI-H460 non-small cell lung cancer, and A498 and 786-O renal cell cancer, based on two experimental end-points: ATP content and colony formation. Clonal colony formation by human bone marrow CFU-GM was used to assess risk of enhanced toxicity. The concentration ranges tested for each drug were selected to encompass the clinical C-max concentrations. The combination regimens were found to be additive to sub-additive by both methods of data analysis, but synergy was not detected. The non-small cell lung cancer cell lines were the most responsive among the tumor lines tested and the renal cell carcinoma lines were the least responsive. The bone marrows CFU-GM were more sensitive to the combination regimens than were the tumor cell lines. Based upon these data, it appears that the possibility of enhanced efficacy from combining 6-mercaptopurine (6-MP) and dasatinib would be associated with increased risk of severe bone marrow toxicity, so the combination is unlikely to provide a therapeutic advantage for treating solid tumor patients where adequate bone marrow function must be preserved.
C1 [Kaur, Gurmeet] Frederick Natl Lab Canc Res, Div Canc Treatment & Diag, Dev Therapeut Program, Mol Pharmacol Branch, Frederick, MD 21702 USA.
[Behrsing, Holger; Parchment, Ralph E.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Dev Res Directorate, Lab Invest Toxicol, Frederick, MD 21702 USA.
[Millin, Myrtle Davis] NCI, Toxicol & Pharmacol Branch, Rockville, MD 20852 USA.
[Teicher, Beverly A.] NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Mol Pharmacol Branch, Rockville, MD 20852 USA.
RP Kaur, G (reprint author), Frederick Natl Lab Canc Res, Div Canc Treatments & Diag, Dev Therapeut Program, Mol Pharmacol Branch, 1050 Boyles St,Bldg 321 Room 122, Frederick, MD 21702 USA.
EM kaurgu@mail.nih.gov
FU Developmental Therapeutics Program in the Division of Cancer Treatment
and Diagnosis of the National Cancer Institute; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX This research was supported (in part) by the Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute. This project has been funded in whole or in
part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract no. HHSN261200800001E. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products or organizations imply endorsement by
the U.S. Government.
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PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD JUL
PY 2013
VL 43
IS 1
BP 13
EP 22
DI 10.3892/ijo.2013.1930
PG 10
WC Oncology
SC Oncology
GA 172RR
UT WOS:000321023100002
PM 23652925
ER
PT J
AU Hasan, UA
Zannetti, C
Parroche, P
Goutagny, N
Malfroy, M
Roblot, G
Carreira, C
Hussain, I
Muller, M
Taylor-Papadimitriou, J
Picard, D
Sylla, BS
Trinchieri, G
Medzhitov, R
Tommasino, M
AF Hasan, Uzma A.
Zannetti, Claudia
Parroche, Peggy
Goutagny, Nadege
Malfroy, Marine
Roblot, Guillaume
Carreira, Christine
Hussain, Ishraq
Mueller, Martin
Taylor-Papadimitriou, Joyce
Picard, Didier
Sylla, Bakary S.
Trinchieri, Giorgio
Medzhitov, Ruslan
Tommasino, Massimo
TI The Human papillomavirus type 16 E7 oncoprotein induces a
transcriptional repressor complex on the Toll-like receptor 9 promoter
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID PLASMACYTOID DENDRITIC CELLS; HISTONE DEACETYLASE INHIBITORS;
CERVICAL-CANCER; IMMUNE FUNCTIONS; GENE-EXPRESSION; MOUSE MODEL;
ESTROGEN; TLR9; RECOGNITION; SKIN
AB Human papillomavirus type 16 (HPV16) and other oncogenic viruses have been reported to deregulate immunity by suppressing the function of the double-stranded DNA innate sensor TLR9. However, the mechanisms leading to these events remain to be elucidated. We show that infection of human epithelial cells with HPV16 promotes the formation of an inhibitory transcriptional complex containing NF-kappa Bp50-p65 and ER alpha induced by the E7 oncoprotein. The E7-mediated transcriptional complex also recruited the histone demethylase JARID1B and histone deacetylase HDAC1. The entire complex bound to a specific region on the TLR9 promoter, which resulted in decreased methylation and acetylation of histones upstream of the TLR9 transcriptional start site. The involvement of NF-kappa B and ER alpha in the TLR9 down-regulation by HPV16 E7 was fully confirmed in cervical tissues from human patients. Importantly, we present evidence that the HPV16-induced TLR9 down-regulation affects the interferon response which negatively regulates viral infection. Our studies highlight a novel HPV16-mediated mechanism that combines epigenetic and transcriptional events to suppress a key innate immune sensor.
C1 [Hasan, Uzma A.; Carreira, Christine; Sylla, Bakary S.; Tommasino, Massimo] Int Agcy Res Canc, Infect & Canc Biol Grp, F-69008 Lyon, France.
[Hasan, Uzma A.; Zannetti, Claudia; Parroche, Peggy; Roblot, Guillaume] Univ Lyon, Ecole Normale Super, INSERM U1111, CIRI,Hosp Civils Lyon,CNRS UMR5308, F-69000 Lyon, France.
[Goutagny, Nadege; Malfroy, Marine] Ctr Leon Berard, UMR INSERM CNRS 1052 5286, CRCL, F-69008 Lyon, France.
[Hussain, Ishraq] SK Alusteng, Div Vet Biochem FVSc & AH, Kashmir 190006, India.
[Mueller, Martin] DKFZ, Programme Infect & Canc, D-69120 Heidelberg, Germany.
[Taylor-Papadimitriou, Joyce] Kings Coll London, Sch Med, Guys Hosp, Breast Canc Biol Grp, London SE1 9RT, England.
[Picard, Didier] Univ Geneva, CH-1211 Geneva 4, Switzerland.
[Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Medzhitov, Ruslan] Yale Univ, Sch Med, New Haven, CT 06510 USA.
RP Hasan, UA (reprint author), Int Agcy Res Canc, Infect & Canc Biol Grp, F-69008 Lyon, France.
EM uzma.hasan@inserm.fr; tommasinom@iarc.fr
RI hasan, uzma/G-3247-2013;
OI Hussain, Ishraq/0000-0001-8449-1617
FU EMBO Fellowship Program; La Ligue Regionale de la Loire contre le
Cancer; la Fondation pour la Recherche Medicale; l'Association Research
sur la Cancer; CLARA Procan Axe II innate sensors platform, Lyon
FX This study was supported by the EMBO Fellowship Program (U.A. Hasan), La
Ligue Regionale de la Loire contre le Cancer (U.A. Hasan), la Fondation
pour la Recherche Medicale (U.A. Hasan), l'Association Research sur la
Cancer (U.A. Hasan), and CLARA Procan Axe II innate sensors platform,
Lyon (M. Tommasino).
NR 85
TC 32
Z9 32
U1 2
U2 16
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUL 1
PY 2013
VL 210
IS 7
BP 1369
EP 1387
DI 10.1084/jem.20122394
PG 19
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 170NY
UT WOS:000320860700006
PM 23752229
ER
PT J
AU Yang, JJ
Zhang, RH
Lu, GM
Shen, Y
Peng, L
Zhu, C
Cui, M
Wang, WD
Arnaboldi, P
Tang, M
Gupta, M
Qi, CF
Jayaraman, P
Zhu, HF
Jiang, B
Chen, SH
He, JCJ
Ting, AT
Zhou, MM
Kuchroo, VK
Morse, HC
Ozato, K
Sikora, AG
Xiong, HB
AF Yang, Jianjun
Zhang, Ruihua
Lu, Geming
Shen, Yu
Peng, Liang
Zhu, Chen
Cui, Miao
Wang, Weidong
Arnaboldi, Paul
Tang, Meng
Gupta, Monica
Qi, Chen-Feng
Jayaraman, Padmini
Zhu, Hongfa
Jiang, Bo
Chen, Shu-hsia
He, John Cijiang
Ting, Adrian T.
Zhou, Ming-Ming
Kuchroo, Vijay K.
Morse, Herbert C., III
Ozato, Keiko
Sikora, Andrew G.
Xiong, Huabao
TI T cell-derived inducible nitric oxide synthase switches off T(H)17 cell
differentiation
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
KAPPA-B ACTIVATION; HELPER-CELLS; TH17 CELLS; TGF-BETA; EXPERIMENTAL
STROKE; TYROSINE NITRATION; INFLAMMATION; RECEPTOR
AB ROR gamma t is necessary for the generation of T(H)17 cells but the molecular mechanisms for the regulation of T(H)17 cells are still not fully understood. We show that activation of CD4(+) T cells results in the expression of inducible nitric oxide synthase (iNOS). iNOS-deficient mice displayed enhanced T(H)17 cell differentiation but without major effects on either T(H)1 or T(H)2 cell lineages, whereas endothelial NOS (eNOS) or neuronal NOS (nNOS) mutant mice showed comparable T(H)17 cell differentiation compared with wild-type control mice. The addition of N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL), the iNOS inhibitor, significantly enhanced T(H)17 cell differentiation, and S-nitroso-N-acetylpenicillamine (SNAP), the NO donor, dose-dependently reduced the percentage of IL-17-producing CD4(+) T cells. NO mediates nitration of tyrosine residues in ROR gamma t, leading to the suppression of ROR gamma t-induced IL-17 promoter activation, indicating that NO regulates IL-17 expression at the transcriptional level. Finally, studies of an experimental model of colitis showed that iNOS deficiency results in more severe inflammation with an enhanced T(H)17 phenotype. These results suggest that NO derived from iNOS in activated T cells plays a negative role in the regulation of T(H)17 cell differentiation and highlight the importance of intrinsic programs for the control of T(H)17 immune responses.
C1 [Yang, Jianjun; Zhang, Ruihua; Lu, Geming; Shen, Yu; Peng, Liang; Cui, Miao; Arnaboldi, Paul; Jayaraman, Padmini; Jiang, Bo; Chen, Shu-hsia; He, John Cijiang; Ting, Adrian T.; Sikora, Andrew G.; Xiong, Huabao] Mt Sinai Sch Med, Dept Med, Inst Immunol, New York, NY 10029 USA.
[Jayaraman, Padmini; Sikora, Andrew G.] Mt Sinai Sch Med, Dept Otolaryngol Head & Neck Surg, New York, NY 10029 USA.
[Zhu, Hongfa] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA.
[Zhou, Ming-Ming] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA.
[Zhu, Chen; Kuchroo, Vijay K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Wang, Weidong] Cornell Univ, Weill Med Coll, Ronald O Perelman & Claudia Cohen Ctr Reprod Med, New York, NY 10021 USA.
[Tang, Meng] Southeast Univ, Sch Publ Hlth, Minist Educ, Key Lab Environm Med & Engn, Nanjing 210009, Jiangsu, Peoples R China.
[Gupta, Monica; Ozato, Keiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Programs Genom Differentiat, Bethesda, MD 20892 USA.
[Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Xiong, HB (reprint author), Mt Sinai Sch Med, Dept Med, Inst Immunol, New York, NY 10029 USA.
EM Huabao.Xiong@mssm.edu
OI Morse, Herbert/0000-0002-9331-3705; Arnaboldi, Paul/0000-0002-4005-4412
FU National Institutes of Health (NIH) [P01 DK072201, R56AI091871]; Broad
Medical Research Program of The Broad Foundation; National Natural
Science Foundation of China [30972504]; National Important Project on
Scientific Research of China [2011CB933404]; Intramural Research Program
of the NIH, National Institute of Allergy and Infectious Diseases
FX H. Xiong was supported by the National Institutes of Health (NIH)
funding (P01 DK072201 and R56AI091871) and The Broad Medical Research
Program of The Broad Foundation. M. Tang was supported by National
Natural Science Foundation of China (No. 30972504) and National
Important Project on Scientific Research of China (No. 2011CB933404).
This work was supported in part by the Intramural Research Program of
the NIH, National Institute of Allergy and Infectious Diseases.
NR 51
TC 30
Z9 32
U1 0
U2 11
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUL 1
PY 2013
VL 210
IS 7
BP 1447
EP 1462
DI 10.1084/jem.20122494
PG 16
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 170NY
UT WOS:000320860700011
PM 23797094
ER
PT J
AU Zanker, D
Waithman, J
Yewdell, JW
Chen, WS
AF Zanker, Damien
Waithman, Jason
Yewdell, Jonathan W.
Chen, Weisan
TI Mixed Proteasomes Function To Increase Viral Peptide Diversity and
Broaden Antiviral CD8(+) T Cell Responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INFLUENZA-A VIRUS; ANTIGEN PRESENTATION; IMMUNODOMINANCE HIERARCHY;
IN-VIVO; IMMUNOGENICITY; EPITOPES; REPERTOIRE; RESIDUES; MEMORY
AB The three proteasome subunits with proteolytic activity are encoded by standard or immunoproteasome genes. Many proteasomes expressed by normal cells and cells exposed to cytokines are "mixed", that is, contain both standard and immunoproteasome subunits. Using a panel of 38 defined influenza A virus-derived epitopes recognized by C57BL/6 mouse CD8(+) T cells, we used mice with targeted disruption of beta 1i, beta 2i, or beta 5i/beta 2i genes to examine the contribution of mixed proteasomes to the immunodominance hierarchy of antiviral CD8(+) T cells. We show that each immunoproteasome subunit has large effects on the primary and recall immunodominance hierarchies due to modulating both the available T cell repertoire and generation of individual epitopes as determined both biochemically and kinetically in Ag presentation assays. These findings indicate that mixed proteasomes function to enhance the diversity of peptides and support a broad CD8(+) T cell response. The Journal of Immunology, 2013, 191: 52-59.
C1 [Zanker, Damien; Chen, Weisan] La Trobe Univ, Sch Mol Sci, Bundoora, Vic 3086, Australia.
[Waithman, Jason] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Perth, WA 6872, Australia.
[Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, WS (reprint author), La Trobe Univ, Sch Mol Sci, Bundoora, Vic 3086, Australia.
EM weisan.chen@latrobe.edu.au
OI Zanker, Damien/0000-0003-1163-9902
FU National Health and Medical Research Council [433608, 542508, 567122,
487926, 603100, 603104]
FX This work was supported in part by National Health and Medical Research
Council Project Grants 433608 and 542508 (to W.C.) and by National
Health and Medical Research Council Program Grant 567122. D.Z. was
supported by National Health and Medical Research Council Biomedical
Postgraduate Scholarship 487926. J.W. is a National Health and Medical
Research Council Biomedical Training Fellow (Grant 603100), and W.C. is
a National Health and Medical Research Council Senior Research Fellow
(Grant 603104).
NR 33
TC 19
Z9 19
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 1
PY 2013
VL 191
IS 1
BP 52
EP 59
DI 10.4049/jimmunol.1300802
PG 8
WC Immunology
SC Immunology
GA 169FQ
UT WOS:000320765000009
PM 23709680
ER
PT J
AU Sandgren, KJ
Smed-Sorensen, A
Forsell, MN
Soldemo, M
Adams, WC
Liang, F
Perbeck, L
Koup, RA
Wyatt, RT
Hedestam, GBK
Lore, K
AF Sandgren, Kerrie J.
Smed-Sorensen, Anna
Forsell, Mattias N.
Soldemo, Martina
Adams, William C.
Liang, Frank
Perbeck, Leif
Koup, Richard A.
Wyatt, Richard T.
Hedestam, Gunilla B. Karlsson
Lore, Karin
TI Human Plasmacytoid Dendritic Cells Efficiently Capture HIV-1 Envelope
Glycoproteins via CD4 for Antigen Presentation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPIDERMAL LANGERHANS CELLS; T-CELLS;
ANTIBODY-RESPONSES; CROSS-PRESENTATION; IN-VIVO; DC-SIGN;
TRANS-INFECTION; MEDIATED UPTAKE; TYPE-1 GP120
AB Advances in HIV-1 vaccine clinical trials and preclinical research indicate that the virus envelope glycoproteins (Env) are likely to be an essential component of a prophylactic vaccine. Efficient Ag uptake and presentation by dendritic cells (DCs) is important for strong CD4(+) Th cell responses and the development of effective humoral immune responses. In this study, we examined the capacity of distinct primary human DC subsets to internalize and present recombinant Env to CD4(+) T cells. Consistent with their specific receptor expression, skin DCs bound and internalized Env via C-type lectin receptors, whereas blood DC subsets, including CD1c(+) myeloid DCs, CD123(+) plasmacytoid DCs (PDCs), and CD141(+) DCs exhibited a restricted repertoire of C-type lectin receptors and relied on CD4 for uptake of Env. Despite a generally poor capacity for Ag uptake compared with myeloid DCs, the high expression of CD4 on PDCs allowed them to bind and internalize Env very efficiently. CD4-mediated uptake delivered Env to EEA1(+) endosomes that progressed to Lamp1(+) and MHC class II+ lysosomes where internalized Env was degraded rapidly. Finally, all three blood DC subsets were able to internalize an Env-CMV pp65 fusion protein via CD4 and stimulate pp65-specific CD4(+) T cells. Thus, in the in vitro systems described in this paper, CD4-mediated uptake of Env is a functional pathway leading to Ag presentation, and this may therefore be a mechanism used by blood DCs, including PDCs, for generating immune responses to Env-based vaccines. The Journal of Immunology, 2013, 191: 60-69.
C1 [Sandgren, Kerrie J.; Adams, William C.; Liang, Frank; Lore, Karin] Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, S-14186 Huddinge, Sweden.
[Smed-Sorensen, Anna; Soldemo, Martina; Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-14186 Huddinge, Sweden.
[Forsell, Mattias N.] Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden.
[Perbeck, Leif] Karolinska Univ Hosp Solna, Dept Surg, S-17176 Stockholm, Sweden.
[Koup, Richard A.; Lore, Karin] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Wyatt, Richard T.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
RP Lore, K (reprint author), Karolinska Inst, Karolinska Univ Hosp Huddinge, Ctr Infect Med, F59, S-14186 Huddinge, Sweden.
EM karin.lore@ki.se
FU Swedish International Development Agency; Swedish Research Council;
Swedish Governmental Agency for Innovation Systems (Vinnova); Swedish
Society of Medicine; Swedish Society of Medical Research; Fernstrom
Foundation; Foundation for AIDS Research (amfAR) in basic biomedical
research
FX This work was supported by grants from the Swedish International
Development Agency (to A.S.-S., G.B.K.H., and K.L.), the Swedish
Research Council (to K.L.), and the Swedish Governmental Agency for
Innovation Systems (Vinnova) (to K.L.). K.J.S. and F.L. are recipients
of scholarships from the Swedish Society of Medicine, the Swedish
Society of Medical Research, and the Fernstrom Foundation. M.N.F. is
supported by a Mathilde Krim fellowship from The Foundation for AIDS
Research (amfAR) in basic biomedical research.
NR 69
TC 11
Z9 11
U1 0
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 1
PY 2013
VL 191
IS 1
BP 60
EP 69
DI 10.4049/jimmunol.1202489
PG 10
WC Immunology
SC Immunology
GA 169FQ
UT WOS:000320765000010
PM 23729440
ER
PT J
AU Shi, GP
Vistica, BP
Nugent, LF
Tan, CY
Wawrousek, EF
Klinman, DM
Gery, I
AF Shi, Guangpu
Vistica, Barbara P.
Nugent, Lindsey F.
Tan, Cuiyan
Wawrousek, Eric F.
Klinman, Dennis M.
Gery, Igal
TI Differential Involvement of Th1 and Th17 in Pathogenic Autoimmune
Processes Triggered by Different TLR Ligands
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS SYNOVIUM;
ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; IMMUNE-RESPONSES; CYTOKINE
PRODUCTION; B-CELLS; DISEASE; ACTIVATION
AB The interaction between TLRs and their cognate ligands triggers both the innate and adaptive immune systems, and thus can play a pivotal role in the defense against pathogen invasion. This work investigates the differentiation of naive CD4 cells into Th1 or Th17 phenotypes in mice treated with different TLR ligands. We use a model system in which naive transgenic cells specific to hen egg lysozyme are adoptively transferred into recipients that express hen egg lysozyme in the lens of the eye. The transferred naive T cells induce ocular inflammation only in recipients treated with TLR ligands. Treatment with LPS preferentially stimulated IL-17 production, whereas CpG oligodeoxynucleotide and polyinosinic: polycytidylic acid primarily stimulated Th1 cells. Peptidoglycan stimulated the two Th subpopulations equally. The preferential induction of Th1 or Th17 by the four ligands was detected in the spleen (where a major portion of the adoptively transferred cells homed) and in the eyes, where activated Th cells initiate inflammation. Analysis of the cytokines present in recipient mice suggests that Th1 induction is elicited by IL-12 and/or IFN-alpha, whereas Th17 generation is preferentially mediated by IL-6. Importantly, we show in this article that treatment with LPS selectively promoted in the recipient mice the generation of IL-6-producing activated B cells. An inverse correlation was found between the level of regulatory T cells and severity of inflammation induced by the donor cells. Taken together, our data show that specific TLR ligands differentially activate the immune system as evidenced by the generation of distinct Th phenotypes from naive CD4 cells.
C1 [Shi, Guangpu; Vistica, Barbara P.; Nugent, Lindsey F.; Tan, Cuiyan; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wawrousek, Eric F.] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Klinman, Dennis M.] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA.
RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N208, Bethesda, MD 20892 USA.
EM geryi@nei.nih.gov
FU National Eye Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Eye Institute, National Institutes of Health.
NR 42
TC 15
Z9 16
U1 0
U2 10
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 1
PY 2013
VL 191
IS 1
BP 415
EP 423
DI 10.4049/jimmunol.1201732
PG 9
WC Immunology
SC Immunology
GA 169FQ
UT WOS:000320765000047
PM 23720812
ER
PT J
AU Ramos, VFML
Karp, BI
Lungu, C
Alter, K
Hallett, M
AF Ramos, V. F. M. L.
Karp, B., I
Lungu, C.
Alter, K.
Hallett, M.
TI Response to incobotulinumtoxinA after resistance to onabotulinumtoxinA
and rimabotulinumtoxinB
SO JOURNAL OF NEURAL TRANSMISSION
LA English
DT Meeting Abstract
CT 2nd International Congress on Treatment of Dystonia together with the
1st International Congress on Rehabilitation of Dystonia
CY MAY 08-11, 2013
CL Hannover, GERMANY
C1 [Ramos, V. F. M. L.; Karp, B., I; Lungu, C.; Hallett, M.] NIH, Bethesda, MD 20892 USA.
[Alter, K.] NIH, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA.
[Alter, K.] Mt Washington Pediat Hosp, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0300-9564
J9 J NEURAL TRANSM
JI J. Neural Transm.
PD JUL
PY 2013
VL 120
IS 7
BP 1153
EP 1153
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 169RV
UT WOS:000320798800061
ER
PT J
AU Ramos, VFML
Karp, BI
Hallett, M
AF Ramos, V. F. M. L.
Karp, B., I
Hallett, M.
TI Tricks to treatments: sensory tricks in dystonia
SO JOURNAL OF NEURAL TRANSMISSION
LA English
DT Meeting Abstract
CT 2nd International Congress on Treatment of Dystonia together with the
1st International Congress on Rehabilitation of Dystonia
CY MAY 08-11, 2013
CL Hannover, GERMANY
C1 [Ramos, V. F. M. L.; Karp, B., I; Hallett, M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0300-9564
J9 J NEURAL TRANSM
JI J. Neural Transm.
PD JUL
PY 2013
VL 120
IS 7
BP 1153
EP 1153
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 169RV
UT WOS:000320798800060
ER
PT J
AU Penzes, P
Buonanno, A
Passafaro, M
Sala, C
Sweet, RA
AF Penzes, Peter
Buonanno, Andres
Passafaro, Maria
Sala, Carlo
Sweet, Robert A.
TI Developmental vulnerability of synapses and circuits associated with
neuropsychiatric disorders
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Review
DE Alzheimer's disease; autism; dendritic spine; dopamine; ErbB4; GABAergic
interneuron
ID LINKED MENTAL-RETARDATION; AUTISM SPECTRUM DISORDER;
CENTRAL-NERVOUS-SYSTEM; PARVALBUMIN-POSITIVE INTERNEURONS; HIPPOCAMPAL
GAMMA OSCILLATIONS; DENDRITIC SPINE MORPHOGENESIS; GLUTAMIC-ACID
DECARBOXYLASE; 22Q13.3 DELETION SYNDROME; INCREASED FAMILIAL RISK;
EARLY-ONSET PSYCHOSIS
AB Psychiatric and neurodegenerative disorders, including intellectual disability, autism spectrum disorders (ASD), schizophrenia (SZ), and Alzheimer's disease, pose an immense burden to society. Symptoms of these disorders become manifest at different stages of life: early childhood, adolescence, and late adulthood, respectively. Progress has been made in recent years toward understanding the genetic substrates, cellular mechanisms, brain circuits, and endophenotypes of these disorders. Multiple lines of evidence implicate excitatory and inhibitory synaptic circuits in the cortex and hippocampus as key cellular substrates of pathogenesis in these disorders. Excitatory/inhibitory balance - modulated largely by dopamine - critically regulates cortical network function, neural network activity (i.e. gamma oscillations) and behaviors associated with psychiatric disorders. Understanding the molecular underpinnings of synaptic pathology and neuronal network activity may thus provide essential insight into the pathogenesis of these disorders and can reveal novel drug targets to treat them. Here, we discuss recent genetic, neuropathological, and molecular studies that implicate alterations in excitatory and inhibitory synaptic circuits in the pathogenesis of psychiatric disorders across the lifespan.
C1 [Penzes, Peter] Northwestern Univ, Dept Physiol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Penzes, Peter] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
[Buonanno, Andres] Eunice Shriver Kennedy NICHD, Mol Neurobiol Sect, NIH, Program Dev Neurobiol, Bethesda, MD USA.
[Passafaro, Maria; Sala, Carlo] Univ Milan, CNR Inst Neurosci, Milan, Italy.
[Passafaro, Maria; Sala, Carlo] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy.
[Passafaro, Maria] CNR, Inst Neurosci, Dulbecco Telethon Inst, I-20133 Milan, Italy.
[Sala, Carlo] Neurol Inst, Milan, Italy.
[Sala, Carlo] Fdn Carlo Besta, Milan, Italy.
[Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA.
[Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
RP Penzes, P (reprint author), Northwestern Univ, Dept Physiol, Feinberg Sch Med, 303 E,Chicago Ave, Chicago, IL 60611 USA.
EM p-penzes@northwestern.edu
RI Penzes, Peter/L-3987-2016; Sala, Carlo/A-2493-2009
OI Penzes, Peter/0000-0001-5449-1640; Sala, Carlo/0000-0003-0662-9523
FU NIH [MH071316, MH097216, MH071533, AG027224]; Eunice Shriver Kennedy
National Institute of Child Health and Human Development Intramural
Research Program; Veterans Health Administration [BX000452]; Comitato
Telethon Fondazione Onlus [GGP09196, GGP11095, GGP12097, GGP11116B];
Fondazione CARI-PLO project [2009.264]; Italian Institute of Technology,
Seed Grant, Ministry of Health in the frame of ERA-NET NEURON and
PNR-CNR Aging Program
FX This study was supported by NIH grants MH071316 and MH097216 to P. P.,
Eunice Shriver Kennedy National Institute of Child Health and Human
Development Intramural Research Program to A. B., Veterans Health
Administration Grant BX000452 and NIH Grants MH071533 and AG027224 to R.
A. S. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the Department of
Veterans Affairs, the National Institutes of Health, or the United
States government. We thank Ruoqi Gao for assistance with editing the
manuscript. This study was financially supported by Comitato Telethon
Fondazione Onlus, grant n. GGP09196 and GGP11095 (to CS), n. GGP12097
and GGP11116B (to MP) Fondazione CARI-PLO project number 2009.264,
Italian Institute of Technology, Seed Grant, Ministry of Health in the
frame of ERA-NET NEURON and PNR-CNR Aging Program 2012-2014 (to CS). The
authors declare no conflicts of interest.
NR 217
TC 40
Z9 41
U1 5
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD JUL
PY 2013
VL 126
IS 2
BP 165
EP 182
DI 10.1111/jnc.12261
PG 18
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 175DY
UT WOS:000321211700004
PM 23574039
ER
PT J
AU Whiting, DM
Tomycz, ND
Bailes, J
de Jonge, L
Lecoultre, V
Wilent, B
Alcindor, D
Prostko, ER
Cheng, BC
Angle, C
Cantella, D
Whiting, BB
Mizes, JS
Finnis, KW
Ravussin, E
Oh, MY
AF Whiting, Donald M.
Tomycz, Nestor D.
Bailes, Julian
de Jonge, Lilian
Lecoultre, Virgile
Wilent, Bryan
Alcindor, Dunbar
Prostko, E. Richard
Cheng, Boyle C.
Angle, Cynthia
Cantella, Diane
Whiting, Benjamin B.
Mizes, J. Scott
Finnis, Kirk W.
Ravussin, Eric
Oh, Michael Y.
TI Lateral hypothalamic area deep brain stimulation for refractory obesity:
a pilot study with preliminary data on safety, body weight, and energy
metabolism Clinical article
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE obesity; weight loss; deep brain stimulation; energy metabolism;
functional neurosurgery; respiratory chamber
ID VENTROMEDIAL HYPOTHALAMUS; RATS; LESIONS; PREVALENCE; OVERWEIGHT;
HUMANS; GAIN
AB Object. Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans.
Methods. Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, underwent bilateral implantation of LHA DBS electrodes as part of an institutional review board and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism.
Results. No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30-39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber.
Conclusions. Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first "proof of principle" for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy.
C1 [Whiting, Donald M.; Tomycz, Nestor D.; Alcindor, Dunbar; Prostko, E. Richard; Cheng, Boyle C.; Angle, Cynthia; Cantella, Diane; Whiting, Benjamin B.; Oh, Michael Y.] Allegheny Gen Hosp, Dept Neurosurg, Pittsburgh, PA 15212 USA.
[Lecoultre, Virgile; Ravussin, Eric] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Wilent, Bryan] Sentient Med Syst, Clin Neurophysiol, Philadelphia, PA USA.
[Mizes, J. Scott] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA.
[Bailes, Julian] Univ Chicago, Pritzker Sch Med, NorthShore Univ Hlth Syst, Evanston, IL USA.
[de Jonge, Lilian] NIH, Bethesda, MD 20892 USA.
[Finnis, Kirk W.] Medtron Neuromodulat, Minneapolis, MN USA.
RP Tomycz, ND (reprint author), Allegheny Gen Hosp, 420 East North Ave,Suite 302, Pittsburgh, PA 15212 USA.
EM ndtomycz@gmail.com
FU Medtronic Co.; West Virginia University
FX Medtronic Co. provided DBS hardware and financial support for this
study. Medtronic Co. was not involved in preparation or submission of
the manuscript. West Virginia University supplied grant support for this
study. Dr. Tomycz participated on the Surgeon Advisory Board for St.
Jude. Dr. Finnis is an employee of Medtronic. Dr. Oh is a consultant for
St. Jude.
NR 21
TC 33
Z9 34
U1 1
U2 10
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD JUL
PY 2013
VL 119
IS 1
BP 56
EP 63
DI 10.3171/2013.2.JNS12903
PG 8
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 168WT
UT WOS:000320739300015
PM 23560573
ER
PT J
AU Johnson, KA
Minoshima, S
Bohnen, NI
Donohoe, KJ
Foster, NL
Herscovitch, P
Karlawish, JH
Rowe, CC
Hedrick, S
Pappas, V
Carrillo, MC
Hartley, DM
AF Johnson, Keith A.
Minoshima, Satoshi
Bohnen, Nicolaas I.
Donohoe, Kevin J.
Foster, Norman L.
Herscovitch, Peter
Karlawish, Jason H.
Rowe, Christopher C.
Hedrick, Saima
Pappas, Virginia
Carrillo, Maria C.
Hartley, Dean M.
TI Update on Appropriate Use Criteria for Amyloid PET Imaging: Dementia
Experts, Mild Cognitive Impairment, and Education
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE amyloid PET; dementia; Alzheimer disease
ID ALZHEIMERS ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL
INSTITUTE; RECOMMENDATIONS; DISEASE
AB Amyloid PET imaging is a novel diagnostic test that can detect in living humans one of the two defining pathologic lesions of Alzheimer disease, amyloid-beta deposition in the brain. The Amyloid Imaging Task Force of the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging previously published appropriate use criteria for amyloid PET as an important tool for increasing the certainty of a diagnosis of Alzheimer disease in specific patient populations. Here, the task force further clarifies and expands 3 topics discussed in the original paper: first, defining dementia experts and their use of proper documentation to demonstrate the medical necessity of an amyloid PET scan; second, identifying a specific subset of individuals with mild cognitive impairment for whom an amyloid PET scan is appropriate; and finally, developing educational programs to increase awareness of the amyloid PET appropriate use criteria and providing instructions on how this test should be used in the clinical decision-making process.
C1 [Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Minoshima, Satoshi] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Bohnen, Nicolaas I.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
[Bohnen, Nicolaas I.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA.
[Bohnen, Nicolaas I.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Donohoe, Kevin J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Foster, Norman L.] Univ Utah, Dept Neurol, Salt Lake City, UT USA.
[Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Karlawish, Jason H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Rowe, Christopher C.] Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia.
[Rowe, Christopher C.] Austin Hlth, Ctr PET, Melbourne, Vic, Australia.
[Hedrick, Saima; Pappas, Virginia] Soc Nucl Med & Mol Imaging, Reston, VA USA.
[Carrillo, Maria C.; Hartley, Dean M.] Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL 60601 USA.
RP Carrillo, MC (reprint author), Alzheimers Assoc, Div Med & Sci Relat, 225 N Michigan Ave, Chicago, IL 60601 USA.
EM maria.carrillo@alz.org
FU NIA NIH HHS [P30 AG010124]
NR 4
TC 19
Z9 19
U1 0
U2 3
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD JUL 1
PY 2013
VL 54
IS 7
BP 1011
EP 1013
DI 10.2967/jnumed.113.127068
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 173WR
UT WOS:000321113500005
PM 23753186
ER
PT J
AU Gill, JM
Saligan, L
Lee, H
Rotolo, S
Szanton, S
AF Gill, Jessica M.
Saligan, Leorey
Lee, Hyunhwa
Rotolo, Susan
Szanton, Sarah
TI Women in recovery from PTSD have similar inflammation and quality of
life as non-traumatized controls (vol 74, pg 301, 2013)
SO JOURNAL OF PSYCHOSOMATIC RESEARCH
LA English
DT Correction
C1 [Gill, Jessica M.; Saligan, Leorey; Lee, Hyunhwa] NINR, NIH, Bethesda, MD 20892 USA.
[Gill, Jessica M.] George Mason Univ, Sch Nursing, Fairfax, VA 22030 USA.
[Szanton, Sarah] Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21218 USA.
RP Gill, JM (reprint author), NINR, NIH, Bethesda, MD 20892 USA.
EM jgill1376@yahoo.com
NR 1
TC 0
Z9 0
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3999
J9 J PSYCHOSOM RES
JI J. Psychosomat. Res.
PD JUL
PY 2013
VL 75
IS 1
BP 92
EP 92
DI 10.1016/j.jpsychores.2013.03.012
PG 1
WC Psychiatry
SC Psychiatry
GA 170CF
UT WOS:000320826500017
ER
PT J
AU Madden, JT
Toth, SJ
Dettmar, CM
Newman, JA
Oglesbee, RA
Hedderich, HG
Everly, RM
Becker, M
Ronau, JA
Buchanan, SK
Cherezov, V
Morrow, ME
Xu, SL
Ferguson, D
Makarov, O
Das, C
Fischetti, R
Simpson, GJ
AF Madden, Jeremy T.
Toth, Scott J.
Dettmar, Christopher M.
Newman, Justin A.
Oglesbee, Robert A.
Hedderich, Hartmut G.
Everly, R. Michael
Becker, Michael
Ronau, Judith A.
Buchanan, Susan K.
Cherezov, Vadim
Morrow, Marie E.
Xu, Shenglan
Ferguson, Dale
Makarov, Oleg
Das, Chittaranjan
Fischetti, Robert
Simpson, Garth J.
TI Integrated nonlinear optical imaging microscope for on-axis crystal
detection and centering at a synchrotron beamline
SO JOURNAL OF SYNCHROTRON RADIATION
LA English
DT Article
DE XRD; NLO; SHG; SONICC; centering; protein; TPE-UVF; microscopy; LCP;
two-photon
ID X-RAY-DIFFRACTION; THROUGHPUT MACROMOLECULAR CRYSTALLOGRAPHY; PROTEIN
CRYSTALS; LIPIDIC MESOPHASES; MEMBRANE-PROTEINS; RADIATION-DAMAGE;
FLUORESCENCE; CRYSTALLIZATION; PHOTODAMAGE; SCATTERING
AB Nonlinear optical (NLO) instrumentation has been integrated with synchrotron X-ray diffraction (XRD) for combined single-platform analysis, initially targeting applications for automated crystal centering. Second-harmonic-generation microscopy and two-photon-excited ultraviolet fluorescence microscopy were evaluated for crystal detection and assessed by X-ray raster scanning. Two optical designs were constructed and characterized; one positioned downstream of the sample and one integrated into the upstream optical path of the diffractometer. Both instruments enabled protein crystal identification with integration times between 80 and 150 ms per pixel, representing a similar to 10(3)-10(4)-fold reduction in the per-pixel exposure time relative to X-ray raster scanning. Quantitative centering and analysis of phenylalanine hydroxylase from Chromobacterium violaceum cPAH, Trichinella spiralis deubiquitinating enzyme TsUCH37, human kappa-opioid receptor complex kOR-T4L produced in lipidic cubic phase (LCP), intimin prepared in LCP, and alpha-cellulose samples were performed by collecting multiple NLO images. The crystalline samples were characterized by single-crystal diffraction patterns, while alpha-cellulose was characterized by fiber diffraction. Good agreement was observed between the sample positions identified by NLO and XRD raster measurements for all samples studied.
C1 [Madden, Jeremy T.; Toth, Scott J.; Dettmar, Christopher M.; Newman, Justin A.; Oglesbee, Robert A.; Hedderich, Hartmut G.; Everly, R. Michael; Ronau, Judith A.; Morrow, Marie E.; Das, Chittaranjan; Simpson, Garth J.] Purdue Univ, Dept Chem, W Lafayette, IN 47906 USA.
[Becker, Michael; Xu, Shenglan; Ferguson, Dale; Makarov, Oleg; Fischetti, Robert] Argonne Natl Lab, Adv Photon Source, GM CA APS, Argonne, IL 60439 USA.
[Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20814 USA.
[Cherezov, Vadim] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
RP Simpson, GJ (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47906 USA.
EM gsimpson@purdue.edu
RI Cherezov, Vadim/L-9812-2013
OI Cherezov, Vadim/0000-0002-5265-3914
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [DE-SC0000997]; NIH-NIGMS [R01GM-103401]; National Cancer
Institute [Y1-CO-1020]; National Institute of General Medical Sciences
[Y1-GM-1104]; US Department of Energy, Basic Energy Sciences, Office of
Science [DE-AC02-06CH11357]; NIH [P50 GM073197]; Intramural Research
Program of the NIH, National Institute of Diabetes and Digestive and
Kidney Diseases
FX The authors acknowledge Huixian Wu, Victoria J. Hall, Emma L. DeWalt,
Valerie Pye, Martin Caffrey, Nicholas Noinaj and James W. Fairman for
aiding in sample preparation. Instrumentation development was supported
in part by the Center for Direct Catalytic Conversion of Biomass to
Biofuels (C3Bio), an Energy Frontier Research Center funded by the US
Department of Energy, Office of Science, Office of Basic Energy
Sciences, Award No. DE-SC0000997, and by the NIH-NIGMS through the
R01GM-103401. GM/CA@APS has been funded in whole or in part with federal
funds from the National Cancer Institute (Y1-CO-1020) and the National
Institute of General Medical Sciences (Y1-GM-1104). Use of the Advanced
Photon Source was supported by the US Department of Energy, Basic Energy
Sciences, Office of Science, under contract No. DE-AC02-06CH11357.
Support is also acknowledged from the NIH Common Fund in Structural
Biology, grant P50 GM073197. SKB is supported by the Intramural Research
Program of the NIH, National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 46
TC 15
Z9 15
U1 2
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0909-0495
J9 J SYNCHROTRON RADIAT
JI J. Synchrot. Radiat.
PD JUL
PY 2013
VL 20
BP 531
EP 540
DI 10.1107/S0909049513007942
PN 4
PG 10
WC Instruments & Instrumentation; Optics; Physics, Applied
SC Instruments & Instrumentation; Optics; Physics
GA 163UZ
UT WOS:000320363700003
PM 23765294
ER
PT J
AU McDermott, A
Jesus, AA
Liu, Y
Kim, P
Jacks, J
Sanchez, GAM
Chen, YQ
Kannan, A
Schnebelen, A
Emanuel, PD
Shalin, S
Hiatt, K
Goldbach-Mansky, R
Gao, L
AF McDermott, Amelia
Jesus, Adriana Almeida
Liu, Yin
Kim, Peter
Jacks, Jennifer
Sanchez, Gina A. Montealegre
Chen, Yongqing
Kannan, Aarthi
Schnebelen, Alicia
Emanuel, Peter D.
Shalin, Sara
Hiatt, Kim
Goldbach-Mansky, Raphaela
Gao, Ling
TI A case of proteasome-associated auto-inflammatory syndrome with compound
heterozygous mutations
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Letter
ID SUBUNIT; LIPODYSTROPHY
C1 [McDermott, Amelia] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA.
[Kannan, Aarthi; Gao, Ling] Univ Arkansas Med Sci, Dept Dermatol, Little Rock, AR 72205 USA.
[Schnebelen, Alicia; Shalin, Sara] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA.
[Emanuel, Peter D.] Univ Arkansas Med Sci, Div Hematol Oncol, Little Rock, AR 72205 USA.
[Jesus, Adriana Almeida; Liu, Yin; Kim, Peter; Sanchez, Gina A. Montealegre; Chen, Yongqing; Goldbach-Mansky, Raphaela] NIAMSD, Bethesda, MD 20892 USA.
[Jacks, Jennifer] Jacks Dermatol, Pine Bluff, AR USA.
[Hiatt, Kim] Dermatol PLLC PA, Little Rock, AR USA.
RP Gao, L (reprint author), Univ Arkansas Med Sci, Dept Dermatol, 4301 W Markham,Slot 576, Little Rock, AR 72205 USA.
EM LGAO@uams.edu
OI Hiatt, Kim/0000-0003-3214-4917; Emanuel, Peter/0000-0002-9764-2434
FU Intramural NIH HHS [ZIA AR041138-08, ZIA AR041138-09, ZIA AR041138-10]
NR 5
TC 6
Z9 6
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD JUL
PY 2013
VL 69
IS 1
BP E29
EP E32
DI 10.1016/j.jaad.2013.01.015
PG 5
WC Dermatology
SC Dermatology
GA 165UG
UT WOS:000320510100011
PM 23768303
ER
PT J
AU Osinusi, A
Naggie, S
AF Osinusi, Anuoluwapo
Naggie, Susanna
TI Boceprevir for HCV in patients with HIV: where next?
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID CHRONIC HEPATITIS-C; ALPHA-2A PLUS RIBAVIRIN; GENOTYPE 1 INFECTION;
VIRUS
C1 [Osinusi, Anuoluwapo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Naggie, Susanna] Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA.
RP Osinusi, A (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM susanna.naggie@duke.edu
NR 15
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2013
VL 13
IS 7
BP 563
EP 564
DI 10.1016/S1473-3099(13)70162-2
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 172UN
UT WOS:000321030500004
PM 23768748
ER
PT J
AU Redd, AD
Quinn, TC
Tobian, AAR
AF Redd, Andrew D.
Quinn, Thomas C.
Tobian, Aaron A. R.
TI Frequency and implications of HIV superinfection
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG USERS; TYPE-1
SUPERINFECTION; PRIMARY INFECTION; VIRAL LOAD; ANTIRETROVIRAL THERAPY;
DISEASE PROGRESSION; MALE CIRCUMCISION; AMSTERDAM COHORT;
SEXUAL-BEHAVIOR
AB HIV superinfection occurs when an individual with HIV is infected with a new distinct HIV viral strain. Superinfection has been reported throughout the world, and studies have recorded incidence rates of 0-7-7% per year. Use of next-generation sequencing has improved detection of superinfection, which can be transmitted by injecting drug use and sexual intercourse. Superinfection might have incidence rates comparable to those of initial HIV infection. Clinicians should encourage safe sexual and injecting drug use practices for HIV-infected patients because superinfection has detrimental effects on clinical outcomes and could pose a concern for large-scale antiretroviral treatment plans. The occurrence of superinfection has implications for vaccine research, since it seems initial HIV infection is not fully protective against a subsequent infection. Additional collaborative research could benefit care of patients and inform future vaccine design.
C1 [Redd, Andrew D.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Tobian, Aaron A. R.] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA.
RP Tobian, AAR (reprint author), Johns Hopkins Univ, Dept Pathol, Carnegie 437,600 North Wolfe St, Baltimore, MD 21287 USA.
EM atobian1@jhmi.edu
FU NIH [1K23AI093152-01A1]; Doris Duke Charitable Foundation Clinician
Scientist Development Award [22006.02]; Division of Intramural Research,
National Institutes of Allergy and Infectious Diseases, National
Institutes of Health
FX AART is supported by the NIH (1K23AI093152-01A1) and Doris Duke
Charitable Foundation Clinician Scientist Development Award (#22006.02).
ADR and TCQ are supported by the Division of Intramural Research,
National Institutes of Allergy and Infectious Diseases, National
Institutes of Health. These funding sources had no involvement in the
writing of the manuscript or the decision to submit it for publication.
NR 73
TC 34
Z9 37
U1 0
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2013
VL 13
IS 7
BP 622
EP 628
DI 10.1016/S1473-3099(13)70066-5
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 172UN
UT WOS:000321030500022
PM 23726798
ER
PT J
AU Scalzo, F
Alger, JR
Hu, X
Saver, JL
Dani, KA
Muir, KW
Demchuk, AM
Coutts, SB
Luby, M
Warach, S
Liebeskind, DS
AF Scalzo, Fabien
Alger, Jeffry R.
Hu, Xiao
Saver, Jeffrey L.
Dani, Krishna A.
Muir, Keith W.
Demchuk, Andrew M.
Coutts, Shelagh B.
Luby, Marie
Warach, Steven
Liebeskind, David S.
CA STIR VISTA Imaging Investigators
TI Multi-center prediction of hemorrhagic transformation in acute ischemic
stroke using permeability imaging features
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Brain ischemia; Hemorrhagic transformation; Prediction; Acute stroke
diagnostic; Stroke; Permeability
ID BRAIN-BARRIER-PERMEABILITY; TISSUE FATE; THROMBOLYSIS; MODEL; MRI
AB Permeability images derived from magnetic resonance (MR) perfusion images are sensitive to blood brain barrier derangement of the brain tissue and have been shown to correlate with subsequent development of hemorrhagic transformation (HT) in acute ischemic stroke. This paper presents a multi-center retrospective study that evaluates the predictive power in terms of HT of six permeability MRI measures including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and percentage recovery (%R). Dynamic T2*-weighted perfusion MR images were collected from 263 acute ischemic stroke patients from four medical centers. An essential aspect of this study is to exploit a classifier-based framework to automatically identify predictive patterns in the overall intensity distribution of the permeability maps. The model is based on normalized intensity histograms that are used as input features to the predictive model. Linear and nonlinear predictive models are evaluated using a cross-validation to measure generalization power on new patients and a comparative analysis is provided for the different types of parameters. Results demonstrate that perfusion imaging in acute ischemic stroke can predict HT with an average accuracy of more than 85% using a predictive model based on a nonlinear regression model. Results also indicate that the permeability feature based on the percentage of recovery performs significantly better than the other features. This novel model may be used to refine treatment decisions in acute stroke. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Scalzo, Fabien; Alger, Jeffry R.; Saver, Jeffrey L.; Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
[Hu, Xiao] Univ Calif Los Angeles, Neurosurg Neural Syst & Dynam Lab NSDL, Los Angeles, CA USA.
[Dani, Krishna A.; Muir, Keith W.] Univ Glasgow, Inst Neurosci & Psychol, Glasgow G12 8QQ, Lanark, Scotland.
[Demchuk, Andrew M.; Coutts, Shelagh B.] Univ Calgary, Hotchkiss Brain Inst, Dept Radiol, Calgary, AB, Canada.
[Demchuk, Andrew M.; Coutts, Shelagh B.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada.
[Luby, Marie; Warach, Steven] NIH, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
RP Scalzo, F (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
EM fabien.scalzo@gmail.com
RI Muir, Keith/A-7670-2011;
OI Muir, Keith/0000-0001-9535-022X; Saver, Jeffrey/0000-0001-9141-2251
FU National Institute of Neurological Disorders and Stroke (NINDS);
National Institutes of Health [K23-NS054084, P50-NS044378,
R01-NS066008]; Canadian Institutes for Health Research (CIHR)
[MOP-118096]; Heart and Stroke Foundation (HSF) of Alberta; NWT; Nunavut
FX This work was supported by the National Institute of Neurological
Disorders and Stroke (NINDS), grants from the National Institutes of
Health K23-NS054084, P50-NS044378, R01-NS066008, and the Canadian
Institutes for Health Research (CIHR MOP-118096) and Heart and Stroke
Foundation (HSF) of Alberta, NWT and Nunavut. STIR and VISTA Imaging
steering committee: Steven Warach (co-chair), Gregory Albers, Stephen
Davis, Geoffrey Donnan, Marc Fisher, Tony Furlan, James Grotta, Werner
Hacke, Dong-Wha Kang, Chelsea Kidwell, Walter Koroshetz, Kennedy R.
Lees, Michael Lev, David Liebeskind, A. Gregory Sorensen, Vincent Thijs,
Gotz Thomalla, Joanna Wardlaw, Max Wintermark (co-chair).
NR 31
TC 12
Z9 13
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD JUL
PY 2013
VL 31
IS 6
BP 961
EP 969
DI 10.1016/j.mri.2013.03.013
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 169ZF
UT WOS:000320818600020
PM 23587928
ER
PT J
AU Lopez, G
Sidransky, E
AF Lopez, Grisel
Sidransky, Ellen
TI Predicting parkinsonism: New opportunities from Gaucher disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Editorial Material
DE Parkinson disease; Gaucher disease; Presymptomatic; Optical coherence
tomography; Glucocerebrosidase; Biomarker
C1 [Lopez, Grisel; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Intramural NIH HHS [Z99 HG999999]
NR 14
TC 1
Z9 1
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JUL
PY 2013
VL 109
IS 3
BP 235
EP 236
DI 10.1016/j.ymgme.2013.04.012
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 170DB
UT WOS:000320829000001
PM 23665160
ER
PT J
AU Kano, S
Colantuoni, C
Han, F
Zhou, Z
Yuan, Q
Wilson, A
Takayanagi, Y
Lee, Y
Rapoport, J
Eaton, W
Cascella, N
Ji, H
Goldman, D
Sawa, A
AF Kano, S.
Colantuoni, C.
Han, F.
Zhou, Z.
Yuan, Q.
Wilson, A.
Takayanagi, Y.
Lee, Y.
Rapoport, J.
Eaton, W.
Cascella, N.
Ji, H.
Goldman, D.
Sawa, A.
TI Genome-wide profiling of multiple histone methylations in olfactory
cells: further implications for cellular susceptibility to oxidative
stress in schizophrenia
SO MOLECULAR PSYCHIATRY
LA English
DT Letter
ID CHIP-SEQ DATA
C1 [Kano, S.; Colantuoni, C.; Wilson, A.; Cascella, N.; Sawa, A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Colantuoni, C.; Han, F.; Ji, H.] Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Zhou, Z.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, Bethesda, MD USA.
[Takayanagi, Y.; Eaton, W.] Johns Hopkins Univ, Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Lee, Y.; Rapoport, J.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Sawa, A (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
EM asawa1@jhmi.edu
RI Goldman, David/F-9772-2010; Kano, Shin-ichi/F-4144-2015
OI Goldman, David/0000-0002-1724-5405; Kano, Shin-ichi/0000-0002-5171-3436
FU Intramural NIH HHS [Z01 AA000301-09]; NIMH NIH HHS [K99 MH093458]
NR 10
TC 34
Z9 34
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUL
PY 2013
VL 18
IS 7
BP 740
EP 742
DI 10.1038/mp.2012.120
PG 3
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 168NL
UT WOS:000320712700001
PM 22925834
ER
PT J
AU Kano, S
Colantuoni, C
Han, F
Zhou, Z
Yuan, Q
Wilson, A
Takayanagi, Y
Lee, Y
Rapoport, J
Eaton, W
Cascella, N
Ji, H
Goldman, D
Sawa, A
AF Kano, S.
Colantuoni, C.
Han, F.
Zhou, Z.
Yuan, Q.
Wilson, A.
Takayanagi, Y.
Lee, Y.
Rapoport, J.
Eaton, W.
Cascella, N.
Ji, H.
Goldman, D.
Sawa, A.
TI PAC1 receptor (ADCYAP1R1) genotype is associated with dark-enhanced
startle in children
SO MOLECULAR PSYCHIATRY
LA English
DT Letter
ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY
C1 [Kano, S.; Colantuoni, C.; Wilson, A.; Cascella, N.; Sawa, A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Colantuoni, C.; Han, F.] Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Zhou, Z.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, Bethesda, MD USA.
[Takayanagi, Y.; Eaton, W.] Johns Hopkins Univ, Dept Mental Hlth, Sch Publ Hlth, Baltimore, MD USA.
[Lee, Y.; Rapoport, J.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Sawa, A (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
EM asawa1@jhmi.edu
OI Ressler, Kerry/0000-0002-5158-1103
NR 10
TC 0
Z9 0
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUL
PY 2013
VL 18
IS 7
BP 742
EP 743
DI 10.1038/mp.2012.98
PG 3
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 168NL
UT WOS:000320712700002
ER
PT J
AU Stewart, SE
Yu, D
Scharf, JM
Neale, BM
Fagerness, JA
Mathews, CA
Arnold, PD
Evans, PD
Gamazon, ER
Osiecki, L
McGrath, L
Haddad, S
Crane, J
Hezel, D
Illman, C
Mayerfeld, C
Konkashbaev, A
Liu, C
Pluzhnikov, A
Tikhomirov, A
Edlund, CK
Rauch, SL
Moessner, R
Falkai, P
Maier, W
Ruhrmann, S
Grabe, HJ
Lennertz, L
Wagner, M
Bellodi, L
Cavallini, MC
Richter, MA
Cook, EH
Kennedy, JL
Rosenberg, D
Stein, DJ
Hemmings, SMJ
Lochner, C
Azzam, A
Chavira, DA
Fournier, E
Garrido, H
Sheppard, B
Umana, P
Murphy, DL
Wendland, JR
Veenstra-VanderWeele, J
Denys, D
Blom, R
Deforce, D
Van Nieuwerburgh, F
Westenberg, HGM
Walitza, S
Egberts, K
Renner, T
Miguel, EC
Cappi, C
Hounie, AG
do Rosario, MC
Sampaio, AS
Vallada, H
Nicolini, H
Lanzagorta, N
Camarena, B
Delorme, R
Leboyer, M
Pato, CN
Pato, MT
Voyiaziakis, E
Heutink, P
Cath, DC
Posthuma, D
Smit, JH
Samuels, J
Bienvenu, OJ
Cullen, B
Fyer, AJ
Grados, MA
Greenberg, BD
McCracken, JT
Riddle, MA
Wang, Y
Coric, V
Leckman, JF
Bloch, M
Pittenger, C
Eapen, V
Black, DW
Ophoff, RA
Strengman, E
Cusi, D
Turiel, M
Frau, F
Macciardi, F
Gibbs, JR
Cookson, MR
Singleton, A
Hardy, J
Crenshaw, AT
Parkin, MA
Mirel, DB
Conti, DV
Purcell, S
Nestadt, G
Hanna, GL
Jenike, MA
Knowles, JA
Cox, N
Pauls, DL
AF Stewart, S. E.
Yu, D.
Scharf, J. M.
Neale, B. M.
Fagerness, J. A.
Mathews, C. A.
Arnold, P. D.
Evans, P. D.
Gamazon, E. R.
Osiecki, L.
McGrath, L.
Haddad, S.
Crane, J.
Hezel, D.
Illman, C.
Mayerfeld, C.
Konkashbaev, A.
Liu, C.
Pluzhnikov, A.
Tikhomirov, A.
Edlund, C. K.
Rauch, S. L.
Moessner, R.
Falkai, P.
Maier, W.
Ruhrmann, S.
Grabe, H-J
Lennertz, L.
Wagner, M.
Bellodi, L.
Cavallini, M. C.
Richter, M. A.
Cook, E. H., Jr.
Kennedy, J. L.
Rosenberg, D.
Stein, D. J.
Hemmings, S. M. J.
Lochner, C.
Azzam, A.
Chavira, D. A.
Fournier, E.
Garrido, H.
Sheppard, B.
Umana, P.
Murphy, D. L.
Wendland, J. R.
Veenstra-VanderWeele, J.
Denys, D.
Blom, R.
Deforce, D.
Van Nieuwerburgh, F.
Westenberg, H. G. M.
Walitza, S.
Egberts, K.
Renner, T.
Miguel, E. C.
Cappi, C.
Hounie, A. G.
do Rosario, M. Conceicao
Sampaio, A. S.
Vallada, H.
Nicolini, H.
Lanzagorta, N.
Camarena, B.
Delorme, R.
Leboyer, M.
Pato, C. N.
Pato, M. T.
Voyiaziakis, E.
Heutink, P.
Cath, D. C.
Posthuma, D.
Smit, J. H.
Samuels, J.
Bienvenu, O. J.
Cullen, B.
Fyer, A. J.
Grados, M. A.
Greenberg, B. D.
McCracken, J. T.
Riddle, M. A.
Wang, Y.
Coric, V.
Leckman, J. F.
Bloch, M.
Pittenger, C.
Eapen, V.
Black, D. W.
Ophoff, R. A.
Strengman, E.
Cusi, D.
Turiel, M.
Frau, F.
Macciardi, F.
Gibbs, J. R.
Cookson, M. R.
Singleton, A.
Hardy, J.
Crenshaw, A. T.
Parkin, M. A.
Mirel, D. B.
Conti, D. V.
Purcell, S.
Nestadt, G.
Hanna, G. L.
Jenike, M. A.
Knowles, J. A.
Cox, N.
Pauls, D. L.
CA North Amer Brain Expression Consor
UK Brain Expression Database
TI Genome-wide association study of obsessive-compulsive disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE DLGAP; genetic; genomic; GWAS; neurodevelopmental disorder;
obsessive-compulsive disorder
ID OCD COLLABORATIVE GENETICS; FAMILY-BASED ASSOCIATION; QUANTITATIVE TRAIT
LOCI; TRANSPORTER GENE; LINKAGE; SLC1A1; SNPS; TWIN; REPLICATION;
EXPRESSION
AB Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469 410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P = 2.49 x 10(-6) and P = 3.44 x 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value = 3.84 x 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 x 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P < 0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P = 0.001) was observed within the top-ranked SNPs (P < 0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
C1 [Stewart, S. E.; Yu, D.; Scharf, J. M.; Neale, B. M.; Fagerness, J. A.; Osiecki, L.; McGrath, L.; Haddad, S.; Crane, J.; Hezel, D.; Illman, C.; Mayerfeld, C.; Purcell, S.; Jenike, M. A.; Pauls, D. L.] Harvard Univ, Sch Med, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA.
[Stewart, S. E.; Yu, D.; Scharf, J. M.; Fagerness, J. A.; Osiecki, L.; McGrath, L.; Haddad, S.; Crane, J.; Hezel, D.; Illman, C.; Mayerfeld, C.; Purcell, S.; Jenike, M. A.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Stewart, S. E.] Univ British Columbia, British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 1M9, Canada.
[Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Scharf, J. M.; Purcell, S.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Neale, B. M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Scharf, J. M.; Neale, B. M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Mathews, C. A.; Azzam, A.; Sheppard, B.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Arnold, P. D.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
[Arnold, P. D.; Richter, M. A.; Kennedy, J. L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Evans, P. D.; Gamazon, E. R.; Konkashbaev, A.; Pluzhnikov, A.; Tikhomirov, A.; Cox, N.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA.
[Liu, C.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Edlund, C. K.; Conti, D. V.] Univ So Calif, Zilkha Neurogenet Inst, Keck Sch Med, Dept Preventat Med,Div Biostat, Los Angeles, CA USA.
[Edlund, C. K.; Conti, D. V.] Univ So Calif, Keck Sch Med, Epigenome Ctr, Los Angeles, CA 90033 USA.
[Rauch, S. L.] Partners Psychiat, Boston, MA USA.
[Rauch, S. L.] McLean Hosp, Boston, MA USA.
[Moessner, R.; Maier, W.; Lennertz, L.; Wagner, M.] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany.
[Falkai, P.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany.
[Ruhrmann, S.] Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany.
[Grabe, H-J] Univ Med Greifswald, Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany.
[Bellodi, L.] Psychiat Univ Vita Salute San Raffaele, Milan, Italy.
[Cavallini, M. C.] Fdn Ctr San Raffaele Monte Tabor, Milan, Italy.
[Richter, M. A.] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Toronto, ON M4N 3M5, Canada.
[Cook, E. H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
[Kennedy, J. L.] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Rosenberg, D.] Wayne State Univ, Detroit, MI USA.
[Rosenberg, D.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Stein, D. J.] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Hemmings, S. M. J.; Lochner, C.] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa.
[Chavira, D. A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Fournier, E.; Garrido, H.; Umana, P.] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica.
[Murphy, D. L.; Wendland, J. R.] NIMH, Lab Clin Sci, Intramural Res Program, Bethesda, MD 20892 USA.
[Wendland, J. R.] F Hoffmann Roche Ltd, CNS Clin Biomarker Grp, Pharma Res & Early Dev, Basel, Switzerland.
[Veenstra-VanderWeele, J.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN 37235 USA.
[Veenstra-VanderWeele, J.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Pediat, Nashville, TN 37235 USA.
[Veenstra-VanderWeele, J.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Pharmacol, Nashville, TN 37235 USA.
[Veenstra-VanderWeele, J.] Vanderbilt Univ, Inst Brain, Nashville, TN 37235 USA.
[Denys, D.; Blom, R.; Westenberg, H. G. M.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands.
[Denys, D.; Blom, R.; Westenberg, H. G. M.] Netherlands Inst Neurosci, Amsterdam, Netherlands.
[Deforce, D.; Van Nieuwerburgh, F.] Univ Ghent, Lab Pharmaceut Biotechnol, B-9000 Ghent, Belgium.
[Walitza, S.] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland.
[Egberts, K.; Renner, T.] Univ Wurzburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-97070 Wurzburg, Germany.
[Miguel, E. C.; Cappi, C.; Hounie, A. G.; do Rosario, M. Conceicao; Sampaio, A. S.; Vallada, H.] Univ Sao Paulo, Fac Med, Dept Psychiat, Sao Paulo, Brazil.
[Sampaio, A. S.] Univ Fed Bahia, Univ Hlth Care Serv SMURB, Salvador, BA, Brazil.
[Nicolini, H.] Univ Mexico City, Ctr Genom Sci, Mexico City, DF, Mexico.
[Nicolini, H.; Lanzagorta, N.] Carracci Med Grp, Mexico City, DF, Mexico.
[Camarena, B.] Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Depto Genet Psiquiatr, Mexico City, DF, Mexico.
[Delorme, R.; Leboyer, M.] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, INSERM,U955, F-75019 Paris, France.
[Delorme, R.; Leboyer, M.] Inst Mondor Rech Biomed, Creteil, France.
[Delorme, R.; Leboyer, M.] French Natl Sci Fdn, Fdn Fondamental, Creteil, France.
[Pato, C. N.; Pato, M. T.; Voyiaziakis, E.; Knowles, J. A.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA.
[Heutink, P.; Posthuma, D.] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Clin Genet, Sect Med Gen, Amsterdam, Netherlands.
[Cath, D. C.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Utrecht, Netherlands.
[Cath, D. C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands.
[Cath, D. C.; Smit, J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, Utrecht, Netherlands.
[Samuels, J.; Bienvenu, O. J.; Cullen, B.; Grados, M. A.; Riddle, M. A.; Wang, Y.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Greenberg, B. D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[McCracken, J. T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Coric, V.; Leckman, J. F.; Bloch, M.; Pittenger, C.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Coric, V.; Bloch, M.; Pittenger, C.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Eapen, V.] Univ New S Wales, Acad Unit Child Psychiat, South West Sydney AUCS, Sydney, NSW, Australia.
[Black, D. W.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA.
[Ophoff, R. A.; Strengman, E.] UCLA Ctr Neurobehav Genet, Los Angeles, CA USA.
[Ophoff, R. A.; Strengman, E.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Cusi, D.; Frau, F.] Univ Milan, Grad Sch Nephrol, Dept Med Surg & Dent, Milan, Italy.
[Cusi, D.] San Paolo Hosp, Div Nephrol, Milan, Italy.
[Turiel, M.] Univ Milan, Dept Hlth Technol, Milan, Italy.
[Frau, F.] Filarete Fdn, Milan, Italy.
[Macciardi, F.] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Irvine, CA 92717 USA.
[Gibbs, J. R.; Cookson, M. R.; Singleton, A.] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA.
[Hardy, J.] UCL, Dept Mol Neurosci, Inst Neurol, London, England.
[Crenshaw, A. T.; Parkin, M. A.; Mirel, D. B.; Purcell, S.] Broad Inst Harvard MIT, Cambridge, MA USA.
RP Stewart, SE (reprint author), Univ British Columbia, Dept Psychiat, OCD Clin, BCMHARI,CFRI, A3-118,938 West 28th Ave, Vancouver, BC V5Z 4H4, Canada.
EM sevelynstewart@gmail.com; dpauls@pngu.mgh.harvard.edu
RI Macciardi, Fabio/N-3768-2014; Wagner, Michael/E-2325-2011; Stein,
Dan/A-1752-2008; Trabzuni, Daniah/C-4034-2012; Vallada,
Homero/D-1333-2014; Traynor, Bryan/G-5690-2010; Renner,
Tobias/I-2120-2013; Hardy, John/C-2451-2009; Deforce,
Dieter/J-4725-2013; SAMPAIO, ALINE/M-1229-2013; Singleton,
Andrew/C-3010-2009; Weale, Michael/F-2587-2010; Stewart,
Evelyn/K-6961-2014; Van Nieuwerburgh, Filip/H-9697-2015;
Veenstra-VanderWeele, Jeremy/K-1935-2015;
OI Macciardi, Fabio/0000-0003-0537-4266; Wagner,
Michael/0000-0003-2589-6440; Stein, Dan/0000-0001-7218-7810; Trabzuni,
Daniah/0000-0003-4826-9570; Nicolini, Humberto/0000-0003-2494-0067;
Hanna, Gregory/0000-0002-0742-6990; Samuels, Jack/0000-0002-6715-7905;
Azzam, Amin/0000-0002-7024-7450; Walitza, Susanne/0000-0002-8161-8683;
Vallada, Homero/0000-0001-5123-8295; Deforce,
Dieter/0000-0002-0635-661X; SAMPAIO, ALINE/0000-0001-5568-6167; Weale,
Michael/0000-0003-4593-1186; Van Nieuwerburgh,
Filip/0000-0001-8815-5485; Veenstra-VanderWeele,
Jeremy/0000-0002-6349-1076; Hemmings, Sian/0000-0001-8461-1017;
Zonderman, Alan B/0000-0002-6523-4778; Stewart, S.
Evelyn/0000-0002-0994-6383; Lanzagorta, Nuria/0000-0001-6769-6813;
Gamazon, Eric/0000-0003-4204-8734
FU Judah Foundation; NIH [MH079489, MH073250]; American Recovery and
Re-investment Act (ARRA) awards [NS40024-07S1, NS16648-29S1]; American
Academy of Child and Adolescent Psychiatry (AACAP); Anxiety Disorders
Association of America (ADAA); University of British Columbia; Michael
Smith Foundation Clinical Research Scholar Award; Tourette Syndrome
Association; American Academy of Neurology Foundation; National Center
for Research Resources [RR020278]; NIH Genes, Environment and Health
Initiative [GEI] [U01 HG004422]; NIH GEI [U01HG004438]; National
Institute on Alcohol Abuse and Alcoholism; National Institute on Drug
Abuse; NIH contract 'High throughput genotyping for studying the genetic
contributions to human disease' [HHSN268200782096C]; UK Medical Research
Council; National Institute on Aging, National Institutes of Health,
Department of Health and Human Services [Z01 AG000932-02]
FX The authors would like to express their utmost gratitude to the
OCD-affected families who participated in this research. In addition,
they would like to thank the International OCD Foundation (IOCDF) for
their role in establishing the IOCDF Genetics Collaborative, as well as
other individuals who played roles in assisting this study, including
Rhonda Ellwyn, Katherine Beattie, Colm O'Dushlaine, Doug Ruderfer, Priya
Moorjani and V. Guttenthaler. This work was supported primarily by a
grant from the Judah Foundation (a private, non-industry related
foundation established by a family affected by OCD), NIH grants MH079489
and MH073250 to DLP, American Recovery and Re-investment Act (ARRA)
awards NS40024-07S1 and NS16648-29S1 to DLP, by an American Academy of
Child and Adolescent Psychiatry (AACAP) Early Investigator Research
Grant, an Anxiety Disorders Association of America (ADAA) Junior
Investigator Research Grant, the University of British Columbia and a
Michael Smith Foundation Clinical Research Scholar Award to SES, and
grants from the Tourette Syndrome Association (DLP and JMS), the
American Academy of Neurology Foundation (JMS) and NIH grant MH085057 to
JMS. The Broad Institute Center for Genotyping and Analysis was
supported by grant U54 RR020278 from the National Center for Research
Resources. Funding support for the Study of Addiction: Genetics and
Environment (SAGE) was provided through the NIH Genes, Environment and
Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide
association studies funded as part of the Gene Environment Association
Studies (GENEVA) under GEI. Assistance with phenotype harmonization and
genotype cleaning, as well as with general study coordination, was
provided by the GENEVA Coordinating Center (U01 HG004446). Assistance
with data cleaning was provided by the National Center for Biotechnology
Information. Support for collection of data sets and samples was
provided by the Collaborative Study on the Genetics of Alcoholism (COGA;
U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence
(COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD;
R01 DA013423). Funding support for related genotyping, which was
performed at the Johns Hopkins University Center for Inherited Disease
Research, was provided by the NIH GEI (U01HG004438), the National
Institute on Alcohol Abuse and Alcoholism, the National Institute on
Drug Abuse, and the NIH contract 'High throughput genotyping for
studying the genetic contributions to human disease'
(HHSN268200782096C). The data sets used for the analyses described in
this manuscript were obtained from dbGaP at
http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi/study_id =
phs000092.v1.p1 through dbGaP accession number phs000092.v1.p. Frontal
lobe eQTL data was provided by the North American Brain Expression
Consortium and the UK Human Brain Expression Database. Funding support
for generation of the eQTL data was provided by the UK Medical Research
Council and the Intramural Research Program of the National Institute on
Aging, National Institutes of Health, Department of Health and Human
Services project Z01 AG000932-02. The North American Brain Expression
Consortium comprises: Sampath Arepalli, Mark R Cookson, Allissa Dillman,
Luigi Ferrucci, J Raphael Gibbs, Dena G Hernandez, Robert Johnson, Dan L
Longo, Michael A Nalls, Richard O0Brien, Andrew Singleton, Bryan
Traynor, Juan Troncoso, Marcel van der Brug, H Ronald Zielke and Alan
Zonderman.; The UK Human Brain Expression Database membership comprises:
John A Hardy, Mina Ryten, Colin Smith, Daniah Trabzuni, Robert Walker
and Mike Weale. None of the funding sources supporting this work had any
influence or played any role in: (a) the design or conduct of the study;
(b) management, analysis or interpretation of the data; or c)
preparation, review or approval of the manuscript.
NR 71
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U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUL
PY 2013
VL 18
IS 7
BP 788
EP 798
DI 10.1038/mp.2012.85
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 168NL
UT WOS:000320712700012
PM 22889921
ER
PT J
AU Gunduz-Cinar, O
MacPherson, KP
Cinar, R
Gamble-George, J
Sugden, K
Williams, B
Godlewski, G
Ramikie, TS
Gorka, AX
Alapafuja, SO
Nikas, SP
Makriyannis, A
Poulton, R
Patel, S
Hariri, AR
Caspi, A
Moffitt, TE
Kunos, G
Holmes, A
AF Gunduz-Cinar, O.
MacPherson, K. P.
Cinar, R.
Gamble-George, J.
Sugden, K.
Williams, B.
Godlewski, G.
Ramikie, T. S.
Gorka, A. X.
Alapafuja, S. O.
Nikas, S. P.
Makriyannis, A.
Poulton, R.
Patel, S.
Hariri, A. R.
Caspi, A.
Moffitt, T. E.
Kunos, G.
Holmes, A.
TI Convergent translational evidence of a role for anandamide in
amygdala-mediated fear extinction, threat processing and
stress-reactivity
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE amygdala; anxiety; cannabinoid; fear; gene; stress
ID ACID AMIDE HYDROLASE; PROBLEM DRUG-USE; ENDOCANNABINOID SYSTEM;
INDIVIDUAL-DIFFERENCES; BASOLATERAL AMYGDALA; CONDITIONED FEAR; CB1
RECEPTORS; SHORT-TERM; MONOACYLGLYCEROL LIPASE; PREFRONTAL CORTEX
AB Endocannabinoids are released 'on-demand' on the basis of physiological need, and can be pharmacologically augmented by inhibiting their catabolic degradation. The endocannabinoid anandamide is degraded by the catabolic enzyme fatty acid amide hydrolase (FAAH). Anandamide is implicated in the mediation of fear behaviors, including fear extinction, suggesting that selectively elevating brain anandamide could modulate plastic changes in fear. Here we first tested this hypothesis with preclinical experiments employing a novel, potent and selective FAAH inhibitor, AM3506 (5-(4-hydroxyphenyl)pentanesulfonyl fluoride). Systemic AM3506 administration before extinction decreased fear during a retrieval test in a mouse model of impaired extinction. AM3506 had no effects on fear in the absence of extinction training, or on various non-fear-related measures. Anandamide levels in the basolateral amygdala were increased by extinction training and augmented by systemic AM3506, whereas application of AM3506 to amygdala slices promoted long-term depression of inhibitory transmission, a form of synaptic plasticity linked to extinction. Further supporting the amygdala as effect-locus, the fear-reducing effects of systemic AM3506 were blocked by intra-amygdala infusion of a CB1 receptor antagonist and were fully recapitulated by intra-amygdala infusion of AM3506. On the basis of these preclinical findings, we hypothesized that variation in the human FAAH gene would predict individual differences in amygdala threat-processing and stress-coping traits. Consistent with this, carriers of a low-expressing FAAH variant (385A allele; rs324420) exhibited quicker habituation of amygdala reactivity to threat, and had lower scores on the personality trait of stress-reactivity. Our findings show that augmenting amygdala anandamide enables extinction-driven reductions in fear in mouse and may promote stress-coping in humans.
C1 [Gunduz-Cinar, O.; MacPherson, K. P.; Holmes, A.] NIAAA, Lab Behav & Genom Neurosci, Sect Behav Sci & Genet, NIH, Bethesda, MD USA.
[Gunduz-Cinar, O.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Cinar, R.; Godlewski, G.; Kunos, G.] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
[Gamble-George, J.; Ramikie, T. S.; Patel, S.] Vanderbilt Univ, Med Ctr, Dept Psychiat & Mol Physiol & Biophys, Nashville, TN USA.
[Sugden, K.; Williams, B.; Gorka, A. X.; Hariri, A. R.; Caspi, A.; Moffitt, T. E.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
[Sugden, K.; Williams, B.; Caspi, A.; Moffitt, T. E.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA.
[Sugden, K.; Williams, B.; Hariri, A. R.; Caspi, A.; Moffitt, T. E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA.
[Sugden, K.; Williams, B.; Caspi, A.; Moffitt, T. E.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, London WC2R 2LS, England.
[Alapafuja, S. O.; Nikas, S. P.; Makriyannis, A.] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA.
[Poulton, R.] Univ Otago, Dunedin Sch Med, Dunedin, New Zealand.
RP Holmes, A (reprint author), NIAAA, Lab Behav & Genom Neurosci, Sect Behav Sci & Genet, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
EM Andrew.Holmes@nih.gov
RI Patel, Sachin/E-5608-2012; caspi, avshalom/D-5294-2011; Moffitt,
Terrie/D-5295-2011; Gunduz Cinar, Ozge/E-5756-2010
OI CINAR, RESAT/0000-0002-8597-7253; Moffitt, Terrie/0000-0002-8589-6760;
Gamble-George, Joyonna/0000-0002-5492-9216; Gunduz Cinar,
Ozge/0000-0002-3826-8905
FU NIAAA Intramural Research Program; Department of Defense in the Center
for Neuroscience and Regenerative Medicine; NIA [AG032282]; MRC
[G0100527]; NIDA [DA031579]; NIMH [MH077874, MH072837, MH090412]; Royal
Society
FX This work was supported by the NIAAA Intramural Research Program (OGC,
KPM, RC, GK, AH), Department of Defense in the Center for Neuroscience
and Regenerative Medicine (OGC, AH), NIA (AG032282 to TEM), MRC
(G0100527 to TEM), NIDA (DA031579 to ARH) and NIMH (MH077874 to AC;
MH072837 to ARH, MH090412 to SP). AC is a Royal Society Wolfson Merit
Award holder. We thank Daniel Fisher and Caitlin Schaapveld for
assistance with behavioral experiments.
NR 58
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUL
PY 2013
VL 18
IS 7
BP 813
EP 823
DI 10.1038/mp.2012.72
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 168NL
UT WOS:000320712700015
PM 22688188
ER
PT J
AU Kerkar, SP
Leonardi, AJ
van Panhuys, N
Zhang, L
Yu, ZY
Crompton, JG
Pan, JH
Palmer, DC
Morgan, RA
Rosenberg, SA
Restifo, NP
AF Kerkar, Sid P.
Leonardi, Anthony J.
van Panhuys, Nicolas
Zhang, Ling
Yu, Zhiya
Crompton, Joseph G.
Pan, Jenny H.
Palmer, Douglas C.
Morgan, Richard A.
Rosenberg, Steven A.
Restifo, Nicholas P.
TI Collapse of the Tumor Stroma is Triggered by IL-12 Induction of Fas
SO MOLECULAR THERAPY
LA English
DT Article
ID T-CELL THERAPY; IMMUNE ESCAPE; ANTITUMOR IMMUNITY; SUPPRESSOR-CELLS;
GENE-EXPRESSION; DENDRITIC CELLS; INTERLEUKIN-12; CANCER;
MICROENVIRONMENT; IMMUNOTHERAPY
AB Engineering CD8(+) T cells to deliver interleukin 12 -(IL-12) to the tumor site can lead to striking improvements in the ability of adoptively transferred T cells to induce the regression of established murine cancers. We have recently shown that IL-12 triggers an acute inflammatory environment that reverses dysfunctional antigen presentation by myeloid-derived cells within tumors and leads to an increase in the infiltration of adoptively transferred antigen-specific CD8(+) T cells. Here, we find that local delivery of IL-12 increased the expression of Fas within tumor-infiltrating macrophages, dendritic cells, and myeloid-derived suppressor cells (MDSC), and that these changes were abrogated in mice deficient in IL-12-receptor signaling. Importantly, upregulation of Fas in host mice played a critical role in the proliferation and antitumor activity of adoptively transferred IL-12-modified CD8(+) T cells. We also observed higher percentages of myeloid-derived cell populations within tumors in Fas-deficient mice, indicating that tumor stromal destruction was dependent on the Fas death receptor. Taken together, these results describe the likely requirement for costimulatory reverse signaling through Fasl on T cells that successfully infiltrate tumors, a mechanism triggered by the induction of Fas expression on myeloid-derived cells by IL-12 and the subsequent collapse of the tumor stroma.
C1 [Leonardi, Anthony J.; Zhang, Ling; Yu, Zhiya; Crompton, Joseph G.; Pan, Jenny H.; Palmer, Douglas C.; Morgan, Richard A.; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kerkar, Sid P.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD USA.
[van Panhuys, Nicolas] NIAID, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Kerkar, SP (reprint author), NCI, NIH, Room 3-5762,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kerkars@mail.nih.gov; restifon@nih.gov
RI Palmer, Douglas/B-9454-2008; van Panhuys, Nicholas/E-1812-2011;
OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas
P./0000-0003-4229-4580; van Panhuys, Nicholas/0000-0003-2199-852X
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The authors
declare no conflict of interest.
NR 43
TC 33
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U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUL
PY 2013
VL 21
IS 7
BP 1369
EP 1377
DI 10.1038/mt.2013.58
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 173WL
UT WOS:000321112500011
PM 23568260
ER
PT J
AU Mendell, JR
Lloyd-Puryear, M
AF Mendell, Jerry R.
Lloyd-Puryear, Michele
TI Report of MDA muscle disease symposium on newborn screening for Duchenne
muscular dystrophy
SO MUSCLE & NERVE
LA English
DT Article
DE Committee on Heritable Disorders for Newborns and Children; Department
of Health and Human Services; Duchenne muscular dystrophy; Newborn
Screening; Recommended Uniform Screening Panel; Secretary's Advisory
ID CORTICOSTEROID TREATMENT; FOLLOW-UP; RESTORATION; PREDNISONE; PRO051;
TRIAL; GENE
AB This report summarizes the progress made in newborn screening for Duchenne muscular dystrophy (DMD). This subject was discussed fully at a symposium held on September 11-12, 2012, in Bethesda, Maryland, by a group of experts from multiple disciplines. The meeting was triggered by the simultaneous combination of improvements in methods for newborn screening for DMD and greater potential for treatment. On the screening side, a two-tier system of newborn screening was introduced that enabled creatine kinase levels and DMD gene analysis to be done on the same dried blood spots obtained at birth. Treatment improvements included promising results from exon skipping as well as multiple studies showing long-term benefits of glucocorticoids and data indicating that early intervention of both forms of therapy was the most beneficial. Conclusions from this symposium with supportive data could have a significant impact on propelling efforts for approval of newborn screening for DMD. Muscle Nerve, 2013
C1 [Mendell, Jerry R.] Ohio State Univ, Nationwide Childrens Hosp, Paul D Wellstone Muscular Dystrophy Cooperat Res, Columbus, OH 43205 USA.
[Mendell, Jerry R.] Ohio State Univ, Dept Pediat, Columbus, OH 43205 USA.
[Lloyd-Puryear, Michele] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
RP Mendell, JR (reprint author), Ohio State Univ, Nationwide Childrens Hosp, Paul D Wellstone Muscular Dystrophy Cooperat Res, 700 Childrens Dr, Columbus, OH 43205 USA.
EM jerry.mendell@nationwidechildrens.org
FU Muscular Dystrophy Association; Centers for Disease Control and
Prevention [5U50DD000030, 1R18DD000344]; Research Institute at
Nationwide Children's Hospital, Columbus, OH
FX The following individuals significantly contributed to the success of
this Symposium through discussions on individual topics or participation
in Panels: Sanjay Bidichandani, Jeffrey Bosco, Amy Brower, Michele
Caggana, Ram Chandrasekar, Pat Furlong, Scott Grosse, Madhuri Hedge, R.
Rodney Howell, Alex Kemper, Anne Kennedy, Bruce Korf, Fred Lorey, Craig
McDonald, Francesco Muntoni, John Porter, Piero Rinaldo, Robert Saul,
Robert Weiss. The symposium was supported by the Muscular Dystrophy
Association. The Symposium was dependent on the organization of Sanjay
Bidichandani, MBBS, Ph.D., Vice President of Research and Paul Muhlrad,
Ph.D., Director of Basic Research at the Muscular Dystrophy Association.
The Muscular Dystrophy Association supported the Symposium on Newborn
Screening. The two-tier system of screening used in the State of Ohio
newborn screening was supported by cooperative agreements from the
Centers for Disease Control and Prevention (5U50DD000030 and
1R18DD000344) and the Research Institute at Nationwide Children's
Hospital, Columbus, OH; Paul D. Wellstone Cooperative Muscular Dystrophy
Center, Nationwide Children's Hospital (1U54HD066409-01;JRM); and Ohio
Department of Health (J.R.M.).
NR 19
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U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD JUL
PY 2013
VL 48
IS 1
BP 21
EP 26
DI 10.1002/mus.23810
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 169NT
UT WOS:000320787700003
PM 23716304
ER
PT J
AU Belkaid, Y
Naik, S
AF Belkaid, Yasmine
Naik, Shruti
TI Compartmentalized and systemic control of tissue immunity by commensals
SO NATURE IMMUNOLOGY
LA English
DT Article
ID DENDRITIC CELLS; INTESTINAL MICROBIOTA; SKIN MICROBIOME; GUT MICROBIOTA;
TOXOPLASMA-GONDII; INNATE IMMUNITY; GERM-FREE; BACTERIA; DISEASE;
INFLAMMATION
AB The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective, we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology.
C1 [Belkaid, Yasmine; Naik, Shruti] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, US National Institutes of Health
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, US National Institutes of Health. We
thank members of the Belkaid laboratory for helpful discussions,
particularly S. Spencer and J. Grainger for critical reading of the
manuscript.
NR 102
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U1 4
U2 64
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2013
VL 14
IS 7
BP 646
EP 653
DI 10.1038/ni.2604
PG 8
WC Immunology
SC Immunology
GA 165UB
UT WOS:000320509100002
PM 23778791
ER
PT J
AU Van Rhijn, I
Kasmar, A
de Jong, A
Gras, S
Bhati, M
Doorenspleet, ME
de Vries, N
Godfrey, DI
Altman, JD
de Jager, W
Rossjohn, J
Moody, DB
AF Van Rhijn, Ildiko
Kasmar, Anne
de Jong, Annemieke
Gras, Stephanie
Bhati, Mugdha
Doorenspleet, Marieke E.
de Vries, Niek
Godfrey, Dale I.
Altman, John D.
de Jager, Wilco
Rossjohn, Jamie
Moody, D. Branch
TI A conserved human T cell population targets mycobacterial antigens
presented by CD1b
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TUBERCULOSIS INFECTION; LIPID ANTIGENS; ALPHA-CHAIN; MAIT CELLS;
RECEPTOR; RECOGNITION; RESPONSES; EXPRESSION; LYMPHOCYTES; MEMORY
AB Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR alpha-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an alpha-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCR alpha sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen.
C1 [Van Rhijn, Ildiko; Kasmar, Anne; de Jong, Annemieke; Moody, D. Branch] Harvard Univ, Sch Med, Dept Rheumatol & Immunol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Van Rhijn, Ildiko] Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Utrecht, Netherlands.
[Gras, Stephanie; Bhati, Mugdha; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic, Australia.
[Doorenspleet, Marieke E.; de Vries, Niek] Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1012 WX Amsterdam, Netherlands.
[Godfrey, Dale I.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia.
[Altman, John D.] NIH Tetramer Core Facil, Emory Vaccine Ctr, Atlanta, GA USA.
[de Jager, Wilco] Univ Utrecht, Med Ctr, Dept Pediat Immunol, Utrecht, Netherlands.
[Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales.
RP Moody, DB (reprint author), Harvard Univ, Sch Med, Dept Rheumatol & Immunol, Brigham & Womens Hosp, Boston, MA 02115 USA.
EM i.vanrhijn@uu.nl; bmoody@rics.bwh.harvard.edu
RI de Vries, Niek/J-9348-2013;
OI de Vries, Niek/0000-0002-6257-8604; de Jong,
Annemieke/0000-0001-6707-6585; Rossjohn, Jamie/0000-0002-2020-7522
FU US National Institute of Allergy and Infectious Diseases [AI04393,
AR048632, K08 AI089858]; Burroughs Wellcome Fund; Nederlands
Wetenschappelijk Onderzoek (Meervoud) [836.08.001]; National Health and
Medical Research Council; Australian Research Council
FX We thank the Tetramer Core Facility of the US National Institutes of
Health for CD1b protein; M. Turner, C. Seshadri and the Shattuck
Hospital for clinical collaboration; L. Tan for technical help; and the
beamline staff at the Australian synchrotron for assistance with data
collection. Supported by the US National Institute of Allergy and
Infectious Diseases (AI04393, AR048632 to D. B. M., and K08 AI089858 to
A. K.) the Burroughs Wellcome Fund, Nederlands Wetenschappelijk
Onderzoek (Meervoud 836.08.001 to I. V. R.), the National Health and
Medical Research Council (D. I. G. and J.R.) and the Australian Research
Council (S.G.).
NR 48
TC 65
Z9 65
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2013
VL 14
IS 7
BP 706
EP +
DI 10.1038/ni.2630
PG 10
WC Immunology
SC Immunology
GA 165UB
UT WOS:000320509100012
PM 23727893
ER
PT J
AU Bunting, SF
Nussenzweig, A
AF Bunting, Samuel F.
Nussenzweig, Andre
TI End-joining, translocations and cancer
SO NATURE REVIEWS CANCER
LA English
DT Review
ID DOUBLE-STRAND BREAKS; CLASS-SWITCH RECOMBINATION; DNA-DAMAGE-RESPONSE;
RECURRENT CHROMOSOMAL TRANSLOCATIONS; FRAGILE SITE INSTABILITY; CYTIDINE
DEAMINASE AID; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; NONHOMOLOGOUS
RECOMBINATION; SACCHAROMYCES-CEREVISIAE
AB Fusion genes that are caused by chromosome translocations have been recognized for several decades as drivers of deregulated cell growth in certain types of cancer. In recent years, oncogenic fusion genes have been found in many haematological and solid tumours, demonstrating that translocations are a common cause of malignancy. Sequencing approaches have now confirmed that numerous, non-clonal translocations are a typical feature of cancer cells. These chromosome rearrangements are often highly complex and contain DNA sequence from multiple genomic sites. The factors and pathways that promote translocations are becoming clearer, with non-homologous end-joining implicated as a key source of genomic rearrangements.
C1 [Bunting, Samuel F.] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Nussenzweig, Andre] NIH, Lab Genome Integr, Bethesda, MD 20892 USA.
RP Bunting, SF (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, Room 337, Piscataway, NJ 08854 USA.
EM bunting@cabm.rutgers.edu; andre_nussenzweig@nih.gov
FU NCI R00 award [RCA 160574A]; Intramural Research Program of the National
Institutes of Health, National Cancer Institute; Center for Cancer
Research; Department of Defense [BC 102335]
FX S.F.B. is a recipient of NCI R00 award RCA 160574A. A.N. was supported
by the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, and the Center for Cancer Research, and by a
Department of Defense grant (BC 102335).
NR 130
TC 110
Z9 111
U1 4
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
EI 1474-1768
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD JUL
PY 2013
VL 13
IS 7
BP 443
EP 454
DI 10.1038/nrc3537
PG 12
WC Oncology
SC Oncology
GA 169HH
UT WOS:000320770200007
PM 23760025
ER
PT J
AU Pancera, M
Shahzad-ul-Hussan, S
Doria-Rose, NA
McLellan, JS
Bailer, RT
Dai, KF
Loesgen, S
Louder, MK
Staupe, RP
Yang, YP
Zhang, BS
Parks, R
Eudailey, J
Lloyd, KE
Blinn, J
Alam, SM
Haynes, BF
Amin, MN
Wang, LX
Burton, DR
Koff, WC
Nabel, GJ
Mascola, JR
Bewley, CA
Kwong, PD
AF Pancera, Marie
Shahzad-ul-Hussan, Syed
Doria-Rose, Nicole A.
McLellan, Jason S.
Bailer, Robert T.
Dai, Kaifan
Loesgen, Sandra
Louder, Mark K.
Staupe, Ryan P.
Yang, Yongping
Zhang, Baoshan
Parks, Robert
Eudailey, Joshua
Lloyd, Krissey E.
Blinn, Julie
Alam, S. Munir
Haynes, Barton F.
Amin, Mohammed N.
Wang, Lai-Xi
Burton, Dennis R.
Koff, Wayne C.
Nabel, Gary J.
Mascola, John R.
Bewley, Carole A.
Kwong, Peter D.
TI Structural basis for diverse N-glycan recognition by HIV-1-neutralizing
V1-V2-directed antibody PG16
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; HIV-1
ENVELOPE GLYCOPROTEINS; HAMSTER OVARY CELLS; GLYCOSYLATION SITES;
CRYSTAL-STRUCTURE; 2G12 RECOGNIZES; GP120; POTENT; COMPLEX
AB HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization.
C1 [Pancera, Marie; Doria-Rose, Nicole A.; McLellan, Jason S.; Bailer, Robert T.; Dai, Kaifan; Louder, Mark K.; Staupe, Ryan P.; Yang, Yongping; Zhang, Baoshan; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Shahzad-ul-Hussan, Syed; Loesgen, Sandra; Bewley, Carole A.] NIDDK, Lab Bioorgan Chem, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E.; Blinn, Julie; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
[Amin, Mohammed N.; Wang, Lai-Xi] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Amin, Mohammed N.; Wang, Lai-Xi] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Cambridge, MA USA.
[Burton, Dennis R.] Harvard Univ, Cambridge, MA 02138 USA.
[Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
[Koff, Wayne C.] Int AIDS Vaccine Initiat, New York, NY USA.
RP Bewley, CA (reprint author), NIDDK, Lab Bioorgan Chem, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM caroleb@mail.nih.gov; pdkwong@nih.gov
FU US National Institutes of Health; International AIDS Vaccine
Initiative's Neutralizing Antibody Consortium; Center for HIV AIDS
Vaccine Immunology from the US National Institutes of Health [AI 5U19 AI
067854-06]; US National Institutes of Health [1R21 AI101035]; US
National Institutes of Health (NIH/NCRR) [P41 RR018502-01]; US
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX We thank J. Stuckey for assistance with figures and members of the
Structural Biology Section and Structural Bioinformatics Core, Vaccine
Research Center for discussions or comments on the manuscript; A. Kumar
for sharing the ELISA binding protocol with biotinylated lectins; P.
Azadi and S. Archer-Hartmann, University of Georgia, for performing
glycan analyses and glycopeptide mapping; J. Baalwa (Department of
Pathology, University of Alabama at Birmingham, Birmingham, Alabama,
USA), D. Ellenberger (International Laboratory Branch, Division of
Global HIV/AIDS, Center for Global Health, Centers for Disease Control
and Prevention, Atlanta, Georgia, USA), D. Gabuzda (Department of Cancer
Immunology and AIDS, Dana-Farber Cancer Institute, Boston,
Massachusetts, USA), F. Gao (Duke Human Vaccine Institute, Duke
University Medical Center, Durham, North Carolina, USA), B. Hahn
(Department of Pathology, University of Alabama at Birmingham,
Birmingham, Alabama, USA), K. Hong (State Key Laboratory for Infectious
Disease Control and Prevention, National Center for AIDS/STD Control and
Prevention, Chinese Center for Disease Control and Prevention, Beijing,
China), J. Kim (US Military HIV Research Program, Henry M. Jackson
Foundation, Bethesda, Maryland, USA), F. McCutchan (US Military HIV
Research Program, Henry M. Jackson Foundation, Bethesda, Maryland, USA),
D. Montefiori (Department of Surgery, Duke University, Durham, North
Carolina, USA), L. Morris, (Centre for HIV and STIs, National Institute
for Communicable Diseases, Johannesburg, South Africa), J. Overbaugh
(Program for Appropriate Technology in Health, Seattle, Washington,
USA), E. Sanders-Buell (US Military HIV Research Program, Henry M.
Jackson Foundation, Bethesda, Maryland, USA), G. Shaw (Department of
Pathology, University of Alabama at Birmingham, Birmingham, Alabama,
USA), R. Swanstrom (University of North Carilina Center for AIDS
Research, University of North Carolina at Chapel Hill, Chapel Hill,
North Carolina, USA), M. Thomson (University of Birmingham, Birmingham,
UK), S. Tovanabutra (Department of Retrovirology, Armed Forces Research
Institute of Medical Sciences, Bangkok, Thailand), C. Williamson
(Institute of Infectious Diseases and Molecular Medicine, Division of
Medical Virology, University of Cape Town and National Health Laboratory
Services, Cape Town, South Africa) and L. Zhang (Department of Public
Health, Center for Disease Control and Prevention in Jiangxi Province,
Nanchang, China) contributing the HIV-1 Envelope plasmids used in our
neutralization panel. Support for this work was provided by the US
National Institutes of Health Intramural Research Programs (Vaccine
Research Center, National Institute of Allergy and Infectious Diseases,
and the National Institute of Diabetes and Digestive and Kidney
Diseases), by grants from the International AIDS Vaccine Initiative's
Neutralizing Antibody Consortium and by the Center for HIV AIDS Vaccine
Immunology Grant AI 5U19 AI 067854-06 from the US National Institutes of
Health (J. E., K. E. L., J. B., S. M. A. and B. F. H.), by US National
Institutes of Health grant 1R21 AI101035 (M. N. A. and L-X. W.) and by
the US National Institutes of Health (NIH/NCRR)-funded grant P41
RR018502-01 to the Complex Carbohydrate Research Center. Use of sector
22 (Southeast Region Collaborative Access team) at the Advanced Photon
Source was supported by the US Department of Energy, Basic Energy
Sciences, Office of Science under contract number W-31-109-Eng-38.
NR 62
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JUL
PY 2013
VL 20
IS 7
BP 804
EP +
DI 10.1038/nsmb.2600
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 175SM
UT WOS:000321253300008
PM 23708607
ER
PT J
AU Yadav, H
Jain, S
AF Yadav, Hariom
Jain, Shalini
TI Herbo-probiotic therapy in cardioprotection: A new way of nature to
nurture
SO NUTRITION
LA English
DT Letter
C1 [Yadav, Hariom; Jain, Shalini] NIH, Natl Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA.
RP Yadav, H (reprint author), NIH, Natl Diabet & Digest & Kidney Dis, Bldg 10, Bethesda, MD 20892 USA.
EM yadavhariom@gmail.com
OI Yadav, Hariom/0000-0003-4504-1597
NR 10
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0899-9007
J9 NUTRITION
JI Nutrition
PD JUL-AUG
PY 2013
VL 29
IS 7-8
BP 1070
EP 1071
DI 10.1016/j.nut.2012.11.001
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 172UF
UT WOS:000321029700025
PM 23352466
ER
PT J
AU Shih, LC
LaFaver, K
Lim, C
Papavassiliou, E
Tarsy, D
AF Shih, Ludy C.
LaFaver, Kathrin
Lim, Chen
Papavassiliou, Efstathios
Tarsy, Daniel
TI Loss of benefit in VIM thalamic deep brain stimulation (DBS) for
essential tremor (ET): How prevalent is it?
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Essential tremor; Deep brain stimulation; Long-term outcome
ID LONG-TERM EFFICACY; MOVEMENT-DISORDERS; FOLLOW-UP; TOLERANCE; NUCLEUS
AB Ventralis intermedius (Vim) thalamic deep brain stimulation for medication-refractory essential tremor (ET) has been shown to significantly improve severity of limb tremor in several large case series with significant reduction in objective motor scores. A variable proportion of patients experience decline in benefit over time, however, most studies have not been designed to describe the phenomenon of waning benefit in terms that are helpful for patient counseling. In this retrospective single center study, we define waning benefit as a phenomenon that occurs after patients begin to require reprogramming visits to optimize DBS benefit on tremor. We employed a survival analysis with time to escape (TTE) as a quantitative measure of time elapsed between implantation and the need for subsequent reprogramming. In our cohort of ET patients operated on with Vim DBS from 1994 to 2009, among 45 subjects who met inclusion criteria, 73% reported waning benefit at some point during a mean follow-up period of 56 months (range 12-152 months). The mean TTE from implantation date was 18 months (range 3-75 months). We conclude that loss of benefit over time from Vim DBS for ET is more prevalent than previously published estimates have indicated and should be discussed during patient counseling regarding durability of expected benefit. In addition, this data suggests that a disease-based explanation rather than technical factors are more likely to explain the decline in benefit. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Shih, Ludy C.; Tarsy, Daniel] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA.
[LaFaver, Kathrin] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Lim, Chen] New York Med Coll, Valhalla, NY 10595 USA.
[Papavassiliou, Efstathios] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Neurosurg,Dept Surg, Boston, MA 02215 USA.
RP Shih, LC (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Kirstein 228,330 Brookline Ave, Boston, MA 02215 USA.
EM lshih@bidmc.harvard.edu
FU Clinical Investigator Training Program: Beth Israel Deaconess Medical
Center; Harvard/MIT Health Science and Technology; Pfizer, Inc.; Merck
Co.
FX L.C. Shih was supported in part by the Clinical Investigator Training
Program: Beth Israel Deaconess Medical Center and Harvard/MIT Health
Science and Technology, in collaboration with Pfizer, Inc. and Merck &
Co. The authors have no relevant financial disclosures to make regarding
relevant companies involved in this work over the past three years.
NR 22
TC 17
Z9 17
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD JUL
PY 2013
VL 19
IS 7
BP 676
EP 679
DI 10.1016/j.parkreldis.2013.03.006
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 169AW
UT WOS:000320750300006
PM 23582712
ER
PT J
AU Samal, B
Ait-Ali, D
Bunn, S
Mustafa, T
Eiden, LE
AF Samal, Babru
Ait-Ali, Djida
Bunn, Stephen
Mustafa, Tomris
Eiden, Lee E.
TI Discrete signal transduction pathway utilization by a neuropeptide
(PACAP) and a cytokine (TNF-alpha) first messenger in chromaffin cells,
inferred from coupled transcriptome-promoter analysis of regulated gene
cohorts
SO PEPTIDES
LA English
DT Article
DE Affymetrix; Agilent; Chromaffin cell; Cyclic AMP; ERK; Gene induction;
Microarray; NF-kB; PACAP; PAC1; Signal transduction; TNF-alpha;
Transcriptional regulation; TNFR2
ID CYCLASE-ACTIVATING POLYPEPTIDE; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR;
CONTROL MAQC PROJECT; IN-VIVO; CATECHOLAMINE SECRETION; RECEPTOR
ACTIVATION; PC12 CELLS; EXPRESSION; NEUROENDOCRINE
AB Cultured bovine adrenal chromaffin cells (BCCs) are employed to study first messenger-specific signaling by cytokines and neurotransmitters occurring in the adrenal medulla following immune-related stress responses. Here, we show that the cytokine TNF-alpha, and the neuropeptide transmitter PACAP, acting through the TNFR2 and PAC1 receptors, activate distinct signaling pathways, with correspondingly distinct transcriptomic signatures in chromaffin cells. We have carried out a comprehensive integrated transcriptome analysis of TNF-alpha and PACAP gene regulation in BCCs using two microarray platforms to maximize transcript identification. Microarray data were validated using qRT-PCR. More than 90% of the transcripts up-regulated either by TNF-alpha or PACAP were specific to a single first messenger. The final list of transcripts induced by each first messenger was subjected to multiple algorithms to identify promoter/ enhancer response elements for trans-acting factors whose activation could account for gene expression by either TNF-alpha or PACAP. Distinct groups of transcription factors potentially controlling the expression of TNF-alpha or PACAP-responsive genes were found: most of the genes up-regulated by TNF-alpha contained transcription factor binding sites for members of the Rel transcription factor family, suggesting TNF-alpha-TNFR2 signaling occurs mainly through the NF-KB signaling pathway. Surprisingly, EGR1 was predicted to be the primary transcription factor controlling PACAP-modulated genes, suggesting PACAP signaling to the nucleus occurs predominantly through ERK, rather than CREB activation. Comparison of TNFR2-dependent versus TNFR1-dependent gene induction, and EGR1-mediated transcriptional activation, may provide a pharmacological avenue to the unique pathways activated by the first messengers TNF-alpha and PACAP in neuronal and endocrine cells. Published by Elsevier Inc.
C1 [Samal, Babru; Ait-Ali, Djida; Mustafa, Tomris; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
[Bunn, Stephen] Univ Otego, Sch Med Sci, Dept Anat, Ctr Neuroendocrinol, Dunedin, New Zealand.
RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU NIMH [ZO1-MH002386]
FX The authors thank Chang-Mei Hsu for expert assistance in chromaffin cell
preparation, treatment, harvesting, and RNA preparation. This work was
supported by the NIMH intramural research program (ZO1-MH002386).
NR 48
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U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD JUL
PY 2013
VL 45
BP 48
EP 60
DI 10.1016/j.peptides.2013.03.020
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 170KW
UT WOS:000320850300008
PM 23608709
ER
PT J
AU Davenport, AP
Alexander, SPH
Sharman, JL
Pawson, AJ
Benson, HE
Monaghan, AE
Liew, WC
Mpamhanga, CP
Bonner, TI
Neubig, RR
Pin, JP
Spedding, M
Harmar, AJ
AF Davenport, Anthony P.
Alexander, Stephen P. H.
Sharman, Joanna L.
Pawson, Adam J.
Benson, Helen E.
Monaghan, Amy E.
Liew, Wen Chiy
Mpamhanga, Chidochangu P.
Bonner, Tom I.
Neubig, Richard R.
Pin, Jean Philippe
Spedding, Michael
Harmar, Anthony J.
TI International Union of Basic and Clinical Pharmacology. LXXXVIII. G
Protein-Coupled Receptor List: Recommendations for New Pairings with
Cognate Ligands
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID LYSOPHOSPHATIDIC ACID RECEPTOR; L-ALPHA-LYSOPHOSPHATIDYLINOSITOL; RAT
ADRENOMEDULLIN RECEPTOR; NEUROPEPTIDE-Y RECEPTOR; BREAST-CANCER CELLS;
ORPHAN RECEPTOR; CANNABINOID RECEPTOR; FATTY-ACIDS; CONSTITUTIVE
ACTIVITY; INSULIN-SECRETION
AB In 2005, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) published a catalog of all of the human gene sequences known or predicted to encode G protein-coupled receptors (GPCRs), excluding sensory receptors. This review updates the list of orphan GPCRs and describes the criteria used by NC-IUPHAR to recommend the pairing of an orphan receptor with its cognate ligand(s). The following recommendations are made for new receptor names based on 11 pairings for class A GPCRs: hydroxycarboxylic acid receptors [HCA(1) (GPR81) with lactate, HCA(2) (GPR109A) with 3-hydroxybutyric acid, HCA(3) (GPR109B) with 3-hydroxyoctanoic acid]; lysophosphatidic acid receptors [LPA(4) (GPR23), LPA(5) (GPR92), LPA(6) (P2Y5)]; free fatty acid receptors [FFA4 (GPR120) with omega-3 fatty acids]; chemerin receptor (CMKLR1; ChemR23) with chemerin; CXCR7 (CMKOR1) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC); succinate receptor (SUCNR1) with succinate; and oxoglutarate receptor [OXGR1 with 2-oxoglutarate]. Pairings are highlighted for an additional 30 receptors in class A where further input is needed from the scientific community to validate these findings. Fifty-seven human class A receptors (excluding pseudogenes) are still considered orphans; information has been provided where there is a significant phenotype in genetically modified animals. In class B, six pairings have been reported by a single publication, with 28 (excluding pseudogenes) still classified as orphans. Seven orphan receptors remain in class C, with one pairing described by a single paper. The objective is to stimulate research into confirming pairings of orphan receptors where there is currently limited information and to identify cognate ligands for the remaining GPCRs. Further information can be found on the IUPHAR Database website (http://www.iuphar-db.org).
C1 [Davenport, Anthony P.] Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 0QQ, England.
[Alexander, Stephen P. H.] Univ Nottingham, Sch Med, Sch Biomed Sci, Nottingham, England.
[Sharman, Joanna L.; Pawson, Adam J.; Benson, Helen E.; Monaghan, Amy E.; Liew, Wen Chiy; Mpamhanga, Chidochangu P.; Harmar, Anthony J.] Univ Edinburgh, Queens Med Res Inst, Univ BHF Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
[Bonner, Tom I.] NIMH, Sect Funct Neurosci, Bethesda, MD 20892 USA.
[Neubig, Richard R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Pin, Jean Philippe] Univ Montpellier, CNRS, Inst Funct Genom, Dept Mol Pharmacol,UMR5203, F-34059 Montpellier, France.
[Spedding, Michael] Les Labs Servier, Suresnes, France.
RP Davenport, AP (reprint author), Univ Cambridge, Ctr Clin Invest, Addenbrookes Hosp, Clin Pharmacol Unit, Level 6,Box 110, Cambridge CB2 0QQ, England.
EM apd10@medschl.cam.ac.uk
RI Alexander, Steve/B-8105-2009; Davenport, Anthony/A-5773-2008; Pawson,
Adam/Q-5678-2016;
OI Alexander, Steve/0000-0003-4417-497X; Davenport,
Anthony/0000-0002-2096-3117; Pawson, Adam/0000-0003-2280-845X; Benson,
Helen/0000-0002-7830-2477; Spedding, Michael/0000-0002-1248-8221;
Sharman, Joanna/0000-0002-5275-6446
FU International Union of Basic and Clinical Pharmacology; British
Pharmacological Society; Wellcome Trust [268427, 085686/2/08,
099156/Z/12/Z]; British Heart Foundation [PS/02/001, PG/09/050/27734];
Pulmonary Hypertension Association; National Institute for Health
Research Cambridge Biomedical Research Centre; National Institutes of
Health [National Institute of Mental Health]
FX The authors thank the International Union of Basic and Clinical
Pharmacology and British Pharmacological Society for support.; This work
was supported in part by the Wellcome Trust [Grants 268427, 085686/2/08;
Biomedical Resources Grant 099156/Z/12/Z] for support for IUPHAR-DB (to
A. H., S. P. H. A., and A. P. D.); the British Heart Foundation [Grants
PS/02/001 and PG/09/050/27734] (to A. P. D.); Pulmonary Hypertension
Association; the National Institute for Health Research Cambridge
Biomedical Research Centre; the Intramural Research Program of the
National Institutes of Health [National Institute of Mental Health] (to
T.B.).
NR 238
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U1 3
U2 37
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
EI 1521-0081
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD JUL
PY 2013
VL 65
IS 3
BP 967
EP 986
DI 10.1124/pr.112.007179
PG 20
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 172FV
UT WOS:000320986500004
PM 23686350
ER
PT J
AU Kleitman, N
Rao, MS
Owens, DF
AF Kleitman, Naomi
Rao, Mahendra S.
Owens, David F.
TI Pluripotent Stem Cells in Translation: A Food and Drug
Administration-National Institutes of Health Collaboration
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Pluripotent stem cells; Stem cells; Clinical translation; Clinical
trials
AB Recently, the U.S. Food and Drug Administration (FDA), the U.S. National Institutes of Health, and the stem cell research community have collaborated on a series of workshops that address moving pluripotent stem cell therapies into the clinic. The first two workshops in the series focused on preclinical science, and a third, future workshop will focus on clinical trials. This summary addresses major points from both of the recent preclinically focused meetings. When entering into a therapeutics developmental program based on pluripotent cells, investigators must make decisions at the very early stages that will have major ramifications during later phases of development. Presentations and discussions from both invited participants and FDA staff described the need to characterize and document the quality, variability, and suitability of the cells and commercial reagents used at every translational stage. This requires consideration of future regulatory requirements, ranging from donor eligibility of the original source material to the late-stage manufacturing protocols. Federal, industrial, and academic participants agreed that planning backward is the best way to anticipate what evidence will be needed to justify human testing of novel therapeutics and to eliminate wasted efforts.
C1 [Kleitman, Naomi; Owens, David F.] NINDS, NIH, Bethesda, MD 20892 USA.
[Rao, Mahendra S.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Rao, MS (reprint author), 50 South Dr, Bethesda, MD 20892 USA.
EM mahendra.rao@nih.gov
OI Kleitman, Naomi/0000-0003-1089-0257
FU NIH
FX We thank the participants of both workshops for providing invaluable
insights into this emerging area, our FDA colleagues for comments on a
draft of this report, and Drs. Story Landis (NINDS/NIH) and Celia Witten
(CBER/FDA) for providing overall leadership. We also thank members of
the planning committees from both the FDA and the NIH for making these
workshops a reality. FDA: Drs. Rachael F. Anatol, Patrick Au, Kimberly
A. Benton, Theresa T. Chen, Donald W. Fink, Thomas P. Finn, Ying Huang,
Deborah A. Hursh, Wei Liang, Malcolm C. Moos, Stephanie L. Simek, and
Steven O. Winitsky. NIH: Drs. Kristin Abraham (National Institute of
Diabetes and Digestive and Kidney Diseases [NIDDK]), Rosemarie Hunziker
(National Institute of Biomedical Imaging and Bioengineering [NIBIB]),
Christine Kelley (NIBIB), Naomi Kleitman (NINDS), Susan Marino (NINDS),
David Owens (NINDS), Mahendra Rao (National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS]), Pamela Robey (National
Institute of Dental and Craniofacial Research), Sheryl Sato (NIDDK),
Sonia Skarlatos (National Heart, Lung, and Blood Institute [NHLBI]), and
John W. Thomas (NHLBI). We would like to also acknowledge the
contributions made by Dr. Laura Cole (National Institute on Deafness and
Other Communication Disorders [NIDCD]), Buck Wong (NIDCD), Dr. Scott
Lipnick (Office of the Director), and Megan Laycock (NIAMS). Funding for
both workshops was provided by the NIH.
NR 7
TC 4
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U1 0
U2 5
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD JUL
PY 2013
VL 2
IS 7
BP 483
EP 487
DI 10.5966/sctm.2013-0042
PG 5
WC Cell & Tissue Engineering
SC Cell Biology
GA 175MU
UT WOS:000321235600010
PM 23757505
ER
PT J
AU Orihuela, R
Kojima, C
Tokar, EJ
Person, RJ
Xu, YY
Qu, W
Waalkes, MP
AF Orihuela, Ruben
Kojima, Chikara
Tokar, Erik J.
Person, Rachel J.
Xu, Yuanyuan
Qu, Wei
Waalkes, Michael P.
TI Oxidative DNA damage after acute exposure to arsenite and
monomethylarsonous acid in biomethylation-deficient human cells
SO TOXICOLOGY MECHANISMS AND METHODS
LA English
DT Article
DE Arsenic; immuno-spin trapping; reactive oxygen species
ID PYRUVATE-DEHYDROGENASE; METHYLATED ARSENICALS; ENDOTHELIAL-CELLS; HUMAN
HEPATOCYTES; REACTIVE OXYGEN; FREE-RADICALS; HUMAN-DISEASE; AS-III;
GLUTATHIONE; STRESS
AB The carcinogen inorganic arsenic (iAs) undergoes biomethylation (BMT) in some cells. The methylated metabolite, monomethylarsonous (MMA(3+)), may cause oxidative DNA damage (ODD). With chronic iAs exposure, BMT-competent cells show ODD while BMT-deficient do not. To further define these events, we studied ODD produced by acute iAs or MMA(3+) in the BMT-deficient human prostate cell line, RWPE-1. ODD, measured by the immuno-spin trapping method, was assessed after exposure to iAs or MMA(3+) alone, with the arsenic BMT inhibitor selenite or after glutathione (GSH) depletion. The expression of oxidative stress-related genes (HO-1, SOD-1, SOD-2, Nrf2 and Keap-1) was also assessed. Exposure to iAs at 24 h (0-20 mu M), stimulated ODD only at levels above the LC50 of a 48 h exposure (17 mu M). If iAs induced ODD, it also activated oxidative stress-related genes. Selenium did not alter iAs-induced ODD. MMA(3+) at 24 h (0-0.5 mu M) caused ODD at levels below the LC50 of a 48 h exposure (1.5 mu M), which were greatly increased by GSH depletion but not selenite. MMA(3+) induced ODD at levels not activating oxidant stress response genes. Overall, iAs induced ODD in BMT-deficient cells only at toxic levels. MMA(3+) caused ODD at non-toxic levels, independently of cellular BMT capacity and in a fashion not requiring further BMT.
C1 [Orihuela, Ruben; Kojima, Chikara; Tokar, Erik J.; Person, Rachel J.; Xu, Yuanyuan; Qu, Wei; Waalkes, Michael P.] NIEHS, Div Natl Toxicol Program, Natl Toxicol Program Lab, Inorgan Toxicol Grp, Res Triangle Pk, NC 27709 USA.
RP Waalkes, MP (reprint author), NIEHS, Div Natl Toxicol Program, Natl Toxicol Program Lab, Inorgan Toxicol Grp, POB 12233,Mail Drop E1-07,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
OI ORIHUELA, RUBEN/0000-0001-6718-6194
NR 44
TC 2
Z9 2
U1 0
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1537-6516
J9 TOXICOL MECH METHOD
JI Toxicol. Mech. Methods
PD JUL
PY 2013
VL 23
IS 6
BP 389
EP 395
DI 10.3109/15376516.2012.762570
PG 7
WC Toxicology
SC Toxicology
GA 173GE
UT WOS:000321065600002
PM 23301828
ER
PT J
AU Perkins, NJ
Schisterman, EF
Vexler, A
AF Perkins, Neil J.
Schisterman, Enrique F.
Vexler, Albert
TI Multivariate Normally Distributed Biomarkers Subject to Limits of
Detection and Receiver Operating Characteristic Curve Inference
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Area under the curve; left censoring; limit of detection; maximum
likelihood; ROC
ID ROC ANALYSIS; SAMPLES
AB Rationale and Objectives: Biomarkers are of ever-increasing importance to clinical practice and epidemiologic research. Multiple biomarkers are often measured per patient. Measurement of true biomarker levels is limited by laboratory precision, specifically measuring relatively low, or high, biomarker levels resulting in undetectable levels below, or above, a limit of detection (LOD). Ignoring these missing observations or replacing them with a constant are methods commonly used although they have been shown to lead to biased estimates of several parameters of interest, including the area under the receiver operating characteristic (ROC) curve and regression coefficients.
Materials and Methods: We developed asymptotically consistent, efficient estimators, via maximum likelihood techniques, for the mean vector and covariance matrix of multivariate normally distributed biomarkers affected by LOD. We also developed an approximation for the Fisher information and covariance matrix for our maximum likelihood estimations (MLEs). We apply these results to an ROC curve setting, generating an MLE for the area under the curve for the best linear combination of multiple biomarkers and accompanying confidence-interval.
Results: Point and confidence interval estimates are scrutinized by simulation study, with bias and root mean square error and coverage probability, respectively, displaying behavior consistent with MLEs. An example using three polychlorinated biphenyls to classify women with and without endometriosis illustrates how the underlying distribution of multiple biomarkers with LOD can be assessed and display increased discriminatory ability over naive methods.
Conclusions: Properly addressing LODs can lead to optimal biomarker combinations with increased discriminatory ability that may have been ignored because of measurement obstacles.
C1 [Perkins, Neil J.; Schisterman, Enrique F.; Vexler, Albert] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20852 USA.
[Vexler, Albert] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA.
RP Perkins, NJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM perkinsn@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Schisterman,
Enrique/0000-0003-3757-641X
FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research was supported by the Intramural Research Program of the
NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 25
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUL
PY 2013
VL 20
IS 7
BP 838
EP 846
DI 10.1016/j.acra.2013.04.001
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 168YT
UT WOS:000320744600007
PM 23747152
ER
PT J
AU Tang, LL
Kang, L
Liu, CL
Schisterman, EF
Liu, AY
AF Tang, Liansheng Larry
Kang, Le
Liu, Chunling
Schisterman, Enrique F.
Liu, Aiyi
TI An Additive Selection of Markers to Improve Diagnostic Accuracy Based on
a Discriminatory Measure
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Receiver operating characteristic (ROC); area under the ROC curves
(AUC); discriminatory score; Box-Cox transformation
ID OPERATING CHARACTERISTIC CURVES; MAXIMUM-LIKELIHOOD-ESTIMATION;
CHARACTERISTIC ROC CURVES; STATISTICAL VALIDATION; MODEL; AREAS
AB Rationale and Objectives: The estimation of the area under the receiver operating characteristic (ROC) curve (AUC) often relies on the assumption that the truly positive population tends to have higher marker results than the truly negative population. The authors propose a discriminatory measure to relax such an assumption and apply the measure to identify the appropriate set of markers for combination.
Materials and Methods: The proposed measure is based on the maximum of the AUC and 1-AUC. The existing methods are applied to estimate the measure. The subset of markers is selected using a combination method that maximizes a function of the proposed discriminatory score with the number of markers as a penalty in the function.
Results: The properties of the estimators for the proposed measure were studied through large-scale simulation studies. The application was illustrated through a real example to identify the set of markers to combine.
Conclusion: Simulation results showed excellent small-sample performance of the estimators for the proposed measure. The application in the example yielded a reasonable subset of markers for combination.
C1 [Tang, Liansheng Larry] George Mason Univ, Dept Stat, Fairfax, VA 22030 USA.
[Kang, Le] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Liu, Chunling] Hong Kong Polytech Univ, Dept Appl Math, Hong Kong, Hong Kong, Peoples R China.
[Schisterman, Enrique F.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Bethesda, MD USA.
EM liua@mail.nih.gov
RI Liu, Chunling/A-4827-2015;
OI Liu, Chunling/0000-0003-3410-445X; Liu, Aiyi/0000-0002-6618-5082;
Schisterman, Enrique/0000-0003-3757-641X
FU Intramural NIH HHS [ZIA HD008875-01]
NR 33
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUL
PY 2013
VL 20
IS 7
BP 854
EP 862
DI 10.1016/j.acra.2013.02.009
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 168YT
UT WOS:000320744600009
PM 23611438
ER
PT J
AU Liu, DP
Zhou, XH
AF Liu, Danping
Zhou, Xiao-Hua
TI ROC Analysis in Biomarker Combination with Covariate Adjustment
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Biomarker combination; covariate adjustment; AUC; covariate
standardization
ID OPERATING CHARACTERISTIC CURVE; REGRESSION; ACCURACY; MARKERS; AREA
AB Rational and Objectives: Receiver operating characteristic (ROC) analysis is often used to find the optimal combination of biomarkers. When the subject level covariates affect the magnitude and/or accuracy of the biomarkers, the combination rule should take into account of the covariate adjustment. The authors propose two new biomarker combination methods that make use of the covariate information.
Materials and Methods: The first method is to maximize the area under the covariate-adjusted ROC curve (AAUC). To overborne the limitations of the AAUC measure, the authors further proposed the area under covariate-standardized ROC curve (SAUC), which is an extension of the covariate-specific ROC curve. With a series of simulation studies, the proposed optimal AAUC and SAUC methods are compared with the optimal AUC method that ignores the covariates. The biomarker combination methods are illustrated by an example from Alzheimer's disease research.
Results: The simulation results indicate that the optimal AAUC combination performs well in the current study population. The optimal SAUC method is flexible to choose any reference populations, and allows the results to be generalized to different populations.
Conclusions: The proposed optimal AAUC and SAUC approaches successfully address the covariate adjustment problem in estimating the optimal marker combination. The optimal SAUC method is preferred-for practical use, because the biomarker combination rule can be easily evaluated for different population of interest.
C1 [Liu, Danping] NICHD, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA.
[Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Liu, DP (reprint author), NICHD, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA.
EM danping.liu@nih.gov
FU National Institute of Health (NIH), Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); NIH/NIA
[U01AG016976]
FX D.L.'s research is supported by the Intramural Research Program of the
National Institute of Health (NIH), Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD). This work was
supported in part by NIH/NIA grant U01AG016976.
NR 16
TC 5
Z9 5
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUL
PY 2013
VL 20
IS 7
BP 874
EP 882
DI 10.1016/j.acra.2013.03.009
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 168YT
UT WOS:000320744600011
PM 23747153
ER
PT J
AU Rudzinski, ER
Teot, LA
Anderson, JR
Moore, J
Bridge, JA
Barr, FG
Gastier-Foster, JM
Skapek, SX
Hawkins, DS
Parham, DM
AF Rudzinski, Erin R.
Teot, Lisa A.
Anderson, James R.
Moore, Julie
Bridge, Julia A.
Barr, Frederic G.
Gastier-Foster, Julie M.
Skapek, Stephen X.
Hawkins, Douglas S.
Parham, David M.
TI Dense Pattern of Embryonal Rhabdomyosarcoma, a Lesion Easily Confused
With Alveolar Rhabdomyosarcoma A Report From the Soft Tissue Sarcoma
Committee of the Children's Oncology Group
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Alveolar rhabdomyosarcoma; Embryonal rhabdomyosarcoma; Histologic
classification; Rhabdomyosarcoma; Myogenin
ID INTERGROUP-RHABDOMYOSARCOMA; FUSION STATUS; STUDY-III; CLASSIFICATION;
DIAGNOSIS; MYOGENIN; VARIANT
AB Objectives: To examine whether the frequency of fusion-negative alveolar rhabdomyosarcoma (ARMSn) increased coincident with changes in the definition of alveolar histology.
Methods: We re-reviewed alveolar rhabdomyosarcoma (ARMS) in the Children's Oncology Group study D9803, comparing histopathology with fusion status.
Results: Our review of 255 original ARMS cases (compared with a control group of 38 embryonal rhabdomyosarcomas [ERMS] cases) revealed that many had an ARMS-like densely cellular pattern with cytologic features and myogenin expression more typical of ERMS. Following re-review, 84 (33%) cases of original ARMS were rediagnosed as ERMS. All reclassified ERMS, including dense ERMS, were fusion negative, whereas 82% of confirmed ARMS cases were fusion positive. Total ARMS diagnoses returned to historic rates of 25% to 30% of all rhabdomyosarcomas, and ARMSn decreased from 37% to 18% of ARMS cases. The outcome of reclassified ERMS was similar to confirmed ERMS.
Conclusions: To address the role of fusion status in risk stratification, pathologists should include both a histologic diagnosis and an evaluation of fusion status for all new ARMS diagnoses.
C1 [Rudzinski, Erin R.; Hawkins, Douglas S.] Seattle Childrens Hosp, Seattle, WA 98015 USA.
[Teot, Lisa A.] Boston Childrens Hosp, Boston, MA USA.
[Anderson, James R.; Bridge, Julia A.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Moore, Julie] Nationwide Childrens Hosp, Columbus, OH USA.
[Barr, Frederic G.] NCI, Bethesda, MD USA.
[Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
[Skapek, Stephen X.] Univ Texas SW Med Ctr Dallas, Dallas, TX USA.
[Hawkins, Douglas S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Hawkins, Douglas S.] Univ Washington, Seattle, WA 98195 USA.
[Parham, David M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
RP Rudzinski, ER (reprint author), Seattle Childrens Hosp, Dept Labs, M-S OC-8-720,4800 Sandpoint Way NE, Seattle, WA 98015 USA.
EM erin.rudzinski@seattlechildrens.org
FU St Baldrick's Foundation, Monrovia, CA [179772]; National Institutes of
Health, Bethesda, MD [NIH-RC2-CA148216, NIH-R01-CA104896,
NIH-U10-CA098412, NIH-U10-CA98543]; Joanna McAfee Childhood Cancer
Foundation, Warner Robins, GA [U-10-CA98543-07]
FX Research support was provided by research grant 179772 from St
Baldrick's Foundation, Monrovia, CA (E.R.R); NIH-RC2-CA148216 (S.X.S.,
J.M.; J.A.B., F.G.B., and J.M.G.-F), NIH-R01-CA104896 (F.G.B.,
J.M.G.-F), NIH-U10-CA098412 (J.R.A.), and NIH-U10-CA98543 (COG Chair's
grant) from the National Institutes of Health, Bethesda, MD; and grants
(F.G.B) and U-10-CA98543-07 (J.A.B.) from the Joanna McAfee Childhood
Cancer Foundation, Warner Robins, GA.
NR 24
TC 20
Z9 20
U1 0
U2 4
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JUL
PY 2013
VL 140
IS 1
BP 82
EP 90
DI 10.1309/AJCPA1WN7ARPCMKQ
PG 9
WC Pathology
SC Pathology
GA 167LS
UT WOS:000320634100009
PM 23765537
ER
PT J
AU Chen, YT
Zheng, TZ
Lan, Q
Kim, C
Qin, Q
Foss, F
Chen, XZ
Holford, T
Leaderer, B
Boyle, P
Wang, CF
Dai, M
Liu, ZJ
Ma, SG
Chanock, SJ
Rothman, N
Zhang, YW
AF Chen, Yingtai
Zheng, Tongzhang
Lan, Qing
Kim, Christopher
Qin, Qin
Foss, Francine
Chen, Xuezhong
Holford, Theodore
Leaderer, Brian
Boyle, Peter
Wang, Chengfeng
Dai, Min
Liu, Zhenjiang
Ma, Shuangge
Chanock, Stephen J.
Rothman, Nathaniel
Zhang, Yawei
TI Polymorphisms in DNA repair pathway genes, body mass index, and risk of
non-Hodgkin lymphoma
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID RAT SKELETAL-MUSCLE; CANCER-RISK; PHYSICAL-ACTIVITY; OXIDATIVE STRESS;
POOLED ANALYSIS; LUNG-CANCER; OBESITY; EXERCISE; WOMEN; MEN
AB We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in DNA repair pathway genes may modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared to those with BMI <25, women with BMI 25 had significantly increased risk of NHL among women who carried BRCA1 (rs799917) CT/TT, ERCC2 (rs13181) AA, XRCC1 (rs1799782) CC, and WRN (rs1801195) GG genotypes, but no increase in NHL risk among women who carried BRCA1 CC, ERCC2 AC/CC, XRCC1 CT/TT, and WRN GT/TT genotypes. A significant interaction with BMI was only observed for WRN (rs1801195; P=0.004) for T-cell lymphoma and ERCC2 (rs13181; P=0.002) for diffuse large B-cell lymphoma. The results suggest that common genetic variation in DNA repair pathway genes may modify the association between BMI and NHL risk. Am. J. Hematol. 88:606-611, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Chen, Yingtai; Wang, Chengfeng; Dai, Min] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China.
[Chen, Yingtai; Zheng, Tongzhang; Kim, Christopher; Holford, Theodore; Leaderer, Brian; Ma, Shuangge; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Lan, Qing; Kim, Christopher; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA.
[Qin, Qin] Univ So Maine, Wise Lab Environm & Genet Toxicol, Portland, ME 04103 USA.
[Foss, Francine] Yale Univ, Sch Med, New Haven, CT USA.
[Chen, Xuezhong] Gansu Prov Canc Hosp, Lanzhou, Peoples R China.
[Boyle, Peter] Int Prevent Res Inst, Lyon, France.
[Liu, Zhenjiang] Gansu Prov Coll Chinese Med, Lanzhou, Peoples R China.
[Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA.
RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St LEPH 440, New Haven, CT 06520 USA.
EM yawei.zhang@yale.edu
RI Boyle, Peter/A-4380-2014
OI Boyle, Peter/0000-0001-6251-0610
FU NIH [CA62006, CA165923, 1D43TW008323, 1D43TW007864, HD70324]; Intramural
Research Program of the National Cancer Institute
FX This research was supported by the NIH grants CA62006, CA165923,
1D43TW008323, 1D43TW007864, and HD70324, and the Intramural Research
Program of the National Cancer Institute.
NR 50
TC 6
Z9 7
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUL
PY 2013
VL 88
IS 7
BP 606
EP 611
DI 10.1002/ajh.23463
PG 6
WC Hematology
SC Hematology
GA 167VB
UT WOS:000320662200013
PM 23619945
ER
PT J
AU Chou, CF
Cotch, MF
Vitale, S
Zhang, XZ
Klein, R
Friedman, DS
Klein, BEK
Saaddine, JB
AF Chou, Chiu-Fang
Cotch, Mary Frances
Vitale, Susan
Zhang, Xinzhi
Klein, Ronald
Friedman, David S.
Klein, Barbara E. K.
Saaddine, Jinan B.
TI Age-Related Eye Diseases and Visual Impairment Among U.S. Adults
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID ANGELES LATINO EYE; BLUE MOUNTAINS EYE; QUALITY-OF-LIFE; UNDERCORRECTED
REFRACTIVE ERRORS; UNITED-STATES; MACULAR DEGENERATION;
SOCIOECONOMIC-FACTORS; VISION IMPAIRMENT; OLDER POPULATION; RISK
INDICATORS
AB Background: Visual impairment is a common health-related disability in the U.S. The association between clinical measurements of age-related eye diseases and visual impairment in data from a national survey has not been reported.
Purpose: To examine common eye conditions and other correlates associated with visual impairment in the U.S.
Methods: Data from the 2005-2008 National Health and Nutrition Examination Survey of 5222 Americans aged >= 40 years were analyzed in 2012 for visual impairment (presenting distance visual acuity worse than 20/40 in the better-seeing eye), and visual impairment not due to refractive error (distance visual acuity worse than 20/40 after refraction). Diabetic retinopathy (DR) and age-related macular degeneration (AMD) were assessed from retinal fundus images; glaucoma was assessed from two successive frequency-doubling tests and a cup-to-disc ratio measurement.
Results: Prevalence of visual impairment and of visual impairment not due to refractive error was 7.5% (95% CI=6.9%, 8.1%) and 2.0% (1.7%, 2.3%), respectively. The prevalence of visual impairment not due to refractive error was significantly higher among people with AMD (2.2%) compared to those without AMD (0.8%), or with DR (3.5%) compared to those without DR (1.2%). Independent predictive factors of visual impairment not due to refractive error were AMD (OR=4.52, 95% CI=2.50, 8.17); increasing age (OR=1.09 per year, 95% CI=1.06, 1.13); and less than a high school education (OR=2.99, 95% CI=1.18, 7.55).
Conclusions: Visual impairment is a public health problem in the U.S. Visual impairment in two thirds of adults could be eliminated with refractive correction. Screening of the older population may identify adults at increased risk of visual impairment due to eye diseases.
C1 [Chou, Chiu-Fang; Zhang, Xinzhi; Saaddine, Jinan B.] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Atlanta, GA 30341 USA.
[Cotch, Mary Frances; Vitale, Susan] NIH, NEI, Div Epidemiol & Clin Applicat, Bethesda, MD USA.
[Friedman, David S.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
RP Chou, CF (reprint author), CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, 4770 Buford Hwy,NE K-10, Atlanta, GA 30341 USA.
EM CChou@cdc.gov
OI Cotch, Mary Frances/0000-0002-2046-4350; Klein,
Ronald/0000-0002-4428-6237
FU National Center for Health Statistics (NCHS), CDC; Division of Diabetes
Translation, CDC [05FED47304]; National Eye Institute, NIH [ZIAEY000402]
FX This study was supported by the National Center for Health Statistics
(NCHS), CDC. Funding for the National Health and Nutrition Examination
Survey (NHANES) retinal and frequency-doubling technology component was
provided by the Intra Agency Agreement 05FED47304 from the Division of
Diabetes Translation, CDC. Funding for the vision component was provided
by the National Eye Institute, NIH, Intramural Research Program award
ZIAEY000402.
NR 39
TC 17
Z9 17
U1 1
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2013
VL 45
IS 1
BP 29
EP 35
DI 10.1016/j.amepre.2013.02.018
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 170CO
UT WOS:000320827500004
PM 23790986
ER
PT J
AU Schnabel, RB
Yin, XY
Larson, MG
Yamamoto, JF
Fontes, JD
Kathiresan, S
Rong, J
Levy, D
Keaney, JF
Wang, TJ
Murabito, JM
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Yin, Xiaoyan
Larson, Martin G.
Yamamoto, Jennifer F.
Fontes, Joao D.
Kathiresan, Sekar
Rong, Jian
Levy, Daniel
Keaney, John F., Jr.
Wang, Thomas J.
Murabito, Joanne M.
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Multiple Inflammatory Biomarkers in Relation to Cardiovascular Events
and Mortality in the Community
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE cardiovascular disease; cohort; epidemiology; inflammation; mortality
ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; CORONARY-HEART-DISEASE;
INTERCELLULAR-ADHESION MOLECULE-1; TYPE-2 DIABETIC-PATIENTS;
RHEUMATOID-ARTHRITIS; BODY-COMPOSITION; RISK-FACTORS; OLDEST-OLD;
MARKERS
AB Objective
Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality.
Approach and Results
We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61 +/- 9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD.
Conclusions
Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.
C1 [Schnabel, Renate B.; Yin, Xiaoyan; Larson, Martin G.; Yamamoto, Jennifer F.; Fontes, Joao D.; Rong, Jian; Levy, Daniel; Murabito, Joanne M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA USA.
[Yin, Xiaoyan; Larson, Martin G.; Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Med Dept, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Fontes, Joao D.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA.
[Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Kathiresan, Sekar] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA.
RP Schnabel, RB (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Bldg E 70 O70,Martinistr 52, D-20246 Hamburg, Germany.
EM schnabelr@gmx.de
RI Schnabel, Renate/F-6527-2014;
OI Murabito, Joanne/0000-0002-0192-7516; Larson,
Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970;
Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health (NIH)/National Heart, Lung, and Blood
Institute [N01-/HC-/25195, 6R01-/NS17950]; NIH [HL064753, HL076784,
AG028321, 1 RO1HL71039, K24 HL04334]; Deutsche Forschungsgemeinschaft
(German Research Foundation) [SCHN 1149/1-/1, SCHN 1149/3-/1]; Doris
Duke Charitable Foundation Clinical Scientist Development Award
[1K23HL083102]
FX This work was supported by National Institutes of Health (NIH)/National
Heart, Lung, and Blood Institute contract N01-/HC-/25195, 6R01-/NS17950,
and NIH grants HL064753, HL076784, AG028321 (E.J. Benjamin), and 1
RO1HL71039 (R.S. Vasan); NIH Research career award K24 HL04334 (R.S.
Vasan); Deutsche Forschungsgemeinschaft (German Research Foundation)
Research Fellowship SCHN 1149/1-/1 and Emmy Noether Program SCHN
1149/3-/1 (R.B. Schnabel); 1K23HL083102, Doris Duke Charitable
Foundation Clinical Scientist Development Award (S. Kathiresan).
NR 49
TC 26
Z9 27
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2013
VL 33
IS 7
BP 1728
EP 1733
DI 10.1161/ATVBAHA.112.301174
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 167YP
UT WOS:000320671800040
PM 23640499
ER
PT J
AU Foran, JM
Pavletic, SZ
Logan, BR
Agovi-Johnson, MA
Perez, WS
Bolwell, BJ
Bornhauser, M
Bredeson, CN
Cairo, MS
Camitta, BM
Copelan, EA
Dehn, J
Gale, RP
George, B
Gupta, V
Hale, GA
Lazarus, HM
Litzow, MR
Maharaj, D
Marks, DI
Martino, R
Maziarz, RT
Rowe, JM
Rowlings, PA
Savani, BN
Savoie, ML
Szer, J
Waller, EK
Wiernik, PH
Weisdorf, DJ
AF Foran, James M.
Pavletic, Steven Z.
Logan, Brent R.
Agovi-Johnson, Manza A.
Perez, Waleska S.
Bolwell, Brian J.
Bornhaeuser, Martin
Bredeson, Christopher N.
Cairo, Mitchell S.
Camitta, Bruce M.
Copelan, Edward A.
Dehn, Jason
Gale, Robert P.
George, Biju
Gupta, Vikas
Hale, Gregory A.
Lazarus, Hillard M.
Litzow, Mark R.
Maharaj, Dipnarine
Marks, David I.
Martino, Rodrigo
Maziarz, Richard T.
Rowe, Jacob M.
Rowlings, Philip A.
Savani, Bipin N.
Savoie, Mary Lynn
Szer, Jeffrey
Waller, Edmund K.
Wiernik, Peter H.
Weisdorf, Daniel J.
TI Unrelated Donor Allogeneic Transplantation after Failure of Autologous
Transplantation for Acute Myelogenous Leukemia: A Study from the Center
for International Blood and Marrow Transplantation Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Acute myelogenous leukemia; Unrelated donor; Transplantation;
Allogeneic; Autologous
ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; CONDITIONING REGIMEN;
ADULT PATIENTS; 1ST REMISSION; HEMATOLOGIC MALIGNANCIES; RELAPSE;
SURVIVAL; CHEMOTHERAPY; THERAPY
AB The survival of patients with relapsed acute myelogenous leukemia (AML) after autologous hematopoietic stem cell transplantation (auto-HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (allo-HCT) from an unrelated donor (URD) using either myeloablative (n = 242) or reduced-intensity conditioning (RIC; n = 60) regimens reported to the Center for International Blood and Marrow Transplantation Research. After a median follow-up of 58 months (range, 2 to 160 months), the probability of treatment-related mortality was 44% (95% confidence interval [CI], 38%-50%) at 1-year. The 5-year incidence of relapse was 32% (95% CI, 27%-38%), and that of overall survival was 22% (95% CI, 18%-27%). Multivariate analysis revealed a significantly better overal survival with RIC regimens (hazard ratio [HR], 0.51; 95% CI, 0.35-0.75; P < .001), with Karnofsky Performance Status score >= 90% (HR, 0.62; 95% CI, 0.47-0.82: P = .001) and in cytomegalovirus-negative recipients (HR, 0.64; 95% CI, 0.44-0.94; P = .022). A longer interval (>18 months) from auto-HCT to URD allo-HCT was associated with significantly lower riak of relapse (HR, 0.19; 95% CI, 0.09-0:38; P < .001) and improved leukemia-free survival (HR, 0.53; 95% CI, 0.34-0.84; P = .006). URD allo-HCT after auto-HCT relapse resulted in 20% long-term leukemia-free survival, with the best results seen in patients with a longer interval to secondary URD transplantation, with a Karnofsky Performance Status score >90%, in complete remission, and using an RIC regimen. Further efforts to reduce treatment-related mortaility and relapse are still needed. (C) 2013 American Society for Blood and Marrow Transplantation.
C1 [Foran, James M.] Mayo Clin Florida, Jacksonville, FL USA.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Logan, Brent R.; Perez, Waleska S.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Agovi-Johnson, Manza A.] Univ S Carolina, Norman J Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
[Bolwell, Brian J.; Copelan, Edward A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Bornhaeuser, Martin] Univ Klinikum Carl Gustav Carus, Dresden, Germany.
[Bredeson, Christopher N.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada.
[Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA.
[Camitta, Bruce M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Dehn, Jason] Natl Marrow Donor Program, Minneapolis, MN USA.
[Gale, Robert P.] Univ London Imperial Coll Sci Technol & Med, London, England.
[George, Biju] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India.
[Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA.
[Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA.
[Litzow, Mark R.] Mayo Clin, Rochester, MN USA.
[Maharaj, Dipnarine] Bethesda Hlth City, Boynton Beach, FL USA.
[Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England.
[Martino, Rodrigo] Hosp Santa Creu & Sant Pau, Barcelona, Spain.
[Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel.
[Rowlings, Philip A.] Calvary Mater Newcastle, Waratah, NSW, Australia.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Brentwood, TN USA.
[Savoie, Mary Lynn] Tom Baker Canc Clin, Calgary, AB, Canada.
[Szer, Jeffrey] Royal Melbourne Hosp, Melbourne, Vic, Australia.
[Waller, Edmund K.] Emory Univ Hosp, Atlanta, GA 30322 USA.
[Wiernik, Peter H.] St Lukes Roosevelt & Beth Israel Med Ctr, Continuum Canc Ctr New York, New York, NY USA.
[Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN 55455 USA.
RP Weisdorf, DJ (reprint author), Univ Minnesota, Med Ctr, 420 Delaware St SE,MMC 480, Minneapolis, MN 55455 USA.
EM weisd001@umn.edu
OI Szer, Jeff/0000-0001-6783-2301
FU Public Health Service Grant/Cooperative Agreement, National Cancer
Institute [U24-CA76518]; National Heart, Lung and Blood Institute;
National Institute of Allergy and Infectious Diseases; National Cancer
Institute [5U01HL069294]; Health Resources and Services Administration
[HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704,
N00014-08-1-0058]; Allos; Amgen; Angioblast
FX The Center for International Blood and Marrow Transplant Research is
supported by Public Health Service Grant/Cooperative Agreement
U24-CA76518 from the National Cancer Institute, the National Heart, Lung
and Blood Institute, and the National Institute of Allergy and
Infectious Diseases; Grant/Cooperative Agreement 5U01HL069294 from the
National Cancer Institute and the National Heart, Lung and Blood
Institute; Contract HHSH234200637015C with the Health Resources and
Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058
from the Office of Naval Research; and grants from Allos, Amgen,
Angioblast, anonymous donation to the Medical College of Wisconsin,
Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association,
Buchanan Family Foundation, CaridianBCT, Celgene, CellGenix, Children's
Leukemia Research Association, Fresenius-Biotech North America, Gamida
Cell Teva Joint Venture, Genentech, Genzyme, GlaxoSmithKline,
HistoGenetics, Kiadis Pharma, Leukemia and Lymphoma Society, Medical
College of Wisconsin, Merck & Co, Millennium: Takeda Oncology, Milliman
USA, Miltenyi Biotec, National Marrow Donor Program, Optum Healthcare
Solutions, Osiris Therapeutics, Otsuka America Pharmaceutical, RemedyMD,
Sanofi, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix,
StemCyte, Stemsoft Software, Swedish Orphan Biovitrum, Tarix
Pharmaceuticals, Teva Neuroscience, Therakos, and Wellpoint. The views
expressed in this article do not reflect the official policy or position
of the National Institute of Health, the Department of the Navy, the
Department of Defense, or any other agency of the US Government.
NR 34
TC 8
Z9 8
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2013
VL 19
IS 7
BP 1102
EP 1108
DI 10.1016/j.bbmt.2013.04.022
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 173QH
UT WOS:000321093500017
PM 23632091
ER
PT J
AU Wee, J
Mortimer, PS
Lindhurst, M
Biesecker, L
Holden, CA
AF Wee, J.
Mortimer, P. S.
Lindhurst, M.
Biesecker, L.
Holden, C. A.
TI Expanding the spectrum of Proteus syndrome: bilateral cerebriform
plantar collagenomas and varicose veins secondary to a mosaic AKT1
mutation
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 93rd Annual Meeting of the British-Association-of-Dermatologists
CY JUL 09-11, 2013
CL Liverpool, ENGLAND
SP British Assoc Dermatologists
C1 [Wee, J.; Mortimer, P. S.] St George Hosp, London, England.
[Lindhurst, M.; Biesecker, L.] NHGRI, Bethesda, MD 20892 USA.
[Holden, C. A.] St Heliers Hosp, Surrey, England.
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 0007-0963
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD JUL
PY 2013
VL 169
SU 1
SI SI
BP 13
EP 14
PG 2
WC Dermatology
SC Dermatology
GA 178JI
UT WOS:000321443500027
ER
PT J
AU Eichmann, K
Krause, RM
AF Eichmann, Klaus
Krause, Richard M.
TI Fred Neufeld and pneumococcal serotypes: foundations for the discovery
of the transforming principle
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE History of infectious diseases; History of bacteriology; Bile
solubility; Quellung reaction; Bacteriotropin
ID SOLUBLE SPECIFIC SUBSTANCE; LOBAR PNEUMONIA; SERUM TREATMENT;
ANTIPNEUMOCOCCIC SERUM; LECTURE
AB During the first decade of the twentieth century, the German bacteriologist Fred Neufeld, later Director of the Robert Koch-Institute in Berlin, first described the differentiation of pneumococci into serotypes on the basis of type-specific antisera. This finding was essential for subsequent research at the Rockefeller Institute of Medical Research (RIMR) in New York, and elsewhere, aiming for the conquest of human pneumococcal pneumonia, including antiserum therapy, the discovery that the type-specific antigens were carbohydrates, and the development of effective multivalent pneumococcal polysaccharide vaccines. Moreover, on the basis of pneumococcal serotypes Fred Griffith, in 1928 in London, discovered pneumococcal transformation, and Oswald T. Avery and coworkers, in 1944 at RIMR, identified DNA as the transforming substance. This sequence of events, leading to today's knowledge that genes consist of DNA, was initiated by a farsighted move of Simon Flexner, first Director of the RIMR, who asked Neufeld to send his pneumococcal typing strains, thus setting the stage for pneumococcal research at RIMR. Here, we describe Fred Neufeld's contributions in this development, which have remained largely unknown.
C1 [Eichmann, Klaus] Max Planck Inst Immunobiol & Epigenet, D-79108 Freiburg, Germany.
[Krause, Richard M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Eichmann, K (reprint author), Max Planck Inst Immunobiol & Epigenet, Stubeweg 51, D-79108 Freiburg, Germany.
EM eichmann@immunbio.mpg.de; Richard_Krause@nih.gov
NR 65
TC 1
Z9 2
U1 1
U2 20
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JUL
PY 2013
VL 70
IS 13
BP 2225
EP 2236
DI 10.1007/s00018-013-1351-z
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 163JR
UT WOS:000320332600002
PM 23689587
ER
PT J
AU Linehan, WM
Rouault, TA
AF Linehan, W. Marston
Rouault, Tracey A.
TI Molecular Pathways: Fumarate Hydratase-Deficient Kidney Cancer-Targeting
the Warburg Effect in Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RENAL-CELL CARCINOMA; HEREDITARY LEIOMYOMATOSIS; UTERINE LEIOMYOMAS; MET
PROTOONCOGENE; HLRCC SYNDROME; MUTATIONS; TUMORS; HIF; FH; INHIBITION
AB Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for development of cutaneous and uterine leiomyomas and an aggressive form of type II papillary kidney cancer. HLRCC is characterized by germline mutation of the tricarboxylic acid (TCA) cycle enzyme, fumarate hydratase (FH). FH-deficient kidney cancer is characterized by impaired oxidative phosphorylation and a metabolic shift to aerobic glycolysis, a form of metabolic reprogramming referred to as the Warburg effect. Increased glycolysis generates ATP needed for increased cell proliferation. In FH-deficient kidney cancer, levels of AMP-activated protein kinase (AMPK), a cellular energy sensor, are decreased resulting in diminished p53 levels, decreased expression of the iron importer, DMT1, leading to low cellular iron levels, and to enhanced fatty acid synthesis by diminishing phosphorylation of acetyl CoA carboxylase, a rate-limiting step for fatty acid synthesis. Increased fumarate and decreased iron levels in FH-deficient kidney cancer cells inactivate prolyl hydroxylases, leading to stabilization of hypoxia-inducible factor (HIF)-1 alpha and increased expression of genes such as VEGF and glucose transporter 1 (GLUT1) to provide fuel needed for rapid growth demands. Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, lactate dehydrogenase A (LDHA), the antioxidant response pathway, the heme oxygenase pathway, and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib. These same types of metabolic shifts, to aerobic glycolysis with decreased oxidative phosphorylation, have been found in a wide variety of other cancer types. Targeting the metabolic basis of a rare cancer such as FH-deficient kidney cancer will hopefully provide insights into the development of effective forms of therapies for other, more common forms of cancer. (C)2013 AACR.
C1 [Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr MSC 1107,CRC Room 1W-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 54
TC 35
Z9 35
U1 0
U2 24
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 1
PY 2013
VL 19
IS 13
BP 3345
EP 3352
DI 10.1158/1078-0432.CCR-13-0304
PG 8
WC Oncology
SC Oncology
GA 173RF
UT WOS:000321095900004
PM 23633457
ER
PT J
AU Shibata, SI
Chung, V
Synold, TW
Longmate, JA
Suttle, AB
Ottesen, LH
Lenz, HJ
Kummar, S
Harvey, RD
Hamilton, AL
O'Neil, BH
Lenz, HJ
Kummar, S
Harvey, RD
Hamilton, AL
O'Neil, BH
Sarantopoulos, J
LoRusso, P
Rudek, MA
Dowlati, A
Mulkerin, DL
Belani, CP
Gandhi, L
Lau, SC
Ivy, SP
Newman, EM
AF Shibata, Stephen I.
Chung, Vincent
Synold, Timothy W.
Longmate, Jeffrey A.
Suttle, A. Benjamin
Ottesen, Lone H.
Lenz, Heinz-Josef
Kummar, Shivaani
Harvey, R. Donald
Hamilton, Anne L.
O'Neil, Bert H.
Lenz, Heinz-Josef
Kummar, Shivaani
Harvey, R. Donald
Hamilton, Anne L.
O'Neil, Bert H.
Sarantopoulos, John
LoRusso, Patricia
Rudek, Michelle A.
Dowlati, Afshin
Mulkerin, Daniel L.
Belani, Chandra P.
Gandhi, Leena
Lau, S. Cecilia
Ivy, S. Percy
Newman, Edward M.
TI Phase I Study of Pazopanib in Patients with Advanced Solid Tumors and
Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction
Working Group Study
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ORAL PAZOPANIB; INHIBITOR; TRIAL
AB Purpose: Pazopanib is a potent, multitargeted receptor tyrosine kinase inhibitor; however, there is limited information regarding the effects of liver function on pazopanib metabolism and pharmacokinetics. The objective of this study was to establish the maximum-tolerated dose (MTD) and pharmacokinetic profile of pazopanib in patients with varying degrees of hepatic dysfunction.
Experimental Design: Patients with any solid tumors or lymphoma were stratified into four groups based on the degree of hepatic dysfunction according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria. Pazopanib was given orally once a day on a 21-day cycle. A modified 3+3 design was used.
Results: Ninety-eight patients were enrolled. Patients in the mild group tolerated 800 mg per day. The moderate and severe groups tolerated 200 mg per day. Pharmacokinetic data in the mild group were similar to the data in the normal group. Comparison of the median C-max and area under the curve [AUC((0-24))] in the moderate or severe groups at 200 mg per day to the values in the normal and mild groups at 800 mg per day indicated less than dose-proportional systemic exposures in patients with moderate and severe hepatic impairment. This suggests that the lower maximum-tolerated dose in the moderate and severe group is not due to a decrease in drug clearance or alteration in the proportion of metabolites.
Conclusions: In patients with mild liver dysfunction, pazopanib is well tolerated at the Food and Drug Administration (FDA)-approved dose of 800 mg per day. Patients with moderate and severe liver dysfunction tolerated 200 mg per day. Clin Cancer Res; 19(13); 3631-9. (C)2013 AACR.
C1 [Shibata, Stephen I.; Chung, Vincent; Synold, Timothy W.; Longmate, Jeffrey A.; Lau, S. Cecilia; Newman, Edward M.] City Hope Natl Med Ctr, Duarte, CA USA.
[Lenz, Heinz-Josef] Univ So Calif, Los Angeles, CA USA.
[Kummar, Shivaani] Natl Canc Inst, Bethesda, MD 20892 USA.
[Ivy, S. Percy] Natl Canc Inst, Bethesda, MD USA.
[Ivy, S. Percy] NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Rudek, Michelle A.] Sidney Kimmel Canc Ctr, Baltimore, MD USA.
[Harvey, R. Donald] Emory Univ, Sch Med, Atlanta, GA USA.
[O'Neil, Bert H.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Sarantopoulos, John] Inst Drug Dev CTRC, San Antonio, TX USA.
[LoRusso, Patricia] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Mulkerin, Daniel L.] Univ Wisconsin, Madison, WI USA.
[Belani, Chandra P.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA.
[Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hamilton, Anne L.] Royal Prince Alfred Hosp, Sydney, NSW, Australia.
RP Newman, EM (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, North,Room 2000A,1500 East Duarte Rd, Duarte, CA 91010 USA.
EM enewman@coh.org
OI Belani, Chandra/0000-0001-5049-5329; Gandhi, Leena/0000-0002-2398-9179
FU NIH [U01-CA062505, P30-CA033572, U01-CA062487, U01-CA099168,
U01-CA70095, P30-CA006973, U01-CA069853, P30-CA054174, U01-CA062490,
U01-CA062502, U01-C 062491]
FX The study was supported by NIH grants: U01-CA062505 and P30-CA033572
(Beckman Research Institute of City of Hope, Duarte, CA); U01-CA062487
(Karmanos Cancer Institute, Detroit, MI); U01-CA099168 (University of
Pittsburgh, Pittsburgh, PA); U01-CA70095 and P30-CA006973 (Johns Hopkins
University, Baltimore, MD); U01-CA069853 and P30-CA054174 (Cancer
Therapy and Research Center at University of Texas Health Science
Center, San Antonio, TX); U01-CA062490 (Dana-Farber Cancer Institute,
Boston, MA); U01-CA062502 (Case Western Reserve, Cleveland, OH); and
U01-C 062491 (University of Wisconsin Paul P Carbone Comprehensive
Cancer Center, Madison, WI).
NR 10
TC 15
Z9 15
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 1
PY 2013
VL 19
IS 13
BP 3631
EP 3639
DI 10.1158/1078-0432.CCR-12-3214
PG 9
WC Oncology
SC Oncology
GA 173RF
UT WOS:000321095900030
PM 23653147
ER
PT J
AU Brauer, MJ
Zhuang, GL
Schmidt, M
Yao, J
Wu, XM
Kaminker, JS
Jurinka, SS
Kolumam, G
Chung, AS
Jubb, A
Modrusan, Z
Ozawa, T
James, CD
Phillips, H
Haley, B
Tam, RNW
Clermont, AC
Cheng, JH
Yang, SX
Swain, SM
Chen, D
Scherer, SJ
Koeppen, H
Yeh, RF
Yue, P
Stephan, JP
Hegde, P
Ferrara, N
Singh, M
AF Zhuang, Guanglei
Schmidt, Maike
Yao, Jenny
Wu, Xiumin
Kaminker, Joshua S.
Jurinka, Stefanie S.
Kolumam, Ganesh
Chung, Alicia S.
Jubb, Adrian
Modrusan, Zora
Ozawa, Tomoko
James, C. David
Phillips, Heidi
Haley, Benjamin
Tam, Rachel N. W.
Clermont, Anne C.
Cheng, Jason H.
Yang, Sherry X.
Swain, Sandra M.
Chen, Daniel
Scherer, Stefan J.
Koeppen, Hartmut
Yeh, Ru-Fang
Yue, Peng
Stephan, Jean-Philippe
Hegde, Priti
Ferrara, Napoleone
Singh, Mallika
Bais, Carlos
TI Identification and Analysis of In Vivo VEGF Downstream Markers Link VEGF
Pathway Activity with Efficacy of Anti-VEGF Therapies
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID METASTATIC COLORECTAL-CANCER; RENAL-CELL CARCINOMA; TUMOR-GROWTH;
ANTIANGIOGENIC THERAPY; INDUCED ANGIOGENESIS; BREAST-CANCER;
BEVACIZUMAB; RESISTANCE; INHIBITION; CHEMOTHERAPY
AB Purpose: The aim of this study was to identify conserved pharmacodynamic and potential predictive biomarkers of response to anti-VEGF therapy using gene expression profiling in preclinical tumor models and in patients.
Experimental Design: Surrogate markers of VEGF inhibition [VEGF-dependent genes or VEGF-dependent vasculature (VDV)] were identified by profiling gene expression changes induced in response to VEGF blockade in preclinical tumor models and in human biopsies from patients treated with anti-VEGF monoclonal antibodies. The potential value of VDV genes as candidate predictive biomarkers was tested by correlating high or low VDV gene expression levels in pretreatment clinical samples with the subsequent clinical efficacy of bevacizumab (anti-VEGF)-containing therapy.
Results: We show that VDV genes, including direct and more distal VEGF downstream endothelial targets, enable detection of VEGF signaling inhibition in mouse tumor models and human tumor biopsies. Retrospective analyses of clinical trial data indicate that patients with higher VDV expression in pretreatment tumor samples exhibited improved clinical outcome when treated with bevacizumab-containing therapies.
Conclusions: In this work, we identified surrogate markers(VDV genes) for in vivo VEGF signaling in tumors and showed clinical data supporting a correlation between pretreatment VEGF bioactivity and the subsequent efficacy of anti-VEGF therapy. We propose that VDV genes are candidate biomarkers with the potential to aid the selection of novel indications as well as patients likely to respond to anti-VEGF therapy. The data presented here define a diagnostic biomarker hypothesis based on translational research that warrants further evaluation in additional retrospective and prospective trials. Clin Cancer Res; 19(13); 3681-92. (C)2013 AACR.
C1 [Zhuang, Guanglei; Schmidt, Maike; Yao, Jenny; Wu, Xiumin; Kaminker, Joshua S.; Jurinka, Stefanie S.; Kolumam, Ganesh; Chung, Alicia S.; Jubb, Adrian; Modrusan, Zora; Phillips, Heidi; Haley, Benjamin; Tam, Rachel N. W.; Clermont, Anne C.; Cheng, Jason H.; Chen, Daniel; Scherer, Stefan J.; Koeppen, Hartmut; Yeh, Ru-Fang; Yue, Peng; Stephan, Jean-Philippe; Hegde, Priti; Ferrara, Napoleone; Bais, Carlos] Genentech Inc, San Francisco, CA 94131 USA.
[Ozawa, Tomoko; James, C. David] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
[Ozawa, Tomoko; James, C. David] Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA USA.
[Singh, Mallika] Novartis Inst Biomed Res, Emeryville, CA USA.
[Yang, Sherry X.] NCI, NIH, Div Canc Treatment & Diag, Nat Clin Target Validat Lab, Bethesda, MD USA.
[Swain, Sandra M.] Medstar Washington Hosp, Washington Canc Inst, Washington, DC USA.
RP Singh, M (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94131 USA.
EM mallika.singh@novartis.com
RI Zhuang, Guanglei/K-6097-2013;
OI Swain, Sandra/0000-0002-1320-3830
NR 50
TC 18
Z9 18
U1 3
U2 19
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 1
PY 2013
VL 19
IS 13
BP 3681
EP 3692
DI 10.1158/1078-0432.CCR-12-3635
PG 12
WC Oncology
SC Oncology
GA 173RF
UT WOS:000321095900035
PM 23685835
ER
PT J
AU Gilbert, J
Lee, JW
Argiris, A
Haigentz, M
Feldman, LE
Jang, M
Arun, P
Van Waes, C
Forastiere, AA
AF Gilbert, Jill
Lee, Ju Whei
Argiris, Athanassios
Haigentz, Missak, Jr.
Feldman, Lawrence Eric
Jang, Minyoung
Arun, Pattatheyil
Van Waes, Carter
Forastiere, Arlene A.
TI Phase II 2-arm trial of the proteasome inhibitor, PS-341 (bortezomib) in
combination with irinotecan or PS-341 alone followed by the addition of
irinotecan at time of progression in patients with locally recurrent or
metastatic squamous cell carcinoma of the head and neck (E1304): A trial
of the Eastern Cooperative Oncology Group
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE head and neck cancer; chemotherapy; bortezomib; irinotecan; phase II
ID FACTOR-KAPPA-B; TUMOR-CELLS; CANCER; THERAPY; DOCETAXEL; CISPLATIN;
ACTIVATOR; PATHWAY; EGFR
AB Background Constitutive activation of nuclear factor B (NF-B) is associated with poor prognosis. Irinotecan demonstrates single-agent activity in head and neck cancer but activates NF-B, promoting cell survival and resistance. Bortezomib is a proteasome inhibitor that inactivates NF-B. Patients and Methods We performed a randomized phase II trial of bortezomib on days 1, 4, 8, and 11 and irinotecan on days 1 and 8 of each 21-day cycle or single-agent bortezomib on days 1, 4, 8, and 11 on a 21-day cycle. The addition of irinotecan to bortezomib was allowed in patients who progressed on bortezomib alone. Results The response rate of bortezomib and irinotecan was 13%. One patient had a partial response to bortezomib alone (response rate 3%). No responses were seen in patients with addition of irinotecan at time of progression on bortezomib. Conclusions The bortezomib-based regimens evaluated in this study have minimal activity in recurrent or metastatic head and neck cancer. Head Neck, 2013
C1 [Gilbert, Jill] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA.
[Lee, Ju Whei] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Argiris, Athanassios] Univ Pittsburgh, Pittsburgh, PA USA.
[Haigentz, Missak, Jr.] Montefiore Hosp & Med Ctr, Bronx, NY USA.
[Feldman, Lawrence Eric] Univ Illinois Chicago MBCCOP, Chicago, IL USA.
[Jang, Minyoung; Arun, Pattatheyil; Van Waes, Carter] NIDCD, Head & Neck Surgey Branch, NIH, Bethesda, MD USA.
[Forastiere, Arlene A.] Johns Hopkins Univ, Baltimore, MD USA.
RP Gilbert, J (reprint author), Vanderbilt Univ, Med Ctr, 2220 Pierce Ave,777 PRB, Nashville, TN 37232 USA.
EM jill.gilbert@vanderbilt.edu
FU Public Health Service from the National Cancer Institute, National
Institutes of Health [CA23318, CA66636, CA21115, CA39229, CA49957,
CA14958, CA16116]; Department of Health and Human Services; Milllennium
Pharmaceuticals
FX This study was conducted by the Eastern Cooperative Oncology Group
(Robert L. Comis, M. D., Chair) and supported in part by Public Health
Service Grants CA23318, CA66636, CA21115, CA39229, CA49957, CA14958,
CA16116 and from the National Cancer Institute, National Institutes of
Health, and the Department of Health and Human Services. Its contents
are solely the responsibility of the authors and do not necessarily
represent the official views of the National Cancer Institute.;
Milllennium Pharmaceuticals provided bortezomib for prior preclinical
studies6 to C. V. W. and bortezomib and funding to NCI for a
prior clinical trial and correlative studies.16
NR 18
TC 10
Z9 12
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1043-3074
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD JUL
PY 2013
VL 35
IS 7
BP 942
EP 948
DI 10.1002/hed.23046
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 168RI
UT WOS:000320723000013
PM 22791234
ER
PT J
AU Mumford, SL
Dasharathy, SS
Pollack, AZ
Perkins, NJ
Mattison, DR
Cole, SR
Wactawski-Wende, J
Schisterman, EF
AF Mumford, Sunni L.
Dasharathy, Sonya S.
Pollack, Anna Z.
Perkins, Neil J.
Mattison, Donald R.
Cole, Stephen R.
Wactawski-Wende, Jean
Schisterman, Enrique F.
TI Serum uric acid in relation to endogenous reproductive hormones during
the menstrual cycle: findings from the BioCycle study
SO HUMAN REPRODUCTION
LA English
DT Article
DE anovulation; estradiol; menstrual cycle; premenopausal women; uric acid
ID POLYCYSTIC-OVARY-SYNDROME; MARGINAL STRUCTURAL MODELS; ESTRADIOL-17-BETA
E2; PREMENOPAUSAL WOMEN; CARDIOVASCULAR RISK; INSULIN-RESISTANCE;
OXIDATIVE STRESS; SEX-DIFFERENCES; METABOLISM; THERAPY
AB Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E-2) and reproductive hormone concentrations in regularly menstruating women?
Mean uric acid concentrations were highest during the follicular phase, and were inversely associated with E-2 and progesterone, and positively associated with FSH.
E-2 may decrease serum levels of uric acid in post-menopausal women; however, the interplay between endogenous reproductive hormones and uric acid levels among regularly menstruating women has not been elucidated.
The BioCycle study was a prospective cohort study conducted at the University at Buffalo research centre from 2005 to 2007, which followed healthy women for one (n 9) or 2 (n 250) menstrual cycle(s).
Participants were healthy women aged 1844 years. Hormones and uric acid were measured in serum eight times each cycle for up to two cycles. Marginal structural models with inverse probability of exposure weights were used to evaluate the associations between endogenous hormones and uric acid concentrations.
Uric acid levels were observed to vary across the menstrual cycle, with the lowest levels observed during the luteal phase. Every log-unit increase in E-2 was associated with a decrease in uric acid of 1.1 ( 0.011; 95 confidence interval (CI): 0.019, 0.004; persistent-effects model), and for every log-unit increase in progesterone, uric acid decreased by 0.8 ( 0.008; 95 CI: 0.012, 0.004; persistent-effects model). FSH was positively associated with uric acid concentrations, such that each log-unit increase was associated with a 1.6 increase in uric acid ( 0.016; 95 CI: 0.005, 0.026; persistent-effects model). Progesterone and FSH were also associated with uric acid levels in acute-effects models. Of 509 cycles, 42 were anovulatory (8.3). Higher uric acid levels were associated with increased odds of anovulation (odds ratio 2.39, 95 CI: 1.25, 4.56).
The change in uric acid levels among this cohort of healthy women was modest, and analysis was limited to two menstrual cycles. The women in this study were healthy and regularly menstruating, and as such there were few women with high uric acid levels and anovulatory cycles.
These findings demonstrate the importance of taking menstrual cycle phase into account when measuring uric acid in premenopausal women, and confirm the hypothesized beneficial lowering effects of endogenous E-2 on uric acid levels. These findings suggest that there could be an underlying association affecting both sporadic anovulation and high uric acid levels among young, regularly menstruating women. Further studies are needed to confirm these findings and elucidate the connection between uric acid and reproductive and later cardiovascular health.
This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract HHSN275200403394C). No competing interests declared.
C1 [Mumford, Sunni L.; Dasharathy, Sonya S.; Pollack, Anna Z.; Perkins, Neil J.; Mattison, Donald R.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Rockville, MD 20852 USA.
[Cole, Stephen R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA.
[Mattison, Donald R.] Risk Sci Int, Ottawa, ON K1N7G2, Canada.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, 6100 Execut Blvd 7B03, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
RI Mattison, Donald/L-4661-2013;
OI Mattison, Donald/0000-0001-5623-0874; Perkins, Neil/0000-0002-6802-4733;
Pollack, Anna/0000-0002-4313-3298; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN275200403394C]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (contract #
HHSN275200403394C).
NR 42
TC 12
Z9 12
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD JUL
PY 2013
VL 28
IS 7
BP 1853
EP 1862
DI 10.1093/humrep/det085
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 170MK
UT WOS:000320855600015
PM 23562957
ER
PT J
AU Chen, CZ
Southall, N
Xiao, JB
Marugan, JJ
Ferrer, M
Hu, X
Jones, RE
Feng, S
Agoulnik, IU
Zheng, W
Agoulnik, AI
AF Chen, Catherine Z.
Southall, Noel
Xiao, Jingbo
Marugan, Juan J.
Ferrer, Marc
Hu, Xin
Jones, Raisa E.
Feng, Shu
Agoulnik, Irina U.
Zheng, Wei
Agoulnik, Alexander I.
TI Identification of Small-Molecule Agonists of Human Relaxin Family
Receptor 1 (RXFP1) by Using a Homogenous Cell-Based cAMP Assay
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE relaxin; GPCR; RXFP1; qHTS; agonist; small molecule
ID PROTEIN-COUPLED RECEPTOR-7; LEUCINE-RICH REPEAT; PEPTIDE RECEPTORS;
SPLICE VARIANTS; LGR7; MEMBRANE
AB The relaxin hormone is involved in a variety of biological functions, including female reproduction and parturition, as well as regulation of cardiovascular, renal, pulmonary, and hepatic functions. It regulates extracellular matrix remodeling, cell invasiveness, proliferation, differentiation, and overall tissue homeostasis. The G protein-coupled receptor (GPCR) relaxin family receptor 1 (RXFP1) is a cognate relaxin receptor that mainly signals through cyclic AMP second messenger. Although agonists of the receptor could have a wide range of pharmacologic utility, until now there have been no reported small-molecule agonists for relaxin receptors. Here, we report the development of a quantitative high-throughput platform for an RXFP1 agonist screen based on homogenous cell-based HTRF cyclic AMP (cAMP) assay technology. Two small molecules of similar structure were independently identified from a screen of more than 365 677 compounds. Neither compound showed activity in a counterscreen with HEK293T cells transfected with an unrelated GPCR vasopressin 1b receptor. These small-molecule agonists also demonstrated selectivity against the RXFP2 receptor, providing a basis for future medicinal chemistry optimization of selective relaxin receptor agonists.
C1 [Chen, Catherine Z.; Southall, Noel; Xiao, Jingbo; Marugan, Juan J.; Ferrer, Marc; Hu, Xin; Jones, Raisa E.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Feng, Shu] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[Agoulnik, Irina U.] Florida Int Univ, Dept Cellular Biol & Pharmacol, Miami, FL 33199 USA.
[Agoulnik, Alexander I.] Florida Int Univ, Dept Human & Mol Genet, Miami, FL 33199 USA.
RP Zheng, W (reprint author), NIH, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov; aagoulni@fiu.edu
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014;
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757;
Agoulnik, Irina/0000-0003-4889-0324; Agoulnik,
Alexander/0000-0001-6587-6845
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research
[U54MH084681, R03 MH085705]; Intramural Research Program of the National
Human Genome Research Institute; National Center for Advancing
Translational Sciences, National Institutes of Health
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This research
was supported by the Molecular Libraries Initiative of the NIH Roadmap
for Medical Research U54MH084681 and R03 MH085705 (to A. I. A.) and the
Intramural Research Program of the National Human Genome Research
Institute and National Center for Advancing Translational Sciences,
National Institutes of Health.
NR 19
TC 9
Z9 9
U1 1
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JUL
PY 2013
VL 18
IS 6
BP 670
EP 677
DI 10.1177/1087057112469406
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 170XI
UT WOS:000320888100004
PM 23212924
ER
PT J
AU McCallum, MM
Nandhikonda, P
Temmer, JJ
Eyermann, C
Simeonov, A
Jadhav, A
Yasgar, A
Maloney, D
Arnold, A
AF McCallum, Megan M.
Nandhikonda, Premchendar
Temmer, Jonathan J.
Eyermann, Charles
Simeonov, Anton
Jadhav, Ajit
Yasgar, Adam
Maloney, David
Arnold, Alexander (Leggy)
TI High-Throughput Identification of Promiscuous Inhibitors from Screening
Libraries with the Use of a Thiol-Containing Fluorescent Probe
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE promiscuous inhibitors; glutathione; fluorescence; high-throughput
screening; thiol-reactive or electrophilic compound
ID COMPOUND LIBRARIES; FALSE POSITIVES; ASSAY; DISCOVERY; REACTIVITY;
RECEPTOR; FILTERS; HTS
AB Testing small molecules for their ability to modify cysteine residues of proteins in the early stages of drug discovery is expected to accelerate our ability to develop more selective drugs with lesser side effects. In addition, this approach also enables the rapid evaluation of the mode of binding of new drug candidates with respect to thiol reactivity and metabolism by glutathione. Herein, we describe the development of a fluorescence-based high-throughput assay that allows the identification of thiol-reactive compounds. A thiol-containing fluorescent probe, MSTI, was synthesized and used to evaluate small molecules from the Library of Pharmacologically Active Compounds (LOPAC) collection of bioactive molecules. LOPAC compounds that are known to react with sulfur nucleophiles were identified with this assay, for example, irreversible protease inhibitors, nitric oxide-releasing compounds, and proton-pump inhibitors. The results confirm that both electrophilic and redox reactive compounds can be quickly identified in a high-throughput manner, enabling the assessment of screening libraries with respect to thiol-reactive compounds.
C1 [McCallum, Megan M.; Nandhikonda, Premchendar; Temmer, Jonathan J.; Arnold, Alexander (Leggy)] Univ Wisconsin, Milwaukee, WI 53211 USA.
[Eyermann, Charles; Simeonov, Anton; Jadhav, Ajit; Yasgar, Adam; Maloney, David] NIH, Bethesda, MD 20892 USA.
RP Arnold, A (reprint author), Univ Wisconsin, Dept Chem & Biochem, 3210 N Cramer St, Milwaukee, WI 53211 USA.
EM Arnold2@uwm.edu
RI Nandhikonda, Premchendar/K-1473-2014
FU University of Wisconsin Milwaukee; UWM Research Growth Initiative (RGI),
National Institute of Drug Abuse [R03DA031090]; UWM Research Foundation;
Lynde and Harry Bradley Foundation; Richard and Ethel Herzfeld
Foundation; Molecular Libraries Initiative of the National Institutes of
Health Roadmap for Medical Research [U54MH084681]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: The work was
supported in part by the University of Wisconsin Milwaukee, the UWM
Research Growth Initiative (RGI), National Institute of Drug Abuse
(R03DA031090), the UWM Research Foundation, the Lynde and Harry Bradley
Foundation, the Richard and Ethel Herzfeld Foundation, and the Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research (U54MH084681).
NR 27
TC 7
Z9 7
U1 2
U2 24
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JUL
PY 2013
VL 18
IS 6
BP 705
EP 713
DI 10.1177/1087057113476090
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 170XI
UT WOS:000320888100008
PM 23446699
ER
PT J
AU Fox, NA
Barker, TV
White, LK
Suway, JG
Pine, DS
AF Fox, Nathan A.
Barker, Tyson V.
White, Lauren K.
Suway, Jenna G.
Pine, Daniel S.
TI Commentary: To intervene or not? Appreciating or treating individual
differences in childhood temperament - remarks on Rapee (2013)
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Editorial Material
ID SOCIAL ANXIETY DISORDER; BEHAVIORAL-INHIBITION; CHILDREN; RISK
C1 [Fox, Nathan A.; Barker, Tyson V.; White, Lauren K.; Suway, Jenna G.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
RP Fox, NA (reprint author), Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA.
EM fox@umd.edu
FU NICHD NIH HHS [T32 HD007542]; NIMH NIH HHS [U01 MH093349]
NR 10
TC 1
Z9 1
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD JUL
PY 2013
VL 54
IS 7
BP 789
EP 790
DI 10.1111/jcpp.12101
PG 2
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 169KF
UT WOS:000320778200010
PM 23746203
ER
PT J
AU Ryschkewitsch, CF
Jensen, PN
Major, EO
AF Ryschkewitsch, Caroline F.
Jensen, Peter N.
Major, Eugene O.
TI Multiplex qPCR assay for ultra sensitive detection of JCV DNA with
simultaneous identification of genotypes that discriminates non-virulent
from virulent variants
SO JOURNAL OF CLINICAL VIROLOGY
LA English
DT Article
DE qPCR; JC Virus; Variants; PML diagnostics
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; REAL-TIME PCR;
NUCLEOTIDE-SEQUENCES; BONE-MARROW; VIRUS-DNA; POLYOMAVIRUS;
PATHOGENESIS; INDIVIDUALS; REGIONS; URINE
AB Background: JC virus (JCV) is the etiologic agent for progressive multifocal leukoencephalopathy (PML), a demyelinating disease occurring in the brain of patients with underlying immune compromised states. All viable JCV genomes contain a conserved region in the T protein coding nucleotide sequence that when detected by PCR in CSF is a confirmatory diagnostic marker for PML along with clinical and neuroradio-logical evidence. The non-coding regulatory region (NCRR) is hypervariable, as evidenced by nucleotide sequence of the non-virulent variant, which is predominantly excreted in urine, versus that of virulent variants found in brain and CSF of PML patients. All variants can be found in blood.
Objective: A single assay that quantifies and identifies JCV DNA in clinical samples and discriminates between variants has significant value to physicians and patients at risk for PML.
Study design: Separate primer pairs were tested together to quantitatively detect conserved viral DNA nucleotide sequence in patient samples, while simultaneously detecting the NCRR specific for the non-virulent variant.
Results: In testing using control plasmids and patients' CSF, blood, and urine, PML patients predictably demonstrated the non-virulent, archetype NCRR in urine, but virulent NCRR variants in CSF and blood.
Conclusion: The JCV qPCR multiplex assay targets two regions in JCV genomes to simultaneously identify and measure viral DNA, as well as distinguish between variants associated with PML and those that are not. The multiplex results could signal risk for PML if patients are viremic with JCV variants closely associated with PML pathogenesis. Published by Elsevier B. V.
C1 [Ryschkewitsch, Caroline F.; Jensen, Peter N.; Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA.
RP Major, EO (reprint author), Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Lab Mol Med & Neurosci, 10 Ctr Dr,Bldg 10,Room 3B14, Bethesda, MD 20892 USA.
EM ryschkec@ninds.nih.gov; JensenP@ninds.nih.gov; majorg@ninds.nih.gov
FU Division of Intramural Research, National Institute of Neurological
Disorders and Stroke
FX Funding is provided through the Division of Intramural Research,
National Institute of Neurological Disorders and Stroke.
NR 19
TC 25
Z9 25
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1386-6532
J9 J CLIN VIROL
JI J. Clin. Virol.
PD JUL
PY 2013
VL 57
IS 3
BP 243
EP 248
DI 10.1016/j.jcv.2013.03.009
PG 6
WC Virology
SC Virology
GA 166XL
UT WOS:000320593300011
PM 23619054
ER
PT J
AU Metayer, C
Colt, JS
Buffler, PA
Reed, HD
Selvin, S
Crouse, V
Ward, MH
AF Metayer, Catherine
Colt, Joanne S.
Buffler, Patricia A.
Reed, Helen D.
Selvin, Steve
Crouse, Vonda
Ward, Mary H.
TI Exposure to herbicides in house dust and risk of childhood acute
lymphoblastic leukemia
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE childhood leukemia; herbicides; pesticides; dust
ID NON-HODGKINS-LYMPHOMA; AGRICULTURAL HEALTH; PESTICIDE EXPOSURE; CANCER
INCIDENCE; FARM-WORKERS; CHILDREN; CALIFORNIA; GERMANY; COHORT;
POLLUTANTS
AB We examine the association between exposure to herbicides and childhood acute lymphoblastic leukemia (ALL). Dust samples were collected from homes of 269 ALL cases and 333 healthy controls (<8 years of age at diagnosis/reference date and residing in same home since diagnosis/reference date) in California, using a high-volume surface sampler or household vacuum bags. Amounts of agricultural or professional herbicides (alachlor, metolachlor, bromoxynil, bromoxynil octanoate, pebulate, butylate, prometryn, simazine, ethalfluralin, and pendimethalin) and residential herbicides (cyanazine, trifluralin, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop, 2,4-dichlorophenoxyacetic acid (2,4-D), chlorthal, and dicamba) were measured. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Models included the herbicide of interest, age, sex, race/ethnicity, household income, year and season of dust sampling, neighborhood type, and residence type. The risk of childhood ALL was associated with dust levels of chlorthal; compared to homes with no detections, ORs for the first, second, and third tertiles were 1.49 (95% CI: 0.82-2.72), 1.49 (95% CI: 0.83-2.67), and 1.57 (95% CI: 0.90-2.73), respectively (P-value for linear trend = 0.05). The magnitude of this association appeared to be higher in the presence of alachlor. No other herbicides were identified as risk factors of childhood ALL. The data suggest that home dust levels of chlorthal, and possibly alachlor, are associated with increased risks of childhood ALL.
C1 [Metayer, Catherine; Buffler, Patricia A.; Selvin, Steve] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94704 USA.
[Colt, Joanne S.; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Bethesda, MD 20892 USA.
[Reed, Helen D.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Bethesda, MD 20892 USA.
[Crouse, Vonda] Childrens Hosp Cent Calif, Dept Pediat Oncol, Madera, CA USA.
RP Metayer, C (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 1995 Univ Ave,Suite 460, Berkeley, CA 94704 USA.
EM cmetayer@berkeley.edu
FU National Institute of Environmental Health Sciences [R01 ES09137,
P42-ES04705]; National Cancer Institute [7590-S-04, 7590-S-01,
N02-CP-11015]; National Institutes of Health
FX This research could not have been conducted without the important
support from our clinical collaborators and participating hospitals,
which include: University of California Davis Medical Center (Dr.
Jonathan Ducore), University of California San Francisco (Dr. Mignon Loh
and Dr. Katherine Matthay), Children's Hospital of Central California
(Dr. Vonda Crouse), Lucile Packard Children's Hospital (Dr. Gary Dahl),
Children's Hospital Oakland (Dr. James Feusner), Kaiser Permanente
Sacramento (Dr. Vincent Kiley), Kaiser Permanente Santa Clara (Dr.
Carolyn Russo and Dr. Alan Wong), Kaiser Permanente San Francisco (Dr.
Kenneth Leung), and Kaiser Permanente Oakland (Dr. Stacy Month), and the
families of the study participants. We also wish to acknowledge the
effort and dedication of all our collaborators at the Northern
California Childhood Leukemia Study who helped make this study possible,
and the staff at the Battelle Memorial Institute, Columbus, OH who
performed laboratory analyses. This work was financially supported by
National Institute of Environmental Health Sciences, Grants R01 ES09137
and P42-ES04705; the Intramural Research Program of the National Cancer
Institute (subcontracts 7590-S-04, 7590-S-01); the National Cancer
Institute (contract N02-CP-11015), and from the National Institutes of
Health. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institute
of Environmental Health Sciences or the National Cancer Institute.
NR 61
TC 16
Z9 17
U1 6
U2 41
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD JUL-AUG
PY 2013
VL 23
IS 4
BP 363
EP 370
DI 10.1038/jes.2012.115
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 166VG
UT WOS:000320586200005
PM 23321862
ER
PT J
AU Schmitt, KC
Rothman, RB
Reith, MEA
AF Schmitt, Kyle C.
Rothman, Richard B.
Reith, Maarten E. A.
TI Nonclassical Pharmacology of the Dopamine Transporter: Atypical
Inhibitors, Allosteric Modulators, and Partial Substrates
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID NEUROTRANSMITTER-SODIUM SYMPORTER; PROTEIN-PROTEIN INTERACTIONS;
BIOGENIC-AMINE TRANSPORTERS; BINDING-SITES; MONOAMINE TRANSPORTERS;
BACTERIAL HOMOLOG; CRYSTAL-STRUCTURE; COCAINE; LEUT; IDENTIFICATION
AB The dopamine transporter (DAT) is a sodium-coupled symporter protein responsible for modulating the concentration of extraneuronal dopamine in the brain. The DAT is a principle target of various psychostimulant, nootropic, and antidepressant drugs, as well as certain drugs used recreationally, including the notoriously addictive stimulant cocaine. DAT ligands have traditionally been divided into two categories: cocaine-like inhibitors and amphetamine-like substrates. Whereas inhibitors block monoamine uptake by the DAT but are not translocated across the membrane, substrates are actively translocated and trigger DAT-mediated release of dopamine by reversal of the translocation cycle. Because both inhibitors and substrates increase extraneuronal dopamine levels, it is often assumed that all DAT ligands possess an addictive liability equivalent to that of cocaine. However, certain recently developed ligands, such as atypical benztropine-like DAT inhibitors with reduced or even a complete lack of cocaine-like rewarding effects, suggest that addictiveness is not a constant property of DAT-affecting compounds. These atypical ligands do not conform to the classic preconception that all DAT inhibitors (or substrates) are functionally and mechanistically alike. Instead, they suggest the possibility that the DAT exhibits some of the ligand-specific pleiotropic functional qualities inherent to G-protein-coupled receptors. That is, ligands with different chemical structures induce specific conformational changes in the transporter protein that can be differentially transduced by the cell, ultimately eliciting unique behavioral and psychological effects. The present overview discusses compounds with conformation-specific activity, useful not only as tools for studying the mechanics of dopamine transport, but also as leads for medication development in addictive disorders.
C1 [Schmitt, Kyle C.] NYU, Sch Med, Dept Neurosurg, New York, NY 10016 USA.
[Reith, Maarten E. A.] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA.
[Reith, Maarten E. A.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA.
[Rothman, Richard B.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Schmitt, KC (reprint author), NYU, Sch Med, Dept Neurosurg, Publ Hlth Labs, 455 1st Ave,8th Floor, New York, NY 10016 USA.
EM kyle.schmitt@nyumc.org
FU National Institutes of Health National Institute on Drug Abuse [R01
DA019676]; National Institutes of Health National Institute of Mental
Health [R01 MH083840]; National Institutes of Health [National Institute
on Drug Abuse]
FX This work was supported by the National Institutes of Health National
Institute on Drug Abuse [Grant R01 DA019676]; the National Institutes of
Health National Institute of Mental Health [Grant R01 MH083840]; and the
Intramural Research Program of the National Institutes of Health
[National Institute on Drug Abuse].
NR 67
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U1 3
U2 11
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUL
PY 2013
VL 346
IS 1
BP 2
EP 10
DI 10.1124/jpet.111.191056
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 164XQ
UT WOS:000320446100001
PM 23568856
ER
PT J
AU Niciu, MJ
Grunschel, BDG
Corlett, PR
Pittenger, C
Bloch, MH
AF Niciu, Mark J.
Grunschel, Beth D. G.
Corlett, Philip R.
Pittenger, Christopher
Bloch, Michael H.
TI Two cases of delayed-onset suicidal ideation, dysphoria and anxiety
after ketamine infusion in patients with obsessive-compulsive disorder
and a history of major depressive disorder
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Article
DE Ketamine; OCD; depression; SAE; suicidality
ID RECEPTOR ANTAGONIST RESPONSE
AB Ketamine is a non-competitive N-methyl-D-aspartate receptor antagonist that is Food and Drug Administration-approved in the United States for anesthesia due to its sedative effects with low risk of severe respiratory depression. Subanesthetic dose intravenous ketamine has rapidly acting antidepressant effects in treatment-resistant unipolar and bipolar depression. We recently reported an open-label trial of ketamine in 10 subjects with treatment-refractory obsessive-compulsive disorder, seven of whom had active comorbid depression. Although ketamine had no sustained anti-obsessive effect, four of the seven subjects with comorbid depression experienced an acute antidepressant effect. However, we unexpectedly observed delayed-onset dysphoria, worsening anxiety and suicidal thinking in two of the three subjects with obsessive-compulsive disorder and extensive psychiatric comorbidity but minimal depressive symptoms at the start of infusion. The implications of these adverse neuropsychiatric effects in two patients with similar psychiatric comorbidity are discussed. We conclude that there remains insufficient data on therapeutic ketamine in the presence of comorbid psychiatric disorders to promote its off-label use in a non-research milieu.
C1 [Niciu, Mark J.; Grunschel, Beth D. G.; Corlett, Philip R.; Pittenger, Christopher; Bloch, Michael H.] Yale Univ, Dept Psychiat, CMHC, CNRU, New Haven, CT 06520 USA.
[Niciu, Mark J.] NIMH, NIH, Bethesda, MD 20814 USA.
[Pittenger, Christopher; Bloch, Michael H.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA.
RP Niciu, MJ (reprint author), NIMH, NIH, Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 7-5545, Bethesda, MD 20814 USA.
EM mark.niciu@nih.gov
RI Niciu, Mark/J-1766-2014
OI Niciu, Mark/0000-0002-5612-3021
FU National Institutes of Health (NIH)/National Institute of Mental Health
(NIMH) [T32MH19961]; Robert L. McNeil Jr. Fellowship in Translational
Research; VA-Connecticut Alcohol Research Center; Yale University
Department of Psychiatry; CTSA from the National Center for Research
Resources (NCRR) [UL1RR024139]; National Center for Advancing
Translational Science (NCATS), NIH; NIH Roadmap for Medical Research;
NIH/NIMH from the NCRR [UL1RR024139, K08MH081190]; NIH/NIMH
[K23MH091240-01]; American Psychiatric Institute for Research and
Education (APIRE)/Eli Lilly and Co. Psychiatric Research Fellowship;
American Academy of Child and Adolescent Psychiatry/Eli Lilly and Co.
Pilot Research Award; Trichotillomania Learning Center; National
Alliance for Research on Schizophrenia and Depression (NARSAD) from the
NCRR [UL1RR024139]
FX Salary support was provided to each author by the following sources:
MJN: National Institutes of Health (NIH)/National Institute of Mental
Health (NIMH) T32MH19961, the Robert L. McNeil Jr. Fellowship in
Translational Research and the VA-Connecticut Alcohol Research Center.
BDGG: Yale University Department of Psychiatry. PRC: CTSA Grant Number
UL1RR024139 from the National Center for Research Resources (NCRR) and
the National Center for Advancing Translational Science (NCATS),
components of the NIH, and NIH Roadmap for Medical Research. CP:
NIH/NIMH K08MH081190, UL1RR024139 from the NCRR and the NIH Roadmap for
Medical Research. MHB: NIH/NIMH support of the Yale Child Study Center
Research Training Program, K23MH091240-01, the American Psychiatric
Institute for Research and Education (APIRE)/Eli Lilly and Co.
Psychiatric Research Fellowship, the American Academy of Child and
Adolescent Psychiatry/Eli Lilly and Co. Pilot Research Award, the
Trichotillomania Learning Center, The National Alliance for Research on
Schizophrenia and Depression (NARSAD), UL1RR024139 from the NCRR and the
NIH Roadmap for Medical Research. The State of Connecticut also provided
resource support to all authors via the Abraham Ribicoff Research
Facilities/CNRU at CMHC, where this research was conducted.
NR 21
TC 15
Z9 15
U1 3
U2 14
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD JUL
PY 2013
VL 27
IS 7
BP 651
EP 654
DI 10.1177/0269881113486718
PG 4
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 168JZ
UT WOS:000320703100010
PM 23676198
ER
PT J
AU Akhtar, A
Kamal, AK
AF Akhtar, Anjum
Kamal, Ayeesha Kamran
TI CLEAR: The Intraventricular Haemorrhage Thrombolysis Trial
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 0
TC 1
Z9 1
U1 0
U2 2
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD JUL
PY 2013
VL 63
IS 7
BP 928
EP 928
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 165LQ
UT WOS:000320485800028
PM 23901725
ER
PT J
AU Lubaki, NM
Ilinykh, P
Pietzsch, C
Tigabu, B
Freiberg, AN
Koup, RA
Bukreyev, A
AF Lubaki, Ndongala M.
Ilinykh, Philipp
Pietzsch, Colette
Tigabu, Bersabeh
Freiberg, Alexander N.
Koup, Richard A.
Bukreyev, Alexander
TI The Lack of Maturation of Ebola Virus-Infected Dendritic Cells Results
from the Cooperative Effect of at Least Two Viral Domains
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; DOUBLE-STRANDED-RNA; INFLUENZA-A VIRUS; VP35
PROTEIN; HEMORRHAGIC-FEVER; MARBURG VIRUSES; IN-VITRO;
NONHUMAN-PRIMATES; INTERFERON ANTAGONISM; VIRION GLYCOPROTEINS
AB Ebola virus (EBOV) infections are characterized by deficient T lymphocyte responses, T lymphocyte apoptosis, and lymphopenia in the absence of direct infection of T lymphocytes. In contrast, dendritic cells (DC) are infected but fail to mature appropriately, thereby impairing the T cell response. We investigated the contributions of EBOV proteins in modulating DC maturation by generating recombinant viruses expressing enhanced green fluorescent protein and carrying mutations affecting several potentially immunomodulating domains. They included envelope glycoprotein (GP) domains, as well as innate response antagonist domains (IRADs) previously identified in the VP24 and VP35 proteins. GP expressed by an unrelated vector, but not the wild-type EBOV, was found to strongly induce DC maturation, and infections with recombinant EBOV carrying mutations disabling GP functional domains did not restore DC maturation. In contrast, each of the viruses carrying mutations disabling any IRAD in VP35 induced a dramatic upregulation of DC maturation markers. This was dependent on infection, but not interaction with GP. Disabling of IRADs also resulted in up to a several hundredfold increase in secretion of cytokines and chemokines. Furthermore, these mutations induced formation of homotypic DC clusters, which represent close correlates of their maturation and presumably facilitate transfer of antigen from migratory DC to lymph node DC. Thus, an individual IRAD is insufficient to suppress DC maturation; rather, the suppression of DC maturation and the "immune paralysis" observed during EBOV infections results from a cooperative effect of two or more individual IRADs.
C1 [Lubaki, Ndongala M.; Ilinykh, Philipp; Pietzsch, Colette; Tigabu, Bersabeh; Freiberg, Alexander N.; Bukreyev, Alexander] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Bukreyev, Alexander] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Lubaki, Ndongala M.; Ilinykh, Philipp; Pietzsch, Colette; Tigabu, Bersabeh; Freiberg, Alexander N.; Bukreyev, Alexander] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Bukreyev, A (reprint author), Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
EM alexander.bukreyev@utmb.edu
RI Ilinykh, Philipp/L-5404-2014
FU University of Texas Medical Branch; John Sealy Memorial Endowment Fund
Pilot Grant "Mechanisms of 'immune paralysis' in Ebola infections";
McLaughlin Fellowship
FX The study was supported by a departmental startup grant from the
University of Texas Medical Branch (A.B.), the John Sealy Memorial
Endowment Fund Pilot Grant "Mechanisms of 'immune paralysis' in Ebola
infections" (A.B.), and the McLaughlin Fellowship (N.M.L.).
NR 82
TC 24
Z9 25
U1 0
U2 16
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUL
PY 2013
VL 87
IS 13
BP 7471
EP 7485
DI 10.1128/JVI.03316-12
PG 15
WC Virology
SC Virology
GA 160JT
UT WOS:000320116500024
PM 23616668
ER
PT J
AU Rasheed, MAU
Latner, DR
Aubert, RD
Gourley, T
Spolski, R
Davis, CW
Langley, WA
Ha, SJ
Ye, LL
Sarkar, S
Kalia, V
Konieczny, BT
Leonard, WJ
Ahmed, R
AF Rasheed, Mohammed Ata Ur
Latner, Donald R.
Aubert, Rachael D.
Gourley, Tania
Spolski, Rosanne
Davis, Carl W.
Langley, William A.
Ha, Sang-Jun
Ye, Lilin
Sarkar, Surojit
Kalia, Vandana
Konieczny, Bogumila T.
Leonard, Warren J.
Ahmed, Rafi
TI Interleukin-21 Is a Critical Cytokine for the Generation of
Virus-Specific Long-Lived Plasma Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID FOLLICULAR-HELPER-CELLS; CHRONIC VIRAL-INFECTION; GERMINAL CENTER
RESPONSES; CXC CHEMOKINE RECEPTOR-5; CD4(+) T-CELLS; HUMAN B-CELLS;
IMMUNOGLOBULIN PRODUCTION; ANTIBODY-PRODUCTION; HUMORAL IMMUNITY; BCL-6
EXPRESSION
AB Long-lived plasma cells that reside in the bone marrow constitutively produce antibody in the absence of antigen and are the cellular basis of durable humoral immunity. The generation of these long-lived plasma cells depends upon a series of highly orchestrated interactions between antigen-specific CD4 T cells and B cells and the formation of germinal centers (GCs). In this study, we have examined the role of the cytokine interleukin-21 (IL-21) in regulating humoral immunity during acute viral infections. Using IL-21 receptor-deficient (IL-21R(-/-)) mice, we found that virus-specific CD4 T cells were generated after infection with lymphocytic choriomeningitis virus (LCMV) and that these CD4 T cells differentiated into T follicular helper (T-FH)-like cells in the absence of IL-21 signaling. There was also no defect in the formation of GCs, although after day 15 these GCs disappeared faster in IL-21R(-/-) mice than in wild-type mice. Isotype switching and the initial LCMV-specific IgG response were normal in IL-21R(-/-) mice. However, these mice exhibited a profound defect in generating long-lived plasma cells and in sustaining antibody levels over time. Similar results were seen after infection of IL-21R(-/-) mice with vesicular stomatitis virus and influenza virus. Using chimeric mice containing wild-type or IL-21R(-/-) CD4 T cells and B cells, we showed that both B and CD4 T cells need IL-21 signaling for generating long-term humoral immunity. Taken together, our results highlight the importance of IL-21 in humoral immunity to viruses.
C1 [Rasheed, Mohammed Ata Ur; Latner, Donald R.; Aubert, Rachael D.; Gourley, Tania; Davis, Carl W.; Langley, William A.; Ha, Sang-Jun; Ye, Lilin; Sarkar, Surojit; Kalia, Vandana; Konieczny, Bogumila T.; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Rasheed, Mohammed Ata Ur; Latner, Donald R.; Aubert, Rachael D.; Gourley, Tania; Davis, Carl W.; Langley, William A.; Ha, Sang-Jun; Ye, Lilin; Sarkar, Surojit; Kalia, Vandana; Konieczny, Bogumila T.; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA.
[Spolski, Rosanne; Leonard, Warren J.] NHLBI, Ctr Immunol, Bethesda, MD 20892 USA.
RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM rahmed@emory.edu
RI Rasheed, Mohammed/N-2749-2013;
OI Ha, Sang-Jun/0000-0002-1192-6031
FU National Institutes of Health (NIH) [P01 AI097092-01A1, RO1 A1030048];
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery grant
[UM1AI100663]; Division of Intramural Research, National Heart, Lung,
and Blood Institute, NIH
FX This work was supported by National Institutes of Health (NIH) grants
P01 AI097092-01A1 (to R.A.) and RO1 A1030048 (to R.A.) and Center for
HIV/AIDS Vaccine Immunology and Immunogen Discovery grant UM1AI100663
(to R.A.). This work was also supported in part by the Division of
Intramural Research, National Heart, Lung, and Blood Institute, NIH (to
W.J.L. and R.S.).
NR 45
TC 42
Z9 42
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL
PY 2013
VL 87
IS 13
BP 7737
EP 7746
DI 10.1128/JVI.00063-13
PG 10
WC Virology
SC Virology
GA 160JT
UT WOS:000320116500047
PM 23637417
ER
PT J
AU Savage, SA
Pulsipher, MA
Romano, A
Berlyne, D
AF Savage, Sharon A.
Pulsipher, Michael A.
Romano, Alessandra
Berlyne, Deborah
TI Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone marrow
failure disease scientific symposium 2012
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Myelodysplastic syndromes; Aplastic anemia; Paroxysmal nocturnal
hemoglobinuria; Bone marrow failure; Epigenetic therapy;
Immunosuppressive therapy; Stem cell transplantation; Complement
ID MYELODYSPLASTIC SYNDROMES
AB Aplastic anemia (AA), myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) are rare disorders of bone marrow failure. Once considered distinct entities, these three diseases are now believed to have overlapping pathophysiologies. The Aplastic Anemia and MDS International Foundation, a nonprofit organization that supports patients and families living with bone marrow failure disorders, sponsored a scientific symposium in Bethesda, MD, in March 2012. This report summarizes the symposium presentations by 30 of the world's leading AA, MDS, and PNH researchers on recent findings, current areas of controversy, and recommendations for basic and clinical research to advance the field. (c) 2013 Published by Elsevier Ltd.
C1 [Savage, Sharon A.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Pulsipher, Michael A.] Univ Utah, Huntsman Canc Inst, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA.
[Romano, Alessandra] Univ Catania, Osped Ferrarotto, Div Clinicizzata Ematol, Catania, Italy.
[Berlyne, Deborah] Aplast Anemia & Myelodysplast Syndrome Int Fdn, Rockville, MD USA.
RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Execut Blvd,EPS 7018, Bethesda, MD 20892 USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015; ROMANO, ALESSANDRA/I-9201-2012
OI Savage, Sharon/0000-0001-6006-0740; ROMANO,
ALESSANDRA/0000-0002-6333-4433
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[1R13HL112578-01]; Office of Rare Disease Research; Division of Cancer
Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health
FX The authors thank all meeting participants for a highly productive
meeting. Funding for this conference was made possible in part by
1R13HL112578-01 from the National Institutes of Health, National Heart,
Lung, and Blood Institute and the Office of Rare Disease Research. This
work was supported, in part, by the intramural research program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health (S.A.S.). The views expressed in written
conference materials or publications and by speakers or moderators do
not necessarily reflect the official policies of the Department of
Health and Human Services; nor does mention of trade names, commercial
practices, or organizations imply endorsement by the U.S. Government.
Author contributions. All authors participated in the AA&MDSIF meeting
and in writing the manuscript. All authors approved of the final
version.
NR 8
TC 1
Z9 2
U1 0
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD JUL
PY 2013
VL 37
IS 7
BP 848
EP 851
DI 10.1016/j.leukres.2013.04.013
PG 4
WC Oncology; Hematology
SC Oncology; Hematology
GA 166UF
UT WOS:000320583100022
PM 23643149
ER
PT J
AU Fernandez-Duenas, V
Gomez-Soler, M
Morato, X
Nunez, F
Das, A
Kumar, TS
Jauma, S
Jacobson, KA
Ciruela, F
AF Fernandez-Duenas, Victor
Gomez-Soler, Maricel
Morato, Xavier
Nunez, Fabiana
Das, Arijit
Kumar, T. Santhosh
Jauma, Serge
Jacobson, Kenneth A.
Ciruela, Francisco
TI Dopamine D-2 receptor-mediated modulation of adenosine A(2A) receptor
agonist binding within the A(2A)R/D2R oligomer framework
SO NEUROCHEMISTRY INTERNATIONAL
LA English
DT Article
DE A(2A)R; D2R; Parkinson's disease; Receptor-receptor allosterism;
Antiparkinsonian drugs
ID PARKINSONS-DISEASE; HETEROMERS; SUBTYPES
AB The molecular interaction between adenosine A(2A) and dopamine D-2 receptors (A(2A)Rs and D(2)Rs, respectively) within an oligomeric complex has been postulated to play a pivotal role in the adenosine-dopamine interplay in the central nervous system, in both normal and pathological conditions (e.g. Parkinson's disease). While the effects of A(2A)R challenge on D2R functioning have been largely studied, the reverse condition is still unexplored, a fact that might have impact in therapeutics. Here, we aimed to examine in a real-time mode the D2R-mediated allosteric modulation of A(2A)R binding when an A(2A)R/D2R oligomer is established. Thus, we synthesized fluorescent A(2A)R agonists and evaluated, by means of a flow cytometry homogeneous no-wash assay and a real-time fluorescence resonance energy transfer (FRET)-based approach, the effects on A(2A)R binding of distinct antiparkinsonian drugs in current clinical use (i.e. pramipexole, rotigotine and apomorphine). Our results provided evidence for the existence of a differential D2R-mediated negative allosteric modulation on A(2A)R agonist binding that was oligomer-formation dependent, and with apomorphine being the best antiparkinsonian drug attenuating A(2A)R agonist binding. Overall, the here-developed methods were found valid to explore the ability of drugs acting on D(2)Rs to modulate A(2A)R binding, thus serving to facilitate the preliminary selection of D2R-like candidate drugs in the management of Parkinson's disease. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Fernandez-Duenas, Victor; Gomez-Soler, Maricel; Morato, Xavier; Nunez, Fabiana; Ciruela, Francisco] Univ Barcelona, Fac Med, IDIBELL, Dept Patol & Terapeut Expt,Unitat Farmacol, Barcelona 08907, Spain.
[Das, Arijit; Kumar, T. Santhosh; Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Jauma, Serge] Hosp Univ Bellvitge, Neurol Serv, Movement Disorders Unit, Barcelona 08907, Spain.
RP Ciruela, F (reprint author), Fac Med Bellvitge, Dept Patol & Terapeut Expt, Unitat Farmacol, Pavello Govern,Av Feixa Llarga S-N, Barcelona 08907, Spain.
EM fciruela@ub.edu
RI Jacobson, Kenneth/A-1530-2009; Ciruela, Francisco/A-5096-2013;
OI Jacobson, Kenneth/0000-0001-8104-1493; Ciruela,
Francisco/0000-0003-0832-3739; Fernandez Duenas,
Victor/0000-0001-7834-2965
FU "Ministerio de Economia y Competitividad" (MINECO) [SAF2011-24779,
CSD2008-00005]; ICREA Academia from the Catalan Institution for Research
and Advanced Studies (ICREA); NIDDK Intramural Research Program of the
National Institutes of Health, Bethesda
FX This work was supported by grants SAF2011-24779 and Consolider-Ingenio
CSD2008-00005 from "Ministerio de Economia y Competitividad" (MINECO)
and ICREA Academia-2010 from the Catalan Institution for Research and
Advanced Studies (ICREA) to FC. Also, VF-D, MG-S, FN and FC belong to
the "Neuropharmacology and Pain" accredited research group (Generalitat
de Catalunya, 2009 SGR 232). Support to KAJ, AD, and TSK from the NIDDK
Intramural Research Program of the National Institutes of Health,
Bethesda, MD, USA is acknowledged. We thank Esther Castano, Eva Julia,
and Benjamin Torrejon, from the Scientific and Technical Services
(SCT)-Bellvitge Campus of the University of Barcelona for the technical
assistance.
NR 13
TC 5
Z9 5
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0197-0186
J9 NEUROCHEM INT
JI Neurochem. Int.
PD JUL
PY 2013
VL 63
IS 1
BP 42
EP 46
DI 10.1016/j.neuint.2013.04.006
PG 5
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 169BE
UT WOS:000320751100005
PM 23619397
ER
PT J
AU Jarcho, JM
Feier, NA
Bert, A
Labus, JA
Lee, M
Stains, J
Ebrat, B
Groman, SM
Tillisch, K
Brody, AL
London, ED
Mandelkern, MA
Mayer, EA
AF Jarcho, Johanna M.
Feier, Natasha A.
Bert, Alberto
Labus, Jennifer A.
Lee, Maunoo
Stains, Jean
Ebrat, Bahar
Groman, Stephanie M.
Tillisch, Kirsten
Brody, Arthur L.
London, Edythe D.
Mandelkern, Mark A.
Mayer, Emeran A.
TI Diminished neurokinin-1 receptor availability in patients with two forms
of chronic visceral pain
SO PAIN
LA English
DT Article
DE PET; NK-1 receptor; Irritable bowel syndrome; Inflammatory bowel
disease; Somatic pain; Quality of life
ID IRRITABLE-BOWEL-SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; QUALITY-OF-LIFE;
SUBSTANCE-P; NK1 RECEPTOR; SPINAL-CORD; HUMAN BRAIN; INFLAMMATORY PAIN;
PLACEBO ANALGESIA; PERSISTENT PAIN
AB Central sensitization and dysregulation of peripheral substance P and neurokinin-1 receptor (NK-1R) signaling are associated with chronic abdominal pain in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Although positron emission tomography (PET) has demonstrated that patients with injury-related chronic pain have diminished NK-1R availability in the brain, it is unknown whether these deficits are present in IBD and IBS patients, who have etiologically distinct forms of non-injury-related chronic pain. This study's aim was to determine if patients with IBD or IBS exhibit deficits in brain expression of NK-1Rs relative to healthy controls (HCs), the extent to which expression patterns differ across patient populations, and if these patterns differentially relate to clinical parameters. PET with [F-18] SPA-RQ was used to measure NK-1R availability by quantifying binding potential (BP) in the 3 groups. Exploratory correlation analyses were performed to detect associations between NK-1R BP and physical symptoms. Compared to HCs, IBD patients had NK-1R BP deficits across a widespread network of cortical and subcortical regions. IBS patients had similar, but less pronounced deficits. BP in a subset of these regions was robustly related to discrete clinical parameters in each patient population. Widespread deficits in NK-1R BP occur in IBD and, to a lesser extent, IBS; however, discrete clinical parameters relate to NK-1R BP in each patient population. This suggests that potential pharmacological interventions that target NK-1R signaling may be most effective for treating distinct symptoms in IBD and IBS. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Jarcho, Johanna M.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Jarcho, Johanna M.; Feier, Natasha A.; Labus, Jennifer A.; Lee, Maunoo; Stains, Jean; Ebrat, Bahar; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Los Angeles, CA 90095 USA.
[Feier, Natasha A.] McGill Univ, Fac Dent, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada.
[Bert, Alberto] SpA, Med Imaging Lab Im3D, Turin, Italy.
[Groman, Stephanie M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Brody, Arthur L.; London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Brody, Arthur L.; London, Edythe D.; Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA.
RP Mayer, EA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, CHS 42-210 MC737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM emayer@ucla.edu
OI Bert, Alberto/0000-0001-8391-7508; Jarcho, Johanna/0000-0001-9075-6968
FU National Institutes of Health [F31-DA021951, T32-MH017140, F31-DA028812,
NIH AT00268]; Tobacco-Related Disease Research Program [19XT-0135];
Department of Veterans Affairs, Office of Research and Development
(Merit Review Award)
FX This work was supported in part by National Institutes of Health Grants
F31-DA021951, T32-MH017140 (J.M.J.), F31-DA028812 (S.M.G.), NIH AT00268
(E.A.M.), and endowments from the Marjorie Greene Family Trust and
National Institute on Drug Abuse (A.L.B. [R01 DA20872]), the
Tobacco-Related Disease Research Program (A.L.B. [19XT-0135]), the
Department of Veterans Affairs, Office of Research and Development
(Merit Review Award [A.L.B.]), and the Thomas P. and Katherine K. Pike
Chair in Addiction Studies (E.D.L.).
NR 85
TC 12
Z9 12
U1 1
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD JUL
PY 2013
VL 154
IS 7
BP 987
EP 996
DI 10.1016/j.pain.2013.02.026
PG 10
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 166XD
UT WOS:000320592200007
PM 23582152
ER
PT J
AU Huang, B
Liu, M
Huang, SG
Wu, B
Guo, H
Su, XZ
Lu, FL
AF Huang, Bo
Liu, Man
Huang, Shiguang
Wu, Bin
Guo, Hong
Su, Xin-zhuan
Lu, Fangli
TI Expression of Tim-1 and Tim-3 in Plasmodium berghei ANKA infection
SO PARASITOLOGY RESEARCH
LA English
DT Article
ID MURINE CEREBRAL MALARIA; IMMUNE-RESPONSE; MICE; CYTOKINES;
SUSCEPTIBILITY; ENCEPHALITIS; PATHOGENESIS; FALCIPARUM; CHILDREN; ASTHMA
AB Cerebral malaria (CM) is a serious and often fatal complication of Plasmodium falciparum infections; however, the precise mechanisms leading to CM is poorly understood. Mouse malaria models have provided insight into the key events in pathogenesis of CM. T-cell immune response is known to play an important role in malaria infection, and members of the T-cell immunoglobulin- and mucin-domain-containing molecule (Tim) family have roles in T-cell-mediated immune responses. Tim-1 and Tim-3 are expressed on terminally differentiated Th2 and Th1 cells, respectively, and participate in the regulation of Th immune response. Until now, the role of Tim family proteins in Plasmodium infection remains unclear. In the present study, the mRNA levels of Tim-1, Tim-3, and some key Th1 and Th2 cytokines in the spleen of Kunming outbred mice infected with Plasmodium berghei ANKA (PbANKA) were determined using real-time polymerase chain reaction (qRT-PCR). Compared with uninfected controls, Tim-1 expression was significantly decreased in infected mice with CM at day 10 postinfection (p.i.) but significantly increased in infected mice with non-CM at day 22 p.i.; in contrast, Tim-3 expression was significantly increased in infected mice both with CM at day 10 p.i. and with non-CM at day 22 p.i. The expressions of IFN-gamma, TNF-alpha, IL-10, and IL-12 were significantly increased but IL-4 was significantly decreased in infected mice with CM at days 10 p.i., whereas the expressions of IFN-gamma, TNF-alpha, IL-4, IL-10, and TGF-beta were significantly increased but IL-12 was significantly decreased in infected mice with non-CM at days 22 p.i. Furthermore, the expression of Tim-1 and Tim-3 could reflect Th2 and Th1 immune response in the spleen of PbANKA-infected mice, respectively. Our data suggest that PbANKA infection could inhibit the differentiation of T lymphocytes toward Th2 cells, promote the Th1 cell differentiation, and induce Th1-biased immune response in the early infective stage, whereas the infection could promote Th2 cell differentiation and induce Th2-biased immune response in the late infective stage. Our data indicate that both Tim-1 and Tim-3 may play a role in the process of PbANKA infection, which may represent a potential therapeutic target.
C1 [Huang, Bo; Liu, Man; Wu, Bin; Lu, Fangli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China.
[Huang, Bo; Liu, Man; Wu, Bin; Lu, Fangli] Sun Yat Sen Univ, Key Lab Trop Dis Control, Minist Educ, Guangzhou 510080, Guangdong, Peoples R China.
[Huang, Shiguang] Jinan Univ, Sch Med, Guangzhou 510632, Guangdong, Peoples R China.
[Guo, Hong] Hainan Med Univ, Publ Lab, Haikou 571199, Hainan Province, Peoples R China.
[Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Su, Xin-zhuan] Xiamen Univ, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian Province, Peoples R China.
[Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, Xiamen 361005, Fujian Province, Peoples R China.
[Liu, Man] Medprin Regenerat Med Technol Co Ltd, Guangzhou 510663, Guangdong, Peoples R China.
RP Lu, FL (reprint author), Sun Yat Sen Univ, Key Lab Trop Dis Control, Minist Educ, Guangzhou 510080, Guangdong, Peoples R China.
EM thshg@126.com; fanglilu@yahoo.com
OI Su, Xinzhuan/0000-0003-3246-3248
FU Fogarty International Center of the National Institutes of Health
[R01TW008151]; Divisions of Intramural Research at the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; Ministry of Education of China [B12003, B06016]; 111 Project;
State Bureau of Foreign Experts
FX Research reported in this publication was supported in part by the
Fogarty International Center of the National Institutes of Health under
Award Number R01TW008151, the Divisions of Intramural Research at the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and the "111 Project" sponsored by the State
Bureau of Foreign Experts and Ministry of Education of China (B12003 and
B06016). The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
NR 36
TC 4
Z9 7
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0932-0113
J9 PARASITOL RES
JI Parasitol. Res.
PD JUL
PY 2013
VL 112
IS 7
BP 2713
EP 2719
DI 10.1007/s00436-013-3442-z
PG 7
WC Parasitology
SC Parasitology
GA 165WO
UT WOS:000320516500034
PM 23653017
ER
PT J
AU Jiang, JY
Ahn, J
Huang, WY
Hayes, RB
AF Jiang, Jieying
Ahn, Jiyoung
Huang, Wen-Yi
Hayes, Richard B.
TI Association of obesity with cardiovascular disease mortality in the PLCO
trial
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Cardiovascular disease; Body-mass index; Obesity
ID BODY-MASS INDEX; CANCER SCREENING TRIAL; CORONARY-HEART-DISEASE;
RISK-FACTORS; OVERWEIGHT; STROKE; WOMEN; PARTICIPANTS; PROSTATE; WEIGHT
AB Objective. Obesity is a risk factor for cardiovascular disease (CVD) mortality, but the association between obesity and specific causes of CVD mortality is still under investigation.
Method. We prospectively examined body-mass index (BMI) in relation to CVD-specific causes of death in approximately 86,000 US men and women in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, followed for up to 13 years. BMI was calculated from self-reported weight and height at baseline. Hazard ratios (HRs) were calculated overall and stratified by sex, smoking status, and educational level.
Result Overweight non-obese participants (BMI: 25.0-29.9) were not at excess risk for CVD mortality (HR and Cis are 1.02 [0.92-1.13]), compared to participants of normal BMI (18.5-24.9). Excess CVD mortality was observed for participants of BMI 30.0-34.9 (HR and Cis: 129[1.13-1.48]), BMI 35.0-39.9 (HR and CIs: 1.87[1.51-232]) and BMI 40.0 + (HR and Us: 221 [1.57-321]) (p < 0.001 for trend). BMI was unrelated to mortality due to stroke. The observed association of BMI with CVD was independent of gender, smoking status and educational level.
Conclusion. Obesity is associated with increased mortality due to CVD. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Jiang, Jieying; Ahn, Jiyoung; Hayes, Richard B.] NYU, Div Epidemiol, Dept Populat Hlth, Sch Med, New York, NY 10016 USA.
[Huang, Wen-Yi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Hayes, RB (reprint author), NYU, Div Epidemiol, Dept Populat Hlth, Sch Med, 650 1st Ave, New York, NY 10016 USA.
EM Richard.B.Hayes@nyumc.org
OI Hayes, Richard/0000-0002-0918-661X
FU New York University School of Medicine; Intramural Research Program of
the Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, National Institutes of Health;
Department of Health and Human Services (DHHS)
FX This research was supported by New York University School of Medicine,
by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics and by contracts from the Division of Cancer
Prevention, National Cancer Institute, National Institutes of Health,
and the Department of Health and Human Services (DHHS). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 39
TC 13
Z9 13
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD JUL
PY 2013
VL 57
IS 1
BP 60
EP 64
DI 10.1016/j.ypmed.2013.04.014
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 164SI
UT WOS:000320429400012
PM 23632233
ER
PT J
AU Moreno, M
Economidou, D
Mar, AC
Lopez-Granero, C
Caprioli, D
Theobald, DE
Fernando, A
Newman, AH
Robbins, TW
Dalley, JW
AF Moreno, M.
Economidou, D.
Mar, A. C.
Lopez-Granero, C.
Caprioli, D.
Theobald, D. E.
Fernando, A.
Newman, A. H.
Robbins, T. W.
Dalley, Jeffrey W.
TI Divergent effects of D-2/3 receptor activation in the nucleus accumbens
core and shell on impulsivity and locomotor activity in high and low
impulsive rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Impulsivity; Locomotion; Quinpirole; Nafadotride; Dopamine; Nucleus
accumbens
ID REACTION-TIME-TASK; DOPAMINE D-3 RECEPTOR; ROMAN HIGH-AVOIDANCE;
ATTENTIONAL PERFORMANCE; DRUG-ADDICTION; BRAIN; ANTAGONIST; LESIONS;
STIMULATION; MODULATION
AB Previously we demonstrated reduced D-2/3 receptor availability in the ventral striatum of hyper-impulsive rats on the five-choice serial reaction time task (5-CSRTT). However, the anatomical locus of D-2/3 receptor dysfunction in high impulsive (HI) rats is unknown.
In the present study, we investigated whether D-2/3 receptor dysfunction in HI rats is localised to the core or shell sub-regions of the nucleus accumbens (NAcb).
Rats were selected for low (low impulsive, LI) and high impulsivity on the 5-CSRTT and implanted with guide cannulae targeting the NAcb core and shell. The D-2/3 receptor agonist quinpirole was locally injected in the NAcb (0.1, 0.3 and 1 mu g per infusion) and its effects investigated on the performance of LI and HI rats on the 5-CSRTT as well as spontaneous locomotor activity in an open field.
Intra-NAcb core quinpirole increased premature responding in HI rats but not in LI rats. In contrast, intra-NAcb shell quinpirole strongly increased locomotor activity in HI rats, unlike LI rats. This effect was blocked by intra-NAcb shell infusions of the D-2/3 receptor antagonist nafadotride (0.03 mu g). However, nafadotride was ineffective in blocking the effects of intra-NAcb core quinpirole on premature responding in HI rats.
These findings indicate that impulsivity and hyperactivity are separately regulated by core and shell sub-regions of the NAcb and that HI rats show an enhanced response to D-2/3 receptor activation in these regions. These results suggest that the symptom clusters of hyperactivity and impulsivity in attention-deficit hyperactivity disorder may be neurally dissociable at the level of the NAcb.
C1 [Moreno, M.; Lopez-Granero, C.] Univ Almeria, Dept Psychol, Almeria, Spain.
[Economidou, D.; Mar, A. C.; Caprioli, D.; Theobald, D. E.; Fernando, A.; Robbins, T. W.; Dalley, Jeffrey W.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England.
[Economidou, D.; Mar, A. C.; Caprioli, D.; Theobald, D. E.; Fernando, A.; Robbins, T. W.; Dalley, Jeffrey W.] Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England.
[Newman, A. H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
[Dalley, Jeffrey W.] Univ Cambridge, Dept Psychiat, Cambridge CB2 2QQ, England.
RP Dalley, JW (reprint author), Univ Cambridge, Dept Psychol, Downing St, Cambridge CB2 3EB, England.
EM jwd20@cam.ac.uk
RI Lopez-Granero, Caridad/C-8316-2013;
OI Lopez-Granero, Caridad/0000-0001-7781-3497; Moreno,
Margarita/0000-0001-7336-6167
FU Medical Research Council [G0701500]; Ministerio de Ciencia e Innovacion
of Spain [PSI2009-08626]; MRC; Wellcome Trust; NIDA-IRP, NIH
FX This study was funded by grants from the Medical Research Council
(G0701500) and the Ministerio de Ciencia e Innovacion of Spain
(PSI2009-08626) and by a joint award from the MRC and Wellcome Trust in
support of the Behavioural and Clinical Neuroscience Institute at
Cambridge University. AHN was supported by the NIDA-IRP, NIH.
NR 55
TC 16
Z9 17
U1 0
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUL
PY 2013
VL 228
IS 1
BP 19
EP 30
DI 10.1007/s00213-013-3010-3
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 163VM
UT WOS:000320365100002
PM 23407782
ER
PT J
AU Sutherland, MT
Carroll, AJ
Salmeron, BJ
Ross, TJ
Stein, EA
AF Sutherland, Matthew T.
Carroll, Allison J.
Salmeron, Betty Jo
Ross, Thomas J.
Stein, Elliot A.
TI Insula's functional connectivity with ventromedial prefrontal cortex
mediates the impact of trait alexithymia on state tobacco craving
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Alexithymia; Craving; Nicotine; Varenicline; Resting-state functional
connectivity; Insula; Ventromedial prefrontal cortex; fMRI
ID IOWA GAMBLING TASK; DECISION-MAKING; EMOTIONAL INTELLIGENCE;
INDIVIDUAL-DIFFERENCES; INTEROCEPTIVE AWARENESS; MAINTAINING ABSTINENCE;
SMOKING-CESSATION; BRAIN ACTIVATION; CINGULATE CORTEX; NEGATIVE FACTOR
AB Alexithymia is a personality trait characterized by difficulty indentifying and describing subjective emotional experiences. Decreased aptitude in the perception, evaluation, and communication of affectively laden mental states has been associated with reduced emotion regulation, more severe drug craving in addicts, and structural/functional alterations in insula and anterior cingulate cortex (ACC). The insula and ACC represent sites of convergence between the putative neural substrates of alexithymia and those perpetuating cigarette smoking.
We examined the interrelations between alexithymia, tobacco craving, and insula/ACC neurocircuitry using resting-state functional connectivity (rsFC).
Overnight-deprived smokers (n = 24) and nonsmokers (n = 20) completed six neuroimaging assessments on different days both in the absence of, and following, varenicline and/or nicotine administration. In this secondary analysis of data from a larger study, we assessed trait alexithymia and state tobacco craving using self-reports and examined the rsFC of bilateral insular subregions (anterior, middle, posterior) and dorsal ACC.
Higher alexithymia in smokers predicted reduced rsFC strength between the right anterior insula (aI) and ventromedial prefrontal cortex (vmPFC). Higher alexithymia also predicted more severe tobacco craving during nicotine withdrawal. Critically, the identified aI-vmPFC circuit fully mediated this alexithymia-craving relation. That is, elevated alexithymia predicted decreased aI-vmPFC rsFC and, in turn, decreased aI-vmPFC rsFC predicted increased craving during withdrawal. A moderated mediation analysis indicated that this aI-vmPFC mediational effect was not observed following drug administration.
These results suggest that a weakened right aI-vmPFC functional circuit confers increased liability for tobacco craving during smoking abstinence. Individual differences in alexithymia and/or aI-vmPFC functional coupling may be relevant factors for smoking cessation success.
C1 [Sutherland, Matthew T.] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA.
[Sutherland, Matthew T.; Carroll, Allison J.; Salmeron, Betty Jo; Ross, Thomas J.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA.
[Sutherland, Matthew T.] Florida Int Univ, Dept Psychol, Deuxieme Maison, Miami, FL 33199 USA.
RP Sutherland, MT (reprint author), Florida Int Univ, Dept Psychol, Deuxieme Maison, RM 295,11299 SW 8th St, Miami, FL 33199 USA.
EM masuther@fiu.edu
RI Salmeron, Betty Jo/M-1793-2016;
OI Salmeron, Betty Jo/0000-0003-1699-9333; Ross, Thomas/0000-0002-7745-3572
FU National Institute on Drug Abuse Intramural Research Program, National
Institutes of Health, Department of Health and Human Services
(NIDA-IRP/NIH/DHHS)
FX This work was sponsored by the National Institute on Drug Abuse
Intramural Research Program, National Institutes of Health, Department
of Health and Human Services (NIDA-IRP/NIH/DHHS). We thank Eliscia
Smith, Angela Neal, Kimberly Slater, Loretta Spurgeon, Anita Signau and
the NIDA-IRP nurses, pharmacy, and recruitment staff for assistance with
data collection.
NR 103
TC 18
Z9 18
U1 3
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUL
PY 2013
VL 228
IS 1
BP 143
EP 155
DI 10.1007/s00213-013-3018-8
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 163VM
UT WOS:000320365100013
PM 23455594
ER
PT J
AU Kakiuchi-Kiyota, S
Crabbs, TA
Arnold, LL
Pennington, KL
Cook, JC
Malarkey, DE
Cohen, SM
AF Kakiuchi-Kiyota, Satoko
Crabbs, Torrie A.
Arnold, Lora L.
Pennington, Karen L.
Cook, Jon C.
Malarkey, David E.
Cohen, Samuel M.
TI Evaluation of Expression Profiles of Hematopoietic Stem Cell,
Endothelial Cell, and Myeloid Cell Antigens in Spontaneous and
Chemically Induced Hemangiosarcomas and Hemangiomas in Mice
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE mouse; hemangiosarcomas; hemangiomas; hematopoietic stem cells;
endothelial progenitor cells; immunohistochemistry
ID PROGENITOR CELLS; HUMAN RELEVANCE; FACTOR-VIII; P53; ANGIOSARCOMAS;
TROGLITAZONE; TUMORS; DIFFERENTIATION; PROLIFERATION; PRECURSORS
AB It is unclear whether the process of spontaneous and chemically induced hemangiosarcoma and hemangioma formation in mice involves the transformation of differentiated endothelial cells (ECs) or recruitment of multipotential bone marrow-derived hematopoietic stem cells or endothelial progenitor cells (EPCs), which show some degree of endothelial differentiation. In the present study, immunohistochemical staining for hematopoietic stem cell markers (CD45 and CD34), EC markers (vascular endothelial growth factor receptor 2 [VEGFR2], CD31, and factor VIII-related antigen), and a myeloid lineage marker (CD14) was employed to better define the origin of hemangiosarcomas and hemangiomas in mice. Staining was negative for CD45, factor VIII-related antigen, and CD14 and positive for CD34, VEGFR2, and CD31, indicating that mouse hemangiosarcomas and hemangiomas are composed of cells derived from EPCs expressing CD34, VEGFR2, and CD31 but not factor VIII-related antigen. The lack of CD45 expression suggests that mouse vascular tumors may arise from EPCs that are at a stage later than hematopoietic stem cells. Since factor VIII-related antigen expression is known to occur later than CD31 expression in EPCs, our observations may indicate that these tumor cells are arrested at a stage prior to complete differentiation. In addition, myeloid lineage cells do not appear to contribute to hemangiosarcoma and hemangioma formation in mice.
C1 [Kakiuchi-Kiyota, Satoko; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
[Kakiuchi-Kiyota, Satoko; Cook, Jon C.] Pfizer Inc, Drug Safety Res & Dev, Groton, CT 06340 USA.
[Crabbs, Torrie A.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
[Malarkey, David E.] NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Malarkey, David E.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Cohen, SM (reprint author), 983135 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM scohen@unmc.edu
FU Division of the National Toxicology Program of the NIH; National
Institute of Environmental Health Sciences
FX The authors gratefully acknowledge Dr. Norimitsu Shirai at Pfizer, Inc.,
for his pathological expertise and the individuals at EPL, Inc.: the
Histology Lab for retrieving the paraffin blocks and cutting sections,
the Photo Lab for taking photos of immunostaining, and Beth Mahler for
editing images. We also gratefully acknowledge the technical expertise
of Heather Jensen, Otis Lyght, Geoffrey Hurlburt, Yvette Rebolloso,
David Olson, Quashana Brown, and Natasha Clayton in the
Immunohistochemistry Lab of the Pathology Support Group of the Cellular
and Molecular Pathology Branch of the National Toxicology Program, NIEHS
for development of the methodology and performance of the
immunohistochemistry. Heather Jensen was particularly helpful
technically and in assisting in preparation of the manuscript. This
research was supported (in part) by the Division of the National
Toxicology Program of the NIH, National Institute of Environmental
Health Sciences. This article may be the work product of an employee or
group of employees of the National Institute of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH); however, the
statements, opinions, or conclusions contained therein do not
necessarily represent the statements, opinions, or conclusions of NIEHS,
NIH, or the U.S. government.
NR 41
TC 8
Z9 8
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JUL
PY 2013
VL 41
IS 5
BP 709
EP 721
DI 10.1177/0192623312464309
PG 13
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 169FK
UT WOS:000320764000002
PM 23125116
ER
PT J
AU Surh, I
Brix, A
French, JE
Collins, BJ
Sanders, JM
Vallant, M
Dunnick, JK
AF Surh, Inok
Brix, Amy
French, John E.
Collins, Bradley J.
Sanders, J. Michael
Vallant, Molly
Dunnick, June K.
TI Toxicology and Carcinogenesis Study of Senna in C3B6.129F1-Trp53
(tm1Brd) N12 Haploinsufficient Mice
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE senna; Trp53; carcinogenesis; toxicity; laxative; large intestine
ID TRANSGENIC MOUSE MODELS; ABERRANT CRYPT FOCI; ANTHRAQUINONE GLYCOSIDES;
CELL-PROLIFERATION; P53-DEFICIENT MICE; COLORECTAL-CANCER;
EATING-DISORDERS; LAXATIVE ABUSE; RAT COLON; IN-VITRO
AB Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes reduce sennosides to rhein-9-anthrone, the active form for the laxative effect. To determine the potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53(tm1Brd) N12 haploinsufficient (p53(+/-)) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed to up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53(+/-) mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53(+/-) males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53(+/-) mouse model. There was no neoplastic change when senna was administered to p53(+/-) mouse.
C1 [Surh, Inok; Brix, Amy; French, John E.; Collins, Bradley J.; Sanders, J. Michael; Vallant, Molly; Dunnick, June K.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Surh, Inok] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
RP Dunnick, JK (reprint author), NIEHS, POB 12233,MD K2-13, Res Triangle Pk, NC 27709 USA.
EM dunnickj@niehs.nih.gov
FU NIEHS [N01-ES-65406, N01-ES-55536]
FX This article may be the work product of an employee or group of
employees of the National Institute of Environmental Health Sciences
(NIEHS), National Institutes of Health (NIH). However, the statements,
opinions, or conclusions contained therein do not necessarily represent
the statements, opinions, or conclusions of NIEHS, NIH, or the U.S.
government. We greatly acknowledge the expert review by Ms. Kristine
Witt and Dr. Arun Pandiri. The in life phase of the study was conducted
under NIEHS contracts N01-ES-65406 and N01-ES-55536. The authors would
like to thank Drs. Milton Hejtmancik, Diane Gerken, Daphne Vasconcelos,
and other staff at Battelle Memorial Institute for helping to conduct
these studies.
NR 66
TC 0
Z9 0
U1 1
U2 16
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JUL
PY 2013
VL 41
IS 5
BP 770
EP 778
DI 10.1177/0192623312464304
PG 9
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 169FK
UT WOS:000320764000007
PM 23125117
ER
PT J
AU Xi, ZX
Li, X
Li, J
Peng, XQ
Song, R
Gaal, J
Gardner, EL
AF Xi, Zheng-Xiong
Li, Xia
Li, Jie
Peng, Xiao-Qing
Song, Rui
Gaal, Jozsef
Gardner, Eliot L.
TI Blockade of dopamine D-3 receptors in the nucleus accumbens and central
amygdala inhibits incubation of cocaine craving in rats
SO ADDICTION BIOLOGY
LA English
DT Article
DE Cocaine; craving; D-3 receptor; dopamine; drug seeking; incubation;
relapse; SB-277011A
ID SELF-ADMINISTERED COCAINE; INDUCED CONDITIONED LOCOMOTION; CUE-INDUCED
REINSTATEMENT; DRUG-SEEKING BEHAVIOR; BASOLATERAL AMYGDALA; DORSAL
STRIATUM; D-AMPHETAMINE; EXCITOTOXIC LESIONS; HUMAN BRAIN; EXTRACELLULAR
DOPAMINE
AB Cue-induced drug seeking progressively increases over time of withdrawal from drug self-administration in rats, a phenomenon called incubation of craving'. The underlying mechanisms have been linked to increased expression of brain-derived neurotrophic factor and GluR2-lacking AMPA receptors in the mesolimbic dopamine (DA) system and also to increased extracellular signal-regulated kinase activation in the central amygdala (CeA). However, it remains unclear whether any DA mechanism is also involved in incubation of craving. Recent research demonstrates that cue-induced cocaine seeking appears to parallel increased DA D3, but not D1 or D2, receptor expression in the nucleus accumbens (NAc) of rats over time of withdrawal, suggesting possible involvement of D3 receptors (D3Rs) in incubation of cocaine craving. Here, we report that systemic or local administration of SB-277011A, a highly selective D3R antagonist, into the NAc (core and shell) or the CeA, but not the dorsal striatum or basolateral amygdala, significantly inhibits expression of incubation of cocaine craving in rats after 2-30 days of withdrawal from previous cocaine self-administration but had no effect on sucrose-seeking behavior in rats after 10-30 days of withdrawal. These data suggest that DA D3Rs in both the NAc and the CeA play an important role in incubation of cocaine craving in rats and support the potential utility of D3R antagonists in the treatment of cocaine addiction.
C1 [Xi, Zheng-Xiong; Li, Xia; Li, Jie; Peng, Xiao-Qing; Song, Rui; Gardner, Eliot L.] NIDA, Intramural Res Program, Baltimore, MD USA.
RP Xi, ZX (reprint author), NIDA, Intramural Res Program, Baltimore, MD USA.
EM zxi@intra.nida.nih.gov
OI PENG, XIAOQING/0000-0002-7272-5428
FU US National Institute on Drug Abuse Intramural Research Program
FX This work was supported by the US National Institute on Drug Abuse
Intramural Research Program.
NR 82
TC 12
Z9 13
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JUL
PY 2013
VL 18
IS 4
BP 665
EP 677
DI 10.1111/j.1369-1600.2012.00486.x
PG 13
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 169IW
UT WOS:000320774700007
PM 22913325
ER
PT J
AU Hoofnagle, JH
Van Natta, ML
Kleiner, DE
Clark, JM
Kowdley, KV
Loomba, R
Neuschwander-Tetri, BA
Sanyal, AJ
Tonascia, J
AF Hoofnagle, J. H.
Van Natta, M. L.
Kleiner, D. E.
Clark, J. M.
Kowdley, K. V.
Loomba, R.
Neuschwander-Tetri, B. A.
Sanyal, A. J.
Tonascia, J.
CA Non-alcoholic Steatohepatitis
TI Vitamin E and changes in serum alanine aminotransferase levels in
patients with non-alcoholic steatohepatitis
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID FATTY LIVER-DISEASE; RANDOMIZED CONTROLLED-TRIAL; TERM-FOLLOW-UP;
E-DEFICIENCY; NATURAL-HISTORY; CANCER; PIOGLITAZONE; PREVENTION;
SUPPLEMENTATION; EPIDEMIOLOGY
AB Background Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury. Aim To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy. Methods The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reassessed for associations among changes in ALT levels, body weight and liver histology. An ALT response was defined as a decrease to 40U/L and by 30% of baseline. Liver biopsies taken before and after treatment were scored for non-alcoholic fatty liver disease activity (NAS) and fibrosis. Results ALT responses were more frequent among vitamin E (48%) than placebo (16%) recipients (P<0.001). Among vitamin E recipients, ALT responses were associated with decreases in NAS (P<0.001), but not fibrosis scores (P=0.34), whereas among placebo recipients, ALT responses were associated with significant decreases in both (P<0.05). Weight loss (2kg) was also associated with ALT response (P<0.001), improvements in NAS (P <0.001) and fibrosis (P<0.02), but vitamin E had an added effect both with and without weight loss. Weight gain (2kg) was associated with lack of ALT response and worsening NAS and fibrosis scores in patients not on vitamin E. Conclusions Decrease of ALT levels to normal in patients with NASH is usually associated with improved histological activity. Management should stress the value of weight loss and strongly discourage weight gain. Vitamin E can improve both ALT levels and histology with and without weight loss. Clinical Trial Number: NCT00063622.
C1 [Hoofnagle, J. H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD USA.
[Van Natta, M. L.; Clark, J. M.; Tonascia, J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kleiner, D. E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Kowdley, K. V.] Virginia Mason Med Ctr, Inst Digest Dis, Seattle, WA 98101 USA.
[Loomba, R.] Univ Calif San Diego, Div Gastroenterol & Epidemiol, San Diego, CA 92103 USA.
[Neuschwander-Tetri, B. A.] St Louis Univ, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA.
[Sanyal, A. J.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA.
RP Hoofnagle, JH (reprint author), NIH, Room 644,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM HoofnagleJ@extra.niddk.nih.gov
RI Vaughn, Ivana/B-6138-2016;
OI Vaughn, Ivana/0000-0002-7201-0289; Kleiner, David/0000-0003-3442-4453
FU Daiichi Sankyo Inc.; Bayer-Onxy; Exhalenz; Genentech; Gilead; Gore;
Ikaria; Intercept; Salix; National Institute of Diabetes and Digestive
and Kidney Diseases [U01DK061718, U01DK061728, U01DK061731, U01DK061732,
U01DK061734, U01DK061737, U01DK0 61738, U01DK061730, U01DK061713];
General Clinical Research Centers or Clinical and Translational Science
Awards [UL1RR024989, UL1RR025761, M01RR00188, UL1RR 024131, UL1RR025014,
UL1RR031990, UL1RR025741, UL1RR029887, UL1RR24156, UL1RR025055, UL1RR
031980]; National Institute of Child Health and Human Development
(NICHD); National Cancer (NCI); NIDDK; Takeda Pharmaceuticals North
America; Pharmavite
FX Declaration of personal interests: JHH, MLVN, DEK, JMC, KVK, RL, BANT
and JT have no conflicts of interest to report. RL serves as a
consultant to Gilead, Corgenix and Daiichi Sankyo Inc and has received
research grant support from Daiichi Sankyo Inc. AJS serves as a
consultant to Abbott, Genfit, Ikaria, Merck, Norgene, Salix and Roche
and has research grant support from Bayer-Onxy, Exhalenz, Genentech,
Gilead, Gore, Ikaria, Intercept and Salix and receives royalties from
Uptodate. Declaration of funding interests: The NASH CRN is a
multicentre prospective study of the natural history and treatment of
non-alcoholic steatohepatitis funded as a cooperative agreement by the
National Institute of Diabetes and Digestive and Kidney Diseases (Grant
numbers: U01DK061718, U01DK061728, U01DK061731, U01DK061732,
U01DK061734, U01DK061737, U01DK0 61738, U01DK061730, U01DK061713). In
conduct of the NASH CRN studies, several clinical centres use support
from General Clinical Research Centers or Clinical and Translational
Science Awards (Grant numbers: UL1RR024989, UL1RR025761, M01RR00188,
UL1RR 024131, UL1RR025014, UL1RR031990, UL1RR025741, UL1RR029887,
UL1RR24156, UL1RR025055, UL1RR 031980). Further support is provided by
the National Institute of Child Health and Human Development (NICHD) and
by the intramural programme of the National Cancer (NCI). The PIVENS
trial was conducted by the NASH CRN and supported in part by
Collaborative Research and Development Agreement (CRADA) between NIDDK
and Takeda Pharmaceuticals North America (for pioglitazone and placebo
tablets and for additional financial support) and a Clinical Trial
Agreement between NIDDK and Pharmavite (for vitamin E and placebo
capsules). Full membership of the NASH CRN is listed in the Table S1.
NR 27
TC 47
Z9 49
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JUL
PY 2013
VL 38
IS 2
BP 134
EP 143
DI 10.1111/apt.12352
PG 10
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 165GV
UT WOS:000320472400006
PM 23718573
ER
PT J
AU Consonni, D
Matteis, SD
Pesatori, AC
Cattaneo, A
Cavallo, DM
Lubin, JH
Tucker, M
Bertazzi, PA
Caporaso, NE
Wacholder, S
Landi, MT
AF Consonni, Dario
Matteis, Sara De
Pesatori, Angela C.
Cattaneo, Andrea
Cavallo, Domenico M.
Lubin, Jay H.
Tucker, Margaret
Bertazzi, Pier Alberto
Caporaso, Neil E.
Wacholder, Sholom
Landi, Maria Teresa
TI Increased lung cancer risk among bricklayers in an italian
population-based case-control study (vol 55, pg 423, 2012)
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Correction
C1 Dept Prevent Med, Epidemiol Unit, Fondazione IRCCS Ca Granda Osped Maggiore Policli, Milan, Italy.
Univ Studi Milano, Dept Occupat & Environm Hlth, Milan, Italy.
Univ Studi dellInsubria, Dept Chem & Environm Sci, Como, Italy.
Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA.
RP Consonni, D (reprint author), Dept Prevent Med, Epidemiol Unit, Fondazione IRCCS Ca Granda Osped Maggiore Policli, Via San Barnaba, I-820122 Milan, Italy.
RI Cavallo, Domenico Maria/F-9881-2013; Tucker, Margaret/B-4297-2015;
Consonni, Dario/K-7943-2016; bertazzi, pietro alberto/D-5039-2017
OI Cavallo, Domenico Maria/0000-0003-1853-2999; Consonni,
Dario/0000-0002-8935-3843; bertazzi, pietro alberto/0000-0003-3475-2449
NR 1
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
J9 AM J IND MED
JI Am. J. Ind. Med.
PD JUL
PY 2013
VL 56
IS 7
BP 825
EP 825
DI 10.1002/ajim.22154
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 165GM
UT WOS:000320471400010
ER
PT J
AU Gilbert, JR
Pillai, AS
Horwitz, B
AF Gilbert, Jessica R.
Pillai, Ajay S.
Horwitz, Barry
TI Assessing crossmodal matching of abstract auditory and visual stimuli in
posterior superior temporal sulcus with MEG
SO BRAIN AND COGNITION
LA English
DT Article
DE Crossmodal matching; Audio-visual processing; pSTS;
Magnetoencephalography
ID MULTISENSORY INTEGRATION; AUDIOVISUAL SPEECH; BRAIN OSCILLATIONS;
MEMORY; CORTEX; FMRI; TIME; MAGNETOENCEPHALOGRAPHY; SYNCHRONIZATION;
INFORMATION
AB Associating crossmodal auditory and visual stimuli is an important component of perception, with the posterior superior temporal sulcus (pSTS) hypothesized to support this. However, recent evidence has argued that the pSTS serves to associate two stimuli irrespective of modality. To examine the contribution of pSTS to crossmodal recognition, participants (N = 13) learned 12 abstract, non-linguistic pairs of stimuli over 3 weeks. These paired associates comprised four types: auditory-visual (AV), auditory-auditory (AA), visual-auditory (VA), and visual-visual (VV). At week four, participants were scanned using magnetoencephalography (MEG) while performing a correct/incorrect judgment on pairs of items. Using an implementation of synthetic aperture magnetometry that computes real statistics across trials (SAMspm), we directly contrasted crossmodal (AV and VA) with unimodal (AA and VV) pairs from stimulus-onset to 2 s in theta (4-8 Hz), alpha (9-15 Hz), beta (16-30 Hz), and gamma (31-50 Hz) frequencies. We found pSTS showed greater desynchronization in the beta frequency for crossmodal compared with unimodal trials, suggesting greater activity during the crossmodal pairs, which was not influenced by congruency of the paired stimuli. Using a sliding window SAM analysis, we found the timing of this difference began in a window from 250 to 750 ms after stimulus-onset. Further, when we directly contrasted all sub-types of paired associates from stimulus-onset to 2 s, we found that pSTS seemed to respond to dynamic, auditory stimuli, rather than crossmodal stimuli per se. These findings support an early role for pSTS in the processing of dynamic, auditory stimuli, and do not support claims that pSTS is responsible for associating two stimuli irrespective of their modality. Published by Elsevier Inc.
C1 [Gilbert, Jessica R.; Pillai, Ajay S.; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, Bethesda, MD 20892 USA.
RP Gilbert, JR (reprint author), Natl Inst Deafness & Other Commun Disorders NIDCD, NIH, Brain Imaging & Modeling Sect, 10 Ctr Dr,Room 5039, Bethesda, MD 20892 USA.
EM jessica.gilbert@nih.gov
FU National Institute on Deafness and Other Communication Disorders of the
National Institutes of Health
FX This work was supported by the intramural program of the National
Institute on Deafness and Other Communication Disorders of the National
Institutes of Health. The authors thank Tom Holroyd, Fred Carver, and
Jason Smith for technical advice and helpful discussions.
NR 37
TC 0
Z9 0
U1 1
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0278-2626
J9 BRAIN COGNITION
JI Brain Cogn.
PD JUL
PY 2013
VL 82
IS 2
BP 161
EP 170
DI 10.1016/j.bandc.2013.03.004
PG 10
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 160WZ
UT WOS:000320152500005
PM 23665947
ER
PT J
AU Zhou, Q
Gil-Krzewska, A
Peruzzi, G
Borrego, F
AF Zhou, Q.
Gil-Krzewska, A.
Peruzzi, G.
Borrego, F.
TI Matrix metalloproteinases inhibition promotes the polyfunctionality of
human natural killer cells in therapeutic antibody-based anti-tumour
immunotherapy
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Article
DE monoclonal antibody; NK cell; polyfunctionality; tumour immunotherapy
ID VIRUS TYPE-1 INFECTION; IFN-GAMMA; TUMOR-DEVELOPMENT; FC-RECEPTORS; NK
CELLS; T-CELLS; IN-VIVO; IGG FC; CD16; CANCER
AB Activation of human natural killer (NK) cells is associated with the cleavage of CD16 from the cell surface, a process mediated by matrix metalloproteinases (MMPs). In this report, we examined whether inhibition of MMPs would lead to improved NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) function. Using an in-vitroADCC assay, we tested the anti-tumour function of NK cells with three different therapeutic monoclonal antibodies (mAbs) in the presence of MMPs inhibitor GM6001 or its control. Loss of CD16 was observed when NK cells were co-cultured with tumour targets in the presence of specific anti-tumour antibodies, and was found particularly on the majority of degranulating NK responding cells. Treatment with MMPs inhibitors not only prevented CD16 down-regulation, but improved the quality of the responding cells significantly, as shown by an increase in the percentage of polyfunctional NK cells that are capable of both producing cytokines and degranulation. Furthermore, MMPs inhibition resulted in augmented and sustained CD16-mediated signalling, as shown by increased tyrosine phosphorylation of CD3 and other downstream signalling intermediates, which may account for the improved NK cell function. Collectively, our results provide a foundation for combining MMPs inhibitors and therapeutic mAbs in new clinical trials for cancer treatment.
C1 [Zhou, Q.; Gil-Krzewska, A.; Borrego, F.] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, OBP,CDER, Bethesda, MD 20892 USA.
[Peruzzi, G.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, Rockville, MD USA.
RP Borrego, F (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, OBP,CDER, Bldg 29B,Room 3NN18,29 Lincoln Dr,HFD 123, Bethesda, MD 20892 USA.
EM Francisco.BorregoRabasco@osakidetza.net
OI Peruzzi, Giovanna/0000-0002-6517-9107
FU US Food and Drug Administration; NCI-FDA Interagency Oncology Task Force
fellowship programme
FX This work was supported by the intramural programme of the US Food and
Drug Administration and by the NCI-FDA Interagency Oncology Task Force
fellowship programme. The authors would like to thank Dr Wen Jin Wu and
Dr Milos Dokmanovic for their generous gift of trastuzumab.
NR 42
TC 20
Z9 20
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD JUL
PY 2013
VL 173
IS 1
BP 131
EP 139
DI 10.1111/cei.12095
PG 9
WC Immunology
SC Immunology
GA 159GA
UT WOS:000320032400015
PM 23607800
ER
PT J
AU Chinn, IK
Milner, JD
Scheinberg, P
Douek, DC
Markert, ML
AF Chinn, I. K.
Milner, J. D.
Scheinberg, P.
Douek, D. C.
Markert, M. L.
TI Thymus transplantation restores the repertoires of forkhead box protein
3 (FoxP3)+ and FoxP3-T cells in complete DiGeorge anomaly
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Article
DE DiGeorge; FoxP3; repertoire; thymus; transplantation
ID REGULATORY T-CELLS; EXPRESSION; IMMUNODEFICIENCY; ENTEROPATHY
AB The development of T cells with a regulatory phenotype after thymus transplantation has not been examined previously in complete DiGeorge anomaly (cDGA). Seven athymic infants with cDGA and non-maternal pretransplantation T cell clones were assessed. Pretransplantation forkhead box protein 3 (Foxp3)+ T cells were detected in five of the subjects. Two subjects were studied in greater depth. T cell receptor variable chain (TCR-V) expression was assessed by flow cytometry. In both subjects, pretransplantation FoxP3+ and total CD4+ T cells showed restricted TCR-V expression. The development of naive T cells and diverse CD4+ TCR-V repertoires following thymic transplantation indicated successful thymopoiesis from the thymic tissue grafts. Infants with atypical cDGA develop rashes and autoimmune phenomena before transplantation, requiring treatment with immunosuppression, which was discontinued successfully subsequent to the observed thymopoiesis. Post-transplantation, diverse TCR-V family expression was also observed in FoxP3+ CD4+ T cells. Interestingly, the percentages of each of the TCR-V families expressed on FoxP3+ and total CD4+ T cells differed significantly between these T lymphocyte subpopulations before transplantation. By 16 months post-transplantation, however, the percentages of expression of each TCR-V family became significantly similar between FoxP3+ and total CD4+ T cells. Sequencing of TCRBV DNA confirmed the presence of clonally amplified pretransplantation FoxP3+ and FoxP3- T cells. After thymus transplantation, increased polyclonality was observed for both FoxP3+ and FoxP3- cells, and pretransplantation FoxP3+ and FoxP3- clonotypes essentially disappeared. Thus, post-transplantation thymic function was associated with the development of a diverse repertoire of FoxP3+ T cells in cDGA, corresponding with immunological and clinical recovery.
C1 [Chinn, I. K.; Markert, M. L.] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA.
[Markert, M. L.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
[Milner, J. D.] NIAID, Lab Allerg Dis, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Scheinberg, P.; Douek, D. C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Scheinberg, P.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Chinn, IK (reprint author), Duke Univ, Med Ctr, Box 103020, Durham, NC 27710 USA.
EM chinn001@mc.duke.edu
OI Scheinberg, Phillip/0000-0002-9047-4538
FU American Academy of Allergy, Asthma and Immunology Senior
Allergy/Immunology Fellow Transition Award; NIH [R01 AI 047040, R01 AI
054843, M03 RR 30, T32 AI 007062 28A2, 2 K12 HD043494 06]; National
Institute of Allergy and Infectious Diseases
FX This work was supported by the American Academy of Allergy, Asthma and
Immunology 2008 Senior Allergy/Immunology Fellow Transition Award and
NIH grants R01 AI 047040, R01 AI 054843, M03 RR 30 (General Clinical
Research Center, National Center for Research Resources), T32 AI 007062
28A2 and 2 K12 HD043494 06. This effort was also supported by the
intramural research programme of the National Institute of Allergy and
Infectious Diseases. The authors appreciate the assistance of Dr J.
Michael Cook of the Duke Comprehensive Cancer Center flow cytometry
facility in processing samples. The statistical support provided by Dr
Yi-Ju Li of the Duke Translational Medicine Institute is kindly
acknowledged. The authors express gratitude to Dr Gregory D. Sempowski
of the Duke Human Vaccine Institute for assistance with reviewing the
manuscript. The authors thank Dr Blythe H. Devlin, Jie Li, Chia-San
Hsieh, Dr Bin Li, Stephanie E. Gupton, Elizabeth A. McCarthy, Michele E.
Cox and Judy Stelling for technical, laboratory and clinical research
support. The clinical care of the subjects provided by the Duke
Pediatric Allergy and Immunology faculty and fellows is appreciated. The
authors are grateful for the efforts of the referring physicians in
obtaining and sending blood samples and data for the research.
NR 32
TC 8
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD JUL
PY 2013
VL 173
IS 1
BP 140
EP 149
DI 10.1111/cei.12088
PG 10
WC Immunology
SC Immunology
GA 159GA
UT WOS:000320032400016
PM 23607606
ER
PT J
AU Zhao, Z
Moley, KH
Gronowski, AM
AF Zhao, Zhen
Moley, Kelle H.
Gronowski, Ann M.
TI Diagnostic potential for miRNAs as biomarkers for pregnancy-specific
diseases
SO CLINICAL BIOCHEMISTRY
LA English
DT Review
DE miRNA; Pregnancy; Biomarker
ID RECURRENT SPONTANEOUS-ABORTION; CIRCULATING MICRORNAS; MATERNAL
CIRCULATION; ECTOPIC PREGNANCY; HUMAN PLACENTAS; UNITED-STATES;
PREECLAMPSIA; EXPRESSION; PLASMA; GROWTH
AB Discovery of circulating miRNAs in maternal blood has not only facilitated the understanding of their role in normal pregnancy, but also paved new avenues for biomarker discovery to detect pregnancy-associated complications, such as preeclampsia, ectopic pregnancy, gestational diabetes mellitus, fetal growth restriction, recurrent pregnancy loss, and preterm delivery. In this review, we summarize the studies to date of miRNAs in maternal circulation and placental tissue in human. This brief review does not cover all aspects of this intriguing field but focuses on some new and interesting findings of diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases. (C) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
C1 [Zhao, Zhen] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Moley, Kelle H.; Gronowski, Ann M.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
[Gronowski, Ann M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
RP Gronowski, AM (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, Box 8118,660 S Euclid, St Louis, MO 63110 USA.
EM gronowski@wustl.edu
NR 47
TC 31
Z9 32
U1 3
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0009-9120
J9 CLIN BIOCHEM
JI Clin. Biochem.
PD JUL
PY 2013
VL 46
IS 10-11
SI SI
BP 953
EP 960
DI 10.1016/j.clinbiochem.2013.01.026
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 163PS
UT WOS:000320350000015
PM 23396163
ER
PT J
AU Roux, A
Mourin, G
Fastenackels, S
Almeida, JR
Iglesias, MC
Boyd, A
Gostick, E
Larsen, M
Price, DA
Sacre, K
Douek, DC
Autran, B
Picard, C
de Miranda, S
Sauce, D
Stern, M
Appay, V
AF Roux, Antoine
Mourin, Gisele
Fastenackels, Solene
Almeida, Jorge R.
Iglesias, Maria Candela
Boyd, Anders
Gostick, Emma
Larsen, Martin
Price, David A.
Sacre, Karim
Douek, Daniel C.
Autran, Brigitte
Picard, Clement
de Miranda, Sandra
Sauce, Delphine
Stern, Marc
Appay, Victor
TI CMV driven CD8(+) T-cell activation is associated with acute rejection
in lung transplantation
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Cytomegalovirus; T-lymphocyte; Immune activation; Lung transplantation;
Acute rejection
ID CYTOMEGALOVIRUS-SPECIFIC CD4(+); ALLOGRAFT-REJECTION; PREVENT
CYTOMEGALOVIRUS; ANTIGEN-EXPRESSION; IMMUNE-RESPONSE; INFECTION;
RECIPIENTS; DISEASE; DIFFERENTIATION; LYMPHOCYTES
AB Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Roux, Antoine; Mourin, Gisele; Fastenackels, Solene; Iglesias, Maria Candela; Larsen, Martin; Sacre, Karim; Autran, Brigitte; Sauce, Delphine; Appay, Victor] Univ Paris 06, Hop La Pitie Salpetriere, INSERM, UMR S 945, F-75013 Paris, France.
[Roux, Antoine; Picard, Clement; de Miranda, Sandra; Stern, Marc] Hop Foch, Serv Pneumol, F-92151 Suresnes, France.
[Almeida, Jorge R.; Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Boyd, Anders] Univ Paris 06, Hop St Antoine, INSERM, UMR S 707, F-75012 Paris, France.
[Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[Autran, Brigitte; Appay, Victor] Grp Hosp Pitie Salpetriere, AP HP, Lab Immunol Cellulaire & Tissulaire, F-75013 Paris, France.
RP Roux, A (reprint author), Hop La Pitie Salpetriere, INSERM, U945, F-75013 Paris, France.
EM a.roux@hopital-foch.org; victor.appay@upmc.fr
RI Price, David/C-7876-2013; sauce, delphine/H-1990-2014; Larsen,
Martin/A-7316-2014;
OI Price, David/0000-0001-9416-2737; sauce, delphine/0000-0003-4596-7373;
Larsen, Martin/0000-0003-1375-4816; Ramos de Almeida,
Jorge/0000-0002-5009-8478; STERN, Marc/0000-0001-5275-6959
FU Vaincre la Mucoviscidose (VLM); National Institutes of Allergy and
Infectious Diseases; Fondation pour la Recherche Medicate (FRM)
FX This work was supported by Vaincre la Mucoviscidose (VLM), as well as by
the Intramural Program of the National Institutes of Allergy and
Infectious Diseases (DCD and JRA). AR is supported by VLM and the
Fondation pour la Recherche Medicate (FRM).
NR 55
TC 7
Z9 8
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD JUL
PY 2013
VL 148
IS 1
BP 16
EP 26
DI 10.1016/j.clim.2013.03.012
PG 11
WC Immunology
SC Immunology
GA 164RN
UT WOS:000320427300003
PM 23644452
ER
PT J
AU Degheidy, HA
Gadalla, SM
Farooqui, MZH
Abbasi, F
Arthur, DC
Bauer, SR
Wilson, WH
Wiestner, A
Stetler-Stevenson, MA
Marti, GE
AF Degheidy, Heba A.
Gadalla, Shahinaz M.
Farooqui, Mohammed Z. H.
Abbasi, Fatima
Arthur, Diane C.
Bauer, Steven R.
Wilson, Wyndham H.
Wiestner, Adrian
Stetler-Stevenson, M. A.
Marti, Gerald E.
TI Bcl-2 level as a biomarker for 13q14 deletion in CLL
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
DE chronic lymphocytic leukemia; Bcl-2; flow cytometry; del 13q14;
hemizygous; homozygous deletion
ID CHRONIC-LYMPHOCYTIC-LEUKEMIA; B-CELLS; EXPRESSION; APOPTOSIS; MICRORNAS;
SURVIVAL; ASSOCIATION; GENES; RNA; ACCUMULATION
AB Background Deletion 13q14.3 is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL). Previously it was reported that miR-15/16 is the target of 13q14 deletions and plays a tumor suppressor role by suppressing Bcl-2. Therefore, Bcl-2 expression was examined more closely to determine whether it would predict 13q14 deletion status. Methods A multi-color flow panel consisting of anti-Bcl-2/anti-lambda/anti-kappa/CD19/CD5/CD3/CD20 was performed. The ability of Bcl-2 to predict 13q14 deletion was tested using the conventional Bcl-2 index (c-index): mean fluorescence intensity (MFI) of CLL clone/MFI of residual T cells. Fifty-four untreated CLL/MBL patients were studied. Bimodal Bcl-2 expression was evaluated to test the ability of Bcl-2 to detect intraclonal heterogeneity. Other CLL prognostic markers including CD38, CD49d, CD26, and CD69 were evaluated. FISH was performed on selected sorted populations. Results The Bcl-2 c-index strongly predicts del13q14 P < 0.0001. A statistically significant association was observed between the percentage of cells carrying the deletion and the level of Bcl-2 expression P < 0.05. Cells sorted based on Bcl-2 expression showed enrichment of both hemizygous and homozygous del 13q14 cells. Also, we observed that an alteration in Bcl-2 level over time predicts changes in 13q14 deletion status. And a statistically significant correlation between the bimodal pattern of CD69 expression and the presence of 13q14 deletion was found P < 0.0001. Conclusion Bcl-2 expression using the c-index strongly predicts 13q14 deletion and can be used to distinguish homozygous, heterozygous, and diploid CLL clonal cells. Further systematic studies of this biomarker are needed for confirmation and expansion of these findings. Published 2013 Wiley-Periodicals, Inc.
C1 [Degheidy, Heba A.; Abbasi, Fatima; Bauer, Steven R.; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Degheidy, Heba A.; Marti, Gerald E.] Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Gadalla, Shahinaz M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Arthur, Diane C.; Stetler-Stevenson, M. A.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Wilson, Wyndham H.] NCI, Metab Branch, Bethesda, MD 20892 USA.
RP Marti, GE (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM gemarti@mac.com
OI Bauer, Steven/0000-0003-2831-846X
FU Oak Ridge Institute for Science and Education through US DOE; Oak Ridge
Institute for Science and Education through US FDA; National, Heart,
Lung and Blood Institute, National Institutes of Health and the National
Cancer Institute
FX Grant sponsor: Oak Ridge Institute for Science and Education through US
DOE and US FDA (Heba Degheidy's appointment to the Research
Participation Program at CBER); Intramural Research Program of the
National, Heart, Lung and Blood Institute, National Institutes of Health
and the National Cancer Institute.
NR 39
TC 6
Z9 7
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD JUL-AUG
PY 2013
VL 84B
IS 4
BP 237
EP 247
DI 10.1002/cyto.b.21090
PG 11
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 168VC
UT WOS:000320732900006
PM 23674504
ER
PT J
AU Paul, R
Minniti, CP
Nouraie, M
Luchtman-Jones, L
Campbell, A
Rana, S
Onyekwere, O
Darbari, DS
Ajayi, O
Arteta, M
Ensing, G
Sable, C
Dham, N
Kato, GJ
Gladwin, MT
Castro, OL
Gordeuk, VR
AF Paul, Rabindra
Minniti, Caterina P.
Nouraie, Mehdi
Luchtman-Jones, Lori
Campbell, Andrew
Rana, Sohail
Onyekwere, Onyinye
Darbari, Deepika S.
Ajayi, Olaid
Arteta, Manuel
Ensing, Gregory
Sable, Craig
Dham, Niti
Kato, Gregory J.
Gladwin, Mark T.
Castro, Oswaldo L.
Gordeuk, Victor R.
TI Clinical correlates of acute pulmonary events in children and
adolescents with sickle cell disease
SO EUROPEAN JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE sickle cell disease; acute chest syndrome; vaso-occlusive crisis;
asthma; pain
ID ACUTE CHEST SYNDROME; REGURGITANT JET VELOCITY;
SOCIETY-OF-ECHOCARDIOGRAPHY; RISK-FACTORS; TASK-FORCE; HYPERTENSION;
ANEMIA; ASTHMA; COMPLICATIONS; ASSOCIATION
AB Objectives We aimed to identify risk factors for acute pulmonary events in children and adolescents in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study. Methods Patients with hemoglobin SS (n=376) and other sickle cell genotypes (n=127) aged 3-20yrs were studied at four centers in a cross-sectional manner. A subgroup (n=293) was followed for a median of 21months (range 9-35). Results A patient-reported history of one or more acute pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in 195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By logistic regression, history of acute pulmonary events was independently associated with patient-reported history of asthma (P<0.0001), older age (P=0.001), >3 severe pain episodes in the preceding 12months (P=0.002), higher tricuspid regurgitation velocity (TRV) (P=0.028), and higher white blood cell (WBC) count (P=0.043) among hemoglobin SS patients. History of acute pulmonary events was associated with >3 severe pain episodes (P=0.009) among patients with other genotypes. During follow-up, 43 patients (15%) had at least one new ACS episode including 11 without a baseline history of acute pulmonary events. History of acute pulmonary events (odds ratio 5.0; P<0.0001) and younger age (odds ratio 0.9; P=0.007) were independently associated with developing a new episode during follow-up. Conclusions Asthma history, frequent pain, and higher values for TRV and WBC count were independently associated with history of acute pulmonary events in hemoglobin SS patients and frequent pain was associated in those with other genotypes. Measures to reduce pain episodes and control asthma may help to decrease the incidence of acute pulmonary events in SCD.
C1 [Paul, Rabindra; Nouraie, Mehdi; Rana, Sohail; Onyekwere, Onyinye; Ajayi, Olaid; Castro, Oswaldo L.] Howard Univ, Washington, DC 20059 USA.
[Minniti, Caterina P.; Darbari, Deepika S.; Kato, Gregory J.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Luchtman-Jones, Lori; Darbari, Deepika S.; Sable, Craig; Dham, Niti] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Campbell, Andrew; Arteta, Manuel; Ensing, Gregory] Univ Michigan, Ann Arbor, MI 48109 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA.
[Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Gordeuk, Victor R.] Univ Illinois, Chicago, IL 60612 USA.
RP Gordeuk, VR (reprint author), Univ Illinois, Sickle Cell Ctr M C 712, Suite 172,Clin Sci Bldg,820 South Wood St, Chicago, IL 60612 USA.
EM vgordeuk@uic.edu
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU NHLBI [2 R25 HL003679-08, 1 R01 HL079912-02]; Howard University GCRC
from NCRR, NIH, Bethesda, MD [2MOI RR10284-10]; NIH [1 ZIA HL006016-03]
FX Supported in part by grant nos. 2 R25 HL003679-08 and 1 R01 HL079912-02
from NHLBI, by Howard University GCRC grant no 2MOI RR10284-10 from
NCRR, NIH, Bethesda, MD, and by NIH intramural funding 1 ZIA
HL006016-03.
NR 38
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0902-4441
J9 EUR J HAEMATOL
JI Eur. J. Haematol.
PD JUL
PY 2013
VL 91
IS 1
BP 62
EP 68
DI 10.1111/ejh.12118
PG 7
WC Hematology
SC Hematology
GA 168QO
UT WOS:000320720800008
PM 23560516
ER
PT J
AU Orjuela-Sanchez, P
Sa, JM
Brandi, MCC
Rodrigues, PT
Bastos, MS
Amaratunga, C
Duong, S
Fairhurst, RM
Ferreira, MU
AF Orjuela-Sanchez, Pamela
Sa, Juliana M.
Brandi, Michelle C. C.
Rodrigues, Priscila T.
Bastos, Melissa S.
Amaratunga, Chanaki
Duong, Socheat
Fairhurst, Rick M.
Ferreira, Marcelo U.
TI Higher microsatellite diversity in Plasmodium vivax than in sympatric
Plasmodium falciparum populations in Pursat, Western Cambodia
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Plasmodium vivax; Plasmodium falciparum; Population structure; Genetic
diversity; Microsatellites
ID GENETIC DIVERSITY; RURAL AMAZONIA; MALARIA; INFECTIONS; MARKERS;
DYNAMICS; SAMPLES; REGION; PREVALENCE; FREQUENCY
AB Previous microsatellite analyses of sympatric populations of Plasmodium vivax and Plasmodium falciparum in Brazil revealed higher diversity in the former species. However, it remains unclear whether regional species-specific differences in prevalence and transmission levels might account for these findings. Here, we examine sympatric populations of P. vivax (n = 87) and P. falciparum (n = 164) parasites from Pursat province, Western Cambodia, where both species are similarly prevalent. Using 10 genome-wide microsatellites for P. falciparum and 13 for P. vivax, we found that the P. vivax population was more diverse than the sympatric P. falciparum population (average virtual heterozygosity [H-E], 0.87 vs. 0.66, P = 0.003), with more multiple-clone infections (89.6% vs. 47.6%) and larger mean number of alleles per marker (16.2 vs. 11.1, P = 0.07). Both populations showed significant multi-locus linkage disequilibrium suggestive of a predominantly clonal mode of parasite reproduction. The higher microsatellite diversity found in P. vivax isolates, compared to sympatric P. falciparum isolates, does not necessarily result from local differences in transmission level and may reflect differences in population history between species or increased mutation rates in P. vivax. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Orjuela-Sanchez, Pamela; Brandi, Michelle C. C.; Rodrigues, Priscila T.; Bastos, Melissa S.; Ferreira, Marcelo U.] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, Brazil.
[Orjuela-Sanchez, Pamela] La Jolla Bioengn Inst, San Diego, CA USA.
[Sa, Juliana M.; Amaratunga, Chanaki; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Duong, Socheat] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
RP Ferreira, MU (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, Brazil.
EM muferrei@usp.br
RI Ferreira, Marcelo/G-8289-2011
OI Ferreira, Marcelo/0000-0002-5293-9090
FU National Institutes of Health (NIH) [RO1 AI 075416]; Conselho Nacional
de Desenvolvimento Cientifico e Tecnologico (CNPq) [470570/2006-7];
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
[07/51199-0]; National Institute of Allergy and Infectious Diseases
(NIAID), NIH; CNPq; FAPESP
FX This research was supported by funds from the National Institutes of
Health (NIH) Grant RO1 AI 075416 to M.U.F., the Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq) Grant 470570/2006-7 to
M.U.F. and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
(FAPESP) Grant 07/51199-0 to M.U.F. This study was supported in part by
funds from the Intramural Research Program of the National Institute of
Allergy and Infectious Diseases (NIAID), NIH, provided to R.M.F. P.O.S.
and M.U.F. received scholarships from CNPq, and P.T.R. received a
scholarship from FAPESP. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. We thank the patients from Pursat province for their
cooperation, and Seila Suon and Sokunthea Sreng for their collaborative
efforts in Pursat. We also thank Carmen S. A. Takata, Marcio M.
Yamamoto, Erika S. Phelps and Michael A. Krause for laboratory and
analytical support.
NR 41
TC 21
Z9 21
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 0014-4894
J9 EXP PARASITOL
JI Exp. Parasitol.
PD JUL
PY 2013
VL 134
IS 3
BP 318
EP 326
DI 10.1016/j.exppara.2013.03.029
PG 9
WC Parasitology
SC Parasitology
GA 165JX
UT WOS:000320481300009
PM 23562882
ER
PT J
AU Egervari, K
Potter, G
Guzman-Hernandez, ML
Salmon, P
Balla, T
Wehrle-Haller, B
Kiss, JZ
AF Egervari, K.
Potter, G.
Guzman-Hernandez, M. -L.
Salmon, P.
Balla, T.
Wehrle-Haller, B.
Kiss, J. Z.
TI INTRACELLULAR TRAFFICKING, MATRIX ASSOCIATION AND FUNCTION OF VEGF IN
ASTROGLIAL CELLS
SO GLIA
LA English
DT Meeting Abstract
CT 11th European Meeting on Glial Cell Function in Health and Disease
CY JUL 03-06, 2013
CL Berlin, GERMANY
C1 [Egervari, K.; Potter, G.; Salmon, P.; Wehrle-Haller, B.; Kiss, J. Z.] Univ Geneva, Geneva, Switzerland.
[Guzman-Hernandez, M. -L.; Balla, T.] NICHHD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-1491
J9 GLIA
JI Glia
PD JUL
PY 2013
VL 61
SU 1
BP S88
EP S88
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 164KQ
UT WOS:000320408400273
ER
PT J
AU Fields, RD
AF Fields, R. D.
TI REGULATION OF SCHWANN CELL DEVELOPMENT AND MYELINATION BY ACTION
POTENTIALS
SO GLIA
LA English
DT Meeting Abstract
CT 11th European Meeting on Glial Cell Function in Health and Disease
CY JUL 03-06, 2013
CL Berlin, GERMANY
C1 [Fields, R. D.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-1491
J9 GLIA
JI Glia
PD JUL
PY 2013
VL 61
SU 1
BP S47
EP S47
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 164KQ
UT WOS:000320408400144
ER
PT J
AU Gao, H
Zhou, H
Hong, JS
AF Gao, H.
Zhou, H.
Hong, J. -S.
TI PATTERN RECOGNITION-RELATED INFLAMMATORY OXIDATIVE INSULT FROM MICROGLIA
MEDIATES CHRONIC NEURODEGENERATION
SO GLIA
LA English
DT Meeting Abstract
CT 11th European Meeting on Glial Cell Function in Health and Disease
CY JUL 03-06, 2013
CL Berlin, GERMANY
C1 [Gao, H.] Nanjing Univ, Nanjing 210008, Jiangsu, Peoples R China.
[Zhou, H.; Hong, J. -S.] NIEHS, NIH, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-1491
J9 GLIA
JI Glia
PD JUL
PY 2013
VL 61
SU 1
BP S19
EP S19
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 164KQ
UT WOS:000320408400041
ER
PT J
AU Tata, AM
Uggenti, C
De Stefano, ME
Pisano, A
Costantino, M
Loreti, S
Talora, C
Wess, J
Magnaghi, V
Ricordy, R
AF Tata, A. M.
Uggenti, C.
De Stefano, M. E.
Pisano, A.
Costantino, M.
Loreti, S.
Talora, C.
Wess, J.
Magnaghi, V.
Ricordy, R.
TI ACETYLCHOLINE AND M2 MUSCARINIC RECEPTOR CONTRIBUTE TO MODULATE SCHWANN
CELL PROLIFERATION AND DIFFERENTIATION
SO GLIA
LA English
DT Meeting Abstract
CT 11th European Meeting on Glial Cell Function in Health and Disease
CY JUL 03-06, 2013
CL Berlin, GERMANY
C1 [Tata, A. M.; Uggenti, C.; De Stefano, M. E.; Pisano, A.; Costantino, M.; Loreti, S.; Talora, C.] Univ Roma La Sapienza, I-00185 Rome, Italy.
[Wess, J.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Magnaghi, V.] Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy.
[Ricordy, R.] CNR, Biol & Mol Pathol 3Inst, Rome, Italy.
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 0894-1491
J9 GLIA
JI Glia
PD JUL
PY 2013
VL 61
SU 1
BP S47
EP S48
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 164KQ
UT WOS:000320408400147
ER
PT J
AU Zhang, CL
Bao, W
Rong, Y
Yang, HX
Bowers, K
Yeung, E
Kiely, M
AF Zhang, Cuilin
Bao, Wei
Rong, Ying
Yang, Huixia
Bowers, Katherine
Yeung, Edwina
Kiely, Michele
TI Genetic variants and the risk of gestational diabetes mellitus: a
systematic review
SO HUMAN REPRODUCTION UPDATE
LA English
DT Article
DE gestational diabetes mellitus; single nucleotide polymorphism; gene;
genetic factors
ID GENOME-WIDE ASSOCIATION; BETA(3)-ADRENERGIC RECEPTOR GENE;
POLYCYSTIC-OVARY-SYNDROME; INSULIN-SECRETION; TCF7L2 GENE;
TRANSCRIPTION-FACTOR-7-LIKE-2 TCF7L2; TRP(64)ARG POLYMORPHISM;
MEXICAN-AMERICANS; GREEK POPULATION; GLUCOKINASE GENE
AB Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.
Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNPGDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95 confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.
Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95 CIs) of 1.44 (1.291.60, P 0.001) per T allele of rs7903146 and 1.46 (1.151.84, P 0.002) per T allele of rs12255372.
In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
C1 [Zhang, Cuilin; Bao, Wei; Bowers, Katherine; Yeung, Edwina; Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
[Rong, Ying] Huazhong Univ Sci & Technol, Dept Nutr & Food Hyg, Hubei Key Lab Food Nutr & Safety, Sch Publ Hlth,Tongji Med Coll, Wuhan 430030, Peoples R China.
[Yang, Huixia] Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100034, Peoples R China.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM zhangcu@mail.nih.gov; wei.bao@nih.gov
RI Yeung, Edwina/F-5992-2015; Bowers, Katherine/N-5226-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Bao, Wei/0000-0002-7301-5786
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX W.B., K.B., E.Y., M.K. and C.Z. are supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health.
NR 70
TC 52
Z9 55
U1 0
U2 22
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1355-4786
EI 1460-2369
J9 HUM REPROD UPDATE
JI Hum. Reprod. Update
PD JUL-AUG
PY 2013
VL 19
IS 4
BP 376
EP 390
DI 10.1093/humupd/dmt013
PG 15
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 165DP
UT WOS:000320463500006
PM 23690305
ER
PT J
AU Bourbakis, N
Makrogiannis, SK
Dakopoulos, D
AF Bourbakis, Nikolaos
Makrogiannis, Sokratis K.
Dakopoulos, Dimitrios
TI A System-Prototype Representing 3D Space via Alternative-Sensing for
Visually Impaired Navigation
SO IEEE SENSORS JOURNAL
LA English
DT Article
DE 2-D vibration arrays; alternative sensing; assistive technologies;
blind's navigation; high-to-low image representation; human computer
interface; motion detection
ID BLIND; AID; TECHNOLOGY; WATERSHEDS
AB Offering an alternative mode of interaction with the surrounding 3-D space to the visually impaired for collision free navigation is a goal of great significance that includes several key challenges. In this paper, we study the alternative 3-D space sensation that is interpreted by our computer vision prototype system and transferred to the user via a vibration array. There are two main tasks for conducting such a study. The first task is to detect obstacles in close proximity, and motion patterns in image sequences, both important issues for a safe navigation in a 3-D dynamic space. To achieve this task, the images from the left and right cameras are acquired to produce new stereo images, followed by video stabilization as a preprocessing stage, a nonlinear spatio-temporal diffusion and kernel based density estimation method to assess the motion activity, and finally watershed-based detection of moving regions (or obstacles) of interest. The second task is to efficiently represent the information of the captured static and dynamic visual scenes as 3-D detectable patterns of vibrations applied on the human body to create a 3-D sensation of the space during navigation. To accomplish this task, considering the current limitations imposed by the technology, we create a high-to-low (H-L) image resolution representation scheme to facilitate the mapping onto a low-resolution 2-D array of vibrators. The H-L scheme uses pyramidal modeling to obtain low-resolution images of interest-preserving motion and obstacles-that are mapped onto a vibration array. These patterns are utilized to train and test the performance of the users in free space navigation. Thus, in this paper we study the synergy of these two important schemes to offer an alternative sensation of the 3-D space to the visually impaired via an array of vibrators. Particularly, the motion component is employed as an element for the identification of visual information of interest to be retained during the H-L transformation. The role of the array vibrators is to create a small-scale front representation of the space via various levels of vibrations. Thus, 3-D vibrations applied on the user's body (chest, abdomen) offer a 3-D sensation of the surrounding space and the motion in it. In addition, we present experimental results that indicate the efficiency of this navigation scheme in creating low-resolution 3-D views of the free navigation space and detecting obstacles and moving areas.
C1 [Bourbakis, Nikolaos; Dakopoulos, Dimitrios] Wright State Univ, Assist Technol Res Ctr, Dayton, OH 45435 USA.
[Makrogiannis, Sokratis K.] NIA, NIH, Baltimore, MD 21225 USA.
RP Bourbakis, N (reprint author), Wright State Univ, Assist Technol Res Ctr, Dayton, OH 45435 USA.
EM nikolaos.bourbakis@wright.edu; makrogianniss@mail.nih.gov;
dakopoulos.2@wright.edu
FU NSF; AIIS Inc.
FX Manuscript received November 5, 2012; revised January 29, 2013; accepted
March 11, 2013. Date of publication March 19, 2013; date of current
version May 29, 2013. This work was supported by NSF and AIIS Inc. for
the Tyflos Project. The associate editor coordinating the review of this
paper and approving it for publication was Prof. Subhas C. Mukhopadhyay.
NR 34
TC 8
Z9 8
U1 0
U2 17
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1530-437X
EI 1558-1748
J9 IEEE SENS J
JI IEEE Sens. J.
PD JUL
PY 2013
VL 13
IS 7
BP 2535
EP 2547
DI 10.1109/JSEN.2013.2253092
PG 13
WC Engineering, Electrical & Electronic; Instruments & Instrumentation;
Physics, Applied
SC Engineering; Instruments & Instrumentation; Physics
GA 158VF
UT WOS:000320001100005
ER
PT J
AU Vahedi, G
Kanno, Y
Sartorelli, V
O'Shea, JJ
AF Vahedi, Golnaz
Kanno, Yuka
Sartorelli, Vittorio
O'Shea, John J.
TI Transcription factors and CD4 T cells seeking identity: masters,
minions, setters and spikers
SO IMMUNOLOGY
LA English
DT Review
DE enhancers; epigenomics; master regulators; STATs; T helper cells
ID ENHANCER LANDSCAPE; DIFFERENTIATION; SPECIFICATION
AB Naive T cells differentiate and become distinct subsets in response to changes in the cytokine milieu. Such specialization arises through a complex and dynamic utilization of cis-regulatory enhancer elements. In this brief essay, we review recent findings on the relative contributions of sensors of the cytokine milieu, especially the signal transducer and activator of transcription family transcription factors, master regulators', and other transcription factors in the enhancer architecture of T cells. These findings provide new insights into how signal transduction impinges upon the genome.
C1 [Vahedi, Golnaz; Kanno, Yuka; O'Shea, John J.] Mol Immunol & Inflammat Branch, Lymphocyte Cell Biol Sect, Bethesda, MD USA.
[Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
RP Vahedi, G (reprint author), 10 Ctr Dr,Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM vahedig@mail.nih.gov; osheaj@arb.niams.nih.gov
RI Kanno, Yuka/B-5802-2013;
OI Kanno, Yuka/0000-0001-5668-9319
NR 17
TC 16
Z9 16
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD JUL
PY 2013
VL 139
IS 3
BP 294
EP 298
DI 10.1111/imm.12113
PG 5
WC Immunology
SC Immunology
GA 164EU
UT WOS:000320392500004
PM 23586907
ER
PT J
AU Kim, SH
Thurm, A
Shumway, S
Lord, C
AF Kim, So Hyun
Thurm, Audrey
Shumway, Stacy
Lord, Catherine
TI Multisite Study of New Autism Diagnostic Interview-Revised (ADI-R)
Algorithms for Toddlers and Young Preschoolers
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Early diagnosis; Autism spectrum disorders; Autism diagnostic
interview-revised
ID SPECTRUM DISORDERS; OBSERVATION SCHEDULE; AGREEMENT; VALIDITY; CHILDREN;
ADOS
AB Using two independent datasets provided by National Institute of Health funded consortia, the Collaborative Programs for Excellence in Autism and Studies to Advance Autism Research and Treatment (n = 641) and the National Institute of Mental Health (n = 167), diagnostic validity and factor structure of the new Autism Diagnostic Interview (ADI-R) algorithms for toddlers and young preschoolers were examined as a replication of results with the 2011 Michigan sample (Kim and Lord in J Autism Dev Disord 42(1): 82-93, 2012). Sensitivities and specificities and a three-factor solution were replicated. Results suggest that the new ADI-R algorithms can be appropriately applied to existing research databases with children from 12 to 47 months and down to nonverbal mental ages of 10 months for diagnostic grouping.
C1 [Kim, So Hyun] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06510 USA.
[Thurm, Audrey; Shumway, Stacy] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
[Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Developing Brain, White Plains, NY 10605 USA.
RP Kim, SH (reprint author), Yale Univ, Sch Med, Yale Child Study Ctr, 40 Temple St,Suite 7-D, New Haven, CT 06510 USA.
EM so-hyun.kim@yale.edu
OI Manwaring, Stacy/0000-0002-0835-9398
FU Intramural NIH HHS; NIMH NIH HHS [R25MH067723, F32 MH066469,
R01MH066469, R25 MH067723]
NR 31
TC 13
Z9 13
U1 4
U2 29
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD JUL
PY 2013
VL 43
IS 7
BP 1527
EP 1538
DI 10.1007/s10803-012-1696-4
PG 12
WC Psychology, Developmental
SC Psychology
GA 165TO
UT WOS:000320507200004
PM 23114567
ER
PT J
AU Atsawasuwan, P
Lu, X
Ito, Y
Chen, Y
Gopinathan, G
Evans, CA
Kulkarni, AB
Gibson, CW
Luan, X
Diekwisch, TGH
AF Atsawasuwan, P.
Lu, X.
Ito, Y.
Chen, Y.
Gopinathan, G.
Evans, C. A.
Kulkarni, A. B.
Gibson, C. W.
Luan, X.
Diekwisch, T. G. H.
TI Expression and Function of Enamel-related Gene Products in Calvarial
Development
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE amelogenin; ameloblastin; osteoblast; calvaria; evolution; suture
ID BONE-MARROW; AMELOGENIN; CELLS; AMELOBLASTIN; PROTEIN; PROLIFERATION;
OSTEOCLASTOGENESIS; DIFFERENTIATION; EVOLUTION; MICE
AB Enamel-related gene products (ERPs) are detected in non-enamel tissues such as bone. We hypothesized that, if functional, ERP expression corresponds with distinct events during osteoblast differentiation and affects bone development and mineralization. In mouse calvariae and MC3T3 cells, expression profiles of enamel-related gene products (ERPs) correlated with key events in post-natal calvarial development and MC3T3 cell mineralization. Developing skulls from both Amel- and Ambn-deficient animals were approximately 15% shorter when compared with those of wild-type controls, and their sutures remained patent for a longer period of time. Analysis of Amel- and Ambn-deficient calvariae and calvarial osteoblast cultures revealed a dramatic reduction in mineralized nodules, a significant reduction in Runx2, Sp7, Ibsp, and Msx2 expression, and a reduction in Alx4 in Amel-deficient calvariae vs. an increase in Alx4 in Ambn-deficient calvariae. Analysis of these data indicates that ERP expression follows defined developmental profiles and affects osteoblast differentiation, mineralization, and calvarial bone development. We propose that, in parallel to their role in the developing enamel matrix, ERPs have retained an evolutionary conserved function related to the biomineralization of bones.
C1 [Atsawasuwan, P.; Lu, X.; Ito, Y.; Gopinathan, G.; Luan, X.; Diekwisch, T. G. H.] Univ Illinois, Brodie Lab Craniofacial Genet, Chicago, IL 60612 USA.
[Atsawasuwan, P.; Chen, Y.; Evans, C. A.; Luan, X.; Diekwisch, T. G. H.] Univ Illinois, Dept Orthodont, Chicago, IL 60612 USA.
[Luan, X.; Diekwisch, T. G. H.] Coll Dent, UIC Dept Oral Biol, Chicago, IL USA.
[Kulkarni, A. B.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Gibson, C. W.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.
RP Diekwisch, TGH (reprint author), Univ Illinois, Brodie Lab Craniofacial Genet, Chicago, IL 60612 USA.
EM tomdkw@uic.edu
OI Atsawasuwan, Phimon/0000-0002-2576-060X
FU NIDCR [DE18057, DE19155, DE18900]; Thomas M. Graber AAOF fellowship
FX This study was supported by the NIDCR (grants DE18057 and DE19155 to XL;
grant DE18900 to TGHD) and by the Thomas M. Graber AAOF fellowship (to
PA). The authors declare no potential conflicts of interest with respect
to the authorship and/or publication of this article.
NR 26
TC 13
Z9 14
U1 1
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD JUL
PY 2013
VL 92
IS 7
BP 622
EP 628
DI 10.1177/0022034513487906
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 164TH
UT WOS:000320432100009
PM 23625374
ER
PT J
AU Zadeh, ES
Lungu, AO
Cochran, EK
Brown, RJ
Ghany, MG
Heller, T
Kleiner, DE
Gorden, P
AF Zadeh, Elika Safar
Lungu, Andreea O.
Cochran, Elaine K.
Brown, Rebecca J.
Ghany, Marc G.
Heller, Theo
Kleiner, David E.
Gorden, Phillip
TI The liver diseases of lipodystrophy: The long-term effect of leptin
treatment
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Lipodystrophy; Non-alcoholic fatty liver disease; Non-alcoholic
steatohepatitis; Leptin; Metabolic syndrome
ID NONALCOHOLIC FATTY LIVER; INSULIN-RESISTANCE; METABOLIC SYNDROME;
STEATOHEPATITIS; MODELS
AB Background & Aims: Lipodystrophies are hypoleptinemic conditions characterized by fat loss, severe insulin resistance, hypertriglyceridemia, and ectopic fat accumulation. Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are also features of this condition. We studied the spectrum of liver disease in lipodystrophy and the effects of leptin replacement.
Methods: This was an open-label, prospective study of leptin therapy in patients with inherited and acquired lipodystrophy at the National Institutes of Health. Liver biopsies were performed at baseline (N = 50) and after leptin replacement (N = 27). NASH activity was assessed using the NASH Clinical Research Network (CRN) scoring system. Fasting blood glucose, triglyceride, hemoglobin A(1c), and liver enzymes were measured at baseline and at the time of the final liver biopsy.
Results: In leptin-treated patients, 86% met criteria for NASH at baseline, while only 33% had NASH after leptin replacement for 25.8 +/- 3.7 months (mean SE, p = 0.0003). There were significant improvements in steatosis grade (reduction of mean score from 1.8 to 0.9) and ballooning injury scores (from 1.2 to 0.4), with a 44.2% reduction in mean NAFLD activity score (p <0.0001). Patients who already had fibrosis remained stable on leptin replacement. We observed significant improvement in metabolic profile, ALT and AST. In addition to NASH, four patients with acquired generalized lipodystrophy (AGL) had autoimmune hepatitis.
Conclusions: The fundamental liver disease of lipodystrophy is NASH, although autoimmune hepatitis was observed in some patients with AGL. Leptin appears to be a highly effective therapy for NASH in hypoleptinemic lipodystrophic patients. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Zadeh, Elika Safar; Lungu, Andreea O.; Cochran, Elaine K.; Brown, Rebecca J.; Gorden, Phillip] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Ghany, Marc G.; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Gorden, P (reprint author), NIDDK, NIH, Clin Res Ctr, Room 6-5952,10 Ctr Dr, Bethesda, MD 20892 USA.
EM PhillipG@intra.niddk.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Cancer Institute
FX This work was supported by the intramural research programs of the
National Institute of Diabetes and Digestive and Kidney Diseases and the
National Cancer Institute.
NR 25
TC 36
Z9 37
U1 2
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD JUL
PY 2013
VL 59
IS 1
BP 131
EP 137
DI 10.1016/j.jhep.2013.02.007
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 165KF
UT WOS:000320482100021
ER
PT J
AU Emmert, S
Kraemer, KH
AF Emmert, Steffen
Kraemer, Kenneth H.
TI Do Not Underestimate Nucleotide Excision Repair: It Predicts Not Only
Melanoma Risk but Also Survival Outcome
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID CUTANEOUS MELANOMA; XERODERMA-PIGMENTOSUM; POLYMORPHISMS; LIGHT
AB Nucleotide excision repair (NER) removes UV-induced DNA damage and other bulky DNA lesions, thereby maintaining genomic integrity. Dr Qingyi Wei's group demonstrated over the last decade that NER fidelity and single-nucleotide polymorphisms (SNPs) in NER genes constitute melanoma risk biomarkers. In this issue, Li et al. provide evidence that SNPs in NER genes may also predict melanoma survival.
C1 [Emmert, Steffen] Univ Med Ctr Gottingen, Dept Dermatol Venerol & Allergol, Gottingen, Germany.
[Kraemer, Kenneth H.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kraemer, KH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
FU Intramural NIH HHS [Z01 BC004517-31]
NR 11
TC 2
Z9 2
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUL
PY 2013
VL 133
IS 7
BP 1713
EP 1717
DI 10.1038/jid.2013.72
PG 5
WC Dermatology
SC Dermatology
GA 164RY
UT WOS:000320428400006
PM 23760049
ER
PT J
AU Sengupta, A
Lichti, UF
Carlson, BA
Cataisson, C
Ryscavage, AO
Mikulec, C
Conrad, M
Fischer, SM
Hatfield, DL
Yuspa, SH
AF Sengupta, Aniruddha
Lichti, Ulrike F.
Carlson, Bradley A.
Cataisson, Christophe
Ryscavage, Andrew O.
Mikulec, Carol
Conrad, Marcus
Fischer, Susan M.
Hatfield, Dolph L.
Yuspa, Stuart H.
TI Targeted Disruption of Glutathione Peroxidase 4 in Mouse Skin Epithelial
Cells Impairs Postnatal Hair Follicle Morphogenesis that Is Partially
Rescued through Inhibition of COX-2
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID THIOREDOXIN REDUCTASE; LIPID-PEROXIDATION; CHOLESTEROL HYDROPEROXIDES;
CYCLOOXYGENASE-2; EXPRESSION; PHGPX; MICE; GENE; CARCINOGENESIS;
SELENIUM
AB Selenoproteins are essential molecules for the mammalian antioxidant network. We previously demonstrated that targeted loss of all selenoproteins in mouse epidermis disrupted skin and hair development, and caused premature death. In the current study, we targeted specific selenoproteins for epidermal deletion to determine whether similar phenotypes developed. Keratinocyte-specific knockout mice lacking either the glutathione peroxidase 4 (GPx4) or thioredoxin reductase 1 (TR1) gene were generated by cre-lox technology using K14-cre. TR1 knockout mice had a normal phenotype in resting skin, whereas GPx4 loss in the epidermis caused epidermal hyperplasia, dermal inflammatory infiltrate, dysmorphic hair follicles, and alopecia in perinatal mice. Unlike epidermal ablation of all selenoproteins, mice ablated for GPx4 recovered after 5 weeks and had a normal life span. GPx1 and TR1 were upregulated in the skin and keratinocytes of GPx4-knockout mice. GPx4 deletion reduces keratinocyte adhesion in culture and increases lipid peroxidation and cyclooxygenase-2 (COX-2) levels in cultured keratinocytes and whole skin. Feeding a COX-2 inhibitor to nursing mothers partially prevents development of the abnormal skin phenotype in knockout pups. These data link the activity of cutaneous GPx4 to the regulation of COX-2 and hair follicle morphogenesis, and provide insight into the function of individual selenoprotein activity in maintaining cutaneous homeostasis.
C1 [Sengupta, Aniruddha; Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
[Lichti, Ulrike F.; Cataisson, Christophe; Ryscavage, Andrew O.; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Mikulec, Carol; Fischer, Susan M.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Dept Mol Carcinogenesis, Smithville, TX USA.
[Conrad, Marcus] DZNE German Ctr Neurodegenerat Dis, Munich, Germany.
[Conrad, Marcus] Helmholtz Ctr, Munich, Germany.
[Conrad, Marcus] German Res Ctr Environm Hlth, Inst Dev Genet, Neuherberg, Germany.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
EM yuspas@dc37a.nci.nih.gov
OI Conrad, Marcus/0000-0003-1140-5612
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; Deutsche Forschungsgemeinschaft (DFG) [CO
291/2-3]; DFG-Priority Program [SPP1087]
FX We thank Histoserv, Germantown, MD, for preparation of tissue sections,
and members of the Pathology/Histotechnology Laboratory, Center for
Cancer Research, NCI, Frederick, MD, for their help with
immunohistochemical analysis. The help from Raghunath Chatterjee and
Petra Tsuji, NCI, NIH, with the Ingenuity Pathway Analysis is also
acknowledged. This research was supported by the Intramural Research
Program at the Center for Cancer Research, National Cancer Institute,
National Institutes of Health (to DLH and SHY), and by the Deutsche
Forschungsgemeinschaft (DFG) CO 291/2-3 and the DFG-Priority Program
SPP1087 (MC). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 50
TC 11
Z9 11
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUL
PY 2013
VL 133
IS 7
BP 1731
EP 1741
DI 10.1038/jid.2013.52
PG 11
WC Dermatology
SC Dermatology
GA 164RY
UT WOS:000320428400010
PM 23364477
ER
PT J
AU Perdivara, I
Perera, L
Sricholpech, M
Terajima, M
Pleshko, N
Yamauchi, M
Tomer, KB
AF Perdivara, Irina
Perera, Lalith
Sricholpech, Marnisa
Terajima, Masahiko
Pleshko, Nancy
Yamauchi, Mitsuo
Tomer, Kenneth B.
TI Unusual Fragmentation Pathways in Collagen Glycopeptides
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
DE Collagen; Glycopeptide; Hydroxyproline; Galactosylhydroxylysine; Tandem
mass spectrometry; Fragmentation pathway; Mobile proton
ID TANDEM MASS-SPECTROMETRY; O-GLYCOSYLATION SITES; TRIPLE-HELICAL DOMAIN;
SEQUENCE-ANALYSIS; CROSS-LINKING; I COLLAGEN; GELATINASE-B; AMINO-ACID;
PEPTIDE; DISSOCIATION
AB Collagens are the most abundant glycoproteins in the body. One characteristic of this protein family is that the amino acid sequence consists of repeats of three amino acids -(X-Y-Gly)(n). Within this motif, the Y residue is often 4-hydroxyproline (HyP) or 5-hydroxylysine (HyK). Glycosylation in collagen occurs at the 5-OH group in HyK in the form of two glycosides, galactosylhydroxylysine (Gal-HyK) and glucosyl galactosylhydroxylysine (GlcGal-HyK). In collision induced dissociation (CID), collagen tryptic glycopeptides exhibit unexpected gas-phase dissociation behavior compared to typical N- and O-linked glycopeptides (i.e., in addition to glycosidic bond cleavages, extensive cleavages of the amide bonds are observed). The Gal- or GlcGal- glycan modifications are largely retained on the fragment ions. These features enable unambiguous determination of the amino acid sequence of collagen glycopeptides and the location of the glycosylation site. This dissociation pattern was consistent for all analyzed collagen glycopeptides, regardless of their length or amino acid composition, collagen type or tissue. The two fragmentation pathways-amide bond and glycosidic bond cleavage-are highly competitive in collagen tryptic glycopeptides. The number of ionizing protons relative to the number of basic sites (i.e., Arg, Lys, HyK, and N-terminus) is a major driving force of the fragmentation. We present here our experimental results and employ quantum mechanics calculations to understand the factors enhancing the labile character of the amide bonds and the stability of hydroxylysine glycosides in gas phase dissociation of collagen glycopeptides.
C1 [Perdivara, Irina; Tomer, Kenneth B.] NIEHS, Mass Spectrometry Grp, NIH, Res Triangle Pk, NC 27709 USA.
[Perera, Lalith] NIEHS, Computat Chem Grp, NIH, Res Triangle Pk, NC 27709 USA.
[Sricholpech, Marnisa] Srinakharinwirot Univ, Fac Dent, Bangkok, Thailand.
[Terajima, Masahiko; Yamauchi, Mitsuo] Univ N Carolina, Sch Dent, Chapel Hill, NC USA.
[Pleshko, Nancy] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA.
RP Perdivara, I (reprint author), NIEHS, Mass Spectrometry Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM perdivarai@niehs.nih.gov; tomer@niehs.nih.gov
OI Sricholpech, Marnisa/0000-0003-2139-0688
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [ES050171, ES043010]; NIH [AR060978, R01
AR056145]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (ES050171 to K.
B. T. and ES043010 to L. P.), and by the NIH grants AR060978 (M.Y.) and
R01 AR056145 (N.P.). The authors acknowledge Dr. Joshua Sharp (CCRC,
Athens, GA) and Dr. Lee Pedersen (NIEHS/NIH) for the critical review of
the manuscript, and the NIEHS Protein Microcharacterization Core
Facility for the assistance with the in-gel digests.
NR 51
TC 8
Z9 9
U1 3
U2 38
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD JUL
PY 2013
VL 24
IS 7
BP 1072
EP 1081
DI 10.1007/s13361-013-0624-y
PG 10
WC Biochemical Research Methods; Chemistry, Analytical; Chemistry,
Physical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 162RW
UT WOS:000320284000013
PM 23633013
ER
PT J
AU Fair, C
Wiener, L
Zadeh, S
Albright, J
Mellins, CA
Mancilla, M
Tepper, V
Trexler, C
Purdy, J
Osherow, J
Lovelace, S
Kapetanovic, S
AF Fair, Cynthia
Wiener, Lori
Zadeh, Sima
Albright, Jamie
Mellins, Claude Ann
Mancilla, Michael
Tepper, Vicki
Trexler, Connie
Purdy, Julia
Osherow, Janet
Lovelace, Susan
Kapetanovic, Suad
TI Reproductive Health Decision-Making in Perinatally HIV-Infected
Adolescents and Young Adults
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE HIV and reproductive health; Perinatal HIV; HIV-infected youth;
Adolescent reproductive health
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; ANTIRETROVIRAL
THERAPY; FERTILITY DESIRES; POSITIVE WOMEN; NEURODEVELOPMENTAL OUTCOMES;
MEDICATION ADHERENCE; VASCULAR DYSFUNCTION; PREGNANT-WOMEN; CHILDREN
AB With widespread access to antiretroviral therapy in the United States, many perinatally HIV-infected (PHIV+) children are surviving into adolescence and adulthood, becoming sexually active and making decisions about their reproductive health. The literature focusing on the reproductive decisions of individuals behaviorally infected with HIV can serve as a springboard for understanding the decision-making process of PHIV+ youth. Yet, there are many differences that critically distinguish reproductive health and related decision-making of PHIV+ youth. Given the potential public health implications of their reproductive decisions, better understanding of factors influencing the decision-making process is needed to help inform the development of salient treatment and prevention interventions. To begin addressing this understudied area, a "think tank" session, comprised of clinicians, medical providers, and researchers with expertise in the area of adolescent HIV, was held in Bethesda, MD, on September 21, 2011. The focus was to explore what is known about factors that influence the reproductive decision-making of PHIV+ adolescents and young adults, determine what important data are needed in order to develop appropriate intervention for PHIV+ youth having children, and to recommend future directions for the field in terms of designing and carrying out collaborative studies. In this report, we summarize the findings from this meeting. The paper is organized around the key themes that emerged, including utilizing a developmental perspective to create an operational definition of reproductive decision-making, integration of psychosocial services with medical management, and how to design future research studies. Case examples are presented and model program components proposed.
C1 [Fair, Cynthia; Albright, Jamie] Elon Univ, Elon, NC 27244 USA.
[Wiener, Lori] NCI, Ctr Canc Res, Pediat Clin SE 1, Bethesda, MD 20892 USA.
[Zadeh, Sima] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Mellins, Claude Ann] Columbia Univ, HIV Ctr Clin & Behav Studies, Dept Psychiat, New York, NY 10032 USA.
[Mellins, Claude Ann] Columbia Univ, HIV Ctr Clin & Behav Studies, Dept Sociomed Sci, New York, NY 10032 USA.
[Mellins, Claude Ann] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Mancilla, Michael] Childrens Natl Med Ctr, Burgess SIS Clin, Washington, DC 20010 USA.
[Tepper, Vicki] Univ Maryland, Sch Med, Pediat AIDS Program, Baltimore, MD 21201 USA.
[Trexler, Connie] Childrens Natl Med Ctr, Burgess Clin, Washington, DC 20010 USA.
[Purdy, Julia] NIH, Ctr Clin, CCMD, Bethesda, MD 20892 USA.
[Osherow, Janet] Georgetown Univ Hosp, Pediat Infect Dis Dept, PHC, Washington, DC 20007 USA.
[Lovelace, Susan] Univ Maryland, Baltimore, MD 21201 USA.
[Kapetanovic, Suad] NIMH, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
RP Fair, C (reprint author), Elon Univ, CB 2338, Elon, NC 27244 USA.
EM cfair@elon.edu; wienerl@mail.nih.gov; zadehsl@Mail.nih.gov;
jalbright6@elon.edu; cmellins@gmail.com; MMancill@cnmc.org;
vtepper@peds.umaryland.edu; ctrexler@childrensnational.org;
purdyj@cc.nih.gov; JXO10@gunet.georgetown.edu;
slovelac@peds.umaryland.edu; suad.kapetanovic@nih.gov
FU Intramural NIH HHS; NIMH NIH HHS [R01 MH069133]
NR 105
TC 10
Z9 10
U1 2
U2 8
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD JUL
PY 2013
VL 17
IS 5
BP 797
EP 808
DI 10.1007/s10995-012-1070-3
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 163FK
UT WOS:000320321100004
PM 22736033
ER
PT J
AU El-Mohandes, AAE
Windsor, R
Tan, S
Perry, DC
Gantz, MG
Kiely, M
AF El-Mohandes, Ayman A. E.
Windsor, Richard
Tan, Sylvia
Perry, David C.
Gantz, Marie G.
Kiely, Michele
TI A Randomized Clinical Trial of Trans-Dermal Nicotine Replacement in
Pregnant African-American Smokers
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Pregnancy; African-Americans; Smoking; Nicotine replacement therapy
ID SMOKING-CESSATION; BIRTH-WEIGHT; THERAPY
AB We compared acceptability, adherence and efficacy of trans-dermal nicotine patches and cognitive behavioral therapy (Group 1) to cognitive behavioral therapy alone (Group 2) in minority pregnant smokers. This is a randomized controlled trial. 52 women were recruited during pregnancy with a mean gestational age 18.5 +/- A 5.0 weeks and followed through delivery. Randomization was by site and initial cotinine levels. Interventionists and interviewers were blinded to group assignment. Two different nicotine replacement therapy dosing regiments were administered according to the baseline salivary cotinine level. A process evaluation model summarized patient adherence. The main outcome measure was self-report of cessation since last visit, confirmed by exhaled carbon monoxide. Analyses of categorical and continuous measures were conducted as well as linear trend tests of salivary cotinine levels. Women lost to follow-up were considered treatment failures. Participants were on average 27.5 +/- A 5.4 years old, 81 % were single, 69 % unemployed and 96 % were Medicaid eligible. A process evaluation indicated patients in both groups were adherent to scheduled program procedures through Visit 4, but not for Visits 5 and 6. Confirmed quit rates were: at visit 3, 23 (Group 1) and 0 % (Group 2) (p = 0.02); at visits 4 and 5, no difference; at visit 6, 19 (Group 1) and 0 % (Group 2) (p = 0.05). Group 1 delivered infants with a mean gestational age of 39.4 weeks versus 38.4 weeks in Group 2 (p = 0.02). 73 % (52/71) of the eligible smokers agreed to participate and 65 % (17/26) of Group 1 completed the protocol (i.e. attended 6 visits). A comparison of Group 1 and 2 quit rates confirmed a non-significant difference.
C1 [El-Mohandes, Ayman A. E.] Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE USA.
[Windsor, Richard] George Washington Univ, Sch Publ Hlth, Washington, DC USA.
[Tan, Sylvia; Gantz, Marie G.] RTI Int, Rockville, MD USA.
[Perry, David C.] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC USA.
[Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
RP Kiely, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Rm 7B-05, Rockville, MD 20852 USA.
EM kielym@nih.gov
FU Intramural NIH HHS; NICHD NIH HHS [U10 HD036104, U18 HD031206, U18
HD031206-07]
NR 27
TC 4
Z9 4
U1 2
U2 8
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD JUL
PY 2013
VL 17
IS 5
BP 897
EP 906
DI 10.1007/s10995-012-1069-9
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 163FK
UT WOS:000320321100014
PM 22761006
ER
PT J
AU Scharf, M
Neef, S
Freund, R
Geers-Knorr, C
Franz-Wachtel, M
Brandis, A
Krone, D
Schneider, H
Groos, S
Menon, MB
Chang, KC
Kraft, T
Meissner, JD
Boheler, KR
Maier, LS
Gaestel, M
Scheibe, RJ
AF Scharf, Madeleine
Neef, Stefan
Freund, Robert
Geers-Knoerr, Cornelia
Franz-Wachtel, Mirita
Brandis, Almuth
Krone, Dorothee
Schneider, Heike
Groos, Stephanie
Menon, Manoj B.
Chang, Kin-Chow
Kraft, Theresia
Meissner, Joachim D.
Boheler, Kenneth R.
Maier, Lars S.
Gaestel, Matthias
Scheibe, Renate J.
TI Mitogen-Activated Protein Kinase-Activated Protein Kinases 2 and 3
Regulate SERCA2a Expression and Fiber Type Composition To Modulate
Skeletal Muscle and Cardiomyocyte
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID GENE-EXPRESSION; RETICULUM CA2+-ATPASE; TWITCH MUSCLE; HEART-FAILURE;
SLOW-TWITCH; P38 MAPK; TRANSCRIPTIONAL COACTIVATOR; METABOLIC
ADAPTATION; GAMMA COACTIVATOR-1; SIGNAL-TRANSDUCTION
AB The mitogen-activated protein kinase (MAPK)-activated protein kinases 2 and 3 (MK2/3) represent protein kinases downstream of the p38 MAPK. Using MK2/3 double-knockout (MK2/3(-/-)) mice, we analyzed the role of MK2/3 in cross-striated muscle by transcriptome and proteome analyses and by histology. We demonstrated enhanced expression of the slow oxidative skeletal muscle myofiber gene program, including the peroxisome proliferator-activated receptor gamma (PPAR gamma) coactivator 1 alpha (PGC-1 alpha). Using reporter gene and electrophoretic gel mobility shift assays, we demonstrated that MK2 catalytic activity directly regulated the promoters of the fast fiber-specific myosin heavy-chain IId/x and the slow fiber-specific sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) gene. Elevated SERCA2a gene expression caused by a decreased ratio of transcription factor Egr-1 to Sp1 was associated with accelerated relaxation and enhanced contractility in MK2/3(-/-) cardiomyocytes, concomitant with improved force parameters in MK2/3(-/-) soleus muscle. These results link MK2/3 to the regulation of calcium dynamics and identify enzymatic activity of MK2/3 as a critical factor for modulating cross-striated muscle function by generating a unique muscle phenotype exhibiting both reduced fatigability and enhanced force in MK2/3(-/-) mice. Hence, the p38-MK2/3 axis may represent a novel target for the design of therapeutic strategies for diseases related to fiber type changes or impaired SERCA2 function.
C1 [Scharf, Madeleine; Freund, Robert; Krone, Dorothee; Schneider, Heike; Menon, Manoj B.; Gaestel, Matthias; Scheibe, Renate J.] Hannover Med Sch, Dept Biochem, Hannover, Germany.
[Neef, Stefan; Maier, Lars S.] Univ Gottingen, Dept Cardiol & Pneumol, D-37073 Gottingen, Germany.
[Geers-Knoerr, Cornelia; Kraft, Theresia] Hannover Med Sch, Dept Mol & Cellular Physiol, Hannover, Germany.
[Franz-Wachtel, Mirita] Univ Tubingen, Proteome Ctr Tubingen, Interfac Inst Cell Biol, Tubingen, Germany.
[Brandis, Almuth] Hannover Med Sch, Dept Pathol, Hannover, Germany.
[Groos, Stephanie] Hannover Med Sch, Inst Cell Biol, Ctr Anat, Hannover, Germany.
[Chang, Kin-Chow] Univ Nottingham, Sch Vet Med & Sci, Loughborough, England.
[Meissner, Joachim D.] Hannover Med Sch, Dept Vegetat Physiol, Hannover, Germany.
[Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, NIH, Baltimore, MD 21224 USA.
[Boheler, Kenneth R.] Univ Hong Kong, Li Ka Shing Fac Med, Stem Cell & Regenerat Med Consortium, Hong Kong, Hong Kong, Peoples R China.
RP Scheibe, RJ (reprint author), Hannover Med Sch, Dept Biochem, Hannover, Germany.
EM scheibe.renate@mh-hannover.de
RI Menon, Manoj/P-1543-2015
OI Menon, Manoj/0000-0001-5859-0347
FU Deutsche Forschungsgemeinschaft [SCHE 309/5-1]
FX This work was supported by the Deutsche Forschungsgemeinschaft (SCHE
309/5-1).
NR 83
TC 15
Z9 15
U1 3
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUL
PY 2013
VL 33
IS 13
BP 2586
EP 2602
DI 10.1128/MCB.01692-12
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 159FN
UT WOS:000320030900007
PM 23608535
ER
PT J
AU Kondilis-Mangum, HD
Wade, PA
AF Kondilis-Mangum, Hrisavgi D.
Wade, Paul A.
TI Epigenetics and the adaptive immune response
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Review
DE T cells; B cells; Adaptive immunity; Memory; Secondary immune response;
Epigenetics; Histone modifications; DNA methylation; DNA
methyltransferase
ID T-CELL DEVELOPMENT; BETA ALLELIC EXCLUSION; HEAVY-CHAIN GENE; DNA
METHYLTRANSFERASE 1; IFN-GAMMA PROMOTER; V(D)J RECOMBINATION;
CHROMATIN-STRUCTURE; HISTONE H3; CYTIDINE DEAMINASE; B-LYMPHOCYTES
AB Cells of the adaptive immune response undergo dynamic epigenetic changes as they develop and respond to immune challenge. Plasticity is a necessary prerequisite for the chromosomal dynamics of lineage specification, development, and the immune effector function of the mature cell types. The alterations in DNA methylation and histone modification that characterize activation may be integral to the generation of immunologic memory, thereby providing an advantage on secondary exposure to pathogens. While the immune system benefits from the dynamic nature of the epigenome, such benefit comes at a cost - increased likelihood of disease-causing mutation. Published by Elsevier Ltd.
C1 [Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Wade, PA (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr MD D4-04, Res Triangle Pk, NC 27709 USA.
EM wadep2@niehs.nih.gov
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, NIH [ES101965]
FX This work was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, NIH (ES101965 to
P.A.W.). We thank the members of the Wade laboratory for useful
discussions throughout the course of preparation of this manuscript. We
apologize to our many colleagues whose work could not be cited here due
to space constraints.
NR 102
TC 13
Z9 13
U1 5
U2 30
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0098-2997
J9 MOL ASPECTS MED
JI Mol. Asp. Med.
PD JUL-AUG
PY 2013
VL 34
IS 4
SI SI
BP 813
EP 825
DI 10.1016/j.mam.2012.06.008
PG 13
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 165KI
UT WOS:000320482400004
PM 22789989
ER
PT J
AU Liao, XH
Buggey, J
Lee, YK
Kimmel, AR
AF Liao, Xin-Hua
Buggey, Jonathan
Lee, Yun Kyung
Kimmel, Alan R.
TI Chemoattractant stimulation of TORC2 is regulated by receptor/G
protein-targeted inhibitory mechanisms that function upstream and
independently of an essential GEF/Ras activation pathway in
Dictyostelium
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID DIRECTIONAL CELL-MOVEMENT; HETEROTRIMERIC G-PROTEINS; MEDIATED CGMP
RESPONSE; ADENYLYL-CYCLASE; LEADING-EDGE; SPATIOTEMPORAL REGULATION;
EUKARYOTIC CHEMOTAXIS; RAS ACTIVATION; DISCOIDEUM; CAMP
AB Global stimulation of Dictyostelium with different chemoattractants elicits multiple transient signaling responses, including synthesis of cAMP and cGMP, actin polymerization, activation of kinases ERK2, TORC2, and phosphatidylinositide 3-kinase, and Ras-GTP accumulation. Mechanisms that down-regulate these responses are poorly understood. Here we examine transient activation of TORC2 in response to chemically distinct chemoattractants, cAMP and folate, and suggest that TORC2 is regulated by adaptive, desensitizing responses to stimulatory ligands that are independent of downstream, feedback, or feedforward circuits. Cells with acquired insensitivity to either folate or cAMP remain fully responsive to TORC2 activation if stimulated with the other ligand. Thus TORC2 responses to cAMP or folate are not cross-inhibitory. Using a series of signaling mutants, we show that folate and cAMP activate TORC2 through an identical GEF/Ras pathway but separate receptors and G protein couplings. Because the common GEF/Ras pathway also remains fully responsive to one chemoattractant after desensitization to the other, GEF/Ras must act downstream and independent of adaptation to persistent ligand stimulation. When initial chemoattractant concentrations are immediately diluted, cells rapidly regain full responsiveness. We suggest that ligand adaptation functions in upstream inhibitory pathways that involve chemoattractant-specific receptor/G protein complexes and regulate multiple response pathways.
C1 [Liao, Xin-Hua; Buggey, Jonathan; Lee, Yun Kyung; Kimmel, Alan R.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Kimmel, AR (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM alank@helix.nih.gov
FU Intramural Research Program of the National Institutes of
Health/National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank dictyBase (Fey et al., 2009) and colleagues for various
strains. We thank Leung Kim, Pascale Charest, Rick Firtel, and Shi Shu
for providing the Ras-related reagents. This research was supported by
the Intramural Research Program of the National Institutes of
Health/National Institute of Diabetes and Digestive and Kidney Diseases.
NR 51
TC 3
Z9 4
U1 1
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUL 1
PY 2013
VL 24
IS 13
BP 2146
EP 2155
DI 10.1091/mbc.E13-03-0130
PG 10
WC Cell Biology
SC Cell Biology
GA 175AP
UT WOS:000321201800008
PM 23657816
ER
PT J
AU Moon, K
Six, DA
Lee, HJ
Raetz, CRH
Gottesman, S
AF Moon, Kyung
Six, David A.
Lee, Hyun-Jung
Raetz, Christian R. H.
Gottesman, Susan
TI Complex transcriptional and post-transcriptional regulation of an enzyme
for lipopolysaccharide modification
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI LIPOPOLYSACCHARIDE; SMALL RNA; SALMONELLA-ENTERICA;
ENVELOPE-STRESS; OUTER-MEMBRANE; SIGMA-FACTOR; LIPID-A; SYSTEM;
PHOSPHORYLATION; CHROMOSOME
AB The PhoQ/PhoP two-component system activates many genes for lipopolysaccharide (LPS) modification when cells are grown at low Mg2+ concentrations. An additional target of PhoQ and PhoP is MgrR, an Hfq-dependent small RNA that negatively regulates expression of eptB, also encoding a protein that carries out LPS modification. Examination of LPS confirmed that MgrR effectively silences EptB; the phosphoethanolamine modification associated with EptB is found in mgrR::kan but not mgrR+ cells. Sigma E has been reported to positively regulate eptB, although the eptB promoter does not have the expected Sigma E recognition motifs. The effects of Sigma E and deletion of mgrR on levels of eptB mRNA were independent, and the same 5 end was found in both cases. In vitro transcription and the behaviour of transcriptional and translational fusions demonstrate that Sigma E acts directly at the level of transcription initiation for eptB, from the same start point as Sigma 70. The results suggest that when Sigma E is active, synthesis of eptB transcript outstrips MgrR-dependent degradation; presumably the modification of LPS is important under these conditions. Adding to the complexity of eptB regulation is a second sRNA, ArcZ, which also directly and negatively regulates eptB.
C1 [Moon, Kyung; Lee, Hyun-Jung; Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
[Six, David A.; Raetz, Christian R. H.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM Gottesms@helix.nih.gov
RI Six, David/D-6523-2011
OI Six, David/0000-0002-9013-1711
FU NIH, National Cancer Institute, Center for Cancer Research; NIH
[GM-51310]; LIPID MAPS Large Scale Collaborative from NIH [GM-069338]
FX We thank V. Rhodius for his thoughts on the eptB promoter, Dale Lewis
for help with the in vitro transcription experiments, H. Nikaido for
discussions, and K. Potrykus and M. Cashel for providing Sigma E
protein. We thank M. S. Trent, D. Schu, S. Tong, N. De Lay and K.
Ramamurthi for advice and comments on this article. This work was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research and by NIH Grant
GM-51310 to C.R.H.R. The mass spectrometry facility in the Department of
Biochemistry of the Duke University Medical Center is supported by the
LIPID MAPS Large Scale Collaborative Grant number GM-069338 from NIH.
D.A.S. and S.G. dedicate this article to the memory of co-author
Christian R. H. Raetz, whose deep knowledge and interest played a key
role in bringing this work to fruition.
NR 37
TC 14
Z9 16
U1 3
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD JUL
PY 2013
VL 89
IS 1
BP 52
EP 64
DI 10.1111/mmi.12257
PG 13
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 168TN
UT WOS:000320728800004
PM 23659637
ER
PT J
AU Penet, MF
Artemov, D
Farahani, K
Bhujwalla, ZM
AF Penet, Marie-France
Artemov, Dmitri
Farahani, Keyvan
Bhujwalla, Zaver M.
TI MR - eyes for cancer: looking within an impenetrable disease
SO NMR IN BIOMEDICINE
LA English
DT Article
DE MR probes; cancer; tumor microenvironment; receptors imaging;
theranostics
ID MAGNETIC-RESONANCE-SPECTROSCOPY; LYMPH-NODE METASTASES;
SUPERPARAMAGNETIC IRON-OXIDE; TUMOR-ASSOCIATED MACROPHAGES; HUMAN
BREAST-CANCER; IN-VIVO; EXTRACELLULAR PH; NONINVASIVE DETECTION;
NMR-SPECTROSCOPY; PROSTATE-CANCER
AB Probe development is a critical component in cancer imaging, and novel probes are making major inroads in several aspects of cancer detection and image-guided treatments. Intrinsic MR probes such as signals from metabolites and their chemical shifts have been used for more than a decade to understand cancer physiology and metabolism. Through the integration of technology, molecular biology, and chemistry, the last few years have witnessed an explosion of extrinsic probes for molecular and functional imaging of cancer that, together with techniques such as CEST and hyperpolarization, have significantly expanded the repertoire of MR techniques in basic and translational investigations of many different aspects of cancer. Furthermore, incorporation of MR probes into multifunctional nanoparticles and multimodality imaging platforms have opened new opportunities for MR in image-guided diagnosis and therapy of cancer. Here we have provided an overview of recent innovations that have occurred in the development of MRI probes for molecular and functional imaging of cancer. Although most of these novel probes are not clinically available, they offer significant promise for future translational applications. In this review, we have highlighted the areas of future development that are likely to have a profound impact on cancer detection and treatment. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Penet, Marie-France; Artemov, Dmitri; Bhujwalla, Zaver M.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, JHU ICMIC Program,Div Canc Imaging Res, Baltimore, MD 21218 USA.
[Artemov, Dmitri; Bhujwalla, Zaver M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD USA.
[Farahani, Keyvan] NCI, Image Guided Intervent Branch, Canc Imaging Program, Bethesda, MD 20892 USA.
RP Bhujwalla, ZM (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, JHU ICMIC Program,Div Canc Imaging Res, Baltimore, MD 21218 USA.
EM zaver@mri.jhu.edu
FU NIH [P50 CA103175, P30 CA006973, R01 CA73850, R01 CA82337, R01 CA136576,
R01 CA138515, R01 CA138264]; Honorable Tina Brozman Foundation
FX Support from NIH P50 CA103175, P30 CA006973, R01 CA73850, R01 CA82337,
R01 CA136576, R01 CA138515, R01 CA138264 and the Honorable Tina Brozman
Foundation (MFP) is gratefully acknowledged.
NR 86
TC 5
Z9 5
U1 1
U2 24
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD JUL
PY 2013
VL 26
IS 7
SI SI
BP 745
EP 755
DI 10.1002/nbm.2980
PG 11
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 168UC
UT WOS:000320730300004
PM 23784955
ER
PT J
AU Baidoo, KE
Milenic, DE
Brechbiel, MW
AF Baidoo, Kwamena E.
Milenic, Diane E.
Brechbiel, Martin W.
TI Methodology for labeling proteins and peptides with lead-212 (Pb-212)
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Radioimmunotherapy; Alpha targeted therapy; Lead-212; Trastuzumab;
Cancer therapy
ID DISSEMINATED PERITONEAL DISEASE; ALPHA-PARTICLE RADIOIMMUNOTHERAPY;
DNA-DAMAGE REPAIR; CANCER-THERAPY; MONOCLONAL-ANTIBODY; GASTRIC-CANCER;
TARGETING HER2; IN-VIVO; TUMOR; RADIATION
AB Introduction: Alpha particles possess an exquisite degree of cytotoxicity when employed for targeted alpha-particle therapy (TAT) or radioimmunotherapy (RIT). Pb-212, which acts as an in vivo generator of the alpha-emitting nuclide Bi-212 has shown great promise in pre-clinical studies when used to label the HER2 binding antibody, trastuzumab. Currently, the first RIT clinical trial employing Pb-212 radiolabeled trastuzumab is in progress. This report provides detailed current protocol operations and steps that were generated for use in the clinical trial as well as the relevant pre-clinical experimentation, and describes in detail the labeling of proteins or peptides with Pb-212 as provided via a Ra-224 based generator system.
Methods: Pb-212 was eluted from the Ra-224/Pb-212 generator using hydrochloric acid (2 M). The generator eluate was evaporated and digested with nitric acid (8 M) followed by extraction of the Pb-212 with dilute nitric acid (0.1 M). The dilute nitric acid solution of Pb-212 was used to label the immunoconjugate Trastuzumab-TCMC (2-(4-isothiocyanatobenzyl-1,4,7,10-tetraaza-1,4,7,10,tetra-(2-carbamonylmethyl)-cyclododecane) at pH 5.5.
Results: Elution of Pb-212 from the generator was efficient yielding>90% of available Pb-212. Trastuzumab-TCMC was efficiently labeled with a radiochemical yield of 94% +/- 4% (n = 7) by ITLC and an isolated yield of 73% +/- 3% (n = 7).
Conclusions: The results show the feasibility of generating radioimmunoconjugates and peptide conjugates for use as in vivo alpha generator systems in the clinic. The technology holds promise in applications involving the treatment of minimal disease such as micrometastases and residual tumor after surgical debulking, hematological cancers, infections, and compartmental cancers, such as ovarian cancer. Published by Elsevier Inc.
C1 [Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, NIH, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA.
RP Baidoo, KE (reprint author), NCI, NIH, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA.
EM baidook@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 41
TC 8
Z9 8
U1 0
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD JUL
PY 2013
VL 40
IS 5
BP 592
EP 599
DI 10.1016/j.nucmedbio.2013.01.010
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 161TS
UT WOS:000320216800002
PM 23602604
ER
PT J
AU Kang, CS
Song, HA
Milenic, DE
Baidoo, KE
Brechbiel, MW
Chong, HS
AF Kang, Chi Soo
Song, Hyun A.
Milenic, Diane E.
Baidoo, Kwamena E.
Brechbiel, Martin W.
Chong, Hyun-Soon
TI Preclinical evaluation of NETA-based bifunctional ligand for
radioimmunotherapy applications using Bi-212 and Bi-213: Radiolabeling,
serum stability, and biodistribution and tumor uptake studies
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Bi-212; Bi-213; Bifunctional chelator; Serum stability, biodistribution;
Radiolabeling
ID IN-VIVO EVALUATION; MONOCLONAL-ANTIBODY; LEUKEMIA; THERAPY; CANCER;
LU-177; ACID
AB Introduction: Despite the great potential of targeted alpha-radioimmunotherapy (RIT) as demonstrated by preclinical and clinical trials, limited progress has been made on the improvement of chelation chemistry for Bi-212 and Bi-213. A new bifunctional ligand 3p-C-NETA was evaluated for targeted alpha RIT using Bi-212 and Bi-213.
Methods: Radiolabeling of 3p-C-NETA with Bi-205/6, a surrogate of Bi-212 and Bi-213, was evaluated at pH 5.5 and room temperature. In vitro stability of the Bi-205/6-3p-C-NETA-trastuzumab conjugate was evaluated using human serum (pH 7, 37 degrees C). Immunoreactivity and specific activity of the Bi-205/6-3p-C-NETA-trastuzumab conjugate were measured. An in vivo biodistribution study was performed to evaluate the in vivo stability and tumor targeting properties of the Bi-205/6-3p-C-NETA-trastuzumab conjugate in athymic mice bearing subcutaneous LS174T tumor xenografts.
Result: The 3p-C-NETA-trastuzumab conjugate was extremely rapid in complexing with Bi-205/6, and the corresponding Bi-205/6-3p-C-NETA-trastuzumab was stable in human serum. Bi-205/6-3p-C-NETA-trastuzumab was prepared with a high specific activity and retained immunoreactivity. Bi-205/6-3p-C-NETA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low normal organ and high tumor uptake.
Conclusion: The results of the in vitro and in vivo studies indicate that 3p-C-NETA is a promising chelator for RIT applications using Bi-212 and Bi-213. Further detailed in vivo evaluations of 3p-C-NETA for targeted alpha RIT are warranted. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Kang, Chi Soo; Song, Hyun A.; Chong, Hyun-Soon] IIT, Biol & Chem Sci Dept, Div Chem, Chicago, IL 60616 USA.
[Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.] Natl Canc Inst, NIH, Ctr Canc Res, Radiat Oncol Branch,Radioimmune & Inorgan Chem Se, Bethesda, MD USA.
RP Chong, HS (reprint author), IIT, Biol & Chem Sci Dept, Div Chem, Chicago, IL 60616 USA.
EM chong@iit.edu
FU National Institutes of Health [R01CA112503]; NIH
FX Supported by National Institutes of Health (R01CA112503) and NIH
intramural research program.
NR 22
TC 11
Z9 11
U1 4
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD JUL
PY 2013
VL 40
IS 5
BP 600
EP 605
DI 10.1016/j.nucmedbio.2013.01.012
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 161TS
UT WOS:000320216800003
PM 23541026
ER
PT J
AU Peterson, KL
Reid, WC
Freeman, AF
Holland, SM
Pettigrew, RI
Gharib, AM
Hammoud, DA
AF Peterson, Kristin L.
Reid, William C.
Freeman, Alexandra F.
Holland, Steven M.
Pettigrew, Roderic I.
Gharib, Ahmed M.
Hammoud, Dima A.
TI The use of C-14-FIAU to predict bacterial thymidine kinase presence:
Implications for radiolabeled FIAU bacterial imaging
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Bacterial imaging; PET; FIAU; Thymidine kinase
ID POSITRON-EMISSION-TOMOGRAPHY; HYPER-IGE SYNDROMES; INFECTIONS
AB Currently available infectious disease imaging techniques cannot differentiate between infection and sterile inflammation or between different types of infections. Recently, radiolabeled FIAU was found to be a substrate for the thymidine kinase (TK) enzyme of multiple pathogenic bacteria, leading to its translational use in the imaging of bacterial infections. Patients with immunodeficiencies, however, are susceptible to a different group of pathogenic bacteria when compared to immunocompetent subjects. In this study, we wanted to predict the usefulness of radiolabeled FIAU in the detection of bacterial infections commonly occurring in patients with immunodeficiencies, in vitro, prior to attempting in vivo imaging with I-124-FIAU-PET.
Methods: We obtained representative strains of bacterial pathogens isolated from actual patients with genetic immunodeficiencies. We evaluated the bacterial susceptibility of different strains to the effect of incubation with FIAU, which would implicate the presence of the thymidine kinase (TK) enzyme. We also incubated the bacteria with C-14-FIAU and consequently measured its rate of incorporation in the bacterial DNA using a liquid scintillation counter.
Results: Unlike the other bacterial strains, the growth of Pseudomonas aeruginosa was not halted by FIAU at any concentration. All the tested clinical isolates demonstrated different levels of C-14-FIAU uptake, except for P. aeruginosa.
Conclusion: Radiolabeled FIAU has been successful in delineating bacterial infections, both in preclinical and pilot translational studies. In patients with immunodeficiencies, Pseudomonas infections are commonly encountered and are usually difficult to differentiate from fungal infections. The use of radiolabeled FIAU for in vivo imaging of those patients, however, would not be useful, considering the apparent lack of TK enzyme in Pseudomonas. One has to keep in mind that not all pathogenic bacteria possess the TK enzyme and as such will not all retain FIAU. Our technique is simple, and can be easily used to assess whether a certain bacterial strain of interest can or cannot be visualized using radiolabeled FIAU. Published by Elsevier Inc.
C1 [Peterson, Kristin L.; Reid, William C.; Hammoud, Dima A.] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA.
[Pettigrew, Roderic I.; Gharib, Ahmed M.] NIDDK, Biomed & Metab Imaging Branch, NIH, Bethesda, MD USA.
[Freeman, Alexandra F.; Holland, Steven M.] NIAID, NIH, Immunopathogenesis Sect, LCID, Bethesda, MD 20892 USA.
RP Hammoud, DA (reprint author), NIH, Ctr Clin, Bethesda, MD 20814 USA.
EM hammoudd@cc.nih.gov
RI Hammoud, Dima/C-2286-2015; Gharib, Ahmed/O-2629-2016;
OI Gharib, Ahmed/0000-0002-2476-481X; Peterson, Kristin/0000-0003-0796-3611
FU National Institutes of Health
FX National Institutes of Health, Bench to Bedside intramural research
grant (2011-2012).
NR 21
TC 5
Z9 6
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD JUL
PY 2013
VL 40
IS 5
BP 638
EP 642
DI 10.1016/j.nucmedbio.2013.01.005
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 161TS
UT WOS:000320216800008
PM 23541824
ER
PT J
AU Bowers, K
Laughon, SK
Kim, S
Mumford, SL
Brite, J
Kiely, M
Zhang, CL
AF Bowers, Katherine
Laughon, S. Katherine
Kim, Sungduk
Mumford, Sunni L.
Brite, Jennifer
Kiely, Michele
Zhang, Cuilin
TI The Association between a Medical History of Depression and Gestational
Diabetes in a Large Multi-ethnic Cohort in the United States
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE depression; pregnancy; gestational diabetes
ID INCREASING PREVALENCE; MELLITUS; PREGNANCY; WOMEN; HEALTH; RISK
AB Background Both major depression and gestational diabetes mellitus (GDM) are prevalent among women of reproductive age. Our objective was to determine whether a medical history of depression is related to subsequent development of GDM. Methods The Consortium on Safe Labor was a US retrospective cohort study of 228562 births between 2002 and 2008. Exclusion criteria for the present analysis included multiple gestation pregnancies (n=5059), pre-existing diabetes (n=12771), deliveries <24 weeks (n=395), site GDM prevalence (<1%) (n=20721) and missing data on pre-pregnancy body mass index (BMI) (n=61321). Using generalised estimating equations, we estimated the association between a history of depression and a pregnancy complicated by GDM. Results The final analytic population included 121260 women contributing 128295 pregnancies, of which 5606 were affected by GDM. A history of depression was significantly associated with an increased risk of developing GDM (multivariate odds ratio [aOR]=1.42 [95% confidence interval (CI) 1.26, 1.60]). Adjusting for pre-pregnancy BMI and weight gain during pregnancy attenuated the association, although it remained statistically significant (aOR=1.17 [95% CI 1.03, 1.33]). Conclusions A history of depression was significantly associated with an increased GDM risk among a large multi-ethnic US cohort of women. If the association is confirmed, depression presents a potentially modifiable risk factor of GDM and provides additional clues to the underlying pathophysiology of GDM.
C1 [Bowers, Katherine; Laughon, S. Katherine; Kim, Sungduk; Mumford, Sunni L.; Kiely, Michele; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Bowers, Katherine] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA.
[Brite, Jennifer] CUNY, Sch Publ Hlth, New York, NY 10021 USA.
RP Bowers, K (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, 3333 Burnet Ave,MLC 5041, Cincinnati, OH 45229 USA.
EM katherine.bowers@cchmc.org; zhangcu@mail.nih.gov
RI Bowers, Katherine/N-5226-2015;
OI Grantz, Katherine/0000-0003-0276-8534
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN267200603425C]
FX The data included in this paper were obtained from the Consortium on
Safe Labor, which was supported by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, through Contract No.
HHSN267200603425C. Institutions involved in the Consortium include, in
alphabetical order, Baystate Medical Center, Springfield, MA;
Cedars-Sinai Medical Center Burnes Allen Research Center, Los Angeles,
CA; Christiana Care Health System, Newark, DE; Georgetown University
Hospital, MedStar Health, Washington, DC; Indiana University Clarian
Health, Indianapolis, IN; Inter-mountain Healthcare and the University
of Utah, Salt Lake City, Utah; Maimonides Medical Center, Brooklyn, NY;
MetroHealth Medical Center, Cleveland, OH.; Summa Health System, Akron
City Hospital, Akron, OH; The EMMES Corporation, Rockville MD (Data
Coordinating Center); University of Illinois at Chicago, Chicago, IL;
University of Miami, Miami, FL; and the University of Texas Health
Science Center at Houston, Houston, TX. The named authors alone are
responsible for the views expressed in this manuscript, which does not
necessarily represent the decisions or the stated policy of the NICHD.
NR 23
TC 10
Z9 10
U1 2
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD JUL
PY 2013
VL 27
IS 4
BP 323
EP 328
DI 10.1111/ppe.12057
PG 6
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 165HQ
UT WOS:000320474700002
PM 23772933
ER
PT J
AU Jin, TC
Curry, J
Smith, P
Jiang, JS
Xiao, TS
AF Jin, Tengchuan
Curry, James
Smith, Patrick
Jiang, Jiansheng
Xiao, T. Sam
TI Structure of the NLRP1 caspase recruitment domain suggests potential
mechanisms for its association with procaspase-1
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE NLRP1; CARD; death domain fold; electrostatic attraction
ID INFLAMMASOME; ACTIVATION; PLATFORM; NALP1
AB The NLRP1 inflammasome responds to microbial challenges such as Bacillus anthracis infection and is implicated in autoimmune disease such as vitiligo. Human NLRP1 contains both an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain (CARD), with the latter being essential for its association with the downstream effector procaspase-1. Here we report a 2.0 angstrom crystal structure of the human NLRP1 CARD as a fusion with the maltose-binding protein. The structure reveals the six-helix bundle fold of the NLRP1 CARD, typical of the death domain superfamily. The charge surface of the NLRP1 CARD structure and a procaspase-1 CARD model suggests potential mechanisms for their association through electrostatic attraction. Proteins 2013; 81:1266-1270. (c) 2013 Wiley Periodicals, Inc.
C1 [Jin, Tengchuan; Curry, James; Smith, Patrick; Jiang, Jiansheng; Xiao, T. Sam] NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Xiao, TS (reprint author), NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, 4 Mem Dr,Bldg 4,Room 228, Bethesda, MD 20892 USA.
EM xiaot@niaid.nih.gov
RI Xiao, Tsan/I-7616-2013; Xiao, Tsan/A-8590-2010; Jin,
Tengchuan/B-5883-2014
OI Xiao, Tsan/0000-0001-9688-475X; Jin, Tengchuan/0000-0002-1395-188X
FU National Cancer Institute [Y1-CO-1020]; National Institute of General
Medical Sciences [Y1-GM-1104]; US Department of Energy
[DE-AC02-06CH11357]; Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, NIH
FX Grant sponsor: National Cancer Institute; Grand number: Y1-CO-1020;
Grant sponsor: National Institute of General Medical Sciences; Grand
number: Y1-GM-1104; Grant sponsor: US Department of Energy; Grand
number: DE-AC02-06CH11357; Grant sponsor: Division of Intramural
Research, National Institute of Allergy and Infectious Diseases, NIH.
NR 18
TC 17
Z9 17
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD JUL
PY 2013
VL 81
IS 7
BP 1266
EP 1270
DI 10.1002/prot.24287
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 165HK
UT WOS:000320474100016
PM 23508996
ER
PT J
AU Ling, D
Liu, BY
Jawad, S
Thompson, IA
Nagineni, CN
Dailey, J
Chien, J
Sredni, B
Nussenblatt, RB
AF Ling, Diamond
Liu, Baoying
Jawad, Shayma
Thompson, Ian A.
Nagineni, Chandrasekharam N.
Dailey, Jennifer
Chien, Jason
Sredni, Benjamin
Nussenblatt, Robert B.
TI The tellurium redox immunomodulating compound AS101 inhibits IL-1
beta-activated inflammation in the human retinal pigment epithelium
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID NF-KAPPA-B; MACULAR DEGENERATION; GENE-EXPRESSION; CELLS; IL-6;
MECHANISMS; SECRETION; UVEITIS; MICE
AB Purpose AS101 is a non-toxic organotellurium-IV compound with demonstrated immunomodulating activity in vitro and in vivo. Inflammatory responses are attributed to the pathophysiology of numerous ocular diseases. In this study, we wished to elucidate whether AS101 could mitigate pro-inflammatory activity in human retinal pigment epithelial (RPE) cells, which are heavily involved in ocular immune responses, induced by pro-inflammatory IL-beta activity.
Methods Primary and transformed RPE cells treated with varying concentrations of AS101 were used in this study. Real-time PCR and ELISA assays were used to detect cytokine/chemokine mRNA expression and protein production. Western blot was used to detect changes in the NF kappa B pathway. Cell viability and proliferation were detected using a Vi-Cell XR cell counter. To measure the cytoprotective capacity of AS101, cell numbers were compared between cells treated with IL-1 beta or lipopolysaccharide (LPS) and cells treated with IL-1 beta or LPS in the presence of AS101.
Results AS101 inhibited IL-1 beta-induced mRNA expression and protein production of IL-6 and IL-8 in RPE cells. The viability of RPE cells treated with IL-1 beta and LPS was unaffected. AS101 slightly inhibited RPE cell growth in the presence of higher levels of IL-1 beta. Also, AS101 downregulated the IL-1 beta activity by inhibiting the phosphorylation of p65, an NF kappa B subunit.
Conclusions The results demonstrate that AS101 reduces IL-1 beta-induced inflammatory responses in the RPE. In previous studies, AS101 exhibited therapeutic effects in various disease models and was a safe profile in clinical trials. These results suggest that AS101 may have potent anti-inflammatory potential in the eye and confer the downregulation of RPE inflammatory responses in a pathological environment.
C1 [Ling, Diamond; Liu, Baoying; Jawad, Shayma; Thompson, Ian A.; Nagineni, Chandrasekharam N.; Dailey, Jennifer; Chien, Jason; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Sredni, Benjamin] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Safdie AIDS & Immunol Res Ctr, CAIR Inst, Tel Aviv, Israel.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N109,10 Ctr Dr, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU Intramural Research Program of NIH, National Eye Institute, Bethesda,
USA
FX This research was supported by the Intramural Research Program of NIH,
National Eye Institute, Bethesda, USA.
NR 25
TC 5
Z9 6
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUL
PY 2013
VL 97
IS 7
BP 934
EP 938
DI 10.1136/bjophthalmol-2012-301962
PG 5
WC Ophthalmology
SC Ophthalmology
GA 161YH
UT WOS:000320229800028
PM 23624272
ER
PT J
AU Chen, D
Chen, Y
Forrest, D
Bremner, R
AF Chen, D.
Chen, Y.
Forrest, D.
Bremner, R.
TI E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE retinoblastoma; E2f; p53; cone photoreceptor; retina
ID LENS FIBER CELLS; S-PHASE ENTRY; E2F1-INDUCED APOPTOSIS; DNA-SYNTHESIS;
MUTANT MICE; MOUSE MODEL; RB; RETINOBLASTOMA; P53; CYCLE
AB The 'activating' E2fs (E2f1-3) are transcription factors that potently induce quiescent cells to divide. Work on cultured fibroblasts suggested they were essential for division, but in vivo analysis in the developing retina and other tissues disproved this notion. The retina, therefore, is an ideal location to assess other in vivo adenovirus E2 promoter binding factor (E2f) functions. It is thought that E2f1 directly induces apoptosis, whereas other activating E2fs only induce death indirectly by upregulating E2f1 expression. Indeed, mouse retinoblastoma (Rb)-null retinal neuron death requires E2f1, but not E2f2 or E2f3. However, we report an entirely distinct mechanism in dying cone photoreceptors. These neurons survive Rb loss, but undergo apoptosis in the cancer-prone retina lacking both Rb and its relative p107. We show that while E2f1 killed Rb/p107 null rod, bipolar and ganglion neurons, E2f2 was required and sufficient for cone death, independent of E2f1 and E2f3. Moreover, whereas E2f1-dependent apoptosis was p53 and p73-independent, E2f2 caused p53-dependent cone death. Our in vivo analysis of cone photoreceptors provides unequivocal proof that E2f-induces apoptosis independent of E2f1, and reveals distinct E2f1- and E2f2-activated death pathways in response to a single tumorigenic insult.
C1 [Chen, D.; Chen, Y.; Bremner, R.] Univ Toronto, Dept Ophthalmol & Visual Sci, Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada.
[Chen, D.; Chen, Y.; Bremner, R.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada.
[Chen, D.; Chen, Y.; Bremner, R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Chen, D.] Sichuan Univ, Dept Ophthalmol, Ophthalm Lab, Mol Med Res Ctr, Chengdu 610064, Peoples R China.
[Chen, D.] Sichuan Univ, Torsten Wiesel Res Inst, World Eye Org, State Key Lab Biotherapy,West China Hosp, Chengdu 610064, Peoples R China.
[Forrest, D.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD USA.
RP Bremner, R (reprint author), Univ Toronto, Toronto Western Res Inst, Dept Genet & Dev, 399 Bathurst St,Room Mc6-424, Toronto, ON M5T 2S8, Canada.
EM rbremner@uhnres.utoronto.ca
RI Bremner, Rod/I-6490-2012
OI Bremner, Rod/0000-0001-9184-7212
FU Canadian Institutes for Health Research; Foundation Fighting Blindness
Canada
FX We thank G Leone and L van Parijs for plasmids; CM Craft, PA Hargrave, T
Mak and R Molday for antibodies; G Leone and F McKeon for mice and P
Monnier and R Slack for comments on the manuscript. This work was
supported by grants from the Canadian Institutes for Health Research and
the Foundation Fighting Blindness Canada to RB.
NR 60
TC 10
Z9 10
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD JUL
PY 2013
VL 20
IS 7
BP 931
EP 940
DI 10.1038/cdd.2013.24
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 160EO
UT WOS:000320100000013
PM 23558950
ER
PT J
AU Cahoon, EK
Rozhko, A
Hatch, M
Polyanskaya, O
Ostroumova, E
Tang, M
Nadirov, E
Yauseyenka, V
Savasteeva, I
McConnell, RJ
Pfeiffer, RM
Brenner, AV
AF Cahoon, Elizabeth K.
Rozhko, Alexander
Hatch, Maureen
Polyanskaya, Olga
Ostroumova, Evgenia
Tang, Min
Nadirov, Eldar
Yauseyenka, Vasilina
Savasteeva, Irina
McConnell, Robert J.
Pfeiffer, Ruth M.
Brenner, Alina V.
TI Factors associated with serum thyroglobulin levels in a population
living in Belarus
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID DIFFERENTIATED THYROID-CANCER; CHERNOBYL ACCIDENT; IODINE DEFICIENCY;
HEALTHY-SUBJECTS; MARKER; TG; RADIOIMMUNOASSAY; AUTOANTIBODIES;
CARCINOMA; DISEASE
AB Objective Serum thyroglobulin (Tg) has been associated with a number of thyroid disorders and has been proposed as an indicator of iodine deficiency in a population. However, few studies have addressed the epidemiology of Tg in a population-based setting or in the context of exposure to radioactive iodine-131 (I-131). Our objective was to evaluate baseline levels of Tg in relation to sociodemographic characteristics, iodine status and thyroid function for individuals exposed to I-131. Design A population-based cohort assembled in Belarus following the Chornobyl accident provided demographic factors, clinical data and physiological measurements. Participants Our analytical sample included 10344 subjects of whom 7890 had no thyroid disease and 2454 had evidence of structural or functional thyroid abnormality. Measurements Standardized assays were used to measure serum Tg, urinary iodine, TSH and antibodies to Tg and thyroid peroxidase. Ultrasound was used to assess the presence of nodules and estimate thyroid volume. Results In the fully adjusted model, percent change in Tg was significantly increased among females, smokers and subjects of older age and Tg increased with decreasing urinary iodine concentration, increasing serum TSH and increasing thyroid volume (P-values for trend <0 center dot 0001), and presence of thyroid nodules (P<0 center dot 05). We found a complex interaction between region of residence, rural/urban living, presence/absence of thyroid abnormalities and serum Tg (P<0 center dot 0001). Conclusions In residents of Belarus, serum Tg is significantly related to presence of thyroid abnormalities as well as indicators of thyroid function and iodine deficiency and, therefore, could be used to characterize the iodine status and thyroid function of individuals in the context of epidemiological study.
C1 [Cahoon, Elizabeth K.; Hatch, Maureen; Ostroumova, Evgenia; Brenner, Alina V.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA.
[Rozhko, Alexander; Polyanskaya, Olga; Nadirov, Eldar; Yauseyenka, Vasilina; Savasteeva, Irina] Republican Ctr Radiat Med & Human Ecol, Res Dept, Gomel, Byelarus.
[Tang, Min] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Tang, Min] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[McConnell, Robert J.] Columbia Univ, Coll Phys & Surg, Dept Med, Thyroid Ctr, New York, NY USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA.
RP Cahoon, EK (reprint author), 6120 Execut Blvd,EPS,Room 7053,MSC 7238, Bethesda, MD 20892 USA.
EM khaykine@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010132-17]
NR 35
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD JUL
PY 2013
VL 79
IS 1
BP 120
EP 127
DI 10.1111/cen.12107
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 158SP
UT WOS:000319993500018
PM 23190420
ER
PT J
AU Schoonveld, C
Donsante, A
del Gaudio, D
Waggoner, D
Das, S
Kaler, SG
AF Schoonveld, C.
Donsante, A.
del Gaudio, D.
Waggoner, D.
Das, S.
Kaler, S. G.
TI Prenatal diagnostic conundrum involving anovel ATP7A duplication
SO CLINICAL GENETICS
LA English
DT Letter
ID DISEASES
C1 [Schoonveld, C.] Univ Minnesota, Med Ctr, Fairview Hlth Serv, Minneapolis, MN 55455 USA.
[Donsante, A.; Kaler, S. G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD USA.
[del Gaudio, D.; Waggoner, D.; Das, S.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
RP Kaler, SG (reprint author), NICHD, Program Mol Med, NIH, Bldg 10,Room 10N313,MSC 1853, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008768-10]
NR 7
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD JUL
PY 2013
VL 84
IS 1
BP 97
EP 98
DI 10.1111/cge.12041
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 160QE
UT WOS:000320133500019
PM 23151012
ER
PT J
AU Williams, KW
Word, C
Streck, MR
Titus, MO
AF Williams, Kelli W.
Word, Carolyn
Streck, Maria R.
Titus, M. Olivia
TI Parental Education on Asthma Severity in the Emergency Department and
Primary Care Follow-up Rates
SO CLINICAL PEDIATRICS
LA English
DT Article
DE asthma; severity; education; emergency department; follow-up
ID INNER-CITY CHILDREN; NATIONAL GUIDELINES; RANDOMIZED-TRIAL; VISIT;
BARRIERS; MANAGEMENT; EXACERBATIONS; MEDICATION; INITIATION; ADHERENCE
AB Asthma is the most prevalent chronic condition affecting children and a common chief complaint in emergency departments (EDs). We aimed to improve parents' understanding of their child's asthma severity on accessing our pediatric ED for an acute asthma exacerbation. A retrospective chart review was conducted to determine outpatient follow-up rates from our ED in 2010-2011. In an attempt to educate parents at ED discharge about their child's asthma severity at presentation, we included a visual severity scale on their discharge instructions. Postdischarge telephone interviews were completed to determine postintervention follow-up rates. Asthma follow-up rates at 1 week improved from 20.8% to 50% after intervention. This difference was statistically significant after controlling for age and clinical asthma score with logistic regression (P < .0001). Offering predischarge education about a child's initial asthma severity is a simple intervention that significantly improved follow-up rates for children seen in the ED for asthma exacerbation.
C1 [Williams, Kelli W.; Word, Carolyn; Streck, Maria R.; Titus, M. Olivia] Med Univ S Carolina, Charleston, SC 29425 USA.
RP Williams, KW (reprint author), NIAID, ICMOB, DCR, NIH, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA.
EM kelli.williams@nih.gov
RI Webster, Susan/C-7360-2015
OI Webster, Susan/0000-0002-0684-4226
NR 24
TC 3
Z9 3
U1 2
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD JUL
PY 2013
VL 52
IS 7
BP 612
EP 619
DI 10.1177/0009922813479163
PG 8
WC Pediatrics
SC Pediatrics
GA 156IW
UT WOS:000319816300006
PM 23471520
ER
PT J
AU Mandemakers, W
Abuhatzira, L
Xu, H
Caromile, LA
Hebert, SS
Snellinx, A
Morais, VA
Matta, S
Cai, T
Notkins, AL
De Strooper, B
AF Mandemakers, W.
Abuhatzira, L.
Xu, H.
Caromile, L. A.
Hebert, S. S.
Snellinx, A.
Morais, V. A.
Matta, S.
Cai, T.
Notkins, A. L.
De Strooper, B.
TI Co-regulation of intragenic microRNA miR-153 and its host gene Ia-2
beta: identification of miR-153 target genes with functions related to
IA-2 beta in pancreas and brain
SO DIABETOLOGIA
LA English
DT Article
DE Diabetes; Glucose stimulation; IA-2 beta; MicroRNA; miR-153;
Neurodegeneration
ID AMYLOID PRECURSOR PROTEIN; INSULIN-SECRETION; MONOCLONAL-ANTIBODIES;
EXPRESSION; PHOSPHATASE; DISRUPTION; MICE; GRANULES; PHOGRIN; ROLES
AB We analysed the genomic organisation of miR-153, a microRNA embedded in genes that encode two of the major type 1 diabetes autoantigens, islet-associated protein (IA)-2 and IA-2 beta. We also identified miR-153 target genes that correlated with IA-2 beta localisation and function.
A bioinformatics approach was used to identify miR-153's genomic organisation. To analyse the co-regulation of miR-153 and IA-2 beta, quantitative PCR analysis of miR-153 and Ia-2 beta (also known as Ptprn2) was performed after a glucose stimulation assay in MIN6B cells and isolated murine pancreatic islets, and also in wild-type Ia-2 (also known as Ptprn), Ia-2 beta single knockout and Ia-2/Ia-2 beta double knockout mouse brain and pancreatic islets. Bioinformatics identification of miR-153 target genes and validation via luciferase reporter assays, western blotting and quantitative PCR were also carried out.
Two copies of miR-153, miR-153-1 and miR-153-2, are localised in intron 19 of Ia-2 and Ia-2 beta, respectively. In rodents, only miR-153-2 is conserved. We demonstrated that expression of miR-153-2 and Ia-2 beta in rodents is partially co-regulated as demonstrated by a strong reduction of miR-153 expression levels in Ia-2 beta knockout and Ia-2/Ia-2 beta double knockout mice. miR-153 levels were unaffected in Ia-2 knockout mice. In addition, glucose stimulation, which increases Ia-2 and Ia-2 beta expression, also significantly increased expression of miR-153. Several predicted targets of miR-153 were reduced after glucose stimulation in vitro, correlating with the increase in miR-153 levels.
This study suggests the involvement of miR-153, IA-2 beta and miR-153 target genes in a regulatory network, which is potentially relevant to insulin and neurotransmitter release.
C1 [Mandemakers, W.; Hebert, S. S.; Snellinx, A.; Morais, V. A.; Matta, S.; De Strooper, B.] VIB Ctr Biol Dis, Gasthuisberg O&N4, B-3000 Louvain, Belgium.
[Mandemakers, W.; Hebert, S. S.; Snellinx, A.; Morais, V. A.; Matta, S.; De Strooper, B.] KULeuven, Ctr Human Genet, LIND, Louvain, Belgium.
[Mandemakers, W.; Hebert, S. S.; Snellinx, A.; Morais, V. A.; Matta, S.; De Strooper, B.] KULeuven, Univ Ziekenhuizen, Louvain, Belgium.
[Abuhatzira, L.; Xu, H.; Caromile, L. A.; Cai, T.; Notkins, A. L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA.
[De Strooper, B.] VIB Ctr Biol Dis VIB11, Ctr Human Genet CB4, Gasthuisberg O&N4, B-3000 Louvain, Belgium.
RP De Strooper, B (reprint author), VIB Ctr Biol Dis VIB11, Ctr Human Genet CB4, Gasthuisberg O&N4, Herestr 49 Bus 602, B-3000 Louvain, Belgium.
EM bart.destrooper@cme.vib-kuleuven.be
RI Caromile, Leslie/Q-2980-2016
OI Caromile, Leslie/0000-0003-2193-5190
FU National Institute of Dental and Craniofacial Research, NIH, Bethesda,
MD, USA; Marie Curie Intra-European Fellowship (EIF) [041333]; Flemish
community; University of Leuven, Belgium; European Research Commission
(ERC) grant (EU Commission)
FX This work was supported, in part, by the Intramural Research Program of
the National Institute of Dental and Craniofacial Research, NIH,
Bethesda, MD, USA, a Marie Curie Intra-European Fellowship (EIF proposal
number 041333) awarded to W. Mandemakers, and a Methusalem grant
(Flemish community and University of Leuven, Belgium) and European
Research Commission (ERC) grant (EU Commission) to B. De Strooper.
NR 48
TC 13
Z9 13
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD JUL
PY 2013
VL 56
IS 7
BP 1547
EP 1556
DI 10.1007/s00125-013-2901-5
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 157FL
UT WOS:000319881300012
PM 23595248
ER
PT J
AU Goedert, JJ
AF Goedert, James J.
TI The microbiota and human health: beyond exploration
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID DIVERSITY
C1 NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010214-03]
NR 5
TC 3
Z9 3
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD JUL
PY 2013
VL 43
IS 7
BP 657
EP 659
DI 10.1111/eci.12100
PG 3
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 160NW
UT WOS:000320127400001
PM 23611431
ER
PT J
AU Bataller, R
Gao, B
AF Bataller, Ramon
Gao, Bin
TI Dissecting the role of CB1 receptors on chronic liver diseases
SO GUT
LA English
DT Editorial Material
ID MICE
C1 [Bataller, Ramon] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
[Bataller, Ramon] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Bataller, R (reprint author), Univ N Carolina, Dept Med, 2209 McGavran Greenberg, Chapel Hill, NC 27599 USA.
EM bataller@med.unc.edu; bgao@mail.nih.gov
FU Intramural NIH HHS [Z99 AA999999, ZIA AA000369-11]
NR 9
TC 1
Z9 1
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD JUL
PY 2013
VL 62
IS 7
BP 957
EP 958
DI 10.1136/gutjnl-2012-303664
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 158MO
UT WOS:000319975900002
PM 23197412
ER
PT J
AU Narendra, DP
Wang, CX
Youle, RJ
Walker, JE
AF Narendra, Derek P.
Wang, Chunxin
Youle, Richard J.
Walker, John E.
TI PINK1 rendered temperature sensitive by disease-associated and
engineered mutations
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID RECESSIVE PARKINSONISM; DAMAGED MITOCHONDRIA; ACTIVATION SEGMENT;
CRYSTAL-STRUCTURE; PROTEIN-KINASES; MITOPHAGY; RECRUITMENT; P62/SQSTM1;
RECOGNITION; PROTEASOME
AB Mutations in Parkin or PINK1 are the most common cause of recessively inherited parkinsonism. Parkin and PINK1 function in a conserved mitochondrial quality control pathway, in which PINK1, a putative mitochondrial kinase, directs Parkin, a cytosolic E3 ubiquitin ligase, selectively to dysfunctional mitochondria to promote their isolation, immobilization and degradation by macroautophagy (hereafter, mitophagy). As Parkin recruitment to mitochondria is robustly induced by PINK1 expression on the outer mitochondrial membrane, Parkin recruitment to mitochondria was used as an assay for PINK1 function. Unexpectedly, mutation of serine residues within the activation segment of PINK1 uncovered a temperature-sensitive variant of PINK1 (tsPINK1). tsPINK1 allowed for the first time the disassociation of PINK1 activity from its expression and localization. Additionally, extensive mutagenesis identified three disease-associated variants in the activation segment and one in an -helix N-terminal to kinase domain (Q126P) that are similarly thermally labile, suggesting that their activity could be restored post-translationally (e.g. by reducing the temperature or by a chemical or pharmacologic chaperone). Together, these findings suggest that tsPINK1 may represent a valuable tool for the analysis of the PINK1/Parkin pathway in human cells; additionally, as the serine residue promoting thermal lability is conserved among Mus musculus, Danio rerio, Drosophila melanogaster and Caenorhabditis elegans, it may serve as the basis for developing other temperature-sensitive models for the study of recessive parkinsonism and mitophagy. Finally, these results suggest that PINK1 kinase function could be restored for a subset of patients with PINK1 mutations, and perhaps alter the course of their disease.
C1 [Narendra, Derek P.; Walker, John E.] MRC, Mitochondrial Biol Unit, Cambridge CB0 2XY, England.
[Narendra, Derek P.; Wang, Chunxin; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Walker, JE (reprint author), MRC Mitochondrial Biol Unit, Wellcome Trust MRC Bldg,Hills Rd, Cambridge CB2 OXY, England.
EM john.walker@mrc-mbu.cam.ac.uk
RI Wang, Chunxin/B-9312-2016
OI Wang, Chunxin/0000-0001-6015-6806
FU Medical Research Council; National Institute of Neurological Disorders
and Stroke; NIH [1F30AG039185-01]
FX This work received funding support from the Medical Research Council
(J.E.W. and D.P.N.), the intramural program at the National Institute of
Neurological Disorders and Stroke (R.J.Y. and D.P.N.) and NIH training
grant 1F30AG039185-01 (D.P.N.).
NR 42
TC 9
Z9 10
U1 5
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 1
PY 2013
VL 22
IS 13
BP 2572
EP 2589
DI 10.1093/hmg/ddt106
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 160MZ
UT WOS:000320125100003
PM 23459931
ER
PT J
AU Schumacher, FR
Wang, ZM
Skotheim, RI
Koster, R
Chung, CC
Hildebrandt, MAT
Kratz, CP
Bakken, AC
Bishop, DT
Cook, MB
Erickson, RL
Fossa, SD
Greene, MH
Jacobs, KB
Kanetsky, PA
Kolonel, LN
Loud, JT
Korde, LA
Le Marchand, L
Lewinger, JP
Lothe, RA
Pike, MC
Rahman, N
Rubertone, MV
Schwartz, SM
Siegmund, KD
Skinner, EC
Turnbull, C
Van den Berg, DJ
Wu, XF
Yeager, M
Nathanson, KL
Chanock, SJ
Cortessis, VK
McGlynn, KA
AF Schumacher, Fredrick R.
Wang, Zhaoming
Skotheim, Rolf I.
Koster, Roelof
Chung, Charles C.
Hildebrandt, Michelle A. T.
Kratz, Christian P.
Bakken, Anne C.
Bishop, D. Timothy
Cook, Michael B.
Erickson, R. Loren
Fossa, Sophie D.
Greene, Mark H.
Jacobs, Kevin B.
Kanetsky, Peter A.
Kolonel, Laurence N.
Loud, Jennifer T.
Korde, Larissa A.
Le Marchand, Loic
Lewinger, Juan Pablo
Lothe, Ragnhild A.
Pike, Malcolm C.
Rahman, Nazneen
Rubertone, Mark V.
Schwartz, Stephen M.
Siegmund, Kimberly D.
Skinner, Eila C.
Turnbull, Clare
Van den Berg, David J.
Wu, Xifeng
Yeager, Meredith
Nathanson, Katherine L.
Chanock, Stephen J.
Cortessis, Victoria K.
McGlynn, Katherine A.
TI Testicular germ cell tumor susceptibility associated with the UCK2 locus
on chromosome 1q23
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CANCER; RISK; GENES; POLYMORPHISMS; METABOLISM; EXPRESSION; VARIANTS;
RECEPTOR; URIDINE; TRENDS
AB Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four casecontrol studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (P-Combined 6.0 10(9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (P-FBAT 2.3 10(3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.
C1 [Schumacher, Fredrick R.; Lewinger, Juan Pablo; Siegmund, Kimberly D.; Van den Berg, David J.; Cortessis, Victoria K.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Wang, Zhaoming; Chung, Charles C.; Cook, Michael B.; Greene, Mark H.; Jacobs, Kevin B.; Loud, Jennifer T.; Korde, Larissa A.; Yeager, Meredith; Chanock, Stephen J.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wang, Zhaoming; Jacobs, Kevin B.; Yeager, Meredith] NCI Frederick, Canc Genome Res Lab, Div Canc Epidemiol & Genet, Adv Technol Program,SAIC Frederick Inc, Frederick, MD USA.
[Skotheim, Rolf I.; Bakken, Anne C.; Lothe, Ragnhild A.] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Canc Prevent, Oslo, Norway.
[Skotheim, Rolf I.; Bakken, Anne C.; Lothe, Ragnhild A.] Univ Oslo, Fac Med, Ctr Canc Biomed, Oslo, Norway.
[Koster, Roelof; Nathanson, Katherine L.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kanetsky, Peter A.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Kanetsky, Peter A.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Kratz, Christian P.] Hannover Med Sch, Dept Pediat Hematol & Oncol, Ctr Pediat & Adolescent Med, Hannover, Germany.
[Bishop, D. Timothy] St James Univ Hosp, Canc Res UK Clin Ctr Leeds, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds LS9 7TF, W Yorkshire, England.
[Erickson, R. Loren] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Fossa, Sophie D.] Univ Oslo, Norwegian Radium Hosp, Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Korde, Larissa A.] Univ Washington, Div Med Oncol, Seattle Canc Care Alliance, Seattle, WA 98195 USA.
[Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Rahman, Nazneen; Turnbull, Clare] Inst Canc Res, Div Canc Genet, Sutton, Surrey, England.
[Rubertone, Mark V.] USA, Ctr Hlth Promot & Prevent Med, Silver Spring, MD USA.
[Schwartz, Stephen M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Schwartz, Stephen M.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Skinner, Eila C.] Stanford Univ, Dept Urol, Stanford, CA 94305 USA.
RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM preethi.raj@nih.gov; mcglynnk@mail.nih.gov
RI Cook, Michael/A-5641-2009; Koster, Roelof/E-2158-2016;
OI Cook, Michael/0000-0002-0533-7302; Koster, Roelof/0000-0003-1424-8579;
Schwartz, Stephen/0000-0001-7499-8502; Nathanson,
Katherine/0000-0002-6740-0901; Bishop, Tim/0000-0002-8752-8785
FU Intramural Research Program of the National Cancer Institute; Westat,
Inc.; California Cancer Research Program [99-00505V-10260,
03-00174VRS-30021]; National Cancer Institute [1R01 CA102042-01A1];
Whittier Foundation; Abramson Cancer Center at the University of
Pennsylvania; National Institutes of Health [R01CA114478, R01CA085914];
MD Anderson Senior Research Trust Fellowship; Movember; Cancer Research
UK; [HHSN261200655004C]
FX A portion of this work was supported by the Intramural Research Program
of the National Cancer Institute and by support services contract
HHSN261200655004C with Westat, Inc. Support was also provided as
follows: USC GWAS controls were supported by the Multiethnic Cohort
Study (NCI U01-CA98758). USC GWAS testicular cases and Familial Study
were supported by the California Cancer Research Program
(99-00505V-10260, 03-00174VRS-30021) and National Cancer Institute (1R01
CA102042-01A1) grants to V. K. C. and a Whittier Foundation award to the
Norris Comprehensive Cancer Center. Replication effort for the TestPAC
study was supported by the Abramson Cancer Center at the University of
Pennsylvania and National Institutes of Health grant R01CA114478 to P.
A. K. and K.L.N. Replication effort for the ATLAS study was supported by
the National Institutes of Health grant R01CA085914 to S. M. S. MD
Anderson: Center for Translational and Public Health Genomics of the
Duncan Family Institute for Cancer Prevention and Risk Assessment and by
MD Anderson Senior Research Trust Fellowship to X. W. The UK Genetics of
Testicular Cancer Study was supported by Movember and Cancer Research
UK.
NR 33
TC 29
Z9 30
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 1
PY 2013
VL 22
IS 13
BP 2748
EP 2753
DI 10.1093/hmg/ddt109
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 160MZ
UT WOS:000320125100017
PM 23462292
ER
PT J
AU Stambolian, D
Wojciechowski, R
Oexle, K
Pirastu, M
Li, XH
Raffel, LJ
Cotch, MF
Chew, EY
Klein, B
Klein, R
Wong, TY
Simpson, CL
Klaver, CCW
van Duijn, CM
Verhoeven, VJM
Baird, PN
Vitart, V
Paterson, AD
Mitchell, P
Saw, SM
Fossarello, M
Kazmierkiewicz, K
Murgia, F
Portas, L
Schache, M
Richardson, A
Xie, J
Wang, JJ
Rochtchina, E
Viswanathan, AC
Hayward, C
Wright, AF
Polasek, O
Campbell, H
Rudan, I
Oostra, BA
Uitterlinden, AG
Hofman, A
Rivadeneira, F
Amin, N
Karssen, LC
Vingerling, JR
Hosseini, SM
Doring, A
Bettecken, T
Vatavuk, Z
Gieger, C
Wichmann, HE
Wilson, JF
Fleck, B
Foster, PJ
Topouzis, F
McGuffin, P
Sim, XL
Inouye, M
Holliday, EG
Attia, J
Scott, RJ
Rotter, JI
Meitinger, T
Bailey-Wilson, JE
AF Stambolian, Dwight
Wojciechowski, Robert
Oexle, Konrad
Pirastu, Mario
Li, Xiaohui
Raffel, Leslie J.
Cotch, Mary Frances
Chew, Emily Y.
Klein, Barbara
Klein, Ronald
Wong, Tien Y.
Simpson, Claire L.
Klaver, Caroline C. W.
van Duijn, Cornelia M.
Verhoeven, Virginie J. M.
Baird, Paul N.
Vitart, Veronique
Paterson, Andrew D.
Mitchell, Paul
Saw, Seang Mei
Fossarello, Maurizio
Kazmierkiewicz, Krista
Murgia, Federico
Portas, Laura
Schache, Maria
Richardson, Andrea
Xie, Jing
Wang, Jie Jin
Rochtchina, Elena
Viswanathan, Ananth C.
Hayward, Caroline
Wright, Alan F.
Polasek, Ozren
Campbell, Harry
Rudan, Igor
Oostra, Ben A.
Uitterlinden, Andre G.
Hofman, Albert
Rivadeneira, Fernando
Amin, Najaf
Karssen, Lennart C.
Vingerling, Johannes R.
Hosseini, S. M.
Doring, Angela
Bettecken, Thomas
Vatavuk, Zoran
Gieger, Christian
Wichmann, H. -Erich
Wilson, James F.
Fleck, Brian
Foster, Paul J.
Topouzis, Fotis
McGuffin, Peter
Sim, Xueling
Inouye, Michael
Holliday, Elizabeth G.
Attia, John
Scott, Rodney J.
Rotter, Jerome I.
Meitinger, Thomas
Bailey-Wilson, Joan E.
CA DCCT EDIC Res Grp
TI Meta-analysis of genome-wide association studies in five cohorts reveals
common variants in RBFOX1, a regulator of tissue-specific splicing,
associated with refractive error
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; HIGH-GRADE MYOPIA; BEAVER DAM EYE; FAMILIAL
AGGREGATION; SUSCEPTIBILITY LOCUS; OCULAR REFRACTION; OUTDOOR ACTIVITY;
POPULATION; HERITABILITY; CHILDREN
AB Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genome-wide association studies (GWASs) of moderate size have identified several novel risk markers for RE, measured here as mean spherical equivalent (MSE). We performed a GWAS using a total of 7280 samples from five cohorts: the Age-Related Eye Disease Study (AREDS); the KORA study (Cooperative Health Research in the Region of Augsburg); the Framingham Eye Study (FES); the Ogliastra Genetic Park-Talana (OGP-Talana) Study and the Multiethnic Study of Atherosclerosis (MESA). Genotyping was performed on Illumina and Affymetrix platforms with additional markers imputed to the HapMap II reference panel. We identified a new genome-wide significant locus on chromosome 16 (rs10500355, P 3.9 10(9)) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.
C1 [Stambolian, Dwight; Kazmierkiewicz, Krista] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Bethesda, MD USA.
[Wojciechowski, Robert; Simpson, Claire L.; Bailey-Wilson, Joan E.] NHGRI, Bethesda, MD 20892 USA.
[Cotch, Mary Frances; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Oexle, Konrad; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany.
[Pirastu, Mario; Murgia, Federico; Portas, Laura] Natl Res Council Italy, Inst Populat Genet, Sassari, Italy.
[Li, Xiaohui; Raffel, Leslie J.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Klein, Barbara; Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
[Saw, Seang Mei] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Yong Loo Lin Sch Med, Singapore 117548, Singapore.
[Sim, Xueling] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore.
[Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
[Klaver, Caroline C. W.; Verhoeven, Virginie J. M.; Vingerling, Johannes R.] Erasmus MC, Dept Ophthalmol & Epidemiol, Rotterdam, Netherlands.
[van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Rivadeneira, Fernando; Amin, Najaf; Karssen, Lennart C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Baird, Paul N.; Schache, Maria; Richardson, Andrea; Xie, Jing; Wang, Jie Jin] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Vitart, Veronique; Hayward, Caroline; Wright, Alan F.] Univ Edinburgh, IGMM, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Paterson, Andrew D.; Hosseini, S. M.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
[Mitchell, Paul; Wang, Jie Jin; Rochtchina, Elena] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia.
[Mitchell, Paul; Wang, Jie Jin; Rochtchina, Elena] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
[Fossarello, Maurizio] Univ Cagliari, Clin Oculist, Dipartimento Sci Chirurg, Cagliari, Italy.
[DCCT EDIC Res Grp] George Washington Univ, Biostat Ctr, Rockville, MD USA.
[Viswanathan, Ananth C.; Foster, Paul J.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London EC1V 2PD, England.
[Viswanathan, Ananth C.; Foster, Paul J.] UCL Inst Ophthalmol, London EC1V 2PD, England.
[Polasek, Ozren] Univ Split Med Sch, Croatian Ctr Global Hlth, Split, Croatia.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Doring, Angela; Gieger, Christian; Wichmann, H. -Erich] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Bettecken, Thomas; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Vatavuk, Zoran] Hosp Sestre Milosrdnice, Dept Ophthalmol, Zagreb, Croatia.
[Fleck, Brian] Princess Alexandra Eye Pavil, Edinburgh, Midlothian, Scotland.
[Topouzis, Fotis] Aristotle Univ Thessaloniki, AHEPA Hosp, Sch Med, Dept Ophthalmol, GR-54006 Thessaloniki, Greece.
[McGuffin, Peter] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Res Ctr, London WC2R 2LS, England.
[Inouye, Michael] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia.
[Inouye, Michael] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
[Holliday, Elizabeth G.; Attia, John; Scott, Rodney J.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia.
[Holliday, Elizabeth G.; Attia, John; Scott, Rodney J.] Hunter Med Res Inst, Newcastle, NSW, Australia.
[Scott, Rodney J.] Univ Newcastle, Ctr Informat Based Med, Newcastle, NSW 2300, Australia.
[Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia.
[Scott, Rodney J.] John Hunter Hosp, Div Genet, Hunter Area Pathol Serv, Newcastle, NSW, Australia.
RP Bailey-Wilson, JE (reprint author), NHGRI, NIH, 333 Cassell Dr Suite 1200, Baltimore, MD 21131 USA.
EM jebw@mail.nih.gov
RI McGuffin, Peter/A-1565-2012; Attia, John/F-5376-2013; Wang, Jie
Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Meitinger,
Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Klaver,
Caroline/A-2013-2016; Paterson, Andrew/A-4088-2011; Rudan,
Igor/I-1467-2012; Hayward, Caroline/M-8818-2016
OI Bailey-Wilson, Joan/0000-0002-9153-2920; Wojciechowski,
Robert/0000-0002-9593-4652; Baird, Paul/0000-0002-1305-3502; Cotch, Mary
Frances/0000-0002-2046-4350; Gieger, Christian/0000-0001-6986-9554;
Klein, Ronald/0000-0002-4428-6237; Fossarello,
Maurizio/0000-0003-1520-7760; Karssen, Lennart C./0000-0002-1959-342X;
McGuffin, Peter/0000-0002-9888-2907; Hosseini,
Mohsen/0000-0003-3626-9928; Attia, John/0000-0001-9800-1308; Wang, Jie
Jin/0000-0001-9491-4898; Wilson, James F/0000-0001-5751-9178; Polasek,
Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441;
Paterson, Andrew/0000-0002-9169-118X; Rudan, Igor/0000-0001-6993-6884;
Hayward, Caroline/0000-0002-9405-9550
FU Intramural Research Program of the National Human Genome Research
Institute; National Eye Institute; National Institutes of Health; NIH
[RO1EY020483, K08EY022943]; Helmholtz Center Munich; German Federal
Ministry of Education and Research (BMBF); National Heart, Lung and
Blood Institute (NHLBI); MESA; NHLBI [N02-HL-6-4278]; Intramural
Research Program of the National Eye Institute [ZIAEY000403]; National
Center for Research Resources [UL1RR033176]; National Center for
Advancing Translational Sciences [UL1TR000124]; Australian National
Health & Medical Research Council (NHMRC) [974159, 991407, 211069,
457349]; Centre for Clinical Research Excellence (CCRE) in Translational
Clinical Research in Eye Diseases, CCRE in TCR-Eye [529923]; Australian
NHMRC project [512423, 475604, 529912, 590204]; Wellcome Trust, UK, as
part of Wellcome Trust Case Control Consortium 2 [085475/B/08/Z,
085475/08/Z]; NHMRC fellowship scheme [631096, 1028444, 358702, 632909];
Victorian government; Italian Ministry of Education, University and
Research (MIUR) [5571/DSPAR/2002]; Italian Ministry of Education,
University and Research (FIRB) [718/Ric/2005]; National Institute of
Diabetes, Endocrinology and Metabolic Diseases of the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) [N01-DK-6-2204,
R01-DK-077510]; Netherlands Organization of Scientific Research (NWO)
[Vidi 91796357]; Erasmus Medical Center and Erasmus University,
Rotterdam, The Netherlands; Netherlands Organization for Health Research
and Development (ZonMw); UitZicht; Research Institute for Diseases in
the Elderly; Ministry of Education, Culture and Science; Ministry for
Health, Welfare and Sports; European Commission (DG XII); Municipality
of Rotterdam; Netherlands Genomics Initiative/NWO; Center for Medical
Systems Biology of NGI; Lijf en Leven; M.D. Fonds; Henkes Stichting;
Stichting Nederlands Oogheelkundig Onderzoek; Swart van Essen;
Bevordering van Volkskracht; Blindenhulp; Landelijke Stichting voor
Blinden en Slechtzienden; Rotterdamse Vereniging voor Blindenbelangen;
OOG; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid;
Rotterdam Eye Hospital Research Foundation; Topcon Europe; Medical
Research Council (UK); Republic of Croatia Ministry of Science,
Education and Sports [108-1080315-0302]; EU [LSHG-CT-2006-018947]; Chief
Scientist Office of the Scottish Government; Royal Society; Medical
Research Council Human Genetics Unit; European Union framework program 6
EURO-SPAN project [LSHG-CT-2006-018947]; [N01 HC-95159];
[N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163];
[N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167];
[N01-HC-95168]; [N01-HC-95169]; [RR-024156]
FX This work was funded in part by the Intramural Research Program of the
National Human Genome Research Institute (J.E.B.W., R. W., C. L. S.) and
the National Eye Institute (M. C., E.Y.C.), National Institutes of
Health and NIH RO1EY020483 (D. S., J.E.B.W.) and K08EY022943 (R. W.).
The KORA Study is supported by funds from Helmholtz Center Munich and
the German Federal Ministry of Education and Research (BMBF). The
Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health
Association Resource (SHARe) are conducted and supported by the National
Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA
investigators. Support is provided by grants and contracts N01 HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and
RR-024156. Funding for SHARe genotyping was provided by NHLBI Contract
N02-HL-6-4278. Funding for the collection of RE data was supported by
the Intramural Research Program of the National Eye Institute
(ZIAEY000403). Support was also provided by the National Center for
Research Resources, Grant UL1RR033176, and is now at the National Center
for Advancing Translational Sciences, Grant UL1TR000124. The Blue
Mountains Eye Study was supported by the Australian National Health &
Medical Research Council (NHMRC) project grants (IDs 974159, 991407,
211069 and 457349) and Centre for Clinical Research Excellence (CCRE) in
Translational Clinical Research in Eye Diseases, CCRE in TCR-Eye (ID
529923). The Blue Mountains Eye Study GWAS and genotyping costs were
supported by Australian NHMRC project grants (IDs 512423, 475604, 529912
and 590204), and the Wellcome Trust, UK, as part of Wellcome Trust Case
Control Consortium 2 (grant IDs 085475/B/08/Z and 085475/08/Z). E. G. H.
(631096), P.N.B. (1028444) and J.W. (358702 and 632909) are supported by
the NHMRC fellowship scheme. The Center for Eye Research Australia
receives Operational Infrastructure Support from the Victorian
government. OGP-Talana was supported by grants from the Italian Ministry
of Education, University and Research (MIUR) No. 5571/DSPAR/2002 and
(FIRB) D. M no. 718/Ric/2005. The DCCT Research Group is sponsored
through research contracts from the National Institute of Diabetes,
Endocrinology and Metabolic Diseases of the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK, N01-DK-6-2204,
R01-DK-077510) and the National Institutes of Health. A. D. P. holds a
Canada Research Chair in the Genetics of Complex Diseases. The Rotterdam
Study and ERF were supported by the Netherlands Organization of
Scientific Research (NWO) (Vidi 91796357); Erasmus Medical Center and
Erasmus University, Rotterdam, The Netherlands; Netherlands Organization
for Health Research and Development (ZonMw); UitZicht; the Research
Institute for Diseases in the Elderly; the Ministry of Education,
Culture and Science; the Ministry for Health, Welfare and Sports; the
European Commission (DG XII); the Municipality of Rotterdam; the
Netherlands Genomics Initiative/NWO; Center for Medical Systems Biology
of NGI; Lijf en Leven; M.D. Fonds; Henkes Stichting; Stichting
Nederlands Oogheelkundig Onderzoek; Swart van Essen; Bevordering van
Volkskracht; Blindenhulp; Landelijke Stichting voor Blinden en
Slechtzienden; Rotterdamse Vereniging voor Blindenbelangen; OOG;
Algemene Nederlandse Vereniging ter Voorkoming van Blindheid; the
Rotterdam Eye Hospital Research Foundation and Topcon Europe.; The
Croatian studies were funded by grants from the Medical Research Council
(UK), from the Republic of Croatia Ministry of Science, Education and
Sports (108-1080315-0302). We acknowledge the Wellcome Trust Clinical
facility (Edinburgh) for the genotyping of the CROATIA-Vis study, an EU
framework 6 project EUROSPAN (contract no LSHG-CT-2006-018947) for the
genotyping of the CROATIA-Korcula study that was performed at the
Helmholtz Zentrum Munchen (Munich, Germany). ORCADES was supported by
the Chief Scientist Office of the Scottish Government, the Royal
Society, the Medical Research Council Human Genetics Unit and the
European Union framework program 6 EURO-SPAN project (contract no.
LSHG-CT-2006-018947).
NR 57
TC 20
Z9 21
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 1
PY 2013
VL 22
IS 13
BP 2754
EP 2764
DI 10.1093/hmg/ddt116
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 160MZ
UT WOS:000320125100018
PM 23474815
ER
PT J
AU Salehi, B
Preuss, N
van der Veen, JW
Shen, J
Neumeister, A
Drevets, WC
Hodgkinson, C
Goldman, D
Wendland, JR
Singleton, A
Gibbs, JR
Cookson, MR
Hasler, G
AF Salehi, Basira
Preuss, Nora
van der Veen, Jan Willem
Shen, Jun
Neumeister, Alexander
Drevets, Wayne C.
Hodgkinson, Colin
Goldman, David
Wendland, Jens R.
Singleton, Andrew
Gibbs, Jesse R.
Cookson, Mark R.
Hasler, Gregor
TI Age-modulated association between prefrontal NAA and the BDNF gene
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE BDNF; genetic variation; N-acetyl-aspartate; proton magnetic resonance
spectroscopy; SNP
ID MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYL-ASPARTATE; MAJOR DEPRESSIVE
DISORDER; AMINOBUTYRIC-ACID LEVELS; NEUROTROPHIC FACTOR;
ALZHEIMERS-DISEASE; IN-VIVO; BIPOLAR DISORDER; METABOLITE CHANGES; MOOD
DISORDERS
AB Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p=0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480 x age interaction on NAA level (p=0.031). Specifically, the effect of rs1519480 on NAA level became significant at age >= 34.17 yr. NAA level decreased with advancing age for genotype TT (p=0.001) but not for genotype CT (p=0.82) or CC (p=0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.
C1 [Salehi, Basira; Hasler, Gregor] Univ Bern, Psychiat Univ Hosp, Bern, Switzerland.
[Preuss, Nora] Univ Bern, Dept Psychol, Bern, Switzerland.
[van der Veen, Jan Willem; Shen, Jun] NIMH, Magnet Resonance Spect Core, Bethesda, MD 20892 USA.
[Neumeister, Alexander] NYU, Sch Med, New York, NY USA.
[Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] Univ Oklahoma, Coll Med, Laureate Inst Brain Res, Tulsa, OK USA.
[Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA.
[Wendland, Jens R.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
[Singleton, Andrew; Gibbs, Jesse R.; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Hasler, G (reprint author), Psychiat Univ Hosp, Bolligenstr 111, CH-3000 Bern 60, Switzerland.
EM g.hasler@bluewin.ch
RI Singleton, Andrew/C-3010-2009; Hasler, Gregor/E-4845-2012; Goldman,
David/F-9772-2010
OI Hasler, Gregor/0000-0002-8311-0138; Goldman, David/0000-0002-1724-5405
FU Lundebck; Servier; Lilly; Bistol-Myers Squibb; GlaxoSmithKline; Astra
Zeneca; Johnson Johnson; Myriad/Rules Based Medicine; Pfizer; Eisai
FX G. H. received honoraria or consulting fees from Lundebck, Servier,
Lilly, Bistol-Myers Squibb, GlaxoSmithKline and Astra Zeneca for
projects unrelated to this study. W. C. D. received consulting fees from
Johnson & Johnson, Myriad/Rules Based Medicine, Pfizer and Eisai for
projects unrelated to this study. J.R.W. is a current employee of F.
Hoffmann-La Roche.
NR 54
TC 2
Z9 3
U1 0
U2 3
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD JUL
PY 2013
VL 16
IS 6
BP 1185
EP 1193
DI 10.1017/S1461145712001204
PG 9
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 158LS
UT WOS:000319973200001
PM 23253771
ER
PT J
AU Yap, MNF
Bernstein, HD
AF Yap, Mee-Ngan F.
Bernstein, Harris D.
TI Mutations in the Escherichia coli Ribosomal Protein L22 Selectively
Suppress the Expression of a Secreted Bacterial Virulence Factor
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID NASCENT POLYPEPTIDE; TRANSLATION ARREST; EXIT TUNNEL; ERYTHROMYCIN
RESISTANCE; STRUCTURAL BASIS; GENE-EXPRESSION; SECA REGULATION;
OUTER-MEMBRANE; RNA; RECOGNITION
AB Mutations in the ribosomal protein L22 that impair peptide-mediated translation arrest in Escherichia coli have been shown to reduce the expression of several genes, including secA, which encodes an ATPase that drives protein export via the Sec pathway. Here, we used a comparative proteomic approach to obtain insight into the global effects of the L22(Delta 82-84) mutation on gene expression and protein synthesis. While the mutation did not affect or modestly affected the level of most soluble proteins, it dramatically reduced the level of antigen 43 (Ag43), a secreted virulence factor that promotes autoaggregation. The reduced protein concentration correlated with a sharp decrease in the abundance and stability of Ag43 mRNA. We found that the overexpression of secA or the inactivation of genes that encode presecretory and membrane proteins restored Ag43 production in the L22 mutant strain. Furthermore, impairment of the Sec pathway in a wild-type strain reduced Ag43 production but did not significantly affect the synthesis of other presecretory proteins. Taken together, these results indicate that Ag43 gene expression is exquisitely sensitive to the status of the Sec machinery and strongly suggest that the L22 mutation decreases the Ag43 concentration indirectly by reducing secA expression. Our results imply the existence of a novel regulatory mechanism in which the efficiency of protein export is coupled to gene expression and help to explain the modulation of SecA synthesis that has been observed in response to secretion stress.
C1 [Yap, Mee-Ngan F.; Bernstein, Harris D.] NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
[Yap, Mee-Ngan F.] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA.
RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM myap1@slu.edu; harris_bernstein@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of General Medical Sciences [R00GM094212]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and by
grant R00GM094212 (National Institute of General Medical Sciences) to
M.-N.F.Y.
NR 54
TC 3
Z9 3
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD JUL
PY 2013
VL 195
IS 13
BP 2991
EP 2999
DI 10.1128/JB.00211-13
PG 9
WC Microbiology
SC Microbiology
GA 160HH
UT WOS:000320109000005
PM 23625843
ER
PT J
AU Gungor, D
Bornstein, MH
De Leersnyder, J
Cote, L
Ceulemans, E
Mesquita, B
AF Gungor, Derya
Bornstein, Marc H.
De Leersnyder, Jozefien
Cote, Linda
Ceulemans, Eva
Mesquita, Batja
TI Acculturation of Personality: A Three-Culture Study of Japanese,
Japanese Americans, and European Americans
SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY
LA English
DT Article
DE personality; acculturation; Japanese Americans; cultural fit
ID SOJOURNER ADJUSTMENT; PARENTING COGNITIONS; MATERNAL PERSONALITY;
UNITED-STATES; CULTURAL FIT; TRAITS; PROFILES; SELF; PERSPECTIVE;
UNIVERSAL
AB The present study tests the hypothesis that involvement with a new culture instigates changes in personality of immigrants that result in (a) better fit with the norms of the culture of destination and (b) reduced fit with the norms of the culture of origin. Participants were 40 Japanese first-generation immigrants to the United States, 57 Japanese monoculturals, and 60 U.S. monoculturals. All participants completed the Jackson Personality Inventory as a measure of the Big Five; immigrants completed the Japanese American Acculturation Scale. Immigrants' fits with the cultures of destination and origin were calculated by correlating Japanese American mothers' patterns of ratings on the Big Five with the average patterns of ratings of European Americans and Japanese on the same personality dimensions. Japanese Americans became more American and less Japanese in their personality as they reported higher participation in the U.S. culture. The results support the view that personality can be subject to cultural influence.
C1 [Gungor, Derya; De Leersnyder, Jozefien; Ceulemans, Eva; Mesquita, Batja] Univ Louvain, B-3000 Louvain, Belgium.
[Bornstein, Marc H.; Cote, Linda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Bethesda, MD USA.
[Cote, Linda] Marymount Univ, Arlington, VA USA.
RP Gungor, D (reprint author), Univ Louvain, Ctr Social & Cultural Psychol, Tiensestr 102,Bus 3727, B-3000 Louvain, Belgium.
EM Derya.Gungor@ppw.kuleuven.be
OI De Leersnyder, Jozefien/0000-0002-4486-878X
FU Intramural NIH HHS [ZIA HD001119-25, ZIA HD001119-24]
NR 62
TC 8
Z9 8
U1 3
U2 35
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0221
J9 J CROSS CULT PSYCHOL
JI J. Cross-Cult. Psychol.
PD JUL
PY 2013
VL 44
IS 5
BP 701
EP 718
DI 10.1177/0022022112470749
PG 18
WC Psychology, Social
SC Psychology
GA 158OZ
UT WOS:000319983200003
PM 23935211
ER
PT J
AU Hobbs, CV
Tanaka, TQ
Muratova, O
Van Vliet, J
Borkowsky, W
Williamson, KC
Duffy, PE
AF Hobbs, Charlotte V.
Tanaka, Takeshi Q.
Muratova, Olga
Van Vliet, Jillian
Borkowsky, William
Williamson, Kim C.
Duffy, Patrick E.
TI HIV Treatments Have Malaria Gametocyte Killing and Transmission Blocking
Activity
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV; malaria; antiretrovirals; TMP-SMX; gametocytes; transmission
ID PLASMODIUM-FALCIPARUM GAMETOCYTES; TYPE-1 PROTEASE INHIBITORS;
SULFADOXINE-PYRIMETHAMINE; COTRIMOXAZOLE PROPHYLAXIS;
ANTIMALARIAL-DRUGS; GENE-EXPRESSION; IN-VITRO; SULFAMETHOXAZOLE;
TRIMETHOPRIM; MOSQUITO
AB Background. Millions of individuals being treated for human immunodeficiency virus (HIV) live in malaria-endemic areas, but the effects of these treatments on malaria transmission are unknown. While drugs like HIV protease inhibitors (PIs) and trimethoprim-sulfamethoxazole (TMP-SMX) have known activity against parasites during liver or asexual blood stages, their effects on transmission stages require further study.
Methods. The HIV PIs lopinavir and saquinavir, the nonnucleoside reverse-transcriptase inhibitor nevirapine, and the antibiotic TMP-SMX were assessed for activity against Plasmodium falciparum transmission stages. The alamarBlue assay was used to determine the effects of drugs on gametocyte viability, and exflagellation was assessed to determine the effects of drugs on gametocyte maturation. The effects of drug on transmission were assessed by calculating the mosquito oocyst count as a marker for infectivity, using standard membrane feeding assays.
Results. Lopinavir and saquinavir have gametocytocidal and transmission blocking activities at or approaching clinically relevant treatment levels, while nevirapine does not. TMP-SMX is not gametocytocidal, but at prophylactic levels it blocks transmission.
Conclusions. Specific HIV treatments have gametocyte killing and transmission-blocking effects. Clinical studies are warranted to evaluate these findings and their potential impact on eradication efforts.
C1 [Hobbs, Charlotte V.; Muratova, Olga; Van Vliet, Jillian; Duffy, Patrick E.] NIAID, Lab Malaria Vaccinol & Immunol, NIH, Bethesda, MD 20892 USA.
[Tanaka, Takeshi Q.; Williamson, Kim C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Borkowsky, William] NYU, Dept Pediat, Div Infect Dis & Immunol, New York, NY 10016 USA.
[Williamson, Kim C.] Loyola Univ, Dept Biol, Chicago, IL 60626 USA.
RP Hobbs, CV (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM charlotte.hobbs@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Disease, National Institutes of Health; US Public Health
Service, National Institute of Allergy and Infectious Disease, National
Institutes of Health [AI069314]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Disease, National Institutes of
Health; and by the US Public Health Service, National Institute of
Allergy and Infectious Disease, National Institutes of Health (grant
AI069314).
NR 47
TC 12
Z9 13
U1 0
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 1
PY 2013
VL 208
IS 1
BP 139
EP 148
DI 10.1093/infdis/jit132
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 156NX
UT WOS:000319830300019
PM 23539746
ER
PT J
AU Moormann, AM
Sumba, PO
Chelimo, K
Fang, H
Tisch, DJ
Dent, AE
John, CC
Long, CA
Vulule, J
Kazura, JW
AF Moormann, Ann M.
Sumba, Peter Odada
Chelimo, Kiprotich
Fang, Hua
Tisch, Daniel J.
Dent, Arlene E.
John, Chandy C.
Long, Carole A.
Vulule, John
Kazura, James W.
TI Humoral and Cellular Immunity to Plasmodium falciparum Merozoite Surface
Protein 1 and Protection From Infection With Blood-Stage Parasites
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE human immunity; Merozoite Surface Protein 1; humoral immunity; cellular
immunity; interferongamma; interleukin-10; sickle cell trait;
longitudinal study; observational study
ID NATURALLY ACQUIRED-IMMUNITY; MALARIA VACCINE; ANTIBODY-RESPONSES;
INTERFERON-GAMMA; KENYAN ADULTS; CHILDREN; FRAGMENT; ANTIGEN; AREA;
TRANSMISSION
AB Background. Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.
Methods. The relationship between immunoglobulin G (IgG) antibody and both interferon gamma (IFN-gamma) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re) infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya.
Results. Positive IFN-gamma enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP1(42) 3D7 were associated with delayed time to (re) infection, whereas high-titer IgG antibodies to MSP1(42) 3D7 or FVO alleles were not independently predictive of the risk of (re) infection. When IFN-gamma and IL-10 responses were both present, the protective effect of IFN-gamma was abrogated. A Cox proportional hazard model including IFN-gamma, IL-10, MSP1(42) 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-gamma responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia.
Conclusions. Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.
C1 [Moormann, Ann M.; Tisch, Daniel J.; Dent, Arlene E.; Kazura, James W.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
[Dent, Arlene E.] Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Moormann, Ann M.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01605 USA.
[Moormann, Ann M.; Fang, Hua] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA.
[John, Chandy C.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Sumba, Peter Odada; Chelimo, Kiprotich; Vulule, John] Kenya Govt Med Res Ctr, Ctr Global Hlth Res, Kisumu, Kenya.
[Chelimo, Kiprotich] Maseno Univ, Dept Biomed Sci & Technol, Kisumu, Kenya.
RP Moormann, AM (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01605 USA.
EM ann.moormann@umassmed.edu
FU National Institutes of Health [RO1 AI43906, R01 CA134051]; Fogarty
International Center [1D43TW006576]; Burroughs Wellcome Fund [1006818,
UL1RR031982]; National Center for Research Resources; Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases
FX This work was supported by National Institutes of Health RO1 AI43906 (J.
W. K.), R01 CA134051 (A. M. M.), Fogarty International Center
1D43TW006576 (P. O. S., K. C.), Burroughs Wellcome Fund 1006818 (A. E.
D.), UL1RR031982, National Center for Research Resources (H. J. F.) and
the intramural research program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases (C.L.).
NR 50
TC 16
Z9 16
U1 0
U2 14
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 1
PY 2013
VL 208
IS 1
BP 149
EP 158
DI 10.1093/infdis/jit134
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 156NX
UT WOS:000319830300020
PM 23539744
ER
PT J
AU Kutty, G
England, KJ
Kovacs, JA
AF Kutty, Geetha
England, Katherine J.
Kovacs, Joseph A.
TI Expression of Pneumocystis jirovecii Major Surface Glycoprotein in
Saccharomyces cerevisiae
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Pneumocystis jirovecii; major surface glycoprotein; upstream conserved
sequence; antigenic variation; GPI anchored protein
ID CULTURED LUNG-CELLS; CARINII; PROTEINS; SEQUENCE; GENES; WALL; SITE;
VARIANTS; ANTIGEN; REGION
AB The major surface glycoprotein (Msg), which is the most abundant protein expressed on the cell surface of Pneumocystis organisms, plays an important role in the attachment of this organism to epithelial cells and macrophages. In the present study, we expressed Pneumocystis jirovecii Msg in Saccharomyces cerevisiae, a phylogenetically related organism. Full-length P. jirovecii Msg was expressed with a DNA construct that used codons optimized for expression in yeast. Unlike in Pneumocystis organisms, recombinant Msg localized to the plasma membrane of yeast rather than to the cell wall. Msg expression was targeted to the yeast cell wall by replacing its signal peptide, serine-threonine-rich region, and glycophosphatidylinositol anchor signal region with the signal peptide of cell wall protein a-agglutinin of S. cerevisiae, the serine-threonine-rich region of epithelial adhesin (Epa1) of Candida glabrata, and the carboxyl region of the cell wall protein (Cwp2) of S. cerevisiae, respectively. Immunofluorescence analysis and treatment with beta-1,3 glucanase demonstrated that the expressed Msg fusion protein localized to the yeast cell wall. Surface expression of Msg protein resulted in increased adherence of yeast to A549 alveolar epithelial cells. Heterologous expression of Msg in yeast will facilitate studies of the biologic properties of Pneumocystis Msg.
C1 [Kutty, Geetha; England, Katherine J.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Kovacs, JA (reprint author), Bldg 10,Rm 2C145,MSC 1662, Bethesda, MD 20892 USA.
EM jkovacs@mail.nih.gov
FU National Institutes of Health Clinical Center
FX This work was supported by the Intramural Research Program of the
National Institutes of Health Clinical Center.
NR 33
TC 2
Z9 3
U1 1
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 1
PY 2013
VL 208
IS 1
BP 170
EP 179
DI 10.1093/infdis/jit131
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 156NX
UT WOS:000319830300022
PM 23532098
ER
PT J
AU Kiesel, BF
Parise, RA
Tjornelund, J
Christensen, MK
Loza, E
Tawbi, H
Chu, E
Kummar, S
Beumer, JH
AF Kiesel, Brian F.
Parise, Robert A.
Tjornelund, Jette
Christensen, Mette K.
Loza, Einars
Tawbi, Hussein
Chu, Edward
Kummar, Shivaani
Beumer, Jan H.
TI LC-MS/MS assay for the quantitation of the HDAC inhibitor belinostat and
five major metabolites in human plasma
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE HDAC; Belinostat; Tandem mass spectrometry; Metabolites; Assay;
Validation
ID HISTONE DEACETYLASE; CANCER
AB The histone deacetylase inhibitor belinostat is being evaluated clinically as a single agent in the treatment of peripheral T-cell lymphomas and in combination with other anticancer agents to treat a wide range of human cancers including acute leukemias and solid tumors. To determine the pharmacokinetics of belinostat in the NCI ODWG liver dysfunction study, we developed and validated an LC-MS/MS assay for the quantitation of belinostat and five major metabolites in 0.05 mL human plasma. After protein precipitation, chromatographic separation was achieved with a Waters Acquity BEH C18 column and a linear gradient of 0.1% formic acid in acetonitrile and water. Detection with an ABI 4000Q mass spectrometer utilized both electrospray positive and negative mode ionization. The assay was linear from 30 to 5000 ng/mL for all six analytes and proved to be accurate (92.0-104.4%) and precise (CV <13.7%), and fulfilled FDA criteria for bioanalytical method validation. We demonstrated the suitability of this assay for measuring parent drug and five major metabolites in plasma from a patient who was administered belinostat IV at a dose of 400 mg/m(2). The LC-MS/MS assay that has been developed will be an essential tool to further define the metabolism and pharmacology of belinostat in the ongoing liver organ dysfunction as well as other studies that investigate belinostat with other anticancer agents. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Kiesel, Brian F.; Parise, Robert A.; Tawbi, Hussein; Chu, Edward; Beumer, Jan H.] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA.
[Parise, Robert A.; Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA.
[Tjornelund, Jette; Christensen, Mette K.] Topotarget AS, Copenhagen, Denmark.
[Loza, Einars] Latvian Inst Organ Synth, Riga, Latvia.
[Chu, Edward] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA.
[Kummar, Shivaani] NCI, Bethesda, MD 20892 USA.
RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA.
EM beumerj@gmail.com
OI Beumer, Jan/0000-0002-8978-9401
FU Spectrum Pharmaceuticals Inc.; Topotarget A/S [U01-CA099168,
N01-CM62209]; [P30-CA47904]
FX Support: Spectrum Pharmaceuticals Inc., Topotarget A/S, grant
U01-CA099168 and contract N01-CM62209 (NCI-CTEP). This project used the
UPCI Clinical Pharmacology Analytical Facility (CPAF) and was supported
in part by award P30-CA47904.
NR 8
TC 6
Z9 6
U1 0
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JUL-AUG
PY 2013
VL 81-82
BP 89
EP 98
DI 10.1016/j.jpba.2013.03.025
PG 10
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 156AX
UT WOS:000319793500013
PM 23644904
ER
PT J
AU Barrett, MO
Sesma, JI
Ball, CB
Jayasekara, PS
Jacobson, KA
Lazarowski, ER
Harden, TK
AF Barrett, Matthew O.
Sesma, Juliana I.
Ball, Christopher B.
Jayasekara, P. Suresh
Jacobson, Kenneth A.
Lazarowski, Eduardo R.
Harden, T. Kendall
TI A Selective High-Affinity Antagonist of the P2Y(14) Receptor Inhibits
UDP-Glucose-Stimulated Chemotaxis of Human Neutrophils
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; PHOSPHOLIPASE-C; MOLECULAR-MECHANISMS; GPR105
KIAA0001; NUCLEOTIDE; CELLS; ATP; RELEASE; PATHOPHYSIOLOGY;
IDENTIFICATION
AB The nucleotide-sugar-activated P2Y(14) receptor (P2Y(14)-R) is highly expressed in hematopoietic cells. Although the physiologic functions of this receptor remain undefined, it has been strongly implicated recently in immune and inflammatory responses. Lack of availability of receptor-selective high-affinity antagonists has impeded progress in studies of this and most of the eight nucleotide-activated P2Y receptors. A series of molecules recently were identified by Gauthier et al. (Gauthier et al., 2011) that exhibited antagonist activity at the P2Y(14)-R. We synthesized one of these molecules, a 4,7-disubstituted 2-naphthoic acid derivative (PPTN), and studied its pharmacological properties in detail. The concentration-effect curve of UDP-glucose for promoting inhibition of adenylyl cyclase in C6 glioma cells stably expressing the P2Y(14)-R was shifted to the right in a concentration-dependent manner by PPTN. Schild analyses revealed that PPTN-mediated inhibition followed competitive kinetics, with a K-B of 434 pM observed. In contrast, 1 mu M PPTN exhibited no agonist or antagonist effect at the P2Y(1), P2Y(2), P2Y(4), P2Y(6), P2Y(11), P2Y(12), or P2Y(13) receptors. UDP-glucose-promoted chemotaxis of differentiated HL-60 human promyelocytic leukemia cells was blocked by PPTN with a concentration dependence consistent with the K-B determined with recombinant P2Y(14)-R. In contrast, the chemotactic response evoked by the chemoattractant peptide fMetLeuPhe was unaffected by PPTN. UDP-glucose-promoted chemotaxis of freshly isolated human neutrophils also was blocked by PPTN. In summary, this work establishes PPTN as a highly selective high-affinity antagonist of the P2Y(14)-R that is useful for interrogating the action of this receptor in physiologic systems.
C1 [Barrett, Matthew O.; Ball, Christopher B.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Sesma, Juliana I.; Lazarowski, Eduardo R.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA.
[Jayasekara, P. Suresh; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Harden, TK (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
EM tkh@med.unc.edu
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Institutes of Health National Institute of General Medical
Sciences [GM38213]; National Institutes of Health National Heart, Lung,
and Blood Institute [HL34322]; Intramural Research Program of the
National Institutes of Health [National Institute of Diabetes and
Digestive and Kidney Diseases]
FX This research was supported by the National Institutes of Health
National Institute of General Medical Sciences [Grant GM38213]; the
National Institutes of Health National Heart, Lung, and Blood Institute
[Grant HL34322]; and the Intramural Research Program of the National
Institutes of Health [National Institute of Diabetes and Digestive and
Kidney Diseases].
NR 43
TC 23
Z9 23
U1 0
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUL
PY 2013
VL 84
IS 1
BP 41
EP 49
DI 10.1124/mol.113.085654
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 163YF
UT WOS:000320373900004
PM 23592514
ER
PT J
AU Cullinane, AR
Schaffer, AA
Huizing, M
AF Cullinane, Andrew R.
Schaeffer, Alejandro A.
Huizing, Marjan
TI The BEACH Is Hot: A LYST of Emerging Roles for BEACH-Domain Containing
Proteins in Human Disease
SO TRAFFIC
LA English
DT Review
DE autophagy; LRBA; NBEA; NBEAL1; NBEAL2; NSMAF; WDFY3; WDFY4; WDR81
ID CHEDIAK-HIGASHI-SYNDROME; GRAY PLATELET SYNDROME; PLECKSTRIN HOMOLOGY
DOMAINS; NEUTRAL SPHINGOMYELINASE ACTIVATION;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; WD-REPEAT PROTEINS; UNDIAGNOSED DISEASES;
AGGREGATED PROTEINS; CRYSTAL-STRUCTURE; DIVERSE FUNCTIONS
AB BEACH (named after Beige and Chediak-Higashi') is a conserved approximate to 280 residue domain, present in nine human BEACH domain containing proteins (BDCPs). Most BDCPs are large, containing a PH-like domain for membrane association preceding their BEACH domain, and containing WD40 and other domains for ligand binding. Recent studies found that mutations in individual BDCPs cause several human diseases. BDCP alterations affect lysosome size (LYST and NSMAF), apoptosis (NSMAF), autophagy (LYST, WDFY3, LRBA), granule size (LYST, NBEAL2, NBEA) or synapse formation (NBEA). However, the roles of each BDCP in these membrane events remain controversial. After reviewing studies on individual BDCPs, we propose a unifying hypothesis that BDCPs act as scaffolding proteins that facilitate membrane events, including both fission and fusion, determined by their binding partners. BDCPs may also bind each other, enabling fusion or fission of vesicles that are not necessarily of the same type. Such mechanisms explain why different BDCPs may have roles in autophagy; each BDCP is specific for the cell type or the cargo, but not necessarily specific for attaching to the autophagosome. Further elucidation of these mechanisms, preferably carrying out the same experiment on multiple BDCPs, and possibly using patients' cells, may identify potential targets for therapy.
C1 [Cullinane, Andrew R.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Schaeffer, Alejandro A.] NIH, Natl Biotechnol Ctr, US Dept HHS, Bethesda, MD 20894 USA.
RP Huizing, M (reprint author), NHGRI, Med Genet Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM mhuizing@mail.nih.gov
FU National Institutes of Health; NHGRI; NLM
FX We thank Dr Murat Sincam for his skillful assistance with identifying
genetic variants in human BDCPs. We thank the NIH Undiagnosed Diseases
program for providing access to their exome sequencing database. We
thank two reviewers for their helpful corrections and suggestions. This
research was supported by the Intramural Research Programs of the
National Institutes of Health, NHGRI and NLM.
NR 80
TC 35
Z9 35
U1 1
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD JUL
PY 2013
VL 14
IS 7
BP 749
EP 766
DI 10.1111/tra.12069
PG 18
WC Cell Biology
SC Cell Biology
GA 161GL
UT WOS:000320180400002
PM 23521701
ER
PT J
AU Hermone, AR
Gussio, R
AF Hermone, Ann R.
Gussio, Rick
TI Calculation Methods for the Enhancement of Pharmaceutical Properties in
Small Molecules: Estimating the Cationic pK(a)
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Article
DE Solvation energy; continuum dielectric; scoring function; training set;
pK(a) calculations; cations; physical chemical properties; computational
chemistry; small molecules; pharmaceutics
ID AQUEOUS-SOLUTION; PREDICTING PK(A); AB-INITIO; COMPUTER-SIMULATIONS;
CHEMICAL-PROCESSES; FREE-ENERGIES; AMINO-ACIDS; SOLVATION; MODEL;
CONTINUUM
AB In this review, a summary of methodologies is covered to enable medicinal chemists to access an overview of pK(a) estimation devices. In order to stave overutilization of costly synthetic resources, the chemist requires an accurate and computationally tractable solution for estimating a pK(a) of a candidate molecule. We focus on the cationic moieties, since they are so fundamentally important in the chemistry of drugs, and possess unique requirements to obtain a reasonably reliable pK(a) estimation.
C1 [Hermone, Ann R.] NCI, Computat Drug Dev Grp, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Gussio, Rick] NCI, Informat Technol Branch, Computat Drug Dev Grp, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Hermone, AR (reprint author), NCI, Computat Drug Dev Grp, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA.
EM hermonea@mail.nih.gov; gussior@mail.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the Frederick National Laboratory for Cancer Research, 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 the mention of
trade names, commercial products, or organizations imply endorsement by
the U.S. Government.
NR 48
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PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1381-6128
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PD JUL
PY 2013
VL 19
IS 23
BP 4310
EP 4315
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 148SC
UT WOS:000319266600012
PM 23170887
ER
PT J
AU Kabirov, KK
Kapetanovic, IM
Benbrook, DM
Dinger, N
Mankovskaya, I
Zakharov, A
Detrisac, C
Pereira, M
Martin-Jimenez, T
Onua, E
Banerjee, A
van Breemen, RB
Nikolic, D
Chen, L
Lyubimov, AV
AF Kabirov, Kasim K.
Kapetanovic, Izet M.
Benbrook, Doris M.
Dinger, Nancy
Mankovskaya, Irina
Zakharov, Alexander
Detrisac, Carol
Pereira, Marcia
Martin-Jimenez, Tomas
Onua, Emmanuel
Banerjee, Aryamitra
van Breemen, Richard B.
Nikolic, Dejan
Chen, Lian
Lyubimov, Alexander V.
TI Oral toxicity and pharmacokinetic studies of SHetA2, a new
chemopreventive agent, in rats and dogs
SO DRUG AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE SHetA2; chemoprevention; toxicity; pharmacokinetic; rat; Beagle dog
ID RETINOIC ACID RECEPTOR; FLEXIBLE-HETEROAROTINOIDS; INDUCE APOPTOSIS;
CANCER CELLS; MITOCHONDRIA; SUFFICIENT; CARCINOMA
AB SHetA2 is a heteroarotinoid that has shown selective inhibition of cancer cell growth and an induction of apoptosis without activation of nuclear retinoic acid receptors. In the rat study, SHetA2 was administered in 1% aqueous methylcellulose/0.2% Tween 80 by oral gavage at 0, 100, 500, and 2,000 mg/kg/day for 28 days. The high-dose administration induced decreased activity in male rats, decreased body-weight gains and food consumption, and changes in organ weights. The major metabolite of SHetA2 in rat plasma was monohydroxy SHetA2, which was considerably higher than the parent compound after oral and intravenous administration. Pharmacokinetic analysis showed extremely low (<1%) systemic bioavailability of SHetA2 for all doses tested. The dose of 2,000 mg/kg/day was considered as the lowest observed adverse effect level. The no observed adverse effect level (NOAEL) was 500 mg/kg/day. In the dog study, no toxicity of SHetA2 in 30% aqueous Solutol (R) HS 15 was observed in any tested dose groups (0, 100, 400, and 1,500 mg/kg/day). The major metabolite of SHetA2 in dog plasma was also monohydroxy SHetA2, which was equal to or lower than the parent compound after oral administration. SHetA2 levels in dog plasma were notably higher, when compared to levels in rat plasma. However, exposure was not dose proportional, as exemplified by a lack of proportional increase in maximum concentration or area under the plasma concentration-time curve with increasing dose. The NOAEL was not established and was considered to be above 1,500 mg/kg/day.
C1 [Kabirov, Kasim K.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Onua, Emmanuel; Banerjee, Aryamitra; Lyubimov, Alexander V.] Univ Illinois, Dept Pharmacol, Toxicol Res Lab, Chicago, IL 60612 USA.
[Kapetanovic, Izet M.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
[Benbrook, Doris M.] Univ Oklahoma HSC, Dept Obstet & Gynecol, Gynecol Oncol Sect, Oklahoma City, OK USA.
[Benbrook, Doris M.] Univ Oklahoma HSC, Dept Biochem & Mol Biol, Oklahoma City, OK USA.
[Detrisac, Carol] Charles River Co, Chicago Div, Pathol Associates Int, Chicago, IL USA.
[Pereira, Marcia] Histo Sci Res Labs, Mt Jackson, VA USA.
[Martin-Jimenez, Tomas] Univ Tennessee, Coll Vet Med, Knoxville, TN USA.
[van Breemen, Richard B.; Nikolic, Dejan; Chen, Lian] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL USA.
RP Lyubimov, AV (reprint author), Univ Illinois, Toxicol Res Lab, 808 South Wood St, Chicago, IL 60612 USA.
EM lyubimov@uic.edu
RI Chen, Lian/C-5948-2017
FU National Cancer Institute, Division of Cancer Prevention [N01-CN-43306]
FX These studies were supported by contract number N01-CN-43306 from the
National Cancer Institute, Division of Cancer Prevention.
NR 21
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U1 0
U2 50
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0148-0545
J9 DRUG CHEM TOXICOL
JI Drug Chem. Toxicol.
PD JUL
PY 2013
VL 36
IS 3
BP 284
EP 295
DI 10.3109/01480545.2012.710632
PG 12
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology
SC Chemistry; Pharmacology & Pharmacy; Toxicology
GA 154RB
UT WOS:000319692500004
PM 22947079
ER
PT J
AU Trabert, B
Graubard, BI
Erickson, RL
Zhang, YW
McGlynn, KA
AF Trabert, Britton
Graubard, Barry I.
Erickson, Ralph L.
Zhang, Yawei
McGlynn, Katherine A.
TI Second to fourth digit ratio, handedness and. testicular germ cell
tumors
SO EARLY HUMAN DEVELOPMENT
LA English
DT Article
DE Case-control; Testicular cancer; Hand pattern; Left-handed dominance;
Digit ratio
ID BREAST-CANCER RISK; 2D 4D; WOMEN; TESTOSTERONE; LENGTH; COHORT;
DIETHYLSTILBESTROL; LATERALIZATION; LANGUAGE; SIZE
AB Background: Research on early life exposures and testicular germ cell tumors (TGCT) risk has focused on a possible perinatal etiology with a well-known hypothesis suggesting that hormonal involvement during fetal life is associated with risk. Second-to-fourth digit ratio (2D:4D) and left-hand dominance have been proposed as markers of prenatal hormone exposure.
Aim: To evaluate associations between 2D:4D digit ratio, right minus left 2D:4D (Delta(R-L)), and left-hand dominance and TGCT in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study.
Methods: A total of 246 TGCT cases and 236 non-testicular cancer controls participated in the current study, and completed a self-administered questionnaire. Associations between digit ratio, hand dominance and TGCT were estimated using unconditional logistic regression adjusting for identified covariates.
Results: Right 2D:4D was not associated with TGCT [odds ratio (OR) for a one-standard deviation (SD) increase in right-hand 2D:4D: 1.12, 95% confidence interval (CI): 0.93-1.34]. The results were consistent when evaluating the association based on the left hand. The difference between right and left-hand 2D:4D was also not associated with TGCT risk [OR for a one-SD increase in Delta(R-L): 1.03,95% CI: 0.87-1.23]. Compared to men who reported right-hand dominance, ambidexterity [OR (95% CI) = 0.65 (0.30-1.41)] and left-hand dominance [OR (95% Cl) = 0.79 (0.44-1.44)] were not associated with risk.
Conclusions: These results do not support the hypothesis that prenatal hormonal imbalance is associated with TGCT risk. Given the limited sample size, further evaluation of the relationship between TGCT and prenatal hormonal factors using digit ratio, Delta(R-L), or left-hand dominance and larger sample size are warranted. Published by Elsevier Ireland Ltd.
C1 [Trabert, Britton; McGlynn, Katherine A.] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch,DHHS, Rockville, MD 20852 USA.
[Graubard, Barry I.] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA.
[Erickson, Ralph L.] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Zhang, Yawei] Yale Univ, Yale Sch Publ Hlth, New Haven, CT USA.
RP Trabert, B (reprint author), Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch,DHHS, Suite 550,6120 Execut Blvd, Rockville, MD 20852 USA.
EM trabertbl@mail.nih.gov
RI Trabert, Britton/F-8051-2015
FU National Cancer Institute [CA130110]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute and by grant CA130110 from the National Cancer
Institute.
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U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-3782
J9 EARLY HUM DEV
JI Early Hum. Dev.
PD JUL
PY 2013
VL 89
IS 7
BP 463
EP 466
DI 10.1016/j.earlhumdev.2013.04.001
PG 4
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 154YV
UT WOS:000319713500004
PM 23623693
ER
PT J
AU Ranguelova, K
Rice, AB
Lardinois, OM
Triquigneaux, M
Steinckwich, N
Deterding, LJ
Garantziotis, S
Mason, RP
AF Ranguelova, Kalina
Rice, Annette B.
Lardinois, Olivier M.
Triquigneaux, Mathilde
Steinckwich, Natacha
Deterding, Leesa J.
Garantziotis, Stavros
Mason, Ronald P.
TI Sulfite-mediated oxidation of myeloperoxidase to a free radical:
Immuno-spin trapping detection in human neutrophils
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Human neutrophils; Immuno-spin trapping; Sulfite radicals; Sulfite
toxicity; Free radicals
ID HYDROGEN-PEROXIDE; SULFUR-DIOXIDE; EOSINOPHIL PEROXIDASE; CATALYZED
OXIDATION; ASTHMATIC-PATIENTS; REDOX PROPERTIES; SO5-RADICALS; OXIDASE;
INVOLVEMENT; ACTIVATION
AB Previous studies focused on catalyzed oxidation of (bi)sulfite, leading to the formation of the reactive sulfur trioxide ((SO3-)-S-center dot), peroxymonosulfate ((-O3SOO center dot)), and sulfate (SO4(center dot-)) anion radicals, which can damage target proteins and oxidize them to protein radicals. It is known that these very reactive sulfur- and oxygen-centered radicals can be formed by oxidation of (bi)sulfite by peroxidases. Myeloperoxidase (MPO), an abundant heme protein secreted from activated neutrophils that play a central role in host defense mechanisms, allergic reactions, and asthma, is a likely candidate for initiating the respiratory damage caused by sulfur dioxide. The objective of this study was to examine the oxidative damage caused by (bi)sulfite-derived free radicals in human neutrophils through formation of protein radicals. We used immuno-spin trapping and confocal microscopy to study the protein oxidations driven by sulfite-derived radicals. We found that the presence of sulfite can cause MPO-catalyzed oxidation of MPO to a protein radical in phorbol 12-myristate 13-acetate-activated human neutrophils. We trapped the MPO-derived radicals in situ using the nitrone spin trap 5,5-dimethyl-1-pyrroline N- oxide and detected them immunologically as nitrone adducts in cells. Our present study demonstrates that myeloperoxidase initiates (bi)sulfite oxidation leading to MPO radical damage, possibly leading to (bi)sulfite-exacerbated allergic reactions. Published by Elsevier Inc.
C1 [Ranguelova, Kalina; Triquigneaux, Mathilde; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Rice, Annette B.; Garantziotis, Stavros] NIEHS, Clin Res Unit, NIH, Res Triangle Pk, NC 27709 USA.
[Lardinois, Olivier M.; Deterding, Leesa J.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Steinckwich, Natacha] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Mason, RP (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM mason4@niehs.nih.gov
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
FU NIH, NIEHS
FX The authors thank Mrs. Mary J. Mason and Dr. Ann Motten for their help
in the preparation of the manuscript and Jason Williams, Katina Johnson,
and Andrea Adams from the protein micro characterization core facility
of NIEHS for helpful suggestions and assistance. Also, we thank Ms.
Brenda Yingling and Ms. Jamie D. Marshburn for their technical
assistance. This work was supported by the Intramural Research Program
of the NIH, NIEHS.
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U2 35
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL
PY 2013
VL 60
BP 98
EP 106
DI 10.1016/j.freeradbiomed.2013.01.022
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 151UU
UT WOS:000319486500013
PM 23376232
ER
PT J
AU Valente, AJ
Yoshida, T
Clark, RA
Delafontaine, P
Siebenlist, U
Chandrasekar, B
AF Valente, Anthony J.
Yoshida, Tadashi
Clark, Robert A.
Delafontaine, Patrice
Siebenlist, Ulrich
Chandrasekar, Bysani
TI Advanced oxidation protein products induce cardiomyocyte death via
Nox2/Rac1/superoxide-dependent TRAF3IP2/JNK signaling
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE AOPPs; TRAF3IP2; Oxidative stress; Cell death; Myocardial injury; Free
radicals
ID GLYCATION END-PRODUCTS; NF-KAPPA-B; ACUTE CORONARY SYNDROMES; C-REACTIVE
PROTEIN; NADPH OXIDASE; OXIDIZED LDL; ARTERY-DISEASE; NOX FAMILY; CIKS
ACT1; APOPTOSIS
AB Advanced oxidation protein products (AOPPs) are formed during chronic oxidative stress as a result of reactions between plasma proteins and chlorinated oxidants. Their levels are elevated during various cardiovascular diseases. Because elevated AOPPs serve as independent risk factors for ischemic heart disease, and cardiomyocyte death is a hallmark of ischemic heart disease, we hypothesized that AOPPs will induce cardiomyocyte death. AOPP-modified mouse serum albumin (AOPP-MSA) induced significant death of neonatal mouse cardiomyocytes that was attenuated by knockdown of the receptor for advanced glycation end products, but not CD36. Notably, TRAF3-interacting protein 2 (TRAF3IP2; also known as CIKS or Act1) knockdown blunted AOPP-induced apoptosis. AOPP-MSA stimulated Nox2/Rac1-dependent superoxide generation, TRAF3IP2 expression, and TRAF3IP2-dependent JNK activation. The superoxide anion generating xanthine/xanthine oxidase system and hydrogen peroxide both induced TRAF3IP2 expression. Further, AOPP-MSA induced mitochondrial Bax translocation and release of cytochrome c into cytoplasm. Moreover, AOPP-MSA suppressed antiapoptotic Bcl-2 and Bcl-xL expression. These effects were reversed by TRAF3IP2 knockdown or forced expression of mutant JNK. Similar to its effects in neonatal cardiomyocytes, AOPP-MSA induced adult cardiomyocyte death in part via TRAF3IP2. These results demonstrate for the first time that AOPPs induce cardiomyocyte death via Nox2/Rac1/superoxide-dependent TRAF3IP2/JNK activation in vitro and suggest that AOPPs may contribute to myocardial injury in vivo. Thus TRAF3IP2 may represent a potential therapeutic target in ischemic heart disease. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Valente, Anthony J.; Clark, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Valente, Anthony J.; Clark, Robert A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Yoshida, Tadashi; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA.
[Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA.
RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave, New Orleans, LA 70112 USA.
EM bchandra@tulane.edu
OI Delafontaine, Patrice/0000-0003-3744-3617; Yoshida,
Tadashi/0000-0002-4544-1497
FU Department of Veterans Affairs Research Career Scientist Award; VA
Office of Research and Development Biomedical Laboratory Research and
Development Service Award [11O1BX000246]; NHLBI/NIH [HL-86787]; NHLBI
[HL-70241, HL-80682]
FX B.C. is a recipient of the Department of Veterans Affairs Research
Career Scientist Award and is supported by VA Office of Research and
Development Biomedical Laboratory Research and Development Service Award
11O1BX000246 and NHLBI/NIH Grant HL-86787. The contents of this report
do not represent the views of the Department of Veterans Affairs or the
U.S. government. PD is supported by NHLBI Grants HL-70241 and HL-80682.
NR 49
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL
PY 2013
VL 60
BP 125
EP 135
DI 10.1016/j.freeradbiomed.2013.02.012
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 151UU
UT WOS:000319486500016
PM 23453926
ER
PT J
AU Abdelmegeed, MA
Jang, S
Banerjee, A
Hardwick, JP
Song, BJ
AF Abdelmegeed, Mohamed A.
Jang, Sehwan
Banerjee, Atrayee
Hardwick, James P.
Song, Byoung-Joon
TI Robust protein nitration contributes to acetaminophen-induced
mitochondrial dysfunction and acute liver injury
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Acute liver injury; Acetaminophen; CYP2E1; 3-Nitrotyrosine; Protein
nitration; N-acetylcysteine; Mitochondrial dysfunction; Free radicals
ID NITRIC-OXIDE SYNTHASE; INDUCED HEPATOTOXICITY; COVALENT BINDING;
IMMUNOHISTOCHEMICAL LOCALIZATION; SUPEROXIDE-DISMUTASE;
N-ACETYLCYSTEINE; OXIDATIVE STRESS; TERMINAL KINASE; KNOCKOUT MICE;
MOUSE-LIVER
AB Acetaminophen (APAP), a widely used analgesic/antipyretic agent, can cause liver injury through increased nitrative stress, leading to protein nitration. However, the identities of nitrated proteins and their roles in hepatotoxicity are poorly understood. Thus, we aimed at studying the mechanism of APAP-induced hepatotoxicity by systematic identification and characterization of nitrated proteins in the absence or presence of an antioxidant, N-acetylcysteine (NAC). The levels of nitrated proteins markedly increased at 2 h in mice exposed to a single APAP dose (350 mg/kg ip), which caused severe liver necrosis at 24 h. Protein nitration and liver necrosis were minimal in mice exposed to nontoxic 3-hydroxyacetanilide or animals co-treated with APAP and NAC. Mass-spectral analysis of the affinity-purified nitrated proteins identified numerous mitochondrial and cytosolic proteins, including mitochondrial aldehyde dehydrogenase, Mn-superoxide dismutase, glutathione peroxidase, ATP synthase, and 3-ketoacyl-CoA thiolase, involved in antioxidant defense, energy supply, or fatty acid metabolism. Immunoprecipitation followed by immunoblot with anti-3-nitrotyrosine antibody confirmed that the aforementioned proteins were nitrated in APAP-exposed mice but not in NAC-cotreated mice. Consistently, NAC cotreatment significantly restored the suppressed activity of these enzymes. Thus, we demonstrate a new mechanism by which many nitrated proteins with concomitantly suppressed activity promotes APAP-induced mitochondrial dysfunction and hepatotoxicity. Published by Elsevier Inc.
C1 [Abdelmegeed, Mohamed A.; Jang, Sehwan; Banerjee, Atrayee; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Hardwick, James P.] NE Ohio Med Univ, Coll Med, Dept Integrat Med Sci, Rootstown, OH 44272 USA.
RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
EM bj.song@nih.gov
FU National Institute on Alcohol Abuse and Alcoholism
FX This research was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism. We are thankful to
Dr. Klaus Gawrisch for supporting this study. We are grateful to
ProtTech, Inc and Protea Biosciences, Inc. for determining the protein
sequences by mass-spectral analyses.
NR 69
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL
PY 2013
VL 60
BP 211
EP 222
DI 10.1016/j.freeradbiomed.2013.02.018
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 151UU
UT WOS:000319486500025
PM 23454065
ER
PT J
AU Ehrenshaft, M
Roberts, JE
Mason, RP
AF Ehrenshaft, Marilyn
Roberts, Joan E.
Mason, Ronald P.
TI Hypericin-mediated photooxidative damage of alpha-crystallin in human
lens epithelial cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Singlet oxygen; Hypericin; alpha-Crystallin; Actin; Human lens
epithelial cells; N-formylkynurenine; Free radicals
ID ST-JOHNS-WORT; N-FORMYLKYNURENINE; IMMUNOLOGICAL DETECTION;
FLUORESCENCE; PROTEINS; PHOTOTOXICITY; PERFORATUM; DEPRESSION; CULTURE;
DRUGS
AB St. John's wort (Hypericum perforatum), a perennial herb native to Europe, is widely used for and seems to be effective in treatment of mild to moderate depression. Hypericin, a singlet oxygen-generating photosensitizer that absorbs in both the visible and the UVA range, is considered to be one of the bioactive ingredients of St John's wort, and commercial preparations are frequently calibrated to contain a standard concentration. Hypericin can accumulate in ocular tissues, including lenses, and can bind in vitro to alpha-crystallin, a major lens protein. alpha-crystallin is required for lens transparency and also acts as a chaperone to ensure its own integrity and the integrity of all lens proteins. Because there is no crystallin turnover, damage to alpha-crystallin is cumulative over the lifetime of the lens and can lead to cataracts, the principal cause of blindness worldwide. In this work we study hypericin photosensitization of alpha-crystallin and detect extensive polymerization of bovine cc-crystallin exposed in vitro to hypericin and UVA. We use fluorescence confocal microscopy to visualize binding between hypericin and alpha-crystallin in a human lens epithelial (HLE) cell line. Further, we show that UVA irradiation of hypericin-treated HLE cells results in a dramatic decrease in alpha-crystallin detection concurrent with a dramatic accumulation of the tryptophan oxidation product N-formylkynurenine (NFK). Examination of actin in HLE cells indicates that this cytoskeleton protein accumulates NFK resulting from hypericin-mediated photosensitization. This work also shows that filtration of wavelengths <400 nm provides incomplete protection against cc-crystallin modification and NFK accumulation, suggesting that even by wearing UV-blocking sunglasses, routine users of St. John's wort cannot adequately shield their lenses from hypericin-mediated photosensitized damage. Published by Elsevier Inc.
C1 [Ehrenshaft, Marilyn; Roberts, Joan E.; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Roberts, Joan E.] Fordham Univ, Dept Nat Sci, New York, NY 10023 USA.
RP Ehrenshaft, M (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM ehrensh1@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences
FX The authors thank B. Jean Corbett and Mary Mason for their valuable help
in the preparation of the manuscript. We are grateful to Jeff Tucker and
Dr. Agnes Janoshazi for their expert help with confocal microscopy. This
work was supported by the Intramural Research Program of the National
Institutes of Health and the National Institute of Environmental Health
Sciences.
NR 36
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL
PY 2013
VL 60
BP 347
EP 354
DI 10.1016/j.freeradbiomed.2013.02.023
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 151UU
UT WOS:000319486500038
PM 23453985
ER
PT J
AU Muller, HK
Wegener, G
Liebenberg, N
Zarate, CA
Popoli, M
Elfving, B
AF Muller, Heidi Kaastrup
Wegener, Gregers
Liebenberg, Nico
Zarate, Carlos A., Jr.
Popoli, Maurizio
Elfving, Betina
TI Ketamine regulates the presynaptic release machinery in the hippocampus
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Ketamine; SNARE; Synapsin; Synaptotagmin; CaMKII; Antidepressant
ID RAT PREFRONTAL CORTEX; SYNAPTIC VESICLE PROTEINS; EVOKED GLUTAMATE
RELEASE; NMDA RECEPTOR BLOCKADE; METHYL-D-ASPARTATE; MOOD DISORDERS;
SNARE COMPLEX; KINASE-II; NEUROTRANSMITTER RELEASE; DIFFERENTIAL
EXPRESSION
AB In the search for new drug targets, that may help point the way to develop fast-acting treatments for mood disorders, we have explored molecular pathways regulated by ketamine, an NMDA receptor antagonist, which has consistently shown antidepressant response within a few hours of administration. Using Sprague-Dawley rats we investigated the effects of ketamine on the presynaptic release machinery responsible for neurotransmitter release at I, 2 and 4 h as well as 7 days after administration of a single subanesthetic dose of ketamine (15 mg/kg). A large reduction in the accumulation of SNARE complexes was observed in hippocampal synaptic membranes after I, 2 and 4 h of ketamine administration. In parallel, we found a selective reduction in the expression of the synaptic vesicle protein synaptotagmin I and an increase in the levels of synapsin I in hippocampal synaptosomes suggesting a mechanism by which ketamine reduces SNARE complex formation, in part, by regulating the number of synaptic vesicles in the nerve terminals. Moreover, ketamine reduced Thr(286)-phosphorylated alpha CaMKII and its interaction with syntaxin 1A, which identifies CaMKII as a potential target for second messenger-mediated actions of ketamine. In addition, despite previous reports of ketamine-induced inhibition of GSK-3, we were unable to detect regulation of its activity after ketamine administration. Our findings demonstrate that ketamine rapidly induces changes in the hippocampal presynaptic machinery similar to those that are obtained only with chronic treatments with traditional antidepressants. This suggests that reduction of neurotransmitter release in the hippocampus has possible relevance for the rapid antidepressant effect of ketamine. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Muller, Heidi Kaastrup; Wegener, Gregers; Liebenberg, Nico; Elfving, Betina] Aarhus Univ Hosp, Ctr Psychiat Res, DK-8240 Risskov, Denmark.
[Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[Popoli, Maurizio] Univ Milan, Ctr Excellence Neurodegenerat Dis, Lab Neuropsychopharmacol & Funct Neurogen, Dept Pharmacol & Biomol Sci, Milan, Italy.
RP Muller, HK (reprint author), Aarhus Univ Hosp, Ctr Psychiat Res, Skovagervej 2, DK-8240 Risskov, Denmark.
EM heidmull@rm.dk
OI Elfving, Betina/0000-0001-6939-5088; Wegener,
Gregers/0000-0002-0081-0068
FU AU Ideas; Lundbeck Foundation; Augustinus Foundation; Aase and Ejnar
Danielsens Foundation; Gangsted Foundation; Overlaege Dr. Med. Einar
Geert-Jorgensen and Hustru Ellen Geert-Jorgensens Foundation; Direktor
Kurt Bonnelycke and Hustru Fru Grethe Bonnelyckes Foundation; Dagmar
Marshalls Foundation; Else and Mogens Wedell-Wedellsborgs Foundation;
Direktor Jacob Madsen and Hustru Olga Madsens Foundation; Torben and
Alice Frimodts Foundation; Kong Christian den Tiendes Foundation
FX This study was supported by Grants from AU Ideas, the Lundbeck
Foundation, Augustinus Foundation, Aase and Ejnar Danielsens Foundation,
Gangsted Foundation, Overlaege Dr. Med. Einar Geert-Jorgensen and Hustru
Ellen Geert-Jorgensens Foundation, Direktor Kurt Bonnelycke and Hustru
Fru Grethe Bonnelyckes Foundation, Dagmar Marshalls Foundation, Else and
Mogens Wedell-Wedellsborgs Foundation, Direktor Jacob Madsen and Hustru
Olga Madsens Foundation, Torben and Alice Frimodts Foundation, and Kong
Christian den Tiendes Foundation. The authors thank Laura Musazzi for
technical advices and Pia Hogh Plougmann for her technical assistance.
NR 55
TC 19
Z9 19
U1 0
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD JUL
PY 2013
VL 47
IS 7
BP 892
EP 899
DI 10.1016/j.jpsychires.2013.03.008
PG 8
WC Psychiatry
SC Psychiatry
GA 152RR
UT WOS:000319549300006
PM 23548331
ER
PT J
AU Enoch, MA
Hodgkinson, CA
Gorodetsky, E
Goldman, D
Roy, A
AF Enoch, Mary-Anne
Hodgkinson, Colin A.
Gorodetsky, Elena
Goldman, David
Roy, Alec
TI Independent effects of 5 ' and 3 ' functional variants in the serotonin
transporter gene on suicidal behavior in the context of childhood trauma
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE SLC6A4; 5-HTTLPR; Substance dependence; rs3813034; rs1042173; Suicide
attempt
ID 5-HTT GENE; POLYMORPHISM; AMYGDALA; STRESS; POPULATION; EXPRESSION;
DEPRESSION; GENOTYPE; REGION; ABUSE
AB The serotonin transporter, encoded by the SLC6A4 gene, influences the synaptic actions of serotonin and is responsive to stress hormones. We hypothesized that 5-HTTLPR, a functional SLC6A4 promoter polymorphism, and two tightly-linked, putatively functional 3' UTR SNPs (rs3813034, rs1042173) might have independent effects on suicidal behavior in the context of childhood trauma (CT).
DNA and Childhood Trauma Questionnaire scores were available for a total of 474 African Americans, including 112 suicide attempters and 362 non-suicide attempters. Genotyping was performed for the triallelic 5-HTTLPR polymorphism, 14 SLC6A4 haplotype-tagging SNPs, and 186 ancestry informative markers.
There were independent G x E interactive effects of 5-HTTLPR (p = 0.017) and the rs3813034 -rs1042173 diplotype (p = 0.011) on suicidal behavior. In individuals exposed to high CT the risk of suicide attempt was 0.52 in carriers of the low activity 5-HTTLPR variant and 0.32 in medium/high activity variant carriers. Likewise, CT exposed carriers of the major rs3813034 rs1042173 ATAT diplotype had an increased risk of suicidal behavior relative to the ATCG/CGCG diplotype carriers (0.40 vs 0.31). Neither the 5' nor the 3' functional variants had an effect in individuals without CT: suicide attempt risk = 0.12-0.22. In individuals exposed to high CT the prevalence of suicide attempt was 0.56 in carriers of both 5' and 3' risk variants, 0.39 in carriers of one risk variant and 0.25 in individuals without either risk variant.
Our findings suggest that the 5' and 3' SLC6A4 functional variants have independent effects on the risk for suicidal behavior in CT exposed individuals. Published by Elsevier Ltd.
C1 [Enoch, Mary-Anne; Hodgkinson, Colin A.; Gorodetsky, Elena; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Roy, Alec] New Jersey VA Hlth Care Syst, Dept Vet Affairs, Psychiat Serv, E Orange, NJ USA.
RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA.
EM maenoch@niaaa.nih.gov
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institute on Alcohol Abuse and Alcoholism, NIH; National
Institute of Drug Abuse, NIH [RO1 DA 10336-02]
FX This research was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, NIH and in part by
grant RO1 DA 10336-02 to AR from the National Institute of Drug Abuse,
NIH.
NR 28
TC 7
Z9 7
U1 3
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD JUL
PY 2013
VL 47
IS 7
BP 900
EP 907
DI 10.1016/j.jpsychires.2013.03.007
PG 8
WC Psychiatry
SC Psychiatry
GA 152RR
UT WOS:000319549300007
PM 23558235
ER
PT J
AU Goldwyn, EE
Rohani, P
AF Goldwyn, Eli E.
Rohani, Pejman
TI Bias in Pertussis Incidence Data and Its Implications for Public Health
Epidemiology
SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE
LA English
DT Editorial Material
ID UNITED-STATES; ADULT VACCINATION; DYNAMICS; POPULATION; STRATEGIES;
SIMULATIONS; INFECTIONS; ENGLAND; IMPACT; WALES
C1 [Goldwyn, Eli E.] Univ Calif Davis, Dept Math, Davis, CA 95616 USA.
[Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Goldwyn, EE (reprint author), Univ Calif Davis, Dept Math, 1 Shields Ave, Davis, CA 95616 USA.
EM eegoldwyn@ucdavis.edu
FU NIAID NIH HHS [R01AI101155]
NR 36
TC 2
Z9 2
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1078-4659
J9 J PUBLIC HEALTH MAN
JI J. Public Health Manag. Pract.
PD JUL-AUG
PY 2013
VL 19
IS 4
BP 379
EP 382
DI 10.1097/PHH.0b013e31826d7f95
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 154FQ
UT WOS:000319657800018
PM 23128362
ER
PT J
AU Pandya, AA
Yakel, JL
AF Pandya, Anshul A.
Yakel, Jerrel L.
TI Activation of the alpha 7 nicotinic ACh receptor induces anxiogenic
effects in rats which is blocked by a 5-HT1a receptor antagonist
SO NEUROPHARMACOLOGY
LA English
DT Article
DE 5-HT1a receptor (5-HT1a R); Alpha7 (alpha 7) receptor agonist; Anxiety;
Memory and learning; Nicotinic acetylcholine receptors (nAChRs);
Positive allosteric modulators (PAMs)
ID POSITIVE ALLOSTERIC MODULATOR; SOCIAL-INTERACTION TEST; ELEVATED
PLUS-MAZE; ACETYLCHOLINE-RECEPTOR; HIPPOCAMPAL INTERNEURONS;
SYNAPTIC-TRANSMISSION; DORSAL HIPPOCAMPUS; PARTIAL AGONISTS;
ANIMAL-MODELS; IN-VIVO
AB The alpha 7 nicotinic acetylcholine receptor (nAChR) is highly expressed in different regions of the brain and is associated with cognitive function as well as anxiety. Agonists and positive allosteric modulators (PAMs) of the alpha 7 subtype of nAChRs have been shown to improve cognition. Previously nicotine, which activates both alpha 7 and non-alpha 7 subtypes of nAChRs, has been shown to have an anxiogenic effect in behavioral tests. In this study, we compared the effects of the alpha 7-selective agonist (PNU-282987) and PAM (PNU-120596) in a variety of behavioral tests in Sprague Dawley rats to look at their effects on learning and memory as well as anxiety. We found that neither PNU-282987 nor PNU-120596 improved spatial-learning or episodic memory by themselves. However when cognitive impairment was induced in the rats with scopolamine (1 mg/kg), both PNU-120596 and PNU-282987 were able to reverse this memory impairment and restore it back to normal levels. While PNU-120596 reversed the scopolamineinduced cognitive impairment, it did not have any adverse effect on anxiety. PNU-282987 on the other hand displayed an increase in anxiety-like behavior at a higher dose (10 mg/kg) that was significantly reduced by the serotonin 5-HT1a receptor antagonist WAY-100135. However the alpha 7 receptor antagonist methyllycaconitine was unable to reverse these anxiety-like effects seen with PNU-282987. These results suggest that alpha 7 nAChR PAMs are pharmacologically advantageous over agonists, and should be considered for further development as therapeutic drugs targeting the alpha 7 receptors. Published by Elsevier Ltd.
C1 [Pandya, Anshul A.; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, MD F2-08,POB 12233, Res Triangle Pk, NC 27709 USA.
EM pandyaaa@niehs.nih.gov; yakel@niehs.nih.gov
FU National Institute of Environmental Health Sciences, NIH
FX We would like to thank the NIEHS animal facility and specifically Hanna
Harris for taking care of the rats and for performing injections for
this study. We would also like to thank Pattie Lamb for her involvement
in the process of writing the animal safety protocols for behavior tests
described here. We extend our appreciation to C. Erxleben and R. Saha
for advice in preparing the manuscript. This research was supported by
the Intramural Research Program of National Institute of Environmental
Health Sciences, NIH.
NR 70
TC 23
Z9 23
U1 0
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JUL
PY 2013
VL 70
BP 35
EP 42
DI 10.1016/j.neuropharm.2013.01.004
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 153YB
UT WOS:000319637600005
PM 23321689
ER
PT J
AU Li, JM
Xue, ZQ
Deng, SH
Luo, XG
Patrylo, PR
Rose, GW
Cai, HB
Cai, Y
Yan, XX
AF Li, Jian-Ming
Xue, Zhi-Qin
Deng, Si-Hao
Luo, Xue-Gang
Patrylo, Peter R.
Rose, Gregory W.
Cai, Huaibin
Cai, Yan
Yan, Xiao-Xin
TI Amyloid plaque pathogenesis in 5XFAD mouse spinal cord: retrograde
transneuronal modulation after peripheral nerve injury
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Alzheimer's disease; Amyloidogenesis; BACE1; Neuritic dystrophy;
Synaptoplasticity
ID A-BETA PEPTIDES; ALZHEIMERS-DISEASE; BETA-SECRETASE-1 ELEVATION;
PERMANENT AXOTOMY; MEMORY DEFICITS; TRANSGENIC MICE; NEURON LOSS; ADULT
CAT; IN-VIVO; MOTONEURONS
AB The spinal cord is composed of distinct neuronal groups with well-defined anatomic connections. In some transgenic (Tg) models of Alzheimer's disease (AD), amyloid plaques develop in this structure, although the underlying cellular mechanism remains elusive. We attempted to explore the origin, evolution, and modulation of spinal beta-amyloid (A beta) deposition using Tg mice harboring five familiar AD-related mutations (5XFAD) as an experiential model. Dystrophic neuritic elements with enhanced beta-secretase-1 (BACE1) immunoreactivity (IR) appeared as early as 2 months of age, and increased with age up to 12 months examined in this study, mostly over the ventral horn (VH). Extracellular A beta IR emerged and developed during this same period, site-specifically co-existing with BACE1-labeled neurites often in the vicinity of large VH neurons that expressed the mutant human APP. The BACE1-labeled neurites almost invariably colocalized with beta-amyloid precursor protein (APP) and synaptophysin, and frequently with the vesicular glutamate transporter-1 (VGLUT). Reduced IR for the neuronal-specific nuclear antigen (NeuN) occurred in the VH by 12 months of age. In 8-month-old animals surviving 6 months after a unilateral sciatic nerve transection, there were significant increases of A beta, BACE1, and VGLUT IR in the VN of the ipsilateral relative to contralateral lumbar spinal segments. These results suggest that extracellular A beta deposition in 5XFAD mouse spinal cord relates to a progressive and amyloidogenic synaptic pathology largely involving presynaptic axon terminals from projection neurons in the brain. Spinal neuritic plaque formation is enhanced after peripheral axotomy, suggesting a retrograde transneuronal modulation on pathogenesis.
C1 [Li, Jian-Ming] Changsha Med Univ, Neurosci Res Ctr, Changsha 410219, Hunan, Peoples R China.
[Li, Jian-Ming; Xue, Zhi-Qin; Deng, Si-Hao; Luo, Xue-Gang; Cai, Yan; Yan, Xiao-Xin] Cent South Univ Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.
[Xue, Zhi-Qin] Xinjiang Med Univ, Dept Anat, Urumqi 830011, Xinjiang, Peoples R China.
[Patrylo, Peter R.; Rose, Gregory W.; Yan, Xiao-Xin] Southern Illinois Univ Sch Med, Ctr Integrated Res Cognit & Neural Sci, Carbondale, IL 62901 USA.
[Cai, Huaibin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Yan, XX (reprint author), Cent South Univ Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.
EM yanxiaoxin@csu.edu.cn
RI Cai, Huaibin/H-3359-2013
OI Cai, Huaibin/0000-0002-8596-6108
FU Illinois Department of Public Health; National Natural Science
Foundation of China [81171091, 81171160]; Hunan Natural Science
Foundation [11jj5072]; National Institute on Aging, NIH
[Z01-IAAG000944-04]
FX This study was supported by the Illinois Department of Public Health
(X.X.Y.), the National Natural Science Foundation of China (#81171091 to
X.X.Y. and #81171160 to X.G.L), Hunan Natural Science Foundation
(11jj5072 to J.M.L) and the intramural research program of National
Institute on Aging, NIH (Z01-IAAG000944-04 to H.C.). We thank Elan
Pharmaceuticals for providing the 3D6 antibody.
NR 60
TC 4
Z9 5
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
J9 NEUROTOX RES
JI Neurotox. Res.
PD JUL
PY 2013
VL 24
IS 1
BP 1
EP 14
DI 10.1007/s12640-012-9355-2
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 154NK
UT WOS:000319682500001
PM 23055086
ER
PT J
AU Vandenberg, LN
Colborn, T
Hayes, TB
Heindel, JJ
Jacobs, DR
Lee, DH
Myers, JP
Shioda, T
Soto, AM
vom Saal, FS
Welshons, WV
Zoeller, RT
AF Vandenberg, Laura N.
Colborn, Theo
Hayes, Tyrone B.
Heindel, Jerrold J.
Jacobs, David R., Jr.
Lee, Duk-Hee
Myers, John Peterson
Shioda, Toshi
Soto, Ana M.
vom Saal, Frederick S.
Welshons, Wade V.
Zoeller, R. Thomas
TI Regulatory decisions on endocrine disrupting chemicals should be based
on the principles of endocrinology
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Review
DE Weight of evidence; Organizational; Adaptive effect; Hormesis; Human
exposure; Epidemiology; Flare
ID ORGANIZATIONAL-ACTIVATIONAL HYPOTHESIS; PRENATAL PHTHALATE EXPOSURE;
NUCLEAR RECEPTOR SUPERFAMILY; NONMONOTONIC DOSE-RESPONSES; GOOD
LABORATORY PRACTICES; BISPHENOL-A EXPOSURE; OF-EVIDENCE ANALYSIS;
BREAST-CANCER CELLS; ANOGENITAL DISTANCE; RISK-ASSESSMENT
AB For years, scientists from various disciplines have studied the effects of endocrine disrupting chemicals (EDCs) on the health and wellbeing of humans and wildlife. Some studies have specifically focused on the effects of low doses, i.e. those in the range that are thought to be safe for humans and/or animals. Others have focused on the existence of non-monotonic dose response curves. These concepts challenge the way that chemical risk assessment is performed for EDCs. Continued discussions have clarified exactly what controversies and challenges remain. We address several of these issues, including why the study and regulation of EDCs should incorporate endocrine principles; what level of consensus there is for low dose effects; challenges to our understanding of non-monotonicity; and whether EDCs have been demonstrated to produce adverse effects. This discussion should result in a better understanding of these issues, and allow for additional dialog on their impact on risk assessment. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Vandenberg, Laura N.] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA.
[Vandenberg, Laura N.] Tufts Univ, Dept Biol, Medford, MA 02155 USA.
[Colborn, Theo] Endocrine Disrupt Exchange, Paonia, CO USA.
[Hayes, Tyrone B.] Univ Calif Berkeley, Museum Vertebrate Zool, Energy & Resources Grp, Grp Endocrinol,Lab Integrat Studies Amphibian Bio, Berkeley, CA 94720 USA.
[Hayes, Tyrone B.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
[Heindel, Jerrold J.] NIEHS, Div Extramural Res & Training, NIH DHHS, Res Triangle Pk, NC 27709 USA.
[Jacobs, David R., Jr.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN USA.
[Lee, Duk-Hee] Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Taegu, South Korea.
[Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc Res, Mol Profiling Lab, Charlestown, MA USA.
[Soto, Ana M.] Tufts Univ, Sch Med, Dept Anat & Cell Biol, Medford, MA 02155 USA.
[vom Saal, Frederick S.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA.
[Welshons, Wade V.] Univ Missouri, Dept Biomed Sci, Columbia, MO USA.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
RP Vandenberg, LN (reprint author), Tufts Univ, Ctr Regenerat & Dev Biol, 200 Boston Ave,Suite 4600, Medford, MA 02155 USA.
EM laura.vandenberg@tufts.edu
FU NIH [GM 087107, ES 08314, ES 010026, ES 018764, HL 53560, UMC
MO-VMFC0018]; Susan G. Komen for Cure grant [FAS0703860]; Mitchell Kapor
Foundation; Cornell-Douglas Foundation; Wallace Global Fund; Kendeda
Foundation
FX The authors gratefully acknowledge the following funding sources: NIH
grants GM 087107 (to LNV), ES 08314 (to AMS), ES 010026 (to RTZ), ES
018764 (to FSvS), HL 53560 (to DRJ), UMC MO-VMFC0018 (to WVW), a Susan
G. Komen for Cure grant FAS0703860 (to TS), grants from the Mitchell
Kapor Foundation, the Cornell-Douglas Foundation, and the Wallace Global
Fund (to TBH) and a grant from the Kendeda Foundation (to JPM). The
funders had no role in the preparation of this manuscript.
NR 216
TC 54
Z9 58
U1 10
U2 108
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD JUL
PY 2013
VL 38
BP 1
EP 15
DI 10.1016/j.reprotox.2013.02.002
PG 15
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 152MG
UT WOS:000319535200001
PM 23411111
ER
PT J
AU Okpechi, I
Swanepoel, C
Rayner, B
Gcelu, A
Hodkinson, B
Kalla, A
Ramesar, R
Vorster, A
Adeyemo, A
Heering, P
Tiffin, N
AF Okpechi, I
Swanepoel, C.
Rayner, B.
Gcelu, A.
Hodkinson, B.
Kalla, A.
Ramesar, R.
Vorster, A.
Adeyemo, A.
Heering, P.
Tiffin, N.
TI Systemic lupus erythematosus (SLE) in Cape Town: A precursory report of
the ALUGEN registry
SO CLINICAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Okpechi, I; Swanepoel, C.; Rayner, B.] Univ Cape Town, Div Nephrol & Hypertens, ZA-7700 Rondebosch, South Africa.
[Gcelu, A.; Hodkinson, B.; Kalla, A.] Univ Cape Town, Div Rheumatol, ZA-7700 Rondebosch, South Africa.
[Ramesar, R.; Vorster, A.] Univ Cape Town, Dept Human Genet, ZA-7700 Rondebosch, South Africa.
[Adeyemo, A.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Heering, P.] Univ Dusseldorf Germany, Dept Nephrol, Dusseldorf, Germany.
[Tiffin, N.] Univ Western Cape, MRC Unit Bioinformat Capac Dev, South African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa.
RI Ramesar, Raj/I-6941-2015
OI Ramesar, Raj/0000-0001-5688-1634
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0770-3198
EI 1434-9949
J9 CLIN RHEUMATOL
JI Clin. Rheumatol.
PD JUL
PY 2013
VL 32
SU 2
MA P4
BP S140
EP S141
PG 2
WC Rheumatology
SC Rheumatology
GA AU4HN
UT WOS:000345571500064
ER
PT J
AU Merikangas, K
AF Merikangas, Kathleen
TI Breaking Down the Boundaries : Comorbidity of Mental and Physical
Disorders
SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
LA English
DT Meeting Abstract
DE comorbidity; epidemiology; medical disorders; mood disorders; anxiety
disorders; behavior disorders; ADHD
C1 [Merikangas, Kathleen] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1018-8827
EI 1435-165X
J9 EUR CHILD ADOLES PSY
JI Eur. Child Adolesc. Psych.
PD JUL
PY 2013
VL 22
SU 2
MA W2-01
BP S212
EP S212
PG 1
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA V41LO
UT WOS:000209547900338
ER
PT J
AU Anderson, BL
Pearlman, M
Griffin, J
Schulkin, J
AF Anderson, Britta L.
Pearlman, Mark
Griffin, Jennifer
Schulkin, Jay
TI Conflicting and Changing Breast Cancer Screening Recommendations: Survey
Study of a National Sample of ob-gyns after the Release of the 2009
USPSTF Guidelines
SO JOURNAL FOR HEALTHCARE QUALITY
LA English
DT Article
DE breast cancer; evidence-based practice/guidelines; health promotion and
screening; research quantitative
AB Objective: To assess obstetrician-gynecologists' (obgyns') use of multiple conflicting guidelines assess after the release of the 2009 U.S. Preventive Services Task Force (USPSTF) breast cancer screening recommendations.
Study Design: A nationally representative sample of American College of Obstetricians and Gynecologists (ACOG) Fellows were invited to complete a survey.
Results: A total of 235 of 399 ob-gyns responded (59% response rate). Twenty percent and 89% indicated that USPSTF and ACOG guidelines influence their practice, respectively, 84% are influenced by more than one guideline. The plurality of respondents was able to correctly identify ACOG and USPSTF guidelines on 10 of 12 questions. One-third agreed with both ACOG's and USPSTF's recommendations regarding mammography screening for women 40-49 years old. A total of 42% of the sample made at least one change in their practice after the release of the 2009 USPSTF breast cancer screening guidelines.
Conclusion: Some ob-gyns made changes to their practices after the release of the USPSTF guidelines. When multiple guidelines exist, as in the case with breast cancer screening, physicians utilize multiple, and at times conflicting, guidelines. More research will be needed to better understand the impact (negative or positive) of multiple guidelines on the quality of healthcare.
C1 [Anderson, Britta L.; Schulkin, Jay] Amer Coll Obstetricians & Gynecologists, New York, NY 10029 USA.
[Pearlman, Mark] Univ Michigan Hosp & Hlth Ctr, Dept Obstet & Gynecol, Ann Arbor, MI USA.
[Pearlman, Mark] Univ Michigan Hosp & Hlth Ctr, Dept Surg, Ann Arbor, MI USA.
[Pearlman, Mark] Univ Michigan, Ann Arbor, MI 48109 USA.
[Griffin, Jennifer] Univ Nebraska Med Ctr, Dept Obstet & Gynecol, Omaha, NE USA.
[Schulkin, Jay] Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA.
[Schulkin, Jay] NIMH, Behav Endocrinol Branch, Bethesda, MD USA.
RP Anderson, BL (reprint author), Amer Coll Obstetricians & Gynecologists, New York, NY 10029 USA.
EM banderson@acog.org
FU U.S. Department of Health and Human Services, Health Resources and
Services Administration, Maternal and Child Health Research Program
[UA6MC19010]
FX This study is funded by grant, UA6MC19010, through the U.S. Department
of Health and Human Services, Health Resources and Services
Administration, Maternal and Child Health Research Program.
NR 20
TC 7
Z9 7
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1062-2551
EI 1945-1474
J9 J HEALTHC QUAL
JI J. Healthc. Qual.
PD JUL-AUG
PY 2013
VL 35
IS 4
BP 25
EP 35
DI 10.1111/jhq.12009
PG 11
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA V36OU
UT WOS:000209221800003
PM 23590634
ER
PT J
AU Komarow, HD
Young, M
Nelson, C
Metcalfe, DD
AF Komarow, Hirsh D.
Young, Michael
Nelson, Celeste
Metcalfe, Dean D.
TI Vocal Cord Dysfunction as Demonstrated by Impulse Oscillometry
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
LA English
DT Article
DE Vocal cord dysfunction; impulse oscillometry; asthma; laryngoscopy;
spirometry
AB BACKGROUND: Vocal cord dysfunction (VCD) is a respiratory disorder characterized by inappropriate vocal cord adduction during inspiration. The diagnosis of VCD is challenging, because expected flow volume loop abnormalities are uncommonly noted, and laryngoscopy must be timed to coincide with symptoms.
OBJECTIVE: We wanted to determine the potential role of impulse oscillometry (IOS) in the diagnosis of VCD.
METHODS: We conducted an analysis of six patients in which the diagnosis of VCD was being considered as well as seven healthy subjects and five subjects with asthma. All were evaluated with IOS and spirometry, and patients underwent laryngoscopy. Two patients with suspected VCD who did not exhibit symptoms or abnormal pulmonary function at baseline underwent exercise challenge and repeat studies. One patient with suspected VCD underwent an additional irritant challenge.
RESULTS: VCD was diagnosed by laryngoscopy in three of the six patients in whom the diagnosis of VCD was entertained. These three patients as a group all exhibited higher amplitude (mean, 9.3 cm H(2)0/L/second) and more variable spikes (SD, 4.8 cm H(2)0/L/second) on IOS impedance during inspiration, whereas the three patients in whom the diagnosis was not confirmed by endoscopy did not show these findings (mean, 2.0 cm H(2)0/L/second; P < .0002; SD, 0.8 cm H(2)0/L/second; P < .0001). This pattern was also not observed in the healthy volunteers (mean +/- SD, 1.8 +/- 0.7 cm H(2)0/L/second) and patients with asthma at baseline (mean, 4.2 +/- 1.2 cm H(2)0/L/second) or after exercise challenge (mean, 1.5 +/- 0.5 cm H(2)0/L/second).
CONCLUSIONS: These findings support the conclusion that IOS displays a characteristic pattern in patients with VCD and thus may offer a rapid and noninvasive adjunct to the assessment and diagnosis of patients suspected to have this disorder. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology
C1 [Komarow, Hirsh D.; Nelson, Celeste; Metcalfe, Dean D.] NIAID, NIH, LAD, Bethesda, MD 20892 USA.
[Young, Michael] SAIC Frederick Inc, Frederick Natl Lab Clin Res, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA.
RP Komarow, HD (reprint author), NIAID, NIH, LAD, Bldg 10,Rm 1C129A1,10 Ctr Dr, Bethesda, MD 20892 USA.
EM komarowh@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, and in whole or in part by the National Cancer Institute,
National Institutes of Health, contract no. HHSN261200800001E (M.Y.).
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US government.
NR 32
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Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2198
EI 2213-2201
J9 J ALLER CL IMM-PRACT
JI J. Allergy Clin. Immunol.-Pract.
PD JUL-AUG
PY 2013
VL 1
IS 4
BP 387
EP +
DI 10.1016/j.jaip.2013.05.005
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA V38WW
UT WOS:000209374500010
PM 24565544
ER
PT J
AU Spencer, RG
Pleshko, N
AF Spencer, Richard G.
Pleshko, Nancy
TI How Do Statistical Differences in Matrix-sensitive Magnetic Resonance
Outcomes Translate Into Clinical Assignment Rules?
SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS
LA English
DT Editorial Material
C1 [Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA.
[Pleshko, Nancy] Temple Univ, Dept Bioengn, Tissue Imaging & Spect Lab, Philadelphia, PA 19122 USA.
RP Spencer, RG (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA.
FU Intramural NIH HHS [ZIA AG000922-05]
NR 5
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1067-151X
EI 1940-5480
J9 J AM ACAD ORTHOP SUR
JI J. Am. Acad. Orthop. Surg.
PD JUL
PY 2013
VL 21
IS 7
BP 438
EP 439
DI 10.5435/JAAOS-21-07-438
PG 2
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA V37MX
UT WOS:000209281000009
PM 23818031
ER
PT J
AU Bulea, TC
Kilicarslan, A
Ozdemir, R
Paloski, WH
Contreras-Vidal, JL
AF Bulea, Thomas C.
Kilicarslan, Atilla
Ozdemir, Recep
Paloski, William H.
Contreras-Vidal, Jose L.
TI Simultaneous Scalp Electroencephalography (EEG), Electromyography (EMG),
and Whole-body Segmental Inertial Recording for Multi-modal Neural
Decoding
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Behavior; Issue 77; Neuroscience; Neurobiology; Medicine; Anatomy;
Physiology; Biomedical Engineering; Molecular Biology;
Electroencephalography; EEG; Electromyography; EMG;
electroencephalograph; gait; brain-computer interface; brain machine
interface; neural decoding; over-ground walking; robotic gait; brain;
imaging; clinical techniques
AB Recent studies support the involvement of supraspinal networks in control of bipedal human walking. Part of this evidence encompasses studies, including our previous work, demonstrating that gait kinematics and limb coordination during treadmill walking can be inferred from the scalp electroencephalogram (EEG) with reasonably high decoding accuracies. These results provide impetus for development of non-invasive brain-machine-interface (BMI) systems for use in restoration and/or augmentation of gait-a primary goal of rehabilitation research. To date, studies examining EEG decoding of activity during gait have been limited to treadmill walking in a controlled environment. However, to be practically viable a BMI system must be applicable for use in everyday locomotor tasks such as over ground walking and turning. Here, we present a novel protocol for non-invasive collection of brain activity (EEG), muscle activity (electromyography (EMG)), and whole-body kinematic data (head, torso, and limb trajectories) during both treadmill and over ground walking tasks. By collecting these data in the uncontrolled environment insight can be gained regarding the feasibility of decoding unconstrained gait and surface EMG from scalp EEG.
C1 [Bulea, Thomas C.] NIH, Bethesda, MD 20892 USA.
[Bulea, Thomas C.; Kilicarslan, Atilla; Ozdemir, Recep; Contreras-Vidal, Jose L.] Univ Houston, Dept Elect & Comp Engn, Lab Noninvas Brain Machine Interface Syst, Houston, TX 77004 USA.
[Ozdemir, Recep; Paloski, William H.] Univ Houston, Dept Hlth & Human Performance, Houston, TX 77004 USA.
[Ozdemir, Recep; Paloski, William H.; Contreras-Vidal, Jose L.] Univ Houston, Ctr Neuromotor & Biomech Res, Houston, TX 77004 USA.
[Contreras-Vidal, Jose L.] Univ Houston, Dept Biomed Engn, Houston, TX 77004 USA.
RP Bulea, TC (reprint author), NIH, Bethesda, MD 20892 USA.
EM thomas.bulea@nih.gov
FU National Institute of Neurological Disorders and Stroke (NINDS)
[R01NS075889-01]; Intramural Research Program of the NIH, Clinical
Center; APDM, Inc. (Portland, OR)
FX This work was supported by the National Institute of Neurological
Disorders and Stroke (NINDS) grant # R01NS075889-01. This research was
supported in part by the Intramural Research Program of the NIH,
Clinical Center. The authors also thank Shahriar Iqbal and Yongtian He
for assistance with data collection. The cost of open-access publication
of this article was sponsored by APDM, Inc. (Portland, OR;
http://apdm.com).
NR 22
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U1 1
U2 9
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD JUL
PY 2013
IS 77
AR UNSP e50602
DI 10.3791/50602
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RG
UT WOS:000209227900053
ER
PT J
AU Swamydas, M
Lionakis, MS
AF Swamydas, Muthulekha
Lionakis, Michail S.
TI Isolation, Purification and Labeling of Mouse Bone Marrow Neutrophils
for Functional Studies and Adoptive Transfer Experiments
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Immunology; Issue 77; Cellular Biology; Infection; Infectious Diseases;
Molecular Biology; Medicine; Biomedical Engineering; Bioengineering;
Neutrophils; Adoptive Transfer; immunology; Neutrophils; mouse; bone
marrow; adoptive transfer; density gradient; labeling; CellTracker;
cell; isolation; flow cytometry; animal model
AB Neutrophils are critical effector cells of the innate immune system. They are rapidly recruited at sites of acute inflammation and exert protective or pathogenic effects depending on the inflammatory milieu. Nonetheless, despite the indispensable role of neutrophils in immunity, detailed understanding of the molecular factors that mediate neutrophils' effector and immunopathogenic effects in different infectious diseases and inflammatory conditions is still lacking, partly because of their short half life, the difficulties with handling of these cells and the lack of reliable experimental protocols for obtaining sufficient numbers of neutrophils for downstream functional studies and adoptive transfer experiments. Therefore, simple, fast, economical and reliable methods are highly desirable for harvesting sufficient numbers of mouse neutrophils for assessing functions such as phagocytosis, killing, cytokine production, degranulation and trafficking. To that end, we present a reproducible density gradient centrifugation-based protocol, which can be adapted in any laboratory to isolate large numbers of neutrophils from the bone marrow of mice with high purity and viability. Moreover, we present a simple protocol that uses CellTracker dyes to label the isolated neutrophils, which can then be adoptively transferred into recipient mice and tracked in several tissues for at least 4 hr post-transfer using flow cytometry. Using this approach, differential labeling of neutrophils from wild-type and gene-deficient mice with different CellTracker dyes can be successfully employed to perform competitive repopulation studies for evaluating the direct role of specific genes in trafficking of neutrophils from the blood into target tissues in vivo.
C1 [Swamydas, Muthulekha; Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
EM lionakism@mail.nih.gov
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institute of Health (NIH), USA;
Animal Care and Use Committee of the NIAID
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases (NIAID), National
Institute of Health (NIH), USA.; All mice were maintained at an American
Association for the Accreditation of Laboratory Animal Care-accredited
animal facility at the National Institute of Allergy and Infectious
Diseases (NIAID) and housed in accordance with the procedures outlined
in the Guide for the Care and Use of Laboratory Animals under the
auspices of a protocol approved by the Animal Care and Use Committee of
the NIAID.
NR 22
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U1 3
U2 14
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD JUL
PY 2013
IS 77
AR UNSP e50586
DI 10.3791/50586
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RG
UT WOS:000209227900050
PM 23892876
ER
PT J
AU Horkay, F
AF Horkay, Ferenc
TI Ion Polymer Interactions in DNA Solutions and Gels
SO MACROMOLECULAR SYMPOSIA
LA English
DT Proceedings Paper
CT Polymer Networks Conference (PNG)
CY AUG 12-16, 2012
CL WY
DE calcium ion; DNA; osmotic pressure; polyelectrolyte; small angle neutron
scattering; swelling
ID POLYELECTROLYTE SOLUTIONS; CONDENSATION; TRANSITION; NETWORKS; CATIONS
AB Systematic investigations using small angle neutron scattering (SANS) were made to reveal the effect of calcium ions on the structure of DNA gels and solutions in near-physiological salt solutions. To describe the neutron scattering response two characteristic distances are required. The shorter length scale, R (approximate to 10 angstrom), was found to be governed by the geometry of the DNA chain and is close to the cross-sectional radius of the double helix. The longer length scale L corresponds to the mesh size of the network of overlapping polymer chains. L decreases with increasing DNA concentration as L proportional to C-DNA(-0.73). With increasing CaCl2 concentration both L and the scattering intensity increase. The increase in the scattering intensity reflects the reduction of the osmotic modulus as the calcium ion concentration increases. The values of the osmotic modulus derived from osmotic swelling pressure measurements are in reasonable agreement with those obtained from SANS.
C1 NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA.
RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, 13 South Dr, Bethesda, MD 20892 USA.
EM horkayf@helix.nih.gov
NR 42
TC 0
Z9 0
U1 2
U2 5
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1022-1360
EI 1521-3900
J9 MACROMOL SYMP
JI Macromol. Symp.
PD JUL
PY 2013
VL 329
IS 1
BP 19
EP 26
DI 10.1002/masy.201300028
PG 8
WC Polymer Science
SC Polymer Science
GA AG5BR
UT WOS:000335434600003
ER
PT J
AU Betz, JM
AF Betz, J. M.
TI Nature Exposed to Our Method of Questioning: Reliability of Natural
Product Measurements
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural
Products at a Crossroad - Current and Future Directions
CY JUL 14-17, 2013
CL St Louis, MO
SP Amer Soc Pharmacognosy
C1 [Betz, J. M.] US NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2013
VL 79
IS 10
MA AL1
BP 819
EP 819
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AK8RG
UT WOS:000338695100048
ER
PT J
AU Downey, T
Bosserman, M
Noinaj, N
Buchanan, SK
Rohr, J
AF Downey, T.
Bosserman, M.
Noinaj, N.
Buchanan, S. K.
Rohr, J.
TI Investigating and Re-Engineering Baeyer-Villiger Monooxygenase MtmOIV
for Combinatorial Biosynthesis of Novel Aureolic Acid Anticancer Drug
Analogues
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural
Products at a Crossroad - Current and Future Directions
CY JUL 14-17, 2013
CL St Louis, MO
SP Amer Soc Pharmacognosy
C1 [Downey, T.; Bosserman, M.; Rohr, J.] Univ Kentucky, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
[Noinaj, N.; Buchanan, S. K.] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2013
VL 79
IS 10
MA PA5
BP 826
EP 826
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AK8RG
UT WOS:000338695100076
ER
PT J
AU Divlianska, DB
Wright, AE
Francis, S
Walters, MA
Salomon, CE
Diaz, PW
Hassig, CA
O'Keefe, BR
Reed, JC
Roth, GP
AF Divlianska, D. B.
Wright, A. E.
Francis, S.
Walters, M. A.
Salomon, C. E.
Diaz, P. W.
Hassig, C. A.
O'Keefe, B. R.
Reed, J. C.
Roth, G. P.
TI In Search of Novel Cancer Therapeutics: Assessing the NCI Natural
Product Library against Ten Anti-Apoptotic Protein Targets
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural
Products at a Crossroad - Current and Future Directions
CY JUL 14-17, 2013
CL St Louis, MO
SP Amer Soc Pharmacognosy
C1 [Divlianska, D. B.; Diaz, P. W.; Hassig, C. A.; Roth, G. P.] Sanford Burnham Med Res Inst, Orlando, FL 32827 USA.
[Wright, A. E.] Florida Atlantic Univ, Oceanog Inst, Harbor Branch, Ft Pierce, FL 34946 USA.
[Francis, S.; Walters, M. A.] Univ Minnesota, Inst Therapeut Discovery & Dev, Minneapolis, MN 55414 USA.
[Salomon, C. E.] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA.
[O'Keefe, B. R.] NCI, Mol Targets Lab, CCR, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Reed, J. C.] F Hoffmann La Roche Ltd, PRED, CH-4070 Basel, Switzerland.
RI Divlianska, Daniela/I-3567-2016
OI Divlianska, Daniela/0000-0002-6871-2122
NR 0
TC 0
Z9 0
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2013
VL 79
IS 10
MA PF4
BP 834
EP 834
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AK8RG
UT WOS:000338695100110
ER
PT J
AU Castro, A
Smith, EA
Krumpe, LRH
O'Keefe, BR
Staudt, LM
McMahon, JB
Gustafson, KR
AF Castro, A.
Smith, E. A.
Krumpe, Haugh L. R.
O'Keefe, B. R.
Staudt, L. M.
McMahon, J. B.
Gustafson, K. R.
TI Natural Product Inhibitors of the Arginine-Specific Protease Activity of
MALT1
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural
Products at a Crossroad - Current and Future Directions
CY JUL 14-17, 2013
CL St Louis, MO
SP Amer Soc Pharmacognosy
C1 [Castro, A.; Smith, E. A.; Krumpe, Haugh L. R.; O'Keefe, B. R.; McMahon, J. B.; Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Krumpe, Haugh L. R.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Staudt, L. M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2013
VL 79
IS 10
MA PK9
BP 845
EP 845
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AK8RG
UT WOS:000338695100156
ER
PT J
AU Sunassee, SN
Ransom, T
Heinrich, CJ
McMahon, JB
Gustafson, KR
AF Sunassee, S. N.
Ransom, T.
Heinrich, C. J.
McMahon, J. B.
Gustafson, K. R.
TI New Steroidal Alkaloids from the Marine Sponge Corticium niger that
Inhibit Growth of Human Colon Carcinoma Cells
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural
Products at a Crossroad - Current and Future Directions
CY JUL 14-17, 2013
CL St Louis, MO
SP Amer Soc Pharmacognosy
C1 [Sunassee, S. N.; Ransom, T.; Heinrich, C. J.; McMahon, J. B.; Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2013
VL 79
IS 10
MA PK11
BP 845
EP 845
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AK8RG
UT WOS:000338695100158
ER
PT J
AU Zuck, KM
Rosario, M
Widmer, TL
Newman, DJ
AF Zuck, K. M.
Rosario, M.
Widmer, T. L.
Newman, D. J.
TI New Analogs Produced by the Co-Culture of the Endophyte Xylaria sp and
Phytophthora
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural
Products at a Crossroad - Current and Future Directions
CY JUL 14-17, 2013
CL St Louis, MO
SP Amer Soc Pharmacognosy
C1 [Zuck, K. M.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Nat Prod Support Grp, Frederick, MD 21702 USA.
[Rosario, M.; Newman, D. J.] NCI, Frederick Natl Lab Canc Res, DTP, Nat Prod Branch, Frederick, MD 21702 USA.
[Widmer, T. L.] ARS, USDA, FDWSRU, Ft Detrick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2013
VL 79
IS 10
MA PL24
BP 852
EP 852
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AK8RG
UT WOS:000338695100188
ER
PT J
AU Chan, STS
Popplewell, W
Henrich, CJ
Linehan, WM
Bottaro, DP
McMahon, JB
McKee, TC
Gustafson, KR
AF Chan, S. T. S.
Popplewell, W.
Henrich, C. J.
Linehan, W. M.
Bottaro, D. P.
McMahon, J. B.
McKee, T. C.
Gustafson, K. R.
TI Isolation and Identification of Natural Products from Artocarpus
communis
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural
Products at a Crossroad - Current and Future Directions
CY JUL 14-17, 2013
CL St Louis, MO
SP Amer Soc Pharmacognosy
C1 [Chan, S. T. S.; Popplewell, W.; McMahon, J. B.; McKee, T. C.; Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Henrich, C. J.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Linehan, W. M.; Bottaro, D. P.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2013
VL 79
IS 10
MA PN58
BP 870
EP 870
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AK8RG
UT WOS:000338695100262
ER
PT J
AU Deal, C
AF Deal, C.
TI CHALLENGES AND OPPORTUNITIES: POTENTIALS IN RESEARCH ON AMR GONOCOCCI
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Deal, C.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2013
VL 89
SU 1
MA S05.2
BP A11
EP A11
DI 10.1136/sextrans-2013-051184.0032
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V40SD
UT WOS:000209497400028
ER
PT J
AU Grabowski, MK
Gray, RH
Serwadda, D
Kigozi, G
Gravitt, PE
Nalugoda, F
Renyolds, SJ
Wawer, M
Quinn, TC
Tobian, AAR
AF Grabowski, M. K.
Gray, R. H.
Serwadda, D.
Kigozi, G.
Gravitt, P. E.
Nalugoda, F.
Renyolds, S. J.
Wawer, M.
Quinn, T. C.
Tobian, A. A. R.
TI HIGH RISK HUMAN PAPILLOMAVIRUS VIRAL LOAD AND PERSISTENCE AMONG
HIV-NEGATIVE AND HIV-POSITIVE MEN
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Grabowski, M. K.; Gray, R. H.; Gravitt, P. E.; Renyolds, S. J.; Wawer, M.; Quinn, T. C.; Tobian, A. A. R.] Johns Hopkins, Baltimore, MD USA.
[Gray, R. H.; Serwadda, D.; Nalugoda, F.; Renyolds, S. J.; Wawer, M.] Rakai Hlth Sci Program, Entebbe, Uganda.
[Serwadda, D.] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Kigozi, G.] Rakai Hlth Sci Program, En, Uganda.
[Gravitt, P. E.] Perdana Univ, Grad Sch Med, Serdang, Malaysia.
[Renyolds, S. J.; Quinn, T. C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Tobian, A. A. R.] Rakai Hlth Sci Program, Entebbe, Austria.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2013
VL 89
SU 1
MA P3.222
BP A217
EP A218
DI 10.1136/sextrans-2013-051184.0679
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA V40VR
UT WOS:000209506600071
ER
PT J
AU Grabowski, MK
Lessler, J
Redd, A
Kagaayi, J
Laeyendecker, O
Nalugoda, F
Serwadda, D
Wawer, M
Quinn, TC
Gray, RH
AF Grabowski, M. K.
Lessler, J.
Redd, A.
Kagaayi, J.
Laeyendecker, O.
Nalugoda, F.
Serwadda, D.
Wawer, M.
Quinn, T. C.
Gray, R. H.
TI FREQUENT VIRAL INTRODUCTIONS SUSTAIN LOCAL HIV EPIDEMICS IN RURAL AFRICA
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Grabowski, M. K.; Lessler, J.; Laeyendecker, O.; Wawer, M.; Quinn, T. C.; Gray, R. H.] Johns Hopkins, Baltimore, MD USA.
[Redd, A.; Laeyendecker, O.; Quinn, T. C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Kagaayi, J.; Nalugoda, F.; Serwadda, D.; Wawer, M.; Gray, R. H.] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Serwadda, D.] Makerere Univ, Sch Med, Kampala, Uganda.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2013
VL 89
SU 1
MA S15.1
BP A22
EP A22
DI 10.1136/sextrans-2013-051184.0070
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V40SD
UT WOS:000209497400066
ER
PT J
AU Kenney, J
Derby, N
Aravantinou, M
Rana, S
Lifson, JD
Piatak, M
Gettie, A
Blanchard, J
Robbiani, M
AF Kenney, J.
Derby, N.
Aravantinou, M.
Rana, S.
Lifson, J. D.
Piatak, M., Jr.
Gettie, A.
Blanchard, J.
Robbiani, M.
TI A REPEATED LOW DOSE CO-CHALLENGE MODEL OF SHIV-RT AND HSV-2 IN RHESUS
MACAQUES
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Kenney, J.; Derby, N.; Aravantinou, M.; Rana, S.; Robbiani, M.] Populat Council, New York, NY 10021 USA.
[Lifson, J. D.; Piatak, M., Jr.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Gettie, A.] Aaron Diamond AIDS Res Ctr, New York, NY USA.
[Blanchard, J.] Tulane Natl Primate Res Ctr, Covington, LA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2013
VL 89
SU 1
MA P2.091
BP A116
EP A116
DI 10.1136/sextrans-2013-051184.0355
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V40SD
UT WOS:000209497400351
ER
PT J
AU Marrazzo, J
Rabe, L
Kelly, C
Livant, T
Chirenje, M
Richardson, B
Deal, C
Piper, J
Hillier, S
AF Marrazzo, J.
Rabe, L.
Kelly, C.
Livant, T.
Chirenje, M.
Richardson, B.
Deal, C.
Piper, J.
Hillier, S.
TI HERPES SIMPLEX VIRUS (HSV) INFECTION IN THE VOICE (MTN 003) STUDY:
PRE-EXPOSURE PROPHYLAXIS (PREP) FOR HIV WITH DAILY USE OF ORAL
TENOFOVIR, ORAL TENOFOVIR-EMTRICITABINE, OR VAGINAL TENOFOVIR GEL
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Marrazzo, J.] Univ Washington, Seattle, WA 98195 USA.
[Rabe, L.; Livant, T.; Hillier, S.] Magee Womens Res Inst, Pittsburgh, PA USA.
[Kelly, C.; Richardson, B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Chirenje, M.] Univ Harare, Harare, Zimbabwe.
[Deal, C.; Piper, J.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2013
VL 89
SU 1
MA O11.1
BP A46
EP A46
DI 10.1136/sextrans-2013-051184.0143
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V40SD
UT WOS:000209497400139
ER
PT J
AU Plankey, MW
Hoffman, HJ
Springer, G
Cox, C
Young, MA
Margolick, JB
Torre, P
AF Plankey, M. W.
Hoffman, H. J.
Springer, G.
Cox, C.
Young, M. A.
Margolick, J. B.
Torre, P.
TI THE PREVALENCE OF HEARING SENSITIVITY AMONG HIV-SEROPOSITIVE AND
HIV-SERONEGATIVE MEN AND WOMEN
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Plankey, M. W.; Young, M. A.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Hoffman, H. J.] NIDCD, Bethesda, MD USA.
[Springer, G.; Cox, C.; Margolick, J. B.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Torre, P.] San Diego State Univ, San Diego, CA 92182 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2013
VL 89
SU 1
MA P2.119
BP A124
EP A124
DI 10.1136/sextrans-2013-051184.0383
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V40SD
UT WOS:000209497400379
ER
PT J
AU Quinn, TC
AF Quinn, T. C.
TI HIV TRANSMISSION DYNAMICS; CAN WE TRANSLATE KNOWLEDGE INTO ACTION
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Quinn, T. C.] NIAID, Baltimore, MD USA.
[Quinn, T. C.] Johns Hopkins Univ, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2013
VL 89
SU 1
MA PL02.3
BP A2
EP A3
DI 10.1136/sextrans-2013-051184.0005
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA V40SD
UT WOS:000209497400005
ER
PT J
AU Jiraporn, P
Chintrakarn, P
AF Jiraporn, P.
Chintrakarn, P.
TI Corporate social responsibility (CSR) and CEO luck: are lucky CEOs
socially responsible?
SO APPLIED ECONOMICS LETTERS
LA English
DT Article
DE corporate social responsibility; lucky CEOs; option backdating; agency
theory; G30; G34
AB Lucky' CEOs are given stock option grants on days when the stock price is the lowest in the month of the grant, implying opportunistic timing, severe agency problems and poor corporate governance. We find that lucky (opportunistic) CEOs invest significantly less in CSR. The evidence thus does not support the notion that CSR is primarily used to enhance managers' private benefits at the expense of shareholders. Rather, lucky CEOs appear to view CSR investments as depriving them of the free cash flow they could otherwise exploit.
C1 [Jiraporn, P.] Penn State Univ, Sch Grad Profess Studies, Malvern, PA 19355 USA.
[Jiraporn, P.] Thammasat Univ, Bangkok, Thailand.
[Jiraporn, P.] Mahidol Univ, Coll Management, Bangkok 10700, Thailand.
[Jiraporn, P.] NIDA, Fac Business Adm, Bangkok, Thailand.
[Chintrakarn, P.] MUIC, Nakhon Pathom, Thailand.
RP Jiraporn, P (reprint author), Penn State Univ, Sch Grad Profess Studies, Malvern, PA 19355 USA.
EM pjiraporn@gmail.com
NR 6
TC 4
Z9 4
U1 0
U2 34
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1350-4851
J9 APPL ECON LETT
JI Appl. Econ. Lett.
PD JUL 1
PY 2013
VL 20
IS 11
BP 1036
EP 1039
DI 10.1080/13504851.2013.772291
PG 4
WC Economics
SC Business & Economics
GA 150HB
UT WOS:000319379700003
ER
PT J
AU Forrest, D
Visser, TJ
AF Forrest, Douglas
Visser, Theo J.
TI Thyroid hormone signaling Preface
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Editorial Material
C1 [Forrest, Douglas] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD USA.
[Visser, Theo J.] Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands.
RP Forrest, D (reprint author), NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD USA.
EM forrestd@niddk.nih.gov
FU Intramural NIH HHS
NR 0
TC 2
Z9 2
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD JUL
PY 2013
VL 1830
IS 7
SI SI
BP 3859
EP 3859
DI 10.1016/j.bbagen.2013.03.001
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 148KJ
UT WOS:000319243200001
PM 23651664
ER
PT J
AU Grimaldi, A
Buisine, N
Miller, T
Shi, YB
Sachs, LM
AF Grimaldi, Alexis
Buisine, Nicolas
Miller, Thomas
Shi, Yun-Bo
Sachs, Laurent M.
TI Mechanisms of thyroid hormone receptor action during development:
Lessons from amphibian studies
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Review
DE Thyroid hormone; Transcriptional regulation; Histone modification;
Chromatin remodeling; Coregulator; Amphibian metamorphosis
ID RETINOIC ACID RECEPTORS; CHROMATIN REMODELING COMPLEXES; XENOPUS-LAEVIS
METAMORPHOSIS; GENE-EXPRESSION CHANGES; INTESTINAL STEM-CELLS; HISTONE
DEACETYLASE; TRANSCRIPTIONAL REPRESSION; N-COR; NUCLEAR RECEPTORS;
POSTEMBRYONIC DEVELOPMENT
AB Background: Thyroid hormone (TH) receptor (TR) plays critical roles in vertebrate development. However, the in vivo mechanism of TR action remains poorly explored.
Scope of review: Frog metamorphosis is controlled by TH and mimics the postembryonic period in mammals when high levels of TH are also required. We review here some of the findings on the developmental functions of TH and TR and the associated mechanisms obtained from this model system.
Major conclusion: A dual function model for TR in Anuran development was proposed over a decade ago. That is, unliganded TR recruits corepressors to TH response genes in premetamorphic tadpoles to repress these genes and prevent premature metamorphic changes. Subsequently, when TH becomes available, liganded TR recruits coactivators to activate these same genes, leading to metamorphic changes. Over the years, molecular and genetic approaches have provided strong support for this model. Specifically, it has been shown that unliganded TR recruits histone deacetylase containing corepressor complexes during larval stages to control metamorphic timing, while liganded TR recruits multiple histone modifying and chromatin remodeling coactivator complexes during metamorphosis. These complexes can alter chromatin structure via nucleosome position alterations or eviction and histone modifications to contribute to the recruitment of transcriptional machinery and gene activation.
General significance: The molecular mechanisms of TR action in vivo as revealed from studies on amphibian metamorphosis are very likely applicable to mammalian development as well. These findings provide a new perspective for understanding the diverse effects of TH in normal physiology and diseases caused by TH dysfunction. This article is part of a Special Issue entitled Thyroid hormone signalling. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Grimaldi, Alexis; Buisine, Nicolas; Sachs, Laurent M.] Museum Natl Hist Nat, Dept Regulat Dev & Diversite Mol, CNRS UMR7221, Sect Thyroid Hormone Receptor Funct & Mech Act, F-75231 Paris, France.
[Miller, Thomas; Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Sachs, LM (reprint author), MNHN, CNRS, UMR7221, CP 32,7 Rue Cuvier, F-75231 Paris 05, France.
EM sachs@mnhn.fr
FU Centre National de la Recherche Scientifique; Museum National d'Histoire
Naturelle; CRESCENDO; IDEAL [259679]; TRIGGER [ANR-08-JCIC-0100-01];
National Institute of Child Health and Human Development, NIH;
[LSHM-CT-2005-018652]
FX This work was supported by the "Centre National de la Recherche
Scientifique", the "Museum National d'Histoire Naturelle", "CRESCENDO",
a European Integrated Project funding from FP6 (contract no.
LSHM-CT-2005-018652), "IDEAL", a European Large Integrated Project
funding from FP7 (no. 259679) and "TRIGGER" (ANR-08-JCIC-0100-01), and
the Intramural Research Program of the National Institute of Child
Health and Human Development, NIH.
NR 120
TC 18
Z9 18
U1 3
U2 58
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD JUL
PY 2013
VL 1830
IS 7
SI SI
BP 3882
EP 3892
DI 10.1016/j.bbagen.2012.04.020
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 148KJ
UT WOS:000319243200005
PM 22565053
ER
PT J
AU Kim, WG
Cheng, SY
AF Kim, Won Gu
Cheng, Sheue-yann
TI Thyroid hormone receptors and cancer
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Review
DE Thyroid hormone receptor mutant; Thyroid cancer; Phosphatidylinositol 3
kinase; Src kinase; beta-Catenin; Mouse model
ID FOCAL ADHESION KINASE; C-ERBA-BETA; TRANSFORMING GENE PTTG; CLEAR-CELL
CARCINOMA; MOUSE MODEL; PITUITARY-TUMOR; TR-BETA; V-ERBA;
PHOSPHATIDYLINOSITOL 3-KINASE; NUCLEAR RECEPTOR
AB Background: Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that mediate the actions of the thyroid hormone (T3) in development, growth, and differentiation. The THRA and THRB genes encode several TR isoforms that express in a tissue- and development-dependent manner. In the past decades, a significant advance has been made in the understanding of TR actions in maintaining normal cellular functions. However, the roles of TR.s in human cancer are less well understood. The reduced expression of TRs because of hypermethylation, or deletion of TR genes found in human cancers suggests that TRs could function as tumor suppressors. A close association of somatic mutations of TRs with human cancers further supports the notion that the loss of normal functions of TR could lead to uncontrolled growth and loss of cell differentiation.
Scope of review: In line with the findings from association studies in human cancers, mice deficient in total functional TRs (Thra1(-/-)Thrb(-/-) mice) or with a targeted homozygous mutation of the Thrb gene (denoted PV; Thrb(PV/PV) mice) spontaneously develop metastatic thyroid carcinoma. This review will examine the evidence learned from these genetically engineered mice that provided strong evidence to support the critical role of TRs in human cancer.
Major conclusions: Loss of normal functions of TR by deletion or by mutations could contribute to cancer development, progression and metastasis.
General significance: Novel mechanistic insights are revealed in how aberrant TR activities lead to carcinogenesis. Mouse models of thyroid cancer provide opportunities to identify molecular targets as potential treatment modalities. This article is part of a Special Issue entitled Thyroid hormone signalling. Published by Elsevier B.V.
C1 [Kim, Won Gu; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Bldg 37,Rm 5128,37 Convent Dr MSC 4264, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
OI Kim, Won Gu/0000-0002-8404-7759
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX We regret any reference omissions due to length limitation. We wish to
thank all colleagues and collaborators who have contributed to the work
described in this review. The research described in this review by the
authors and their colleagues at National Cancer Institute was supported
by the Intramural Research Program of the Center for Cancer Research,
National Cancer Institute, National Institutes of Health.
NR 97
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Z9 25
U1 3
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD JUL
PY 2013
VL 1830
IS 7
SI SI
BP 3928
EP 3936
DI 10.1016/j.bbagen.2012.04.002
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 148KJ
UT WOS:000319243200010
PM 22507269
ER
PT J
AU Galindo-Fraga, A
Ortiz-Hernandez, AA
Ramirez-Venegas, A
Vazquez, RV
Moreno-Espinosa, S
Llamosas-Gallardo, B
Perez-Patrigeon, S
Salinger, M
Freimanis, L
Huang, CY
Gu, WJ
Guerrero, ML
Beigel, J
Ruiz-Palacios, GM
AF Galindo-Fraga, Arturo
Ortiz-Hernandez, Ana A.
Ramirez-Venegas, Alejandra
Valdez Vazquez, Rafael
Moreno-Espinosa, Sarbelio
Llamosas-Gallardo, Beatriz
Perez-Patrigeon, Santiago
Salinger, Maggie
Freimanis, Laura
Huang, Chiung-yu
Gu, Wenjuan
Lourdes Guerrero, M.
Beigel, John
Ruiz-Palacios, Guillermo M.
CA La Red ILI 002 Study Grp
TI Clinical characteristics and outcomes of influenza and other
influenza-like illnesses in Mexico City
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Respiratory viral pathogens; Epidemiology; Hospital burden of disease;
Influenza; Respiratory syncytial virus; Rhinovirus; Coronavirus
ID COMMUNITY-ACQUIRED PNEUMONIA; RESPIRATORY VIRAL-INFECTIONS;
CRITICALLY-ILL PATIENTS; HOSPITALIZED CHILDREN; A H1N1; ETIOLOGY;
VIRUSES; ADULTS; EPIDEMIOLOGY; SURVEILLANCE
AB Background: Influenza-like illnesses (ILI) are estimated to cause millions of deaths annually. Despite this disease burden, the etiologic causes of ILI are poorly described for many geographical regions.
Methods: Beginning in April 2010, we conducted an observational cohort study at five hospitals in Mexico City, enrolling subjects who met the criteria for ILI. Evaluations were conducted at enrollment and on day 28, with the collection of clinical data and a nasopharyngeal swab (or nasal aspirate in children). Swabs were tested by multiplex PCR for 15 viral pathogens and real-time PCR for influenza.
Results: During the first year, 1065 subjects were enrolled in this study, 55% of whom were hospitalized; 24% of all subjects were children. One or more pathogens were detected by PCR in 64% of subjects, most commonly rhinovirus (25% of all isolates) and influenza (24% of isolates). Six percent of subjects died, and of those, 54% had no pathogen identified. Rhinovirus was the most common pathogen among those who died, although it did not have the highest case fatality rate.
Conclusions: Multiple respiratory viruses beyond influenza are associated with significant morbidity and mortality among adults and children in Mexico City. Detection of these agents could be useful for the adjustment of antibiotic treatment in severe cases. (C) 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
C1 [Galindo-Fraga, Arturo; Perez-Patrigeon, Santiago; Lourdes Guerrero, M.; Ruiz-Palacios, Guillermo M.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico.
[Ortiz-Hernandez, Ana A.; Llamosas-Gallardo, Beatriz] Inst Nacl Pediat, Mexico City, DF, Mexico.
[Ramirez-Venegas, Alejandra] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico.
[Valdez Vazquez, Rafael] Hosp Gen Dr Manuel Gea Gonzalez, Mexico City, DF, Mexico.
[Moreno-Espinosa, Sarbelio] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico.
[Salinger, Maggie; Huang, Chiung-yu] NIAID, Bethesda, MD 20892 USA.
[Freimanis, Laura] WESTAT Corp, Rockville, MD 20850 USA.
[Gu, Wenjuan; Beigel, John] NIAID, SAIC Frederick, Bethesda, MD 20892 USA.
RP Galindo-Fraga, A (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Vasco de Quiroga 15,Col Secc 16, Mexico City 14000, DF, Mexico.
EM galindofraga@yahoo.com
FU Mexico Ministry of Health; U.S. National Institute of Allergy and
Infectious Diseases; CONACYT through FONSEC SSA/IMSS/ISSSTE [71260,
127088]; Westat, Inc. [HHSN2722009000031]; National Cancer Institute,
National Institutes of Health, 318 [HHSN261200800001E]
FX La Red is funded by the Mexico Ministry of Health and the U.S. National
Institute of Allergy and Infectious Diseases. This project has been
funded in part by funding provided by: CONACYT through FONSEC
SSA/IMSS/ISSSTE No. 71260 and No. 127088. Intramural Research Programs
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health. National Institute of Allergy and Infectious
Diseases (NIAID), National Institutes of Health (NIH) through a contract
with Westat, Inc., Contract Number: HHSN2722009000031, Task Order
Number: HHSN27200002. And through the National Cancer Institute,
National Institutes of Health, 318 under Contract No. HHSN261200800001E.
NR 36
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Z9 9
U1 0
U2 12
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD JUL
PY 2013
VL 17
IS 7
BP E510
EP E517
DI 10.1016/j.ijid.2013.01.006
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 144XT
UT WOS:000318976300008
PM 23416208
ER
PT J
AU Lin, CL
Peng, GCY
Karniadakis, G
AF Lin, Ching-Long
Peng, Grace C. Y.
Karniadakis, George
TI Multi-Scale modeling and simulation of biological systems Preface
SO JOURNAL OF COMPUTATIONAL PHYSICS
LA English
DT Editorial Material
C1 [Lin, Ching-Long] Univ Iowa, Iowa City, IA 52242 USA.
[Peng, Grace C. Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Karniadakis, George] Brown Univ, Providence, RI 02912 USA.
RP Lin, CL (reprint author), Univ Iowa, Iowa City, IA 52242 USA.
EM ching-long-lin@uiowa.edu
NR 1
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 0021-9991
J9 J COMPUT PHYS
JI J. Comput. Phys.
PD JUL 1
PY 2013
VL 244
BP 1
EP 3
DI 10.1016/j.jcp.2013.02.004
PG 3
WC Computer Science, Interdisciplinary Applications; Physics, Mathematical
SC Computer Science; Physics
GA 151JO
UT WOS:000319456900001
ER
PT J
AU Cheung, CSF
Lui, JC
Baron, J
AF Cheung, Crystal S. F.
Lui, Julian C.
Baron, Jeffrey
TI Identification of chondrocyte-binding peptides by phage display
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE phage display; peptide; cartilage; chondrocytes; targeted therapy
ID MURINE HYPOPHOSPHATASIA; ENZYME REPLACEMENT; HOMING PEPTIDES; CELLS;
VASCULATURE; CARTILAGE; BONE; OLIGOPEPTIDE; SELECTION; DELIVERY
AB As an initial step toward targeting cartilage tissue for potential therapeutic applications, we sought cartilage-binding peptides using phage display, a powerful technology for selection of peptides that bind to molecules of interest. A library of phage displaying random 12-amino acid peptides was iteratively incubated with cultured chondrocytes to select phage that bind cartilage. The resulting phage clones demonstrated increased affinity to chondrocytes by ELISA, when compared to a wild-type, insertless phage. Furthermore, the selected phage showed little preferential binding to other cell types, including primary skin fibroblast, myocyte and hepatocyte cultures, suggesting a tissue-specific interaction. Immunohistochemical staining revealed that the selected phage bound chondrocytes themselves and the surrounding extracellular matrix. FITC-tagged peptides were synthesized based on the sequence of cartilage-binding phage clones. These peptides, but not a random peptide, bound cultured chondrocytes, and extracelluar matrix. In conclusion, using phage display, we identified peptide sequences that specifically target chondrocytes. We anticipate that such peptides may be coupled to therapeutic molecules to provide targeted treatment for cartilage disorders. (c) 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:10531058, 2013
C1 [Cheung, Crystal S. F.; Lui, Julian C.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Baron, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
EM jeffrey.baron@nih.gov
RI Lui, Chun Kin Julian/E-2253-2012
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Grant sponsor: Eunice Kennedy Shriver National Institute of Child Health
and Human Development (Intramural Research Program).
NR 23
TC 5
Z9 5
U1 1
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD JUL
PY 2013
VL 31
IS 7
BP 1053
EP 1058
DI 10.1002/jor.22325
PG 6
WC Orthopedics
SC Orthopedics
GA 149VW
UT WOS:000319350500009
PM 23440926
ER
PT J
AU Huppmann, AR
Xi, LQ
Raffeld, M
Pittaluga, S
Jaffe, ES
AF Huppmann, Alison R.
Xi, Liqiang
Raffeld, Mark
Pittaluga, Stefania
Jaffe, Elaine S.
TI Subcutaneous panniculitis-like T-cell lymphoma in the pediatric age
group: A lymphoma of low malignant potential
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE lupus panniculitis; pediatric; subcutaneous panniculitis-like T-cell
lymphoma
ID HIGH-DOSE CHEMOTHERAPY; CLASSIFICATION
AB Background Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare neoplasm of mature cytotoxic T-cells. Most commonly occurring in young adults, few reports are described in children. A separate analysis of a significant cohort of pediatric patients has not previously been performed. Procedure We analyzed the pathology including molecular results as well as available clinical data from 16 pediatric patients (age 5 months to 21 years) who had a total of 19 biopsies submitted to the National Cancer Institute from 1999 to 2011. This included 6 males and 10 females. Results Most patients (10/16, 62.5%) had multiple skin lesions at the time of biopsy. Histologic features included rimming of adipocytes by atypical lymphocytes, fat necrosis, and karyorrhectic debris. Four biopsies showed only partial involvement by lymphoma; and plasma cells were identified in 14/19 (74%) cases, including three in which they were focally prominent. The neoplastic cells in general were positive for CD3, CD8, TIA-1, and F1 and were negative for CD4 and CD56. CD5 expression was weak to negative in 5/8 cases (63%). A clonal T-cell receptor gene rearrangement was demonstrated in 11/17 (65%). Patients were treated with a variety of agents. While 5/9 (56%) patients had evidence of recurrent skin lesions, no deaths were attributed to disease for the seven patients with follow-up information. Conclusions Pediatric SPTCL shares many clinical and pathologic features with adult SPTCL. The presence of partial involvement or admixed plasma cells makes the differential diagnosis with reactive conditions challenging in some cases. Pediatr Blood Cancer 2013; 60: 11651170. (c) 2013 Wiley Periodicals, Inc.
C1 [Huppmann, Alison R.; Xi, Liqiang; Raffeld, Mark; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), NCI, NIH, 10 Ctr Dr Bldg 10,Room 2B42, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
NR 9
TC 17
Z9 18
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2013
VL 60
IS 7
BP 1165
EP 1170
DI 10.1002/pbc.24462
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 149ZZ
UT WOS:000319361300026
PM 23382035
ER
PT J
AU Lock, RB
Carol, H
Maris, JM
Kang, MH
Reynolds, CP
Kolb, EA
Gorlick, R
Keir, ST
Billups, CA
Kurmasheva, RT
Houghton, PJ
Smith, MA
AF Lock, Richard B.
Carol, Hernan
Maris, John M.
Kang, Min H.
Reynolds, C. Patrick
Kolb, E. Anders
Gorlick, Richard
Keir, Stephen T.
Billups, Catherine A.
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
TI Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the
pediatric preclinical testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; Hsp90 inhibitors; preclinical testing
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; B-PROGENITOR; ALK; MUTATION; MODELS;
CRLF2; REARRANGEMENT; RESISTANCE; IKZF1; JAK
AB Ganetespib, an Hsp90 inhibitor, was tested against the PPTP in vitro cell line panel and selected xenografts in vivo, including JAK2- and BRAF-mutated models. Ganetespib demonstrated potent in vitro cytotoxic activity (median rIC50 8.8nM, range 4.427.1nM). In vivo, ganetespib induced significant differences in EFS distribution for 4 of 11 xenografts. Intermediate activity (EFS T/C>2) was noted only for the MV4;11 xenograft, and there were no objective responses. Administered as single agents, Hsp90 inhibitors examined by the PPTP have shown limited evidence for a therapeutic window against both solid tumor and leukemia pediatric preclinical models. Pediatr Blood Cancer 2013; 60: E42E45. (c) 2013 Wiley Periodicals, Inc.
C1 [Lock, Richard B.; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW 2, Australia.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Kang, Min H.; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Billups, Catherine A.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Lock, RB (reprint author), Australia Lowy Canc Res Ctr, Leukemia Biol Program, Childrens Canc Inst, High St, Randwick, NSW 2031, Australia.
EM rlock@ccia.unsw.edu.au
RI Carol, Hernan/F-5750-2013; Houghton, Peter/E-3265-2011; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CA21765, CA108786.
NR 23
TC 5
Z9 5
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2013
VL 60
IS 7
BP E42
EP E45
DI 10.1002/pbc.24451
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 149ZZ
UT WOS:000319361300007
PM 23303741
ER
PT J
AU Borthwick, LA
Wynn, TA
Fisher, AJ
AF Borthwick, Lee A.
Wynn, Thomas A.
Fisher, Andrew J.
TI Cytokine mediated tissue fibrosis
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Fibrosis; Cytokine; Macrophage; Fibroblast; Myoflbroblast; Inflammation
ID TUMOR-NECROSIS-FACTOR; BRONCHIOLITIS OBLITERANS SYNDROME;
EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR-BETA; IDIOPATHIC
PULMONARY-FIBROSIS; PERIPHERAL-BLOOD FIBROCYTES; LUNG-TRANSPLANT
RECIPIENTS; HEPATIC STELLATE CELLS; HETEROTOPIC TRACHEAL
TRANSPLANTATION; EGG-INDUCED IMMUNOPATHOLOGY
AB Acute inflammation is a recognised part of normal wound healing. However, when inflammation fails to resolve and a chronic inflammatory response is established this process can become dysregulated resulting in pathological wound repair, accumulation of permanent fibrotic scar tissue at the site of injury and the failure to return the tissue to normal function. Fibrosis can affect any organ including the lung, skin, heart, kidney and liver and it is estimated that 45% of deaths in the western world can now be attributed to diseases where fibrosis plays a major aetiological role. In this review we examine the evidence that cytokines play a vital role in the acute and chronic inflammatory responses that drive fibrosis in injured tissues. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Borthwick, Lee A.; Fisher, Andrew J.] Newcastle Univ, Sch Med, Inst Cellular Med, Tissue Fibrosis & Repair Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Borthwick, Lee A.; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Fisher, Andrew J.] Freeman Rd Hosp, Inst Transplantat, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England.
RP Borthwick, LA (reprint author), Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM Lee.Borthwick@Newcastle.ac.uk
OI Borthwick, Lee/0000-0003-2885-3382
FU European Union; Intramural Research Program of the NIH/NIAID
FX We would like to express our sincere appreciation and thanks to all of
our colleagues, both past and present, for their guidance and support.
We also thank Aaron Gardner for assistance with figure preparation. LAB
is supported by a Marie Curie international outgoing fellowship from the
European Union Framework Programme 7. TAW is supported by the Intramural
Research Program of the NIH/NIAID.
NR 267
TC 49
Z9 53
U1 1
U2 50
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD JUL
PY 2013
VL 1832
IS 7
SI SI
BP 1049
EP 1060
DI 10.1016/j.bbadis.2012.09.014
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 143SC
UT WOS:000318887500023
PM 23046809
ER
PT J
AU Gao, B
Radaeva, S
AF Gao, Bin
Radaeva, Svetlana
TI Natural killer and natural killer T cells in liver fibrosis
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Viral hepatitis; Alcoholic liver disease; NKG2D; NAFLD; IFN-gamma
ID CHRONIC HEPATITIS-C; ACTIVATED STELLATE CELLS; INNATE IMMUNE-SYSTEM;
PHASE I/II TRIAL; NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; INTERFERON-ALPHA;
VIRUS-INFECTION; HCV INFECTION; PIT CELLS
AB The liver lymphocyte population is enriched with natural killer (NK) cells, which plays key role in host defense against viral infection and tumor transformation. Recent evidence from animal models suggests that NK cells also play an important role in inhibiting liver fibrosis by selectively killing early or senescence activated hepatic stellate cells (HSCs) and by producing the-anti-fibrotic cytokine IFN-gamma. Furthermore, clinical studies have revealed that human NK cells can kill primary human HSCs and that the ability of NK cells from HCV patients to kill HSCs is enhanced and correlates inversely with the stages of liver fibrosis. IFN-alpha treatment enhances, while other factors (e.g., alcohol, TGF-beta) attenuate, the cytotoxicity of NK cells against HSCs, thereby differentially regulating liver fibrogenesis. In addition, the mouse liver lymphocyte population is also enriched for natural killer T (NKT) cells, whereas human liver lymphocytes have a much lower percentage of NKT cells. Many studies suggest that NKT cells promote liver fibrogenesis by producing pro-fibrotic cytokines such as IL-4, IL-13, hedgehog ligands, and osteopontin; however, NKT cells may also attenuate liver fibrosis under certain conditions by killing HSCs and by producing IFN-gamma. Finally, the potential for NK and NKT cells to be used as therapeutic targets for anti-fibrotic therapy is discussed. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. Published by Elsevier B.V.
C1 [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
[Radaeva, Svetlana] NIAAA, Div Metab & Hlth Effect, NIH, Bethesda, MD 20892 USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
EM bgao@mail.nih.gov
FU Intramural NIH HHS [ZIA AA000368-10, Z99 AA999999, ZIA AA000369-10]
NR 94
TC 37
Z9 42
U1 0
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD JUL
PY 2013
VL 1832
IS 7
SI SI
BP 1061
EP 1069
DI 10.1016/j.bbadis.2012.09.008
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 143SC
UT WOS:000318887500024
PM 23022478
ER
PT J
AU Tanofsky-Kraff, M
Engel, S
Yanovski, JA
Pine, DS
Nelson, EE
AF Tanofsky-Kraff, Marian
Engel, Scott
Yanovski, Jack A.
Pine, Daniel S.
Nelson, Eric E.
TI Pediatric disinhibited eating: Toward a research domain criteria
framework
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
ID DISORDERS
C1 [Tanofsky-Kraff, Marian] USUHS, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Tanofsky-Kraff, Marian; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD USA.
[Engel, Scott] Neuropsychiat Res Inst, Fargo, ND USA.
[Pine, Daniel S.; Nelson, Eric E.] NIMH, Sect Dev & Affect Neurosci, NIH, DHHS, Bethesda, MD 20892 USA.
RP Tanofsky-Kraff, M (reprint author), USUHS, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM marian.tanofsky-kraff@usuhs.edu
OI Yanovski, Jack/0000-0001-8542-1637; Nelson, Eric/0000-0002-3376-2453
FU Intramural NIH HHS [Z99 HD999999, Z99 MH999999, ZIA HD000641-17, ZIA
MH002781-11]; NCRR NIH HHS [L30 RR033197]; NIDDK NIH HHS [R01 DK080906];
NIMH NIH HHS [L30 MH078171]
NR 7
TC 7
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0276-3478
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD JUL
PY 2013
VL 46
IS 5
SI SI
BP 451
EP 455
DI 10.1002/eat.22101
PG 5
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA 142EJ
UT WOS:000318779000016
PM 23658090
ER
PT J
AU Sykora, P
Yang, JL
Ferrarelli, LK
Tian, JY
Tadokoro, T
Kulkarni, A
Weissman, L
Keijzers, G
Wilson, DM
Mattson, MP
Bohr, VA
AF Sykora, Peter
Yang, Jenq-Lin
Ferrarelli, Leslie K.
Tian, Jingyan
Tadokoro, Takashi
Kulkarni, Avanti
Weissman, Lior
Keijzers, Guido
Wilson, David M., III
Mattson, Mark P.
Bohr, Vilhelm A.
TI Modulation of DNA base excision repair during neuronal differentiation
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE BER; Differentiation; DNA repair; Postmitotic; Aging; Neuron; DNA damage
ID OXIDATIVELY DAMAGED DNA; ALZHEIMERS-DISEASE; STRAND BREAKS; CELL-DEATH;
GLYCOSYLASE; NUCLEAR; BRAIN; REPLICATION; EXPRESSION; PATHWAYS
AB Neurons are terminally differentiated cells with a high rate of metabolism and multiple biological properties distinct from their undifferentiated precursors. Previous studies showed that nucleotide excision DNA repair is downregulated in postmitotic muscle cells and neurons. Here, we characterize DNA damage susceptibility and base excision DNA repair (BER) capacity in undifferentiated and differentiated human neural cells. The results show that undifferentiated human SH-SY5Y neuroblastoma cells are less sensitive to oxidative damage than their differentiated counterparts, in part because they have robust BER capacity, which is heavily attenuated in postmitotic neurons. The reduction in BER activity in differentiated cells correlates with diminished protein levels of key long patch BER components, flap endonuclease-1, proliferating cell nuclear antigen, and ligase I. Thus, because of their higher BER capacity, proliferative neural progenitor cells are more efficient at repairing DNA damage compared with their neuronally differentiated progeny. Published by Elsevier Inc.
C1 [Sykora, Peter; Yang, Jenq-Lin; Ferrarelli, Leslie K.; Tian, Jingyan; Tadokoro, Takashi; Weissman, Lior; Keijzers, Guido; Wilson, David M., III; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Yang, Jenq-Lin; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
[Kulkarni, Avanti] Roche Palo Alto LLC, Palo Alto, CA USA.
[Keijzers, Guido] Univ Copenhagen, Ctr Hlth Aging, Fac Hlth Sci, DK-1168 Copenhagen, Denmark.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd,Ste 100,Room 6B133, Baltimore, MD 21224 USA.
EM bohrv@grc.nia.nih.gov
OI Yang, Jenq-Lin/0000-0002-9897-8087
FU National Institute on Aging, National Institutes of Health
FX The authors thank Dr Robert Bambara for reagents provided, and Dr Misiak
and Dr Illuzzi for critical reading of the manuscript. This research is
supported by intramural research program of National Institute on Aging,
National Institutes of Health.
NR 38
TC 20
Z9 20
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2013
VL 34
IS 7
BP 1717
EP 1727
DI 10.1016/j.neurobiolaging.2012.12.016
PG 11
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 140TS
UT WOS:000318678900001
PM 23375654
ER
PT J
AU Baxter, MG
Roberts, MT
Gee, NA
Lasley, BL
Morrison, JH
Rapp, PR
AF Baxter, Mark G.
Roberts, Mary T.
Gee, Nancy A.
Lasley, Bill L.
Morrison, John H.
Rapp, Peter R.
TI Multiple clinically relevant hormone therapy regimens fail to improve
cognitive function in aged ovariectomized rhesus monkeys
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Ovarian hormones; Aging; Macaque; Learning; Memory; Prefrontal; Temporal
ID HEALTH INITIATIVE MEMORY; CONJUGATED EQUINE ESTROGENS; SURGICALLY
MENOPAUSAL MONKEYS; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN;
PREFRONTAL CORTEX; MACACA-FASCICULARIS; RECOGNITION MEMORY;
ALZHEIMERS-DISEASE; PLUS PROGESTIN
AB Preclinical studies in aged, surgically-menopausal rhesus monkeys have revealed powerful benefits of intermittent estrogen injections on prefrontal cortex-dependent working memory, together with corresponding effects on dendritic spine morphology in the prefrontal cortex. This contrasts with the inconsistent effects of hormone therapy (HT) reported in clinical studies in women. Factors contributing to this discrepancy could include differences in the formulation and sequence of HT regimens, resulting in different neurobiological outcomes. The current study evaluated, in aging surgically menopausal rhesus monkeys, the cognitive effects of 4 HT regimens modeled directly on human clinical practice, including continuous estrogen treatment opposed by progesterone. None of the regimens tested produced any cognitive effect, despite yielding physiologically relevant serum hormone levels, as intended. These findings have implications for the design of regimens that might optimize the benefits of hormone treatment for healthy aging, and suggest that common HT protocols used by women may fail to result in substantial cognitive benefit, at least via direct effects on the prefrontal cortex. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Baxter, Mark G.; Morrison, John H.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
[Baxter, Mark G.; Morrison, John H.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA.
[Roberts, Mary T.; Gee, Nancy A.; Lasley, Bill L.] Calif Natl Primate Res Ctr, Davis, CA USA.
[Gee, Nancy A.; Lasley, Bill L.] Univ Calif, Sch Vet Med, Ctr Hlth & Environm, Dept Populat Hlth & Reprod, Davis, CA USA.
[Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP Baxter, MG (reprint author), Mt Sinai Sch Med, Dept Neurosci, 1 Gustave L Levy Pl,Box 1065, New York, NY 10029 USA.
FU NIA [P01-AG016765]; NCRR [P51-RR000169]
FX We thank Carmel Stanko, Tracy Ojakangas, and Lisa Novik for technical
assistance, and Dr Kari Christe for veterinary advice and support. This
research was supported by NIA grant P01-AG016765, in part by the
Intramural Research Program of the NIA, and was carried out at the
California National Primate Research Center, supported by NCRR grant
P51-RR000169.
NR 43
TC 14
Z9 14
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2013
VL 34
IS 7
BP 1882
EP 1890
DI 10.1016/j.neurobiolaging.2012.12.017
PG 9
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 140TS
UT WOS:000318678900018
PM 23369546
ER
PT J
AU Majounie, E
Cross, W
Newsway, V
Dillman, A
Vandrovcova, J
Morris, CM
Nalls, MA
Ferrucci, L
Owen, MJ
O'Donovan, MC
Cookson, MR
Singleton, AB
de Silva, R
Morris, HR
AF Majounie, Elisa
Cross, William
Newsway, Victoria
Dillman, Allissa
Vandrovcova, Jana
Morris, Christopher M.
Nalls, Michael A.
Ferrucci, Luigi
Owen, Michael J.
O'Donovan, Michael C.
Cookson, Mark R.
Singleton, Andrew B.
de Silva, Rohan
Morris, Huw R.
TI Variation in tau isoform expression in different brain regions and
disease states
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Progressive supranuclear palsy; Tauopathies; MAPT
ID PROGRESSIVE SUPRANUCLEAR PALSY; MESSENGER-RNA ISOFORMS;
ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; PARKINSONS-DISEASE;
GENE-EXPRESSION; MAPT LOCUS; HAPLOTYPE; ASSOCIATION; IDENTIFICATION
AB Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 haplotype of MAPT, the gene encoding tau, is the major risk factor in PSP. A 3-repeat and 4-repeat (4R) tau isoform ratio imbalance has been strongly implicated as a cause of disease. Thus, understanding tau isoform regional expression in disease and pathology-free states is crucial to elucidating the mechanisms involved in PSP and other tauopathies. We used a tau isoform-specific fluorescent assay to investigate relative 4R-tau expression in 6 different brain regions in PSP cases and healthy control samples. We identified a marked difference in 4R-tau relative expression, across brain regions and between MAPT haplotypes. Highest 4R-tau expression levels were identified in the globus pallidus compared with pons, cerebellum, and frontal cortex. 4R-tau expression levels were related to the MAPT H1 and H1c haplotypes. Similar regional variation was seen in PSP case and in control samples. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Majounie, Elisa; Cross, William; Newsway, Victoria; Owen, Michael J.; O'Donovan, Michael C.; Morris, Huw R.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales.
[Majounie, Elisa; Dillman, Allissa; Nalls, Michael A.; Cookson, Mark R.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Vandrovcova, Jana; de Silva, Rohan] UCL Inst Neurol, Reta Lila Weston Inst, London, England.
[Morris, Christopher M.] Newcastle Univ, Inst Neurosci, Med Toxicol Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Morris, Christopher M.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA.
RP Morris, HR (reprint author), Univ Wales Hosp, Cardiff CF14 4XN, S Glam, Wales.
EM morrishr@cf.ac.uk
RI Morris, Huw/B-8527-2008; Singleton, Andrew/C-3010-2009; Cross,
William/G-1299-2015;
OI Morris, Huw/0000-0002-5473-3774; O'Donovan, Michael/0000-0001-7073-2379
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services [Z01
AG000932-03]; PSP (Europe) Association; UK Medical Research Council
[G0501560, G0400074]; Alzheimer's Society; Alzheimer's Research Trust,
Brains for Dementia Research Project; National Institute for Health
Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle
upon Tyne Hospitals NHS Foundation Trust; Newcastle University
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; project number Z01 AG000932-03.
This study was funded by the PSP (Europe) Association and UK Medical
Research Council research grant G0501560 to RdS.; Tissue for this study
was provided by the Newcastle Brain Tissue Resource which is funded in
part by a grant from the UK Medical Research Council (G0400074), the
Alzheimer's Society and Alzheimer's Research Trust as part of the Brains
for Dementia Research Project, and by the National Institute for Health
Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle
upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The
views expressed are those of the author(s) and not necessarily those of
the NHS, the NIHR, or the Department of Health.
NR 22
TC 8
Z9 8
U1 2
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2013
VL 34
IS 7
AR 1922.e7
DI 10.1016/j.neurobiolaging.2013.01.017
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 140TS
UT WOS:000318678900026
PM 23428180
ER
PT J
AU Agster, KL
Mejias-Aponte, CA
Clark, BD
Waterhouse, BD
AF Agster, Kara L.
Mejias-Aponte, Carlos A.
Clark, Brian D.
Waterhouse, Barry D.
TI Evidence for a regional specificity in the density and distribution of
noradrenergic varicosities in rat cortex
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE norepinephrine; prefrontal; somatosensory; motor; locus coeruleus;
stereology
ID MEDIAL PREFRONTAL CORTEX; CENTRAL-NERVOUS-SYSTEM; LOCUS-COERULEUS;
CEREBRAL-CORTEX; VOLUME TRANSMISSION; AXON TERMINALS; LAMINAR
DISTRIBUTION; AWAKE RAT; NOREPINEPHRINE; INNERVATION
AB The brainstem nucleus locus coeruleus (LC) is the sole source of norepinephrine (NE)-containing fibers in the mammalian cortex. Previous studies suggest that the density of noradrenergic fibers in rat is relatively uniform across cortical regions and that cells in the nucleus discharge en masse. This implies that activation of the LC results in equivalent release of NE throughout the cortex. However, it is possible that there could be differences in the density of axonal varicosities across regions, and that these differences, rather than a difference in fiber density, may contribute to the regulation of NE efflux. Quantification of dopamine -hydroxylase (DH)-immunostained varicosities was performed on several cortical regions and in the ventral posterior medial (VPM) thalamus by using unbiased sampling methods. The density of DH varicosities is greater in the prefrontal cortex than in motor, somatosensory, or piriform cortices, greater in superficial than in deep layers of cortex, and greater in the VPM than in the somatosensory cortex. Our results provide anatomical evidence for non-uniform release of NE across functionally discrete cortical regions. This morphology may account for a differential, region-specific, impact of LC output on different cortical areas. J. Comp. Neurol. 521:21952207, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Agster, Kara L.; Clark, Brian D.; Waterhouse, Barry D.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA.
[Mejias-Aponte, Carlos A.] NIDA, Baltimore, MD 21224 USA.
RP Waterhouse, BD (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA.
EM waterhouse@drexelmed.edu
FU National Institute of Drug Abuse [DA017960]; Pennsylvania Department of
Health; National Institute of Neurological Disorders and Stroke
fellowship [T32 NINDS NS 007440]
FX Grant sponsor: National Institute of Drug Abuse; Grant number: DA017960
(to B. D. W.); Grant sponsor: the Pennsylvania Department of Health (to
B. D. W.); Grant sponsor: National Institute of Neurological Disorders
and Stroke fellowship; Grant number: T32 NINDS NS 007440 (to K.L.A.).
NR 50
TC 10
Z9 10
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD JUL 1
PY 2013
VL 521
IS 10
BP 2195
EP 2207
DI 10.1002/cne.23270
PG 13
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 133SO
UT WOS:000318160400002
PM 23184811
ER
PT J
AU Dimitrov, EL
Yanagawa, Y
Usdin, TB
AF Dimitrov, Eugene L.
Yanagawa, Yuchio
Usdin, Ted B.
TI Forebrain GABAergic projections to locus coeruleus in mouse
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE noradrenergic; forebrain; brainstem; GAD67-GFP knockin; anatomical tract
tracing
ID CORTICOTROPIN-RELEASING-FACTOR; IN-SITU HYBRIDIZATION; VENTROLATERAL
PREOPTIC NUCLEUS; LOWER BRAIN-STEM; AFFERENT-PROJECTIONS; HYPOTHALAMIC
PROJECTIONS; NORADRENERGIC SYSTEM; EFFERENT CONNECTIONS; GALANINERGIC
NEURONS; PROTEIN EXPRESSION
AB The noradrenergic locus coeruleus (LC) regulates arousal, memory, sympathetic nervous system activity, and pain. Forebrain projections to LC have been characterized in rat, cat, and primates, but not systematically in mouse. We surveyed mouse forebrain LC-projecting neurons by examining retrogradely labeled cells following LC iontophoresis of Fluoro-Gold and anterograde LC labeling after forebrain injection of biotinylated dextran amine or viral tracer. Similar to other species, the central amygdalar nucleus (CAmy), anterior hypothalamus, paraventricular nucleus, and posterior lateral hypothalamic area (PLH) provide major LC inputs. By using mice expressing green fluorescent protein in -aminobutyric acid (GABA)ergic neurons, we found that more than one-third of LC-projecting CAmy and PLH neurons are GABAergic. LC colocalization of biotinylated dextran amine, following CAmy or PLH injection, with either green fluorescent protein or glutamic acid decarboxylase (GAD)65/67 immunoreactivity confirmed these GABAergic projections. CAmy injection of adeno-associated virus encoding channelrhodopsin-2-Venus showed similar fiber labeling and association with GAD65/67-immunoreactive (ir) and tyrosine hydroxylase (TH)-ir neurons. CAmy and PLH projections were densest in a pericoerulear zone, but many fibers entered the LC proper. Close apposition between CAmy GABAergic projections and TH-ir processes suggests that CAmy GABAergic neurons may directly inhibit noradrenergic principal neurons. Direct LC neuron targeting was confirmed by anterograde transneuronal labeling of LC TH-ir neurons following CAmy or PLH injection of a herpes virus that expresses red fluorescent protein following activation by Cre recombinase in mice that express Cre recombinase in GABAergic neurons. This description of GABAergic projections from the CAmy and PLH to the LC clarifies important forebrain sources of inhibitory control of central nervous system noradrenergic activity. J. Comp. Neurol. 521:23732397, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Dimitrov, Eugene L.; Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
[Yanagawa, Yuchio] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gumma 3718511, Japan.
[Yanagawa, Yuchio] JST, CREST, Maebashi, Gumma 3718511, Japan.
RP Usdin, TB (reprint author), NIMH, Sect Fundamental Neurosci, 35 Convent Dr, Bethesda, MD 20892 USA.
EM usdint@mail.nih.gov
FU National Institute of Mental Health [ZIA MH002685-16]
FX Grant sponsor: the Intramural Program of the National Institute of
Mental Health; Grant number: ZIA MH002685-16.
NR 74
TC 9
Z9 10
U1 0
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
EI 1096-9861
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD JUL 1
PY 2013
VL 521
IS 10
BP 2373
EP 2397
DI 10.1002/cne.23291
PG 25
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 133SO
UT WOS:000318160400011
PM 23296594
ER
PT J
AU Pearce, S
Nezich, CL
Spinazzola, A
AF Pearce, Sarah
Nezich, Catherine Laura
Spinazzola, Antonella
TI Mitochondrial diseases: Translation matters
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Mitochondrial encephalopathies; Translation; Ribosome; Assembly factors
ID HEREDITARY OPTIC NEUROPATHY; SIDEROBLASTIC ANEMIA-MLASA; KEARNS-SAYRE
SYNDROME; 12S RIBOSOMAL-RNA; NADH-QUINONE OXIDOREDUCTASE; NON-SYNDROMIC
DEAFNESS; C-OXIDASE DEFICIENCY; STROKE-LIKE EPISODES; M-AAA PROTEASE;
DIABETES-MELLITUS
AB Mitochondrial diseases comprise a heterogeneous group of disorders characterized by compromised energy production. Since the early days of mitochondrial medical genetics, it has been known that these can be caused by defects in mitochondrial protein synthesis. However, only in recent years have we begun to develop a broader picture of the array of proteins required for mitochondrial translation. With this new knowledge has come the realization that there are many more neurological and other, diseases attributable to impaired mitochondrial translation than previously thought. Perturbation of any part of this intricate machinery, from the primary sequence of transfer or ribosomal RNAs, to the proteolytic processing of ribosomal proteins, can cause mitochondrial dysfunction and disease. In this review we discuss the current understanding of the mechanisms and factors involved in mammalian mitochondrial translation, and the diverse pathologies resulting when it malfunctions. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. (C) 2012 Published by Elsevier Inc.
C1 [Pearce, Sarah; Nezich, Catherine Laura; Spinazzola, Antonella] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
[Nezich, Catherine Laura] NINDS, NIH, Bethesda, MD 20892 USA.
RP Spinazzola, A (reprint author), MRC, Mitochondrial Biol Unit, Wellcome Trust MRC Bldg,Hills Rd, Cambridge CB2 0XY, England.
EM as1@mrc-mbu.cam.ac.uk
FU Medical Research Council, UK; European Union; National Institutes of
Health, Bethesda, USA
FX The authors are supported by the Medical Research Council, UK. A.S. is
in receipt of a European Union Marie Curie Fellowship. C.L.N is
supported by the National Institutes of Health, Bethesda, USA.
NR 132
TC 15
Z9 15
U1 0
U2 32
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1044-7431
EI 1095-9327
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD JUL
PY 2013
VL 55
SI SI
BP 1
EP 12
DI 10.1016/j.mcn.2012.08.013
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 131MZ
UT WOS:000317999100001
PM 22986124
ER
PT J
AU Maris, E
Womelsdorf, T
Desimone, R
Fries, P
AF Maris, Eric
Womelsdorf, Thilo
Desimone, Robert
Fries, Pascal
TI Rhythmic neuronal synchronization in visual cortex entails spatial phase
relation diversity that is modulated by stimulation and attention
SO NEUROIMAGE
LA English
DT Article
DE Phase; Synchronization; Oscillation; Gamma; Alpha; Theta; Attention;
Selection; Monkey; Visual
ID FALSE DISCOVERY RATE; BAND SYNCHRONIZATION; OLFACTORY-BULB; GAMMA CYCLE;
OSCILLATIONS; WAVES; DYNAMICS; V1; SEQUENCES; SELECTION
AB Groups of neurons tend to synchronize in distinct frequency bands. Within a given frequency band, synchronization is defined as the consistency of phase relations between site pairs, over time. This synchronization has been investigated in numerous studies and has been found to be modulated by sensory stimulation or cognitive conditions. Here, we investigate local field potentials (LFPs) and multi-unit activity (MUA) recorded from area V4 of two monkeys performing a selective visual attention task. We show that phase relations, that are consistent over time, are typically diverse across site pairs. That is, across site pairs, mean phase relations differ substantially and this across-site-pair phase-relation diversity (SPHARED, for Spatial PHAse RElation Diversity) is highly reliable. Furthermore, we show that visual stimulation and selective attention can shift the pattern of phase relations across site pairs. These shifts are again diverse and this across-site-pair phase-relation-shift diversity (SPHARESD) is again highly reliable. We find SPHARED for LFP-LFP, LFP-MUA and MUA-MUA pairs, stimulus-induced SPHARESD for LFP-LFP and LFP-MUA pairs, and attention-induced SPHARESD for LFP-LFP pairs. SPHARESD is a highly interesting signal from the perspective of impact on downstream neuronal activity. We provide several pieces of evidence for such a role. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Maris, Eric; Womelsdorf, Thilo; Fries, Pascal] Radboud Univ Nijmegen, Donders Ctr Brain Cognit & Behav, NL-6525 EN Nijmegen, Netherlands.
[Womelsdorf, Thilo] York Univ, Dept Biol, Fac Sci & Engn, N York, ON M3J 1P3, Canada.
[Desimone, Robert] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Desimone, Robert] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[Fries, Pascal] Max Planck Gesell, Ernst Strungmann Inst ESI Neurosci, D-60528 Frankfurt, Germany.
RP Maris, E (reprint author), Radboud Univ Nijmegen, Donders Ctr Brain Cognit & Behav, NL-6525 EN Nijmegen, Netherlands.
EM e.maris@donders.ru.nl
RI Fries, Pascal/E-3196-2010; Maris, Eric/E-4876-2012;
OI Fries, Pascal/0000-0002-4270-1468; Maris, Eric/0000-0001-5166-1800;
Womelsdorf, Thilo/0000-0001-6921-4187
FU BrainGain Smart Mix Programme of the Ministry of Economic Affairs;
Ministry of Education, Culture and Science of the Netherlands; Human
Frontier Science Program Organization [RGP0070/2003]; Volkswagen
Foundation [I/79876]; European Science Foundation European Young
Investigator Award Program; European Union [HEALTH-F2-2008-200728];
Netherlands Organization for Scientific Research [452-03-344,
016-071-079]; National Institute of Mental Health Intramural Research
Program; National Institutes of Health [R01-EY017292]
FX The authors gratefully acknowledge the support of the BrainGain Smart
Mix Programme of the Ministry of Economic Affairs and the Ministry of
Education, Culture and Science of the Netherlands. This work was
supported by Human Frontier Science Program Organization grant
RGP0070/2003 (P.F.), the Volkswagen Foundation grant I/79876 (P.F.), the
European Science Foundation European Young Investigator Award Program
(P.F.), the European Union (HEALTH-F2-2008-200728 to P.F.), the
Netherlands Organization for Scientific Research grants 452-03-344
(P.F.) and 016-071-079 (T.W.), the National Institute of Mental Health
Intramural Research Program (R.D.), and National Institutes of Health
grant R01-EY017292 (R.D.). We thank J. H. Reynolds, A E. Rorie, A. F.
Rossi, and R C. Saunders for help during the experiments.
NR 40
TC 14
Z9 14
U1 1
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUL 1
PY 2013
VL 74
BP 99
EP 116
DI 10.1016/j.neuroimage.2013.02.007
PG 18
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 124CL
UT WOS:000317441300012
PM 23416733
ER
PT J
AU Edwards, D
Cortes, M
Datta, A
Minhas, P
Wassermann, EM
Bikson, M
AF Edwards, Dylan
Cortes, Mar
Datta, Abhishek
Minhas, Preet
Wassermann, Eric M.
Bikson, Marom
TI Physiological and modeling evidence for focal transcranial electrical
brain stimulation in humans: A basis for high-definition tDCS
SO NEUROIMAGE
LA English
DT Article
DE tDCS; TES; TMS; Targeted stimulation; Human head model; Electric fields
ID HUMAN MOTOR CORTEX; RANDOM NOISE STIMULATION; MAGNETIC STIMULATION;
CHRONIC STROKE; COIL DESIGN; CORTICAL STIMULATION; DC STIMULATION;
EXCITABILITY; ACTIVATION; ELECTRODES
AB Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4 x 1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4 x 1 montage (4x cathode, surrounding a single central anode; montage radius similar to 3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4 x 1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject.
We provide direct evidence in humans that TES with a 4 x 1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4 x 1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4 x 1-Ring montage for cortically targeted neuromodulation. (c) 2013 Published by Elsevier Inc.
C1 [Edwards, Dylan; Cortes, Mar] Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA.
[Edwards, Dylan; Cortes, Mar] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY USA.
[Edwards, Dylan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA.
[Edwards, Dylan] Univ Western Australia, Australian Neuromuscular Res Inst, Nedlands, WA 6009, Australia.
[Edwards, Dylan] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, Nedlands, WA 6009, Australia.
[Datta, Abhishek; Minhas, Preet; Bikson, Marom] CUNY City Coll, Dept Biomed Engn, New York, NY 10031 USA.
[Wassermann, Eric M.] Natl Inst Neurol Disorders & Stroke, Behav Neurol Unit, Bethesda, MD USA.
RP Edwards, D (reprint author), Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY USA.
EM dedwards@burke.org
FU NICHD NIH HHS [R01 HD069776]
NR 55
TC 83
Z9 83
U1 2
U2 39
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUL 1
PY 2013
VL 74
BP 266
EP 275
DI 10.1016/j.neuroimage.2013.01.042
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 124CL
UT WOS:000317441300026
PM 23370061
ER
PT J
AU Lam, KH
Ji, HF
Zheng, F
Ren, W
Zhou, QF
Shung, KK
AF Lam, Kwok Ho
Ji, Hong Fen
Zheng, Fan
Ren, Wei
Zhou, Qifa
Shung, K. Kirk
TI Development of lead-free single-element ultrahigh frequency (170-320
MHz) ultrasonic transducers
SO ULTRASONICS
LA English
DT Article
DE UHF ultrasonic transducer; Lead-free; Composite sol-gel; Thick film
ID MEDICAL IMAGING APPLICATIONS; FREE PIEZOELECTRIC CERAMICS; FERROELECTRIC
THICK-FILMS; INTRAVASCULAR ULTRASOUND; 0-3 COMPOSITE; PZT; FABRICATION;
DESIGN; SYSTEM; BIOMICROSCOPY
AB This paper presents the design, fabrication and characterization of single-element ultrahigh frequency (UHF) ultrasonic transducers in which the center frequency ranged from 170 to 320 MHz. The center frequency of > 300 MHz is the highest value of lead-free ceramic ultrasonic transducers ever reported. With concern in the environmental pollution of lead-based materials, the transducer elements presented in this work were lead-free K0.5Na0.5NbO3/Bi0.5Na0.5TiO3 (KNN/BNT) composite thick films. All transducers were evaluated in a pulse-echo arrangement. The measured -6 dB bandwidth of the transducers ranged from 35% to 64%. With the optimized piezoelectric properties of the composite film, the insertion loss of the UHF transducers was measured and determined to range from -50 to -60 dB. In addition to the pulse-echo measurement, a 6 mu m tungsten wire phantom was also imaged with a 205 MHz transducer to demonstrate the imaging capability. The measured -6 dB axial and lateral resolutions were found to be 12 mu m and 50 mu m, respectively. The transducer performance presented in this work is shown to be better or comparable to previously reported results even though the frequency is much higher. (C) 2013 Elsevier B. V. All rights reserved.
C1 [Lam, Kwok Ho; Zheng, Fan; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Lam, Kwok Ho; Zheng, Fan; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Ji, Hong Fen; Ren, Wei] Xi An Jiao Tong Univ, Minist Educ, Key Lab, Elect Mat Res Lab, Xian 710049, Peoples R China.
[Ji, Hong Fen; Ren, Wei] Xi An Jiao Tong Univ, Int Ctr Dielect Res, Xian 710049, Peoples R China.
RP Lam, KH (reprint author), Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
EM kokokhlam@gmail.com
RI Lam, K.H./B-7765-2014
OI Lam, K.H./0000-0003-1456-9049
FU NIH [P41-EB2182]
FX This work was financially supported by NIH Grant P41-EB2182.
NR 39
TC 10
Z9 10
U1 4
U2 76
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0041-624X
J9 ULTRASONICS
JI Ultrasonics
PD JUL
PY 2013
VL 53
IS 5
BP 1033
EP 1038
DI 10.1016/j.ultras.2013.01.012
PG 6
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 120PW
UT WOS:000317184400014
PM 23485349
ER
PT J
AU Camalier, CE
Yi, M
Yu, LR
Hood, BL
Conrads, KA
Lee, YJ
Lin, YM
Garneys, LM
Bouloux, GF
Young, MR
Veenstra, TD
Stephens, RM
Colburn, NH
Conrads, TP
Beck, GR
AF Camalier, Corinne E.
Yi, Ming
Yu, Li-Rong
Hood, Brian L.
Conrads, Kelly A.
Lee, Young Jae
Lin, Yiming
Garneys, Laura M.
Bouloux, Gary F.
Young, Matthew R.
Veenstra, Timothy D.
Stephens, Robert M.
Colburn, Nancy H.
Conrads, Thomas P.
Beck, George R., Jr.
TI An integrated understanding of the physiological response to elevated
extracellular phosphate
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID FIBROBLAST-GROWTH-FACTOR; INHIBITED 3T3 CELLS; FACTOR-I RECEPTOR;
PROTEIN-KINASE PATHWAY; OSTEOBLAST-LIKE CELLS; INORGANIC-PHOSPHATE;
C-FOS; BONE MINERALIZATION; DIETARY PHOSPHATE; VITAMIN-D
AB Recent studies have suggested that changes in serum phosphate levels influence pathological states associated with aging such as cancer, bone metabolism, and cardiovascular function, even in individuals with normal renal function. The causes are only beginning to be elucidated but are likely a combination of endocrine, paracrine, autocrine, and cell autonomous effects. We have used an integrated quantitative biology approach, combining transcriptomics and proteomics to define a multi-phase, extracellular phosphate-induced, signaling network in pre-osteoblasts as well as primary human and mouse mesenchymal stromal cells. We identified a rapid mitogenic response stimulated by elevated phosphate that results in the induction of immediate early genes including c-fos. The mechanism of activation requires FGF receptor signaling followed by stimulation of N-Ras and activation of AP-1 and serum response elements. A distinct long-term response also requires FGF receptor signaling and results in N-Ras activation and expression of genes and secretion of proteins involved in matrix regulation, calcification, and angiogenesis. The late response is synergistically enhanced by addition of FGF23 peptide. The intermediate phase results in increased oxidative phosphorylation and ATP production and is necessary for the late response providing a functional link between the phases. Collectively, the results define elevated phosphate, as a mitogen and define specific mechanisms by which phosphate stimulates proliferation and matrix regulation. Our approach provides a comprehensive understanding of the cellular response to elevated extracellular phosphate, functionally connecting temporally coordinated signaling, transcriptional, and metabolic events with changes in long-term cell behavior. J. Cell. Physiol. 228: 15361550, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Camalier, Corinne E.; Lee, Young Jae; Lin, Yiming; Garneys, Laura M.; Beck, George R., Jr.] Emory Univ, Div Endocrinol, Dept Med, Atlanta, GA 30322 USA.
[Yi, Ming; Stephens, Robert M.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Yu, Li-Rong; Veenstra, Timothy D.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD USA.
[Hood, Brian L.; Conrads, Thomas P.] Inova Hlth Syst, Gynecol Canc Ctr Excellence, Womens Hlth Integrated Res Ctr, Annandale, VA USA.
[Conrads, Kelly A.; Young, Matthew R.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA.
[Lee, Young Jae] Jeju Natl Univ, Coll Vet Med, Cheju, South Korea.
[Bouloux, Gary F.] Emory Univ, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA 30322 USA.
RP Beck, GR (reprint author), Emory Univ, Div Endocrinol Metab & Lipids, Dept Med, 101 Woodruff Circle,Room 1026, Atlanta, GA 30322 USA.
EM george.beck@emory.edu
FU National Cancer Institute [CA84573, CA136059, CA136716]; Emory
University-URC1433; Jeju National University, Korea; National Cancer
Institute, National Institutes of Health [NO1-CO-12400]
FX This project has been funded by grants from the National Cancer
Institute CA84573, CA136059, CA136716, and Emory University-URC1433
(CEC, KAC, YJL, YL, LMG, and GRB Jr.). YJL is also supported by a
research grant from Jeju National University, Korea (2010). This project
has also been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
NO1-CO-12400. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the United States Government.
NR 118
TC 23
Z9 23
U1 1
U2 60
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD JUL
PY 2013
VL 228
IS 7
BP 1536
EP 1550
DI 10.1002/jcp.24312
PG 15
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 113PX
UT WOS:000316681100020
PM 23280476
ER
PT J
AU Rasmussen, B
Allen, S
Rasmussen, ZA
Bajwa, R
AF Rasmussen, Bruce
Allen, Sheldon
Rasmussen, Zeba A.
Bajwa, Rashid
TI Learning from disasters to save lives every day in Pakistan
SO LANCET
LA English
DT Editorial Material
ID FUTURE IMPLICATIONS; NEWBORN SURVIVAL; DECADE; FLOODS
C1 [Rasmussen, Zeba A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bajwa, Rashid] Natl Rural Support Programme, Islamabad, Pakistan.
EM rasmussenbruce@hotmail.com
NR 16
TC 2
Z9 2
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD JUN 29
PY 2013
VL 381
IS 9885
BP 2232
EP 2234
DI 10.1016/S0140-6736(13)60652-2
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 173SU
UT WOS:000321100300008
PM 23684253
ER
PT J
AU Berezhkovskii, AM
Shvartsman, SY
AF Berezhkovskii, Alexander M.
Shvartsman, Stanislav Y.
TI Kinetics of receptor occupancy during morphogen gradient formation
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID NERVOUS-SYSTEM; DIFFUSION
AB During embryogenesis, sheets of cells are patterned by concentration profiles of morphogens, molecules that act as dose-dependent regulators of gene expression and cell differentiation. Concentration profiles of morphogens can be formed by a source-sink mechanism, whereby an extracellular protein is secreted from a localized source, diffuses through the tissue and binds to cell surface receptors. A morphogen molecule bound to its receptor can either dissociate or be internalized by the cell. The effects of morphogens on cells depend on the occupancy of surface receptors, which in turn depends on morphogen concentration. In the simplest case, the local concentrations of the morphogen and morphogen-receptor complexes monotonically increase with time from zero to their steady-state values. Here, we derive analytical expressions for the time scales which characterize the formation of the steady-state concentrations of both the diffusible morphogen molecules and orphogen-receptor complexes at a given point in the patterned tissue. (C) 2013 AIP Publishing LLC.
C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Shvartsman, Stanislav Y.] Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08544 USA.
[Shvartsman, Stanislav Y.] Princeton Univ, Lewis Singler Inst Integrat Genom, Princeton, NJ 08544 USA.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
FU NIH, Center for Information Technology; National Science Foundation
[DMS-1119714, DMS-0718604]
FX A.M.B. was supported by the Intramural Research Program of the NIH,
Center for Information Technology. S.Y.S. acknowledges partial support
by the National Science Foundation [grants DMS-1119714 and DMS-0718604].
The authors thank Bomyi Lim (Princeton) for preparing the figure used in
this paper.
NR 28
TC 4
Z9 4
U1 1
U2 10
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JUN 28
PY 2013
VL 138
IS 24
AR 244105
DI 10.1063/1.4811654
PG 7
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 174IF
UT WOS:000321148200006
ER
PT J
AU Mizurini, DM
Francischetti, IMB
Monteiro, RQ
AF Mizurini, Daniella M.
Francischetti, Ivo M. B.
Monteiro, Robson Q.
TI Aegyptin inhibits collagen-induced coagulation activation in vitro and
thromboembolism in vivo
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Aegyptin; Mosquito saliva; Collagen; Platelets; Blood coagulation;
Pulmonary thromboembolism
ID PLATELET GLYCOPROTEIN-VI; VON-WILLEBRAND-FACTOR; THROMBUS FORMATION;
SALIVARY-GLAND; FACTOR-XII; HEMOSTASIS; ANTICOAGULANTS; TARGETS;
BINDING; MODEL
AB Aegyptin is a mosquito salivary gland protein and potent inhibitor of platelet aggregation. Aegyptin binds to the von Willebrand factor-binding site on collagen and prevents its interaction with platelets. Because collagen also induces plasma clotting by activation of factor XII, we evaluated the effects of aegyptin on collagen-induced coagulation activation and how it interferes with thrombosis in three different in vivo models. Our results demonstrate that aegyptin abolishes collagen-induced clot formation and thrombin generation in platelet-free plasma. Aegyptin has no antithrombotic activity in the arteriovenous shunt model (collagen-independent) but it prevents laser-induced collagen-mediated thrombus formation in rats. Furthermore, aegyptin protects mice from collagen and epinephrine-induced thromboembolism. Therefore, aegyptin has a dual antithrombotic mechanism: inhibition of platelet-collagen interaction and collagen's pro-coagulant activity. This is the first description of a collagen-binding protein that also inhibits collagen-mediated coagulant activity. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Mizurini, Daniella M.; Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, RJ, Brazil.
[Francischetti, Ivo M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Monteiro, RQ (reprint author), Inst Bioquim Med CCS UFRJ, Ave Carlos Chagas Filho 373,Cidade Univ, BR-21941590 Rio De Janeiro, Brazil.
EM robsonqm@bioqmed.ufrj.br
RI Monteiro, Robson/B-8007-2014
FU Brazilian agency: Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico (CNPq); Brazilian agency: Fundacao de Amparo a Pesquisa do
Estado do Rio de Janeiro Carlos Chagas Filho (FAPERJ); Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, USA
FX This research was supported by the following Brazilian agencies:
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq),
Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro Carlos Chagas
Filho (FAPERJ), and the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA.
NR 24
TC 7
Z9 8
U1 1
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 28
PY 2013
VL 436
IS 2
BP 235
EP 239
DI 10.1016/j.bbrc.2013.05.082
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 180NG
UT WOS:000321601300022
PM 23726920
ER
PT J
AU Wyatt, MK
Tsai, JY
Mishra, S
Campos, M
Jaworski, C
Fariss, RN
Bernstein, SL
Wistow, G
AF Wyatt, M. Keith
Tsai, Jen-Yue
Mishra, Sanghamitra
Campos, Maria
Jaworski, Cynthia
Fariss, Robert N.
Bernstein, Steven L.
Wistow, Graeme
TI Interaction of Complement Factor H and Fibulin3 in Age-Related Macular
Degeneration
SO PLOS ONE
LA English
DT Article
ID C-REACTIVE PROTEIN; MALATTIA LEVENTINESE; OXIDATIVE STRESS; TISSUE
INHIBITOR; VARIANT; DRUSEN; RISK; POLYMORPHISM; GENE; SUSCEPTIBILITY
AB Age-related macular degeneration (AMD) is a major cause of vision loss. It is associated with development of characteristic plaque-like deposits (soft drusen) in Bruch's membrane basal to the retinal pigment epithelium (RPE). A sequence variant (Y402H) in short consensus repeat domain 7 (SCR7) of complement factor H (CFH) is associated with risk for "dry'' AMD. We asked whether the eye-targeting of this disease might be related to specific interactions of CFH SCR7 with proteins expressed in the aging human RPE/choroid that could contribute to protein deposition in drusen. Yeast 2-hybrid (Y2H) screens of a retinal pigment epithelium/choroid library derived from aged donors using CFH SCR7 baits detected an interaction with EFEMP1/Fibulin 3 (Fib3), which is the locus for an inherited macular degeneration and also accumulates basal to macular RPE in AMD. The CFH/Fib3 interaction was validated by co-immunoprecipitation of native proteins. Quantitative Y2H and ELISA assays with different recombinant protein constructs both demonstrated higher affinity for Fib3 for the disease-related CFH 402H variant. Immuno-labeling revealed colocalization of CFH and Fib3 in globular deposits within cholesterol-rich domains in soft drusen in two AMD donors homozygous for CFH 402H (H/H). This pattern of labeling was quite distinct from those seen in examples of eyes with Y/Y and H/Y genotypes. The CFH 402H/Fib3 interaction could contribute to the development of pathological aggregates in soft drusen in some patients and as such might provide a target for therapeutic intervention in some forms of AMD.
C1 [Wyatt, M. Keith; Mishra, Sanghamitra; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA.
[Tsai, Jen-Yue; Campos, Maria; Fariss, Robert N.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
[Jaworski, Cynthia] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Bernstein, Steven L.] Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA.
[Bernstein, Steven L.] Univ Maryland, Sch Med, Dept Neurobiol & Genet, Baltimore, MD 21201 USA.
RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA.
EM graeme@helix.nih.gov
FU NEI Intramural Research Program
FX This work was supported by the NEI Intramural Research Program. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 59
TC 15
Z9 15
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 28
PY 2013
VL 8
IS 6
AR e68088
DI 10.1371/journal.pone.0068088
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 174IH
UT WOS:000321148400162
PM 23840815
ER
PT J
AU Koulaouzidis, A
Rondonotti, E
Karargyris, A
AF Koulaouzidis, Anastasios
Rondonotti, Emanuele
Karargyris, Alexandros
TI Small-bowel capsule endoscopy: A ten-point contemporary review
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Review
DE Capsule endoscopy; Calprotectin; Meta-analysis; Review; Preparation;
Reading software; Complication; Indications
ID DOUBLE-BALLOON ENTEROSCOPY; SUSPECTED BLOOD INDICATOR; COMPUTED VIRTUAL
CHROMOENDOSCOPY; FAMILIAL ADENOMATOUS POLYPOSIS; DIAGNOSTIC YIELD;
CROHNS-DISEASE; TRACHEAL ASPIRATION; FECAL CALPROTECTIN; COLOR
ENHANCEMENT; PILLCAM SB
AB The introduction of capsule endoscopy (CE) in clinical practice increased the interest for the study of the small-bowel. Consequently, in about 10 years, an impressive quantity of literature on indications, diagnostic yield (DY), safety profile and technical evolution of CE has been published as well as several reviews. At present time, there are 5 small-bowel capsule enteroscopy (SBCE) models in the worldwide market. Head-to-head trials have showed in the great majority of studies comparable results in terms of DY, image quality and completion rate. CE meta-analyses formed the basis of national/international guidelines; these guidelines place CE in a prime position for the diagnostic workup of patients with obscure gastrointestinal bleeding, known and/or suspected Crohn's disease and possible small-bowel neoplasia. A 2-L polyethylene glycol-based purge, administered the day before the procedure, is the most widely practiced preparation regimen. Whether this regimen can be further improved (i.e., by further decreasing its volume, changing the timing of administration, coupling it with prokinetics and/or other factors) or if it can really affect the DY, is still under discussion. Faecal calprotectin has been used in SBCE studies in two settings: in patients taking nonsteroidal anti-inflammatory drugs, to evaluate the type and extent of mucosal damage and, more importantly from a clinical point of view, in patients with known or suspected Crohn's disease for assessment of inflammation activity. Although there is still a lot of debate around the exact reasons of SBCE poor performance in various small-bowel segments, it is worth to remember that the capsule progress is non-steerable, hence more rapid in the proximal than in lower segments of the small-bowel. Capsule aspiration, a relatively unexpected complication, has been reported with increasing frequency. This is probably related with the increase in the mean age of patients undergoing CE. CE video review is a time-consuming procedure. Therefore, several attempts have been made to develop technical software features, in order to make CE video analysis easier and shorter (without jeopardizing its accuracy). Suspected Blood Indicator, QuickView and Fujinon Intelligent Chromo Endoscopy are some of the software tools that have been checked in various clinical studies to date. (C) 2013 Baishideng. All rights reserved.
C1 [Koulaouzidis, Anastasios] Royal Infirm Edinburgh NHS Trust, Ctr Liver & Digest Disorders, Edinburgh EH16 4SA, Midlothian, Scotland.
[Rondonotti, Emanuele] Osped Valduce, Gastroenterol Unit, I-22100 Como, Italy.
[Karargyris, Alexandros] NIH, Natl Lib Med, Bethesda, MD 20814 USA.
RP Koulaouzidis, A (reprint author), Royal Infirm Edinburgh NHS Trust, Ctr Liver & Digest Disorders, Endoscopy Unit, 51 Little France Crescent,Old Dalkeith Rd, Edinburgh EH16 4SA, Midlothian, Scotland.
EM akoulaouzidis@hotmail.com
NR 144
TC 58
Z9 60
U1 3
U2 14
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 JUN 28
PY 2013
VL 19
IS 24
BP 3726
EP 3746
DI 10.3748/wjg.v19.i24.3726
PG 21
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 173XG
UT WOS:000321115100003
PM 23840112
ER
PT J
AU Friis, S
Sales, KU
Godiksen, S
Peters, DE
Lin, CY
Vogel, LK
Bugge, TH
AF Friis, Stine
Sales, Katiuchia Uzzun
Godiksen, Sine
Peters, Diane E.
Lin, Chen-Yong
Vogel, Lotte K.
Bugge, Thomas H.
TI A Matriptase-Prostasin Reciprocal Zymogen Activation Complex with Unique
Features PROSTASIN AS A NON-ENZYMATIC CO-FACTOR FOR MATRIPTASE
ACTIVATION
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EPITHELIAL SODIUM-CHANNEL; EPIDERMAL BARRIER FUNCTION; SERINE-PROTEASE
INHIBITOR; HAIR FOLLICLE DEVELOPMENT; NEURAL-TUBE CLOSURE; PLASMINOGEN
ACTIVATION; CELL-SURFACE; PLACENTAL DEVELOPMENT; MONOCLONAL-ANTIBODY;
PROTEOLYTIC CASCADE
AB Matriptase and prostasin are part of a cell surface proteolytic pathway critical for epithelial development and homeostasis. Here we have used a reconstituted cell-based system and transgenic mice to investigate the mechanistic interrelationship between the two proteases. We show that matriptase and prostasin form a reciprocal zymogen activation complex with unique features. Prostasin serves as a critical co-factor for matriptase activation. Unexpectedly, however, prostasin-induced matriptase activation requires neither prostasin zymogen conversion nor prostasin catalytic activity. Prostasin zymogen conversion to active prostasin is dependent on matriptase but does not require matriptase zymogen conversion. Consistent with these findings, wild type prostasin, activation cleavage site-mutated prostasin, and catalytically inactive prostasin all were biologically active in vivo when overexpressed in the epidermis of transgenic mice, giving rise to a severe skin phenotype. Our finding of non-enzymatic stimulation of matriptase activation by prostasin and activation of prostasin by the matriptase zymogen provides a tentative mechanistic explanation for several hitherto unaccounted for genetic and biochemical observations regarding these two membrane-anchored serine proteases and their downstream targets.
C1 [Bugge, Thomas H.] NIDCR, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Sales, Katiuchia Uzzun] NIDCR, Clin Res Core, NIH, Bethesda, MD 20892 USA.
[Friis, Stine; Godiksen, Sine; Vogel, Lotte K.] Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark.
[Godiksen, Sine] Univ Copenhagen, Fac Sci, Dept Biol, DK-2200 Copenhagen, Denmark.
[Peters, Diane E.] Tufts Univ, Sch Med, Program Pharmacol & Expt Therapeut, Boston, MA 02111 USA.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Bugge, TH (reprint author), NIDCR, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
FU National Institutes of Health, NIDCR, Intramural Research Program;
Harboe Foundation; Lundbeck Foundation; Foundation of 17.12.1981;
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
FX This work was supported, in whole or in part, by the National Institutes
of Health, NIDCR, Intramural Research Program (to T. H. B). This work
was also supported by the Harboe Foundation, the Lundbeck Foundation,
and the Foundation of 17.12.1981 (to S. F.) and the Augustinus
Foundation, the 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 (to S.G.).
NR 51
TC 28
Z9 28
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 28
PY 2013
VL 288
IS 26
BP 19028
EP 19039
DI 10.1074/jbc.M113.469932
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 176WB
UT WOS:000321335800038
PM 23673661
ER
PT J
AU He, XM
Chatterjee, R
John, S
Bravo, H
Sathyanarayana, BK
Biddie, SC
FitzGerald, PC
Stamatoyannopoulos, JA
Hager, GL
Vinson, C
AF He, Ximiao
Chatterjee, Raghunath
John, Sam
Bravo, Hector
Sathyanarayana, B. K.
Biddie, Simon C.
FitzGerald, Peter C.
Stamatoyannopoulos, John A.
Hager, Gordon L.
Vinson, Charles
TI Contribution of nucleosome binding preferences and co-occurring DNA
sequences to transcription factor binding
SO BMC GENOMICS
LA English
DT Article
DE TFBS; Nucleosome; GR; c-Jun
ID GLUCOCORTICOID-RECEPTOR-BINDING; UCSC GENOME BROWSER; CHIP-SEQ;
CHROMATIN ACCESSIBILITY; GENE-REGULATION; DROSOPHILA; OCCUPANCY;
PROMOTERS; SITES; ORGANIZATION
AB Background: Chromatin plays a critical role in regulating transcription factors (TFs) binding to their canonical transcription factor binding sites (TFBS). Recent studies in vertebrates show that many TFs preferentially bind to genomic regions that are well bound by nucleosomes in vitro. Co-occurring secondary motifs sometimes correlated with functional TFBS.
Results: We used a logistic regression to evaluate how well the propensity for nucleosome binding and co-occurrence of a secondary motif identify which canonical motifs are bound in vivo. We used ChIP-seq data for three transcription factors binding to their canonical motifs: c-Jun binding the AP-1 motif (TGA(C)/(G)TCA), GR (glucocorticoid receptor) binding the GR motif (G-ACA-(T)/(C)GT-C), and Hoxa2 (homeobox a2) binding the Pbx (Pre-B-cell leukemia homeobox) motif (TGATTGAT). For all canonical TFBS in the mouse genome, we calculated intrinsic nucleosome occupancy scores (INOS) for its surrounding 150-bps DNA and examined the relationship with in vivo TF binding. In mouse mammary 3134 cells, c-Jun and GR proteins preferentially bound regions calculated to be well-bound by nucleosomes in vitro with the canonical AP-1 and GR motifs themselves contributing to the high INOS. Functional GR motifs are enriched for AP-1 motifs if they are within a nucleosome-sized 150-bps region. GR and Hoxa2 also bind motifs with low INOS, perhaps indicating a different mechanism of action.
Conclusion: Our analysis quantified the contribution of INOS and co-occurring sequence to the identification of functional canonical motifs in the genome. This analysis revealed an inherent competition between some TFs and nucleosomes for binding canonical TFBS. GR and c-Jun cooperate if they are within 150-bps. Binding of Hoxa2 and a fraction of GR to motifs with low INOS values suggesting they are not in competition with nucleosomes and may function using different mechanisms.
C1 [He, Ximiao; Chatterjee, Raghunath; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[John, Sam; Biddie, Simon C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Sathyanarayana, B. K.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[FitzGerald, Peter C.] NCI, Genome Anal Unit, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Bravo, Hector] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[John, Sam; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Room 3128,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA.
EM Vinsonc@mail.nih.gov
OI Biddie, Simon/0000-0002-8253-0253; Corrada Bravo,
Hector/0000-0002-1255-4444
NR 50
TC 9
Z9 9
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 28
PY 2013
VL 14
AR 428
DI 10.1186/1471-2164-14-428
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 177QV
UT WOS:000321391200001
PM 23805837
ER
PT J
AU Jones, JC
Freeman, GJ
AF Jones, Jennifer C.
Freeman, Gordon J.
TI Costimulatory Genes: Hotspots of Conflict between Host Defense and
Autoimmunity
SO IMMUNITY
LA English
DT Editorial Material
C1 [Jones, Jennifer C.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM Gordon_Freeman@dfci.harvard.edu
RI Jones, Jennifer/C-8691-2015
OI Jones, Jennifer/0000-0002-9488-7719
FU NIAID NIH HHS [R01 AI089955, P01 AI056299, P01 AI080192, U19 AI082630]
NR 10
TC 2
Z9 2
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JUN 27
PY 2013
VL 38
IS 6
BP 1083
EP 1085
DI 10.1016/j.immuni.2013.06.008
PG 4
WC Immunology
SC Immunology
GA AA2TR
UT WOS:000330947500002
PM 23809156
ER
PT J
AU Tai, X
Erman, B
Alag, A
Mu, J
Kimura, M
Katz, G
Guinter, T
McCaughtry, T
Etzensperger, R
Feigenbaum, L
Singer, DS
Singer, A
AF Tai, Xuguang
Erman, Batu
Alag, Amala
Mu, Jie
Kimura, Motoko
Katz, Gil
Guinter, Terry
McCaughtry, Tom
Etzensperger, Ruth
Feigenbaum, Lionel
Singer, Dinah S.
Singer, Alfred
TI Foxp3 Transcription Factor Is Proapoptotic and Lethal to Developing
Regulatory T Cells unless Counterbalanced by Cytokine Survival Signals
SO IMMUNITY
LA English
DT Article
ID NEGATIVE SELECTION; LINEAGE FATE; GENE; SPECIFICITY; APOPTOSIS; THYMUS;
SELF; BIM; DIFFERENTIATION; AUTOIMMUNITY
AB Immune tolerance requires regulatory T (Treg) cells to prevent autoimmune disease, with the transcription factor Foxp3 functioning as the critical regulator of Treg cell development and function. We report here that Foxp3 was lethal to developing Treg cells in the thymus because it induced a unique proapoptotic protein signature (Puma(++) p-Bim(++) p-JNK(++) DUSP6(-)) and repressed expression of prosurvival Bcl-2 molecules. However, Foxp3 lethality was prevented by common gamma chain (gc)-dependent cytokine signals that were present in the thymus in limiting amounts sufficient to support only similar to 1 million Treg cells. Consequently, most newly arising Treg cells in the thymus were deprived of this signal and underwent Foxp3-induced death, with Foxp3(+)CD25(-) Treg precursor cells being the most susceptible. Thus, we identify Foxp3 as a proapoptotic protein that requires developing Treg cells to compete with one another for limiting amounts of gamma c-dependent survival signals in the thymus.
C1 [Tai, Xuguang; Alag, Amala; Mu, Jie; Kimura, Motoko; Katz, Gil; Guinter, Terry; McCaughtry, Tom; Etzensperger, Ruth; Singer, Dinah S.; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Erman, Batu] Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey.
[Feigenbaum, Lionel] SAIC Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM singera@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX We are grateful to P. Henkart for editorial assistance; J. Bluestone, V.
Kuchroo, A. Strasser, and M. A. Farrar for mice; and R. Hodes, J.-H.
Park, and N. Taylor for reading the manuscript. This research was
supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research.
NR 44
TC 55
Z9 57
U1 1
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JUN 27
PY 2013
VL 38
IS 6
BP 1116
EP 1128
DI 10.1016/j.immuni.2013.02.022
PG 13
WC Immunology
SC Immunology
GA AA2TR
UT WOS:000330947500008
PM 23746651
ER
PT J
AU Chappert, P
Bouladoux, N
Naik, S
Schwartz, RH
AF Chappert, Pascal
Bouladoux, Nicolas
Naik, Shruti
Schwartz, Ronald H.
TI Specific Gut Commensal Flora Locally Alters T Cell Tuning to Endogenous
Ligands
SO IMMUNITY
LA English
DT Article
ID SEGMENTED FILAMENTOUS BACTERIA; ADAPTIVE TOLERANCE; IMMUNE-SYSTEM;
INTESTINAL MICROBIOTA; ACTIVATION THRESHOLD; VIRAL-INFECTION; IN-VIVO;
RESPONSES; INDUCTION; CD4(+)
AB Differences in gut commensal flora can dramatically influence autoimmune responses, but the mechanisms behind this are still unclear. We report, in a Th1-cell-driven murine model of autoimmune arthritis, that specific gut commensals, such as segmented filamentous bacteria, have the ability to modulate the activation threshold of self-reactive T cells. In the local microenvironment of gut-associated lymphoid tissues, inflammatory cytokines elicited by the commensal flora dynamically enhanced the antigen responsiveness of T cells that were otherwise tuned down to a systemic self-antigen. Together with subtle differences in early lineage differentiation, this ultimately led to an enhanced recruitment of pathogenic Th1 cells and the development of a more severe form of autoimmune arthritis. These findings define a key role for the gut commensal flora in sustaining ongoing autoimmune responses through the local fine tuning of T-cell-receptor-proximal activation events in autoreactive T cells.
C1 [Chappert, Pascal; Schwartz, Ronald H.] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Bouladoux, Nicolas; Naik, Shruti] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Chappert, P (reprint author), Univ Paris 05, Sorbonne Paris Cite, INSERM U1013, F-75743 Paris 15, France.
EM pascal.chappert@inserm.fr
OI chappert, pascal/0000-0002-9799-4608
FU Intramural Research Program of the NIAID at the National Institutes of
Health, Bethesda, MD, USA
FX We thank N.J. Singh for helpful discussions and comments on the design
of the experiments; N.J. Singh, Y. Belkaid, J. Davoust, and D.A. Gross
for helpful comments on the manuscript; N. Shulzhenko and A. Morgun for
help on the design of the antibiotic-treatment experiments and the
analysis of SFB colonization; E.J. Chuang for technical assistance; and
D. Trageser-celser, C. Acevedo, and the National Institutes of Allergy
and Infectious Diseases (NIAID) germ-free facility for maintaining the
mice used in these experiments and technical assistance. This work was
supported by the Intramural Research Program of the NIAID at the
National Institutes of Health, Bethesda, MD, USA.
NR 47
TC 19
Z9 20
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JUN 27
PY 2013
VL 38
IS 6
BP 1198
EP 1210
DI 10.1016/j.immuni.2013.06.005
PG 13
WC Immunology
SC Immunology
GA AA2TR
UT WOS:000330947500015
PM 23809163
ER
PT J
AU Sonda, N
Simonato, F
Peranzoni, E
Cali, B
Bortoluzzi, S
Bisognin, A
Wang, E
Marincola, FM
Naldini, L
Gentner, B
Trautwein, C
Sackett, SD
Zanovello, P
Molon, B
Bronte, V
AF Sonda, Nada
Simonato, Francesca
Peranzoni, Elisa
Cali, Bianca
Bortoluzzi, Stefania
Bisognin, Andrea
Wang, Ena
Marincola, Francesco M.
Naldini, Luigi
Gentner, Bernhard
Trautwein, Christian
Sackett, Sara Dutton
Zanovello, Paola
Molon, Barbara
Bronte, Vincenzo
TI miR-142-3p Prevents Macrophage Differentiation during Cancer-Induced
Myelopoiesis
SO IMMUNITY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; DENDRITIC CELL-DIFFERENTIATION;
SUPPRESSOR-CELLS; PANCREATIC-CANCER; T-CELLS; GM-CSF; MYELOID CELLS;
MICRORNAS; BETA; PROGRESSION
AB Tumor progression is accompanied by an altered myelopoiesis causing the accumulation of immunosuppressive cells. Here, we showed that miR-142-3p downregulation promoted macrophage differentiation and determined the acquisition of their immunosuppressive function in tumor. Tumorreleased cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP* isoform of C/EBP beta transcription factor, promoting macrophage generation. miR-142-3p downregulated gp130 by canonical binding to its messenger RNA (mRNA) 3' UTR and repressed C/EBP beta LAP* by noncanonical binding to its 5' mRNA coding sequence. Enforced miR expression impaired macrophage differentiation both in vitro and in vivo. Mice constitutively expressing miR-142-3p in the bone marrow showed a marked increase in survival following immunotherapy with tumor-specific T lymphocytes. By modulating a specific miR in bone marrow precursors, we thus demonstrated the feasibility of altering tumor-induced macrophage differentiation as a potent tool to improve the efficacy of cancer immunotherapy.
C1 [Sonda, Nada; Simonato, Francesca; Cali, Bianca; Zanovello, Paola] Univ Padua, Dept Surg Oncol & Gastroenterol, Oncol & Immunol Sect, I-35128 Padua, Italy.
[Sonda, Nada; Peranzoni, Elisa; Zanovello, Paola; Molon, Barbara] IRCCS, Ist Oncol Veneto, I-35128 Padua, Italy.
[Molon, Barbara] Venetian Inst Mol Med, I-35129 Padua, Italy.
[Bortoluzzi, Stefania; Bisognin, Andrea] Univ Padua, Dept Biol, I-35121 Padua, Italy.
[Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Infect Dis & Immunogenet Sect, Ctr Clin, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
[Naldini, Luigi; Gentner, Bernhard] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy.
[Naldini, Luigi; Gentner, Bernhard] Ist Sci San Raffaele, Div Regenerat Med Gene Therapy & Stem Cells, I-20132 Milan, Italy.
[Naldini, Luigi; Gentner, Bernhard] Univ Vita Salute San Raffaele, Sch Med, I-20132 Milan, Italy.
[Trautwein, Christian; Sackett, Sara Dutton] RWTH Univ Hosp, Dept Med 3, D-52074 Aachen, Germany.
[Bronte, Vincenzo] Univ Verona, Verona Univ Hosp, I-37134 Verona, Italy.
[Bronte, Vincenzo] Univ Verona, Dept Pathol, Immunol Sect, I-37134 Verona, Italy.
RP Bronte, V (reprint author), Univ Verona, Verona Univ Hosp, I-37134 Verona, Italy.
EM vincenzo.bronte@univr.it
RI Bronte, Vincenzo/K-7902-2016; Bisognin, Andrea/J-3619-2013;
OI Bronte, Vincenzo/0000-0002-3741-5141; Bisognin,
Andrea/0000-0002-9114-1508; Bortoluzzi, Stefania/0000-0001-8240-3070;
Gentner, Bernhard/0000-0001-6024-4718
FU Italian Ministry of Education, University and Research [RBAP11T3WB_003,
2009NREAT2_003]; Italian Association for Cancer Research (AIRC)
[IG10400, 12182, AGIMM 100005, 6599]; AIRC-Cariparo; BMBF [01KU1214B];
OBIHEP [360365]; Fondazione Telethon
FX We thank Maurizio Buggio, Serena Zilio, and Stefano Ugel for help with
the in vivo experiments and Andrea Predonzani for the generation of
plasmids. This work was supported by grants from the Italian Ministry of
Education, University and Research (FIRB project RBAP11T3WB_003 and MIUR
project 2009NREAT2_003), Italian Association for Cancer Research (AIRC,
Grants IG10400, 12182, AGIMM 100005, and 6599), and AIRC-Cariparo,
Regional Grant 2008. The work of C.T. was supported by the BMBF
01KU1214B (OBIHEP 360365).
NR 56
TC 39
Z9 40
U1 3
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JUN 27
PY 2013
VL 38
IS 6
BP 1236
EP 1249
DI 10.1016/j.immuni.2013.06.004
PG 14
WC Immunology
SC Immunology
GA AA2TR
UT WOS:000330947500018
PM 23809164
ER
PT J
AU Nee, R
Jindal, RM
Little, D
Ramsey-Goldman, R
Agodoa, L
Hurst, FP
Abbott, KC
AF Nee, Robert
Jindal, Rahul M.
Little, Dustin
Ramsey-Goldman, Rosalind
Agodoa, Lawrence
Hurst, Frank P.
Abbott, Kevin C.
TI Racial Differences and Income Disparities Are Associated With Poor
Outcomes in Kidney Transplant Recipients With Lupus Nephritis
SO TRANSPLANTATION
LA English
DT Article
DE USRDS; Lupus nephritis; Median household income
ID 3 ETHNIC-GROUPS; RENAL-TRANSPLANTATION; SOCIOECONOMIC-FACTORS;
ERYTHEMATOSUS; SURVIVAL; RACE/ETHNICITY; FEATURES; RACE
AB Background. An analysis of income and racial/ethnic disparities on renal transplant outcomes in recipients with lupus nephritis (LN) has not been reported. We analyzed the United States Renal Data System database to assess the impact of these disparities on graft loss and death in the LN and non-LN cohorts.
Methods. We identified 4214 patients with LN as the cause of end-stage renal disease in a retrospective cohort of 150,118 patients first transplanted from January 1, 1995 to July 1, 2006. We merged data on median household income from the United States Census based on the ZIP code.
Results. In multivariate Cox regression analyses, African-Americans (AF) recipients with LN (vs. non-AF) had an increased risk of graft loss (adjusted hazard ratio [AHR], 1.39; 95% confidence interval [CI], 1.21-1.60) and death (AHR, 1.33; 95% CI, 1.09-1.63). Furthermore, there were significant associations of lower-income quintiles with higher risk for graft loss and death among AF with LN. In comparison, among non-AF recipients with LN, income levels did not predict risk for transplant outcomes. The racial disparity for both graft loss and death outcomes among AF with LN was greater than among AF without LN (AHR, 1.32; 95% CI, 1.29-1.36 for graft loss and AHR, 1.02; 95% CI, 0.99-1.05 for death).
Conclusions. AF kidney transplant recipients with LN were at increased risk for graft loss and death compared with non-AF. Income levels were associated with the risk of graft loss and death in AF but not in non-AF recipients with LN.
C1 [Nee, Robert; Little, Dustin; Hurst, Frank P.; Abbott, Kevin C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA.
[Jindal, Rahul M.] Walter Reed Natl Mil Med Ctr, Dept Surg, Bethesda, MD 20889 USA.
[Jindal, Rahul M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA.
[Agodoa, Lawrence] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Jindal, RM (reprint author), Walter Reed Natl Mil Med Ctr, Dept Transplantat, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM jindalr@msn.com
OI Abbott, Kevin/0000-0003-2111-7112
NR 30
TC 11
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD JUN 27
PY 2013
VL 95
IS 12
BP 1471
EP 1478
DI 10.1097/TP.0b013e318292520e
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 299EF
UT WOS:000330377600012
PM 23680929
ER
PT J
AU Gea-Banacloche, JC
AF Gea-Banacloche, Juan C.
TI Antiviral cell therapy: is this the future?
SO BLOOD
LA English
DT Editorial Material
ID T-LYMPHOCYTES; DISEASE
C1 NCI, Bethesda, MD 20892 USA.
RP Gea-Banacloche, JC (reprint author), NCI, Bethesda, MD 20892 USA.
NR 10
TC 2
Z9 3
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 27
PY 2013
VL 121
IS 26
BP 5108
EP 5109
DI 10.1182/blood-2013-05-500082
PG 4
WC Hematology
SC Hematology
GA 184OJ
UT WOS:000321900700002
PM 23813935
ER
PT J
AU Morellato-Castillo, L
Acharya, P
Combes, O
Michiels, J
Descours, A
Ramos, OHP
Yang, YP
Vanham, G
Alien, KK
Kwong, PD
Martin, L
Kessler, P
AF Morellato-Castillo, Laurence
Acharya, Priyamvada
Combes, Olivier
Michiels, Johan
Descours, Anne
Ramos, Oscar H. P.
Yang, Yongping
Vanham, Guido
Alien, Kevin K.
Kwong, Peter D.
Martin, Loic
Kessler, Pascal
TI Interfacial Cavity Filling To Optimize CD4-Mimetic Miniprotein
Interactions with HIV-1 Surface Glycoprotein
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; CD4-BOUND
CONFORMATION; ENTRY INHIBITORS; CD4 RECEPTOR; ANTIBODY; BINDING; DESIGN;
CORE; PROTEINS
AB Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids. To increase HIV-1 gp120 affinity for a family of CD4-mimetic miniproteins (miniCD4s), we targeted the gp120 Phe43 cavity with 11 nonnatural phenylalanine derivatives, introduced into a miniCD4 named M48 (1). The best derivative, named M48U12 (13), bound HIV-1 YU2 gp120 with 8 pM affinity and showed potent HIV-1 neutralization. It contained a methylcyclohexyl derivative of 4-aminophenylalanine, and its cocrystal structure. with gp120 revealed the cyclohexane ring buried within the gp120 hydrophobic core but able to assume multiple orientations in the binding pocket, and the aniline nitrogen potentially providing a focus for further improvement Altogether, the results provide a framework for filling the interfacial Phe43 cavity to enhance miniCD4 affinity.
C1 [Morellato-Castillo, Laurence; Combes, Olivier; Descours, Anne; Ramos, Oscar H. P.; Martin, Loic; Kessler, Pascal] CEA, IBiTecS, Serv Ingn Mol Prot, F-91191 Gif Sur Yvette, France.
[Acharya, Priyamvada; Yang, Yongping; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Michiels, Johan; Vanham, Guido; Alien, Kevin K.] Inst Trop Med, Dept Biomed Sci, Virol Unit, B-2000 Antwerp, Belgium.
RP Martin, L (reprint author), CEA, IBiTecS, Serv Ingn Mol Prot, F-91191 Gif Sur Yvette, France.
EM loic.martin@cea.fr; pascal.kessler@cea.fr
FU sixth European Union Framework Program Microbicide Project (EMPRO);
Intramural AIDS Targeted Anti-Retroviral Program (IATAP), NIH;
Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; Seventh Framework Program (FP7) [242135]; EU program EVA/MRC
[QLKZ-CT-1999-00609, GP828102]; UK Medical Research Council; U.S.
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX This work was supported by the sixth European Union Framework Program
Microbicide Project (EMPRO), by the Intramural AIDS Targeted
Anti-Retroviral Program (IATAP), NIH, by the Intramural Research Program
of the Vaccine Research Center, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, and Seventh
Framework Program (FP7/2007-2013) under grant agreement no. 242135
(CHAARM). L120.3 Ab was provided by the Centralised Facility for AIDS
Reagents supported by EU program EVA/MRC (contract QLKZ-CT-1999-00609
and GP828102) and the UK Medical Research Council. We also thank
Novartis Vaccine for providing gp120SF162. Synchrotron: Use of sector 22
(South-east Region Collaborative Access team) at the Advanced Photon
Source was supported by the U.S. Department of Energy, Basic Energy
Sciences, Office of Science, under Contract W-31-109-Eng-38.
NR 47
TC 10
Z9 10
U1 0
U2 6
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 JUN 27
PY 2013
VL 56
IS 12
BP 5033
EP 5047
DI 10.1021/jm4002988
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 175NJ
UT WOS:000321237100017
PM 23710622
ER
PT J
AU Chen, JW
Feng, G
Song, Y
Wardenburg, JB
Lin, S
Inoshima, I
Otto, M
Wunderink, RG
AF Chen, Jiwang
Feng, Gang
Song, Yang
Wardenburg, Juliane B.
Lin, Simon
Inoshima, Ichiro
Otto, Michael
Wunderink, Richard G.
TI Linezolid Exerts Greater Bacterial Clearance but No Modification of Host
Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model
SO PLOS ONE
LA English
DT Article
ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN; ILLUMINA
MICROARRAY; DISEASE-ONTOLOGY; ANTIBIOTICS; INFECTION; SEPSIS;
PATHOGENESIS; MANAGEMENT; CELLS
AB Background: Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.
Methods: A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNF alpha, IL1 beta, Interferon-gamma and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.
Results: LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1 beta, Interferon-gamma and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.
Conclusion: LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.
C1 [Chen, Jiwang; Wunderink, Richard G.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Chen, Jiwang] Univ Illinois, Sect Pulm Crit Care Med Allergy & Sleep, Chicago, IL USA.
[Feng, Gang; Lin, Simon] Northwestern Univ, Biomed Informat Ctr, Chicago, IL 60611 USA.
[Song, Yang] Illinois State Univ, Microbiol Grp, Sch Biol Sci, Normal, IL 61761 USA.
[Wardenburg, Juliane B.; Inoshima, Ichiro] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Lin, Simon] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA.
[Otto, Michael] NIAID, Bethesda, MD 20892 USA.
RP Chen, JW (reprint author), Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
EM chenjw@uic.edu
RI song, yang/P-1033-2015;
OI Otto, Michael/0000-0002-2222-4115; Wunderink,
Richard/0000-0002-8527-4195
FU Pfizer [WS1826185]; National Center for Advancing Translational Sciences
Grant [8UL1TR000150]; NCI Cancer Center Support Grant [NCI CA060553];
Intramural Research Program of the NIAID
FX This study was supported by Pfizer ASPIRE Award, Pfizer
Investigator-Initiated Grant (WS1826185, to JC), the National Center for
Advancing Translational Sciences Grant (8UL1TR000150) and the NCI Cancer
Center Support Grant (NCI CA060553 to GF and SL) and the Intramural
Research Program of the NIAID (to MO). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 36
TC 1
Z9 1
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2013
VL 8
IS 6
AR e67994
DI 10.1371/journal.pone.0067994
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 174IX
UT WOS:000321150000107
PM 23826353
ER
PT J
AU Famooto, A
Almujtaba, M
Dareng, E
Akarolo-Anthony, S
Ogbonna, C
Offiong, R
Olaniyan, O
Wheeler, CM
Doumatey, A
Rotimi, CN
Adeyemo, A
Adebamowo, CA
AF Famooto, Ayo
Almujtaba, Maryam
Dareng, Eileen
Akarolo-Anthony, Sally
Ogbonna, Celestine
Offiong, Richard
Olaniyan, Olayinka
Wheeler, Cosette M.
Doumatey, Ayo
Rotimi, Charles N.
Adeyemo, Adebowale
Adebamowo, Clement A.
TI RPS19 and TYMS SNPs and Prevalent High Risk Human Papilloma Virus
Infection in Nigerian Women
SO PLOS ONE
LA English
DT Article
ID DIAMOND-BLACKFAN-ANEMIA; CERVICAL-CANCER; REGISTRY; ASSOCIATION; TUMORS;
TOOL
AB High risk HPV (hrHPV) infection is a necessary cause of cervical cancer but the host genetic determinants of infection are poorly understood. We enrolled 267 women who presented to our cervical cancer screening program in Abuja, Nigeria between April 2012 and August 2012. We collected information on demographic characteristics, risk factors of cervical cancer and obtained samples of blood and cervical exfoliated cells from all participants. We used Roche Linear Array HPV Genotyping Test(R) to characterize the prevalent HPV according to manufacturer's instruction; Sequenom Mass Array to test 21 SNPs in genes/regions previously associated with hrHPV and regression models to examine independent factors associated with HPV infection. We considered a p<0.05 as significant because this is a replication study. There were 65 women with and 202 women without hrHPV infection. Under the allelic model, we found significant association between two SNPs, rs2305809 on RPS19 and rs2342700 on TYMS, and prevalent hrHPV infection. Multivariate analysis of hrHPV risk adjusted for age, body mass index, smoking, age of menarche, age at sexual debut, lifetime total number of sexual partners and the total number of pregnancies as covariates, yielded a p-value of 0.071 and 0.010 for rs2305809 and rs2342700, respectively. Our findings in this unique population suggest that a number of genetic risk variants for hrHPV are shared with other population groups. Definitive studies with larger sample sizes and using genome wide approaches are needed to understand the genetic architecture of hrHPV risk in multiple populations.
C1 [Famooto, Ayo; Almujtaba, Maryam; Dareng, Eileen; Akarolo-Anthony, Sally; Ogbonna, Celestine; Adebamowo, Clement A.] Inst Human Virol, Dept Res & Training, Abuja, FCT, Nigeria.
[Akarolo-Anthony, Sally; Adebamowo, Clement A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Offiong, Richard] Univ Abuja, Teaching Hosp, Gwagwalada, FCT, Nigeria.
[Olaniyan, Olayinka] Natl Hosp, Abuja, FCT, Nigeria.
[Wheeler, Cosette M.] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Doumatey, Ayo; Rotimi, Charles N.; Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Inst Human Virol, Baltimore, MD 21201 USA.
[Adebamowo, Clement A.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Adebamowo, CA (reprint author), Inst Human Virol, Dept Res & Training, Abuja, FCT, Nigeria.
EM cadebamowo@som.umaryland.edu
OI Adebamowo, Sally/0000-0003-4713-2433; Adeyemo,
Adebowale/0000-0002-3105-3231
FU National Cancer Institute [D43CA153792]
FX The project described was supported by Award Number D43CA153792 from the
National Cancer Institute. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Cancer Institute or the National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 23
TC 2
Z9 2
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2013
VL 8
IS 6
AR e66930
DI 10.1371/journal.pone.0066930
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 174IX
UT WOS:000321150000018
PM 23826176
ER
PT J
AU Gandolfi, B
Alhaddad, H
Affolter, VK
Brockman, J
Haggstrom, J
Joslin, SEK
Koehne, AL
Mullikin, JC
Outerbridge, CA
Warren, WC
Lyons, LA
AF Gandolfi, Barbara
Alhaddad, Hasan
Affolter, Verena K.
Brockman, Jeffrey
Haggstrom, Jens
Joslin, Shannon E. K.
Koehne, Amanda L.
Mullikin, James C.
Outerbridge, Catherine A.
Warren, Wesley C.
Lyons, Leslie A.
TI To the Root of the Curl: A Signature of a Recent Selective Sweep
Identifies a Mutation That Defines the Cornish Rex Cat Breed
SO PLOS ONE
LA English
DT Article
ID AUTOSOMAL RECESSIVE HYPOTRICHOSIS; PROTEIN-COUPLED RECEPTOR;
HYPOHIDROTIC ECTODERMAL DYSPLASIA; HAIR FOLLICLE DEVELOPMENT; WOOLLY
HAIR; DOMESTIC CAT; COAT MUTANT; P2RY5 GENE; LYSOPHOSPHATIDIC ACID;
PHOSPHATIDIC-ACID
AB The cat (Felis silvestris catus) shows significant variation in pelage, morphological, and behavioral phenotypes amongst its over 40 domesticated breeds. The majority of the breed specific phenotypic presentations originated through artificial selection, especially on desired novel phenotypic characteristics that arose only a few hundred years ago. Variations in coat texture and color of hair often delineate breeds amongst domestic animals. Although the genetic basis of several feline coat colors and hair lengths are characterized, less is known about the genes influencing variation in coat growth and texture, especially rexoid - curly coated types. Cornish Rex is a cat breed defined by a fixed recessive curly coat trait. Genome-wide analyses for selection (d(i), Tajima's D and nucleotide diversity) were performed in the Cornish Rex breed and in 11 phenotypically diverse breeds and two random bred populations. Approximately 63K SNPs were used in the analysis that aimed to localize the locus controlling the rexoid hair texture. A region with a strong signature of recent selective sweep was identified in the Cornish Rex breed on chromosome A1, as well as a consensus block of homozygosity that spans approximately 3 Mb. Inspection of the region for candidate genes led to the identification of the lysophosphatidic acid receptor 6 (LPAR6). A 4 bp deletion in exon 5, c.250_253_delTTTG, which induces a premature stop codon in the receptor, was identified via Sanger sequencing. The mutation is fixed in Cornish Rex, absent in all straight haired cats analyzed, and is also segregating in the German Rex breed. LPAR6 encodes a G protein-coupled receptor essential for maintaining the structural integrity of the hair shaft; and has mutations resulting in a wooly hair phenotype in humans.
C1 [Gandolfi, Barbara; Alhaddad, Hasan; Joslin, Shannon E. K.; Lyons, Leslie A.] Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA.
[Affolter, Verena K.; Koehne, Amanda L.] Univ Calif Davis, Sch Vet Med, Dept Pathol, Davis, CA 95616 USA.
[Brockman, Jeffrey] Hills Pet Nutr Ctr, Topeka, KS USA.
[Haggstrom, Jens] Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden.
[Mullikin, James C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Outerbridge, Catherine A.] Univ Calif Davis, Sch Vet Med, Dept Vet Med & Epidemiol, Davis, CA 95616 USA.
[Warren, Wesley C.] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA.
RP Gandolfi, B (reprint author), Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA.
EM bgandolfi@ucdavis.edu
OI Alhaddad, Hasan/0000-0001-7904-2913
FU National Center for Research Resources; Office of Research
Infrastructure Programs of the National Institute of Health [R24
RR016094]; Winn Feline Foundation [W10-14, W11-041]; Center for
Companion Animal Health at University of California Davis [2010-09-F];
George and Phyllis Miller Feline Health Fund of the San Francisco
Foundation [2008-36-F]
FX This project was supported by the National Center for Research Resources
and the Office of Research Infrastructure Programs of the National
Institute of Health through Grant Number R24 RR016094, the Winn Feline
Foundation (W10-14, W11-041), the Center for Companion Animal Health at
University of California Davis (2010-09-F)
(http://www.vetmed.ucdavis.edu/ccah/index.cfm), and the George and
Phyllis Miller Feline Health Fund of the San Francisco Foundation
(2008-36-F). Support for the development of the Illumina Infinium Feline
63K iSelect DNA array was provided by the Morris Animal Foundation
(http://www.morrisanimalfoundation.org)via a donation from Hill's Pet
Food, Inc. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 75
TC 11
Z9 11
U1 1
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2013
VL 8
IS 6
AR e67105
DI 10.1371/journal.pone.0067105
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 174IX
UT WOS:000321150000027
PM 23826204
ER
PT J
AU Lee, SY
Chen, SL
Chang, YH
Chen, PS
Huang, SY
Tzeng, NS
Wang, YS
Wang, LJ
Lee, IH
Wang, TY
Yeh, TL
Yang, YK
Hong, JS
Lu, RB
AF Lee, Sheng-Yu
Chen, Shiou-Lan
Chang, Yun-Hsuan
Chen, Po See
Huang, San-Yuan
Tzeng, Nian-Sheng
Wang, Yu-Shan
Wang, Liang-Jen
Lee, I. Hui
Wang, Tzu-Yun
Yeh, Tzung Lieh
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI Inflammation's Association with Metabolic Profiles before and after a
Twelve-Week Clinical Trial in Drug-Naive Patients with Bipolar II
Disorder
SO PLOS ONE
LA English
DT Article
ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA;
INSULIN-RESISTANCE; MAJOR DEPRESSION; ADIPOSE-TISSUE; FACTOR-ALPHA;
LITHIUM TREATMENT; RATING-SCALE; DOUBLE-BLIND
AB Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naive patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naive patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-alpha, CRP, IL-6, and TGF-beta) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (P = 1.7E-7) and triglyceride (P = 0.005) levels. Changes in plasma TGF-beta 1 were significantly associated with changes in BMI (P = 8.2E-6), cholesterol (P = 0.004), and triglyceride (P = 0.006) levels. However, changes in plasma TNF-alpha and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (P = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (P = 0.006) and TNF-alpha (P = 0.039) levels. Plasma CRP and TGF-beta 1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II.
C1 [Lee, Sheng-Yu; Chen, Shiou-Lan; Chen, Po See; Lee, I. Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Tainan 70101, Taiwan.
[Chen, Shiou-Lan; Wang, Yu-Shan; Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Tainan 70101, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Inst Allied Hlth Sci, Tainan 70101, Taiwan.
[Huang, San-Yuan; Tzeng, Nian-Sheng] Triserv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan.
[Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan.
[Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70101, Taiwan.
[Wang, Tzu-Yun] Tainan Hosp, Dept Hlth, Dept Psychiat, Tainan, Taiwan.
[Hong, Jau-Shyong] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Dept Psychiat, Tainan 70101, Taiwan.
EM rblu@mail.ncku.edu.tw
FU Taiwan National Science Council [NSC98-2314-B-006-022-MY3]; Taiwan
Department of Health [DOH 95-TD-M-113-055]; Taiwan National Health
Research Institute [NHRI-EX-97-9738NI]; National Cheng Kung University
Project for Promoting Academic Excellence and Developing World Class
Research Centers
FX This work was supported in part by grant NSC98-2314-B-006-022-MY3 (to
RBL) and NSC98-2314-B-006-022-MY3 (to SYL) from the Taiwan National
Science Council, grant DOH 95-TD-M-113-055 (to RBL) from the Taiwan
Department of Health, grant NHRI-EX-97-9738NI (to RBL) from the Taiwan
National Health Research Institute, and the National Cheng Kung
University Project for Promoting Academic Excellence and Developing
World Class Research Centers. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 75
TC 17
Z9 17
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2013
VL 8
IS 6
AR e66847
DI 10.1371/journal.pone.0066847
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 174IX
UT WOS:000321150000016
PM 23826157
ER
PT J
AU Masaoka, A
Gassman, NR
Horton, JK
Kedar, PS
Witt, KL
Hobbs, CA
Kissling, GE
Tano, K
Asagoshi, K
Wilson, SH
AF Masaoka, Aya
Gassman, Natalie R.
Horton, Julie K.
Kedar, Padmini S.
Witt, Kristine L.
Hobbs, Cheryl A.
Kissling, Grace E.
Tano, Keizo
Asagoshi, Kenjiro
Wilson, Samuel H.
TI Interaction between DNA Polymerase beta and BRCA1
SO PLOS ONE
LA English
DT Article
ID BASE EXCISION-REPAIR; CELL NUCLEAR ANTIGEN; DOUBLE-STRAND BREAKS;
HOMOLOGOUS RECOMBINATION; MOUSE FIBROBLASTS; OXIDATIVE STRESS; COMET
ASSAY; DAMAGE; CANCER; RADIATION
AB The breast cancer 1 (BRCA1) protein is a tumor suppressor playing roles in DNA repair and cell cycle regulation. Studies of DNA repair functions of BRCA1 have focused on double-strand break (DSB) repair pathways and have recently included base excision repair (BER). However, the function of BRCA1 in BER is not well defined. Here, we examined a BRCA1 role in BER, first in relation to alkylating agent (MMS) treatment of cells and the BER enzyme DNA polymerase beta (pol beta). MMS treatment of BRCA1 negative human ovarian and chicken DT40 cells revealed hypersensitivity, and the combined gene deletion of BRCA1 and pol beta in DT40 cells was consistent with these factors acting in the same repair pathway, possibly BER. Using cell extracts and purified proteins, BRCA1 and pol beta were found to interact in immunoprecipitation assays, yet in vivo and in vitro assays for a BER role of BRCA1 were negative. An alternate approach with the human cells of immunofluorescence imaging and laser-induced DNA damage revealed negligible BRCA1 recruitment during the first 60 s after irradiation, the period typical of recruitment of pol beta and other BER factors. Instead, 15 min after irradiation, BRCA1 recruitment was strong and there was gamma-H2AX co-localization, consistent with DSBs and repair. The rapid recruitment of pol beta was similar in BRCA1 positive and negative cells. However, a fraction of pol beta initially recruited remained associated with damage sites much longer in BRCA1 positive than negative cells. Interestingly, pol beta expression was required for BRCA1 recruitment, suggesting a partnership between these repair factors in DSB repair.
C1 [Masaoka, Aya; Gassman, Natalie R.; Horton, Julie K.; Kedar, Padmini S.; Asagoshi, Kenjiro; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Witt, Kristine L.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC USA.
[Kissling, Grace E.] NIEHS, Biostatist Branch, NIH, Res Triangle Pk, NC USA.
[Hobbs, Cheryl A.] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Tano, Keizo] Kyoto Univ, Inst Res Reactor, Dept Radiat Life Sci & Radiat Med Sci, Kumatori, Osaka 59004, Japan.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01-ES050158,
Z01-ES050159]; Ministry of Education, Culture, Sports, Science and
Technology of Japan [20510051, 24510072]
FX This research was supported by Research Project Numbers Z01-ES050158 and
Z01-ES050159 from the Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences(to SHW), and by Grants-in-Aid (20510051, 24510072) for
Scientific Research from the Ministry of Education, Culture, Sports,
Science and Technology of Japan (to KT). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 39
TC 9
Z9 9
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2013
VL 8
IS 6
AR e66801
DI 10.1371/journal.pone.0066801
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 174IX
UT WOS:000321150000010
PM 23826138
ER
PT J
AU Monfredi, O
Maltseva, LA
Spurgeon, HA
Boyett, MR
Lakatta, EG
Maltsev, VA
AF Monfredi, Oliver
Maltseva, Larissa A.
Spurgeon, Harold A.
Boyett, Mark R.
Lakatta, Edward G.
Maltsev, Victor A.
TI Beat-to-Beat Variation in Periodicity of Local Calcium Releases
Contributes to Intrinsic Variations of Spontaneous Cycle Length in
Isolated Single Sinoatrial Node Cells
SO PLOS ONE
LA English
DT Article
ID PACEMAKER CELLS; DIASTOLIC DEPOLARIZATION; RYANODINE RECEPTOR; CA2+
RELEASES
AB Spontaneous, submembrane local Ca2+ releases LCRs) generated by the sarcoplasmic reticulum in sinoatrial nodal cells, the cells of the primary cardiac pacemaker, activate inward Na+/Ca2+-exchange current to accelerate the diastolic depolarization rate, and therefore to impact on cycle length. Since LCRs are generated by Ca2+ release channel i.e. ryanodine receptor) openings, they exhibit a degree of stochastic behavior, manifested as notable cycle-to-cycle variations in the time of their occurrence. Aim: The present study tested whether variation in LCR periodicity contributes to intrinsic beat-to-beat) cycle length variability in single sinoatrial nodal cells. Methods: We imaged single rabbit sinoatrial nodal cells using a 2D-camera to capture LCRs over the entire cell, and, in selected cells, simultaneously measured action potentials by perforated patch clamp. Results: LCRs begin to occur on the descending part of the action potential-induced whole-cell Ca2+ transient, at about the time of the maximum diastolic potential. Shortly after the maximum diastolic potential mean 54 +/- 7.7 ms, n = 14), the ensemble of waxing LCR activity converts the decay of the global Ca2+ transient into a rise, resulting in a late, whole-cell diastolic Ca2+ elevation, accompanied by a notable acceleration in diastolic depolarization rate. On average, cells n = 9) generate 13.2 +/- 3.7 LCRs per cycle mean +/- SEM), varying in size 7.1 +/- 4.2 mu m) and duration 44.2 +/- 27.1 ms), with both size and duration being greater for later-occurring LCRs. While the timing of each LCR occurrence also varies, the LCR period i.e. the time from the preceding Ca2+ transient peak to an LCR's subsequent occurrence) averaged for all LCRs in a given cycle closely predicts the time of occurrence of the next action potential, i.e. the cycle length. Conclusion: Intrinsic cycle length variability in single sinoatrial nodal cells is linked to beat-to-beat variations in the average period of individual LCRs each cycle.
C1 [Monfredi, Oliver; Maltseva, Larissa A.; Spurgeon, Harold A.; Lakatta, Edward G.; Maltsev, Victor A.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Monfredi, Oliver; Boyett, Mark R.] Univ Manchester, Inst Cardiovasc Sci, Manchester, Lancs, England.
RP Maltsev, VA (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM MaltsevVi@grc.nia.nih.gov
OI Boyett, Mark/0000-0003-3931-2020; Monfredi, Oliver/0000-0003-1292-2902
FU National Institutes of Health, National Institute on Aging; British
Cardiovascular Society; University of Manchester; Higher Education
Funding Council for England
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging and by
the British Cardiovascular Society (OM), the University of Manchester
(OM, MRB) and the Higher Education Funding Council for England (MRB).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 19
TC 11
Z9 11
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2013
VL 8
IS 6
AR e67247
DI 10.1371/journal.pone.0067247
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 174IX
UT WOS:000321150000048
PM 23826247
ER
PT J
AU Little, MP
Zablotska, LB
Lipshultz, SE
AF Little, Mark P.
Zablotska, Lydia B.
Lipshultz, Steven E.
TI Ischemic Heart Disease after Breast Cancer Radiotherapy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID CIRCULATORY DISEASE; CHILDHOOD-CANCER; RADIATION; MORTALITY; EXPOSURE
C1 [Little, Mark P.] NCI, Bethesda, MD 20892 USA.
[Zablotska, Lydia B.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Lipshultz, Steven E.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Little, MP (reprint author), NCI, Bethesda, MD 20892 USA.
EM mark.little@nih.gov
NR 6
TC 4
Z9 4
U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 27
PY 2013
VL 368
IS 26
BP 2523
EP 2524
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 171KQ
UT WOS:000320926900020
PM 23802524
ER
PT J
AU Sharma, V
Misteli, T
AF Sharma, Vivek
Misteli, Tom
TI Non-coding RNAs in DNA damage and repair
SO FEBS LETTERS
LA English
DT Review
DE Non-coding RNA; DNA damage; Repair; miRNA; Long non-coding RNA; Genome
integrity
ID DOUBLE-STRAND BREAKS; CELL-CYCLE; MICRORNA BIOGENESIS; TUMOR-SUPPRESSOR;
DOWN-REGULATION; CHROMATIN-STRUCTURE; IONIZING-RADIATION; END RESECTION;
HOMOLOGOUS RECOMBINATION; TRANSLATIONAL REPRESSION
AB Non-coding RNAs (ncRNAs) are increasingly recognized as central players in diverse biological processes. Upon DNA damage, the DNA damage response (DDR) elicits a complex signaling cascade, which includes the induction of multiple ncRNA species. Recent studies indicate that DNA-damage induced ncRNAs contribute to regulation of cell cycle, apoptosis and DNA repair, and thus play a key role in maintaining genome stability. This review summarizes the emerging role of ncRNAs in DNA damage and repair. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
C1 [Sharma, Vivek; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
FU NIH DBT Khorana-Nirenberg Fellowship; NIH, National Cancer Institute,
Center for Cancer Research
FX V.S. is supported by an NIH DBT Khorana-Nirenberg Fellowship. Work in
the Misteli laboratory is supported by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
authors would like to thank Misteli laboratory members for helpful
feedback on the manuscript.
NR 127
TC 27
Z9 27
U1 1
U2 43
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
EI 1873-3468
J9 FEBS LETT
JI FEBS Lett.
PD JUN 27
PY 2013
VL 587
IS 13
SI SI
BP 1832
EP 1839
DI 10.1016/j.febslet.2013.05.006
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 171FK
UT WOS:000320910300003
PM 23684639
ER
PT J
AU Rebello, A
Smith, MG
Neumeier, JJ
White, BD
Yu, YK
AF Rebello, A.
Smith, M. G.
Neumeier, J. J.
White, B. D.
Yu, Yi-Kuo
TI Transition from one-dimensional antiferromagnetism to three-dimensional
antiferromagnetic order in single-crystalline CuSb2O6
SO PHYSICAL REVIEW B
LA English
DT Article
ID SPIN-PEIERLS TRANSITION; HEISENBERG-CHAINS; COMPOUND CUGEO3; MAGNETIC
ORDER; RANGE; STATE
AB Measurements of magnetic susceptibility, heat capacity, and thermal expansion are reported for single-crystalline CuSb2O6 in the temperature range 5 < T < 350 K. The magnetic susceptibility exhibits a broad peak centered near 60 K that is typical of one-dimensional antiferromagnetic compounds. Long-range antiferromagnetic order at T-N = 8.7 K is accompanied by an energy gap [Delta = 17.48(6) K]. This transition represents a crossover from one- to three-dimensional antiferromagnetic behavior. Both heat capacity and the thermal expansion coefficients exhibit distinct jumps at TN, which are similar to those observed at the normal-superconducting phase transition in a superconductor. This behavior is quite unusual and is presumably associated with a spin-Peierls transition occurring as a result of three-dimensional phonons coupling with Jordan-Wigner-transformed fermions.
C1 [Rebello, A.; Smith, M. G.; Neumeier, J. J.; White, B. D.] Montana State Univ, Dept Phys, Bozeman, MT 59717 USA.
[Yu, Yi-Kuo] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Rebello, A (reprint author), Montana State Univ, Dept Phys, POB 173840, Bozeman, MT 59717 USA.
FU National Science Foundation [DMR-0907036]
FX We thank Anton Vorontsov for valuable discussions. This material is
based on the work supported by the National Science Foundation under
Contract No. DMR-0907036.
NR 33
TC 7
Z9 7
U1 3
U2 27
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1098-0121
J9 PHYS REV B
JI Phys. Rev. B
PD JUN 27
PY 2013
VL 87
IS 22
AR 224427
DI 10.1103/PhysRevB.87.224427
PG 7
WC Physics, Condensed Matter
SC Physics
GA 172JS
UT WOS:000320999800004
ER
PT J
AU Roychoudhuri, R
Hirahara, K
Mousavi, K
Clever, D
Klebanoff, CA
Bonelli, M
Sciume, G
Zare, H
Vahedi, G
Dema, B
Yu, ZY
Liu, H
Takahashi, H
Rao, M
Muranski, P
Crompton, JG
Punkosdy, G
Bedognetti, D
Wang, E
Hoffmann, V
Rivera, J
Marincola, FM
Nakamura, A
Sartorelli, V
Kanno, Y
Gattinoni, L
Muto, A
Igarashi, K
O'Shea, JJ
Restifo, NP
AF Roychoudhuri, Rahul
Hirahara, Kiyoshi
Mousavi, Kambiz
Clever, David
Klebanoff, Christopher A.
Bonelli, Michael
Sciume, Giuseppe
Zare, Hossein
Vahedi, Golnaz
Dema, Barbara
Yu, Zhiya
Liu, Hui
Takahashi, Hayato
Rao, Mahadev
Muranski, Pawel
Crompton, Joseph G.
Punkosdy, George
Bedognetti, Davide
Wang, Ena
Hoffmann, Victoria
Rivera, Juan
Marincola, Francesco M.
Nakamura, Atsushi
Sartorelli, Vittorio
Kanno, Yuka
Gattinoni, Luca
Muto, Akihiko
Igarashi, Kazuhiko
O'Shea, John J.
Restifo, Nicholas P.
TI BACH2 represses effector programs to stabilize T-reg-mediated immune
homeostasis
SO NATURE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; CELL-DIFFERENTIATION;
SUSCEPTIBILITY LOCI; RISK LOCI; B-CELLS; TRANSCRIPTION; DISEASE;
INTERLEUKIN-4; METAANALYSIS
AB Through their functional diversification, distinct lineages of CD4(+) T cells can act to either drive or constrain immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment(1). Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma(2), Crohn's disease(3,4), coeliac disease(5), vitiligo(6), multiple sclerosis(7) and type 1 diabetes(8). Although these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for BACH2 in the maintenance of immune homeostasis has not been established. Here, by studying mice in which the Bach2 gene is disrupted, we define BACH2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programs of multiple effector lineages in CD4(+) T cells. BACH2 was required for efficient formation of regulatory (T-reg) cells and consequently for suppression of lethal inflammation in a manner that was T-reg-cell-dependent. Assessment of the genome-wide function of BACH2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during T-reg polarization resulted in inappropriate diversion to effector lineages. In addition, BACH2 constrained full effector differentiation within T(H)1, T(H)2 and T(H)17 cell lineages. These findings identify BACH2 as a key regulator of CD4(+) T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity.
C1 [Roychoudhuri, Rahul; Clever, David; Klebanoff, Christopher A.; Yu, Zhiya; Rao, Mahadev; Muranski, Pawel; Crompton, Joseph G.; Gattinoni, Luca; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hirahara, Kiyoshi; Bonelli, Michael; Sciume, Giuseppe; Vahedi, Golnaz; Takahashi, Hayato; Kanno, Yuka; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
[Mousavi, Kambiz; Zare, Hossein; Sartorelli, Vittorio] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
[Dema, Barbara; Rivera, Juan] NIAMS, Lab Mol Immunogenet, NIH, Bethesda, MD 20892 USA.
[Liu, Hui; Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Punkosdy, George] NIAID, NIH, Bethesda, MD 20892 USA.
[Hoffmann, Victoria] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
[Nakamura, Atsushi; Muto, Akihiko; Igarashi, Kazuhiko] Tohoku Univ, Grad Sch Med, Dept Biochem, Sendai, Miyagi 9808575, Japan.
[Muto, Akihiko; Igarashi, Kazuhiko] Japan Sci & Technol Agcy, CREST, Sendai, Miyagi 9808575, Japan.
[Restifo, Nicholas P.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Roychoudhuri, R (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM roychoudhuri@mail.nih.gov; osheajo@mail.nih.gov; restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Roychoudhuri, Rahul/A-7442-2010; Kanno,
Yuka/B-5802-2013; Sciume, Giuseppe/K-8985-2016; Hirahara,
Kiyoshi/E-2460-2017;
OI Gattinoni, Luca/0000-0003-2239-3282; Roychoudhuri,
Rahul/0000-0002-5392-1853; Sciume, Giuseppe/0000-0003-0131-512X;
Hirahara, Kiyoshi/0000-0002-9128-9449; Kanno, Yuka/0000-0001-5668-9319;
Bedognetti, Davide/0000-0002-5857-773X; Restifo, Nicholas
P./0000-0003-4229-4580; Igarashi, Kazuhiko/0000-0002-2470-2475
FU Intramural Research Programs of the National Cancer Institute (NIH);
National Institute of Arthritis and Musculoskeletal and Skin Diseases;
NIH Center for Regenerative Medicine; JSPS Research Fellowship for
Japanese Biomedical and Behavioural Researchers at NIH
FX This research was supported by the Intramural Research Programs of the
National Cancer Institute (NIH) and the National Institute of Arthritis
and Musculoskeletal and Skin Diseases, the NIH Center for Regenerative
Medicine and the JSPS Research Fellowship for Japanese Biomedical and
Behavioural Researchers at NIH. We thank D. N. Roychoudhuri, D. C.
Macallan, G. E. Griffin, S. A. Rosenberg, M. S. Rao, Y. Ji, D. Palmer,
M. Sukumar, G. Fabozzi, K. Hanada, E. Lugli, J. H. Pan and N. Van
Panhuys for discussions, A. Mixon and S. Farid for cell sorting, G.
McMullen for mouse handling and Y. Luo, Y. Wakabayashi, J. Zhu, G.
Gutierrez-Cruz and H. W. Sun for help with sequencing and analysis.
NR 35
TC 91
Z9 94
U1 4
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 27
PY 2013
VL 498
IS 7455
BP 506
EP +
DI 10.1038/nature12199
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400057
PM 23728300
ER
PT J
AU Chong, A
Child, R
Wehrly, TD
Rockx-Brouwer, D
Qin, AP
Mann, BJ
Celli, J
AF Chong, Audrey
Child, Robert
Wehrly, Tara D.
Rockx-Brouwer, Dedeke
Qin, Aiping
Mann, Barbara J.
Celli, Jean
TI Structure-Function Analysis of DipA, a Francisella tularensis Virulence
Factor Required for Intracellular Replication
SO PLOS ONE
LA English
DT Article
ID OUTER-MEMBRANE PROTEIN; COILED-COIL DOMAINS; PATHOGENICITY ISLAND;
ESCHERICHIA-COLI; LEGIONELLA-PNEUMOPHILA; MURINE MACROPHAGES;
STREPTOCOCCUS-PNEUMONIAE; PHAGOSOMAL ESCAPE; LIVE VACCINE; VI SECRETION
AB Francisella tularensis is a highly infectious bacterium whose virulence relies on its ability to rapidly reach the macrophage cytosol and extensively replicate in this compartment. We previously identified a novel Francisella virulence factor, DipA (FTT0369c), which is required for intramacrophage proliferation and survival, and virulence in mice. DipA is a 353 amino acid protein with a Sec-dependent signal peptide, four Sel1-like repeats (SLR), and a C-terminal coiled-coil (CC) domain. Here, we determined through biochemical and localization studies that DipA is a membrane-associated protein exposed on the surface of the prototypical F. tularensis subsp. tularensis strain SchuS4 during macrophage infection. Deletion and substitution mutagenesis showed that the CC domain, but not the SLR motifs, of DipA is required for surface exposure on SchuS4. Complementation of the dipA mutant with either DipA CC or SLR domain mutants did not restore intracellular growth of Francisella, indicating that proper localization and the SLR domains are required for DipA function. Co-immunoprecipitation studies revealed interactions with the Francisella outer membrane protein FopA, suggesting that DipA is part of a membrane-associated complex. Altogether, our findings indicate that DipA is positioned at the host-pathogen interface to influence the intracellular fate of this pathogen.
C1 [Chong, Audrey; Child, Robert; Wehrly, Tara D.; Rockx-Brouwer, Dedeke; Celli, Jean] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Qin, Aiping; Mann, Barbara J.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Mann, Barbara J.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
RP Chong, A (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM chonga@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases [AI000953-01]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, project number AI000953-01. The funders have no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 87
TC 6
Z9 6
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 26
PY 2013
VL 8
IS 6
AR e67965
DI 10.1371/journal.pone.0067965
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 178DN
UT WOS:000321424400125
PM 23840797
ER
PT J
AU Fozzatti, L
Park, JW
Zhao, L
Willingham, MC
Cheng, SY
AF Fozzatti, Laura
Park, Jeong Won
Zhao, Li
Willingham, Mark C.
Cheng, Sheue-yann
TI Oncogenic Actions of the Nuclear Receptor Corepressor (NCOR1) in a Mouse
Model of Thyroid Cancer
SO PLOS ONE
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; HORMONE-BETA-RECEPTOR; TUMOR-SUPPRESSOR
P53; VALPROIC ACID; CO-REPRESSOR; IN-VIVO; TRANSCRIPTIONAL ACTIVITY;
BREAST-CANCER; CELL-LINES; GENE
AB Studies have suggested that the nuclear receptor corepressor 1 (NCOR1) could play an important role in human cancers. However, the detailed molecular mechanisms by which it functions in vivo to affect cancer progression are not clear. The present study elucidated the in vivo actions of NCOR1 in carcinogenesis using a mouse model (Thrb(PV/PV) mice) that spontaneously develops thyroid cancer. Thrb(PV/PV) mice harbor a dominantly negative thyroid hormone receptor beta (TR beta) mutant (denoted as PV). We adopted the loss-of-the function approach by crossing Thrb(PV) mice with mice that globally express an NCOR1 mutant protein (NCOR1 Delta ID) in which the receptor interaction domains have been modified so that it cannot interact with the TR beta, or PV, in mice. Remarkably, expression of NCOR1 Delta ID protein reduced thyroid tumor growth, markedly delayed tumor progression, and prolonged survival of Thrb(PV/PV) Ncor1(Delta ID/Delta ID) mice. Tumor cell proliferation was inhibited by increased expression of cyclin-dependent kinase inhibitor 1 (p21(waf1/cip1); Cdkn1A), and apoptosis was activated by elevated expression of pro-apoptotic BCL-Associated X (Bax). Further analyses showed that p53 was recruited to the p53-binding site on the proximal promoter of the Cdkn1A and the Bax gene as a co-repressor complex with PV/NCOR1/histone deacetylas-3 (HDAC-3), leading to repression of the Cdkn1A as well as the Bax gene in thyroids of Thrb(PV/PV) mice. In thyroids of Thrb(PV/PV) Ncor1(Delta ID/Delta ID) mice, the p53/PV complex could not recruit NCOR1 Delta ID and HDAC-3, leading to de-repression of both genes to inhibit cancer progression. The present studies provided direct evidence in vivo that NCOR1 could function as an oncogene via transcription regulation in a mouse model of thyroid cancer.
C1 [Fozzatti, Laura; Park, Jeong Won; Zhao, Li; Willingham, Mark C.; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Intramural Research Program at the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX The present research was supported by the Intramural Research Program at
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.; We thank Dr. A. Hollenberg (Harvard Medical School) for
providing Ncor1 Delta ID mice. The present research was supported by the
Intramural Research Program at the Center for Cancer Research, National
Cancer Institute, National Institutes of Health.
NR 52
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Z9 2
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 26
PY 2013
VL 8
IS 6
AR e67954
DI 10.1371/journal.pone.0067954
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 178DN
UT WOS:000321424400122
PM 23840792
ER
PT J
AU Guo, R
Abdelmohsen, K
Morin, PJ
Gorospe, M
AF Guo, Rong
Abdelmohsen, Kotb
Morin, Patrice J.
Gorospe, Myriam
TI Novel MicroRNA Reporter Uncovers Repression of Let-7 by GSK-3 beta
SO PLOS ONE
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; OVARIAN-CANCER CELLS; KINASE 3-BETA;
POSTTRANSCRIPTIONAL REGULATION; COLORECTAL-CANCER; INDUCE APOPTOSIS;
TUMOR-GROWTH; EXPRESSION; RNA; P53
AB Several members of the let-7 microRNA family are downregulated in ovarian and other cancers. They are thought to act as tumor suppressors by lowering growth-promoting and anti-apoptotic proteins. In order to measure cellular let-7 levels systematically, we have developed a highly sensitive let-7 reporter assay system based on the expression of a chimeric mRNA that contains the luciferase coding region and a 3'-untranslated region (UTR) bearing two let-7-binding sites. In cells expressing the reporter construct, termed pmirGLO-let7, luciferase activity was high when let-7 was absent, while luciferase activity was low when let-7 levels were elevated. The ovarian cancer cell lines BG-1 and UCI-101 were transfected with the let-7 reporter and surveyed with a library of kinase inhibitors in order to identify pathways affecting let-7 activity. Among the inhibitors causing changes in endogenous let-7 abundance, the lowering of glycogen synthase kinase 3 (GSK-3)beta function specifically increased let-7 levels and lowered luciferase activity. Similarly, silencing GSK-3 beta increased both mature and primary-let-7 levels in BG-1 cells, and decreased BG-1 cell survival. Further studies identified p53 as a downstream effector of the GSK-3 beta-mediated repression of let-7 biosynthesis. Our studies highlight GSK-3 beta as a novel therapeutic target in ovarian tumorigenesis.
C1 [Guo, Rong; Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Morin, Patrice J.] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Morin, Patrice J.] Amer Assoc Canc Res, Philadelphia, PA USA.
RP Morin, PJ (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM pat.morin@aacr.org; myriam-gorospe@nih.gov
FU National Institute on Aging-Intramural Research Program of the National
Institutes of Health
FX The work was funded entirely by the National Institute on
Aging-Intramural Research Program of the National Institutes of Health.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 61
TC 4
Z9 4
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 26
PY 2013
VL 8
IS 6
AR e66330
DI 10.1371/journal.pone.0066330
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 178DN
UT WOS:000321424400023
PM 23840442
ER
PT J
AU Jimeno-Yepes, AJ
Plaza, L
Mork, JG
Aronson, AR
Diaz, A
AF Jimeno-Yepes, Antonio J.
Plaza, Laura
Mork, James G.
Aronson, Alan R.
Diaz, Alberto
TI MeSH indexing based on automatically generated summaries
SO BMC BIOINFORMATICS
LA English
DT Article
ID BIOMEDICAL TEXT; RETRIEVAL; DOCUMENTS; MEDLINE
AB Background: MEDLINE citations are manually indexed at the U. S. National Library of Medicine (NLM) using as reference the Medical Subject Headings (MeSH) controlled vocabulary. For this task, the human indexers read the full text of the article. Due to the growth of MEDLINE, the NLM Indexing Initiative explores indexing methodologies that can support the task of the indexers. Medical Text Indexer (MTI) is a tool developed by the NLM Indexing Initiative to provide MeSH indexing recommendations to indexers. Currently, the input to MTI is MEDLINE citations, title and abstract only. Previous work has shown that using full text as input to MTI increases recall, but decreases precision sharply. We propose using summaries generated automatically from the full text for the input to MTI to use in the task of suggesting MeSH headings to indexers. Summaries distill the most salient information from the full text, which might increase the coverage of automatic indexing approaches based on MEDLINE. We hypothesize that if the results were good enough, manual indexers could possibly use automatic summaries instead of the full texts, along with the recommendations of MTI, to speed up the process while maintaining high quality of indexing results.
Results: We have generated summaries of different lengths using two different summarizers, and evaluated the MTI indexing on the summaries using different algorithms: MTI, individual MTI components, and machine learning. The results are compared to those of full text articles and MEDLINE citations. Our results show that automatically generated summaries achieve similar recall but higher precision compared to full text articles. Compared to MEDLINE citations, summaries achieve higher recall but lower precision.
Conclusions: Our results show that automatic summaries produce better indexing than full text articles. Summaries produce similar recall to full text but much better precision, which seems to indicate that automatic summaries can efficiently capture the most important contents within the original articles. The combination of MEDLINE citations and automatically generated summaries could improve the recommendations suggested by MTI. On the other hand, indexing performance might be dependent on the MeSH heading being indexed. Summarization techniques could thus be considered as a feature selection algorithm that might have to be tuned individually for each MeSH heading.
C1 [Jimeno-Yepes, Antonio J.; Mork, James G.; Aronson, Alan R.] Natl Lib Med, Bethesda, MD 20894 USA.
[Jimeno-Yepes, Antonio J.] Natl ICT Australia, Victoria Res Lab, Melbourne, Vic, Australia.
[Plaza, Laura] UNED NLP & IR Grp, Madrid 28040, Spain.
[Diaz, Alberto] UCM NIL Grp, Madrid 28040, Spain.
RP Jimeno-Yepes, AJ (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM antonio.jimeno@gmail.com
OI Diaz, Alberto/0000-0002-7641-8919; DIAZ ESTEBAN,
ALBERTO/0000-0003-1966-3421; Jimeno Yepes, Antonio
Jose/0000-0002-6581-094X
FU NIH, National Library of Medicine; National Library of Medicine; Spanish
Government [TIN2009-14659-C03-01]; Australian Government as by the
Department of Broadband, Communications; Australian Research Council
through the ICT Centre of Excellence program; Digital Economy
FX This work was supported in part by the Intramural Research Program of
the NIH, National Library of Medicine and by an appointment of A.
Jimeno-Yepes to the NLM Research Participation Program sponsored by the
National Library of Medicine and administered by the Oak Ridge Institute
for Science and Education.; This research was also supported by the
Spanish Government through the project TIN2009-14659-C03-01.; National
ICT Australia (NICTA) is funded by the Australian Government as
represented by the Department of Broadband, Communications and the
Digital Economy and the Australian Research Council through the ICT
Centre of Excellence program.
NR 41
TC 9
Z9 9
U1 0
U2 12
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 JUN 26
PY 2013
VL 14
AR 208
DI 10.1186/1471-2105-14-208
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 179FM
UT WOS:000321505200001
PM 23802936
ER
PT J
AU Tovar, A
Hennessy, E
Must, A
Hughes, SO
Gute, DM
Sliwa, S
Boulos, RJ
Vikre, EK
Kamins, CL
Tofuri, K
Pirie, A
Economos, CD
AF Tovar, Alison
Hennessy, Erin
Must, Aviva
Hughes, Sheryl O.
Gute, David M.
Sliwa, Sarah
Boulos, Rebecca J.
Vikre, Emily Kuross
Kamins, Christina Luongo
Tofuri, Kerline
Pirie, Alex
Economos, Christina D.
TI Feeding styles and evening family meals among recent immigrants
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Family meal; Feeding styles; Children; Obesity; Immigrants
ID BODY-MASS INDEX; UNITED-STATES; PARENTING STYLES; WEIGHT STATUS;
LONGITUDINAL ASSOCIATIONS; ADOLESCENT OVERWEIGHT; CHILDHOOD OVERWEIGHT;
AMERICAN CHILDREN; PHYSICAL-ACTIVITY; RISK-FACTORS
AB The protective effect of family meals on unhealthy weight gain and diet has been shown across multiple age groups; however, it is unknown whether a similar effect is present among diverse immigrant populations. In addition, little research has focused on factors associated with the frequency of evening family meals, such as feeding styles (how parents interact with their child around feeding). Therefore the goals of this paper are to explore the 1) association between the frequency of evening family meals and child weight status among new immigrant families, and 2) influence of immigrant mothers' feeding styles on the frequency of evening family meals.
Baseline self-reported socio-demographic information and measured heights and weights were collected for both mother and child (age range: 3-12 years) among 387 mother-child dyads enrolled in Live Well, a community-based, participatory-research, randomized controlled lifestyle intervention to prevent excessive weight gain in recent (<10 years in the U. S.) immigrant mothers and children. For children, height and weight measurements were transformed into BMI z-scores using age-and sex-specific CDC standards and categorized as overweight (85th-94th percentile) and obese (>= 95th percentile); mothers' BMI was calculated. Frequency of evening family meals, eating dinner in front of the TV, acculturation and responses to the Caregiver's Feeding Styles Questionnaire (CFSQ) were also obtained from the mother. Children were categorized as "eating evening family meals regularly" if they had an evening family meal >= 5 times per week.
Overall, 20% of children were overweight and 25% were obese. Less than half (40.9%) of families had regular evening family meals. In multivariate analyses, adjusting for covariates, children who were overweight/obese were significantly less likely to have >= 5 evening family meals/week compared with normal weight children (OR = 0.51, 95% CI 0.32-0.82). Mothers who had a low demanding/high responsive or a low demanding/low responsive feeding style, were less likely to have >= 5 evening family meals/week compared to mothers with a high demanding/high responsive feeding style (OR = 0.41, 95% CI 0.18-0.0.96, OR = 0.33, 95% CI 0.13-0.87, respectively). Future interventions and programs that seek to help parents establish healthy household routines, such as family meals, may consider tailoring to specific maternal feeding styles.
C1 [Tovar, Alison] Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02818 USA.
[Hennessy, Erin] NCI, Hlth Behav Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Must, Aviva] Tufts Univ, Dept Publ Hlth & Community Med, Sch Med, Boston, MA 02111 USA.
[Hughes, Sheryl O.] Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
[Gute, David M.] Tufts Univ, Sch Engn, Dept Civil & Environm Engn, Medford, MA 02155 USA.
[Sliwa, Sarah; Boulos, Rebecca J.; Vikre, Emily Kuross; Kamins, Christina Luongo; Tofuri, Kerline; Economos, Christina D.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Pirie, Alex] Immigrant Serv Providers Grp Hlth, Somerville, MA 02143 USA.
RP Tovar, A (reprint author), Univ Rhode Isl, Dept Nutr & Food Sci, 112 Ranger Hall, Kingston, RI 02818 USA.
EM alison_tovar@mail.uri.edu
FU National Institutes of Health (NIH), Bethesda MD [5R01HD057841]; NIH
FX We would like to thank these members of the Live Well Steering Committee
(Nesly Metayer, Franklin Dalembert, Raymond R. Hyatt, Warren
Goldstein-Gelb, Maria Landaverde, Melissa McWhinney, Joyce Guilhermino
de Padua, Helen Sinzker, Heloisa Galvao, and Ismael Vasquez). In
addition, we thank the Live Well women and their children for
participating in this study. Funding for this research was provided by
grant 5R01HD057841 from the National Institutes of Health (NIH),
Bethesda MD. Postdoctoral research funds for Alison Tovar were provided
by an NIH supplement from this grant.
NR 47
TC 4
Z9 4
U1 4
U2 23
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD JUN 26
PY 2013
VL 10
AR 84
DI 10.1186/1479-5868-10-84
PG 8
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 181IV
UT WOS:000321662100001
PM 23803223
ER
PT J
AU Shrestha, S
Foxman, B
Weinberger, DM
Steiner, C
Viboud, C
Rohani, P
AF Shrestha, Sourya
Foxman, Betsy
Weinberger, Daniel M.
Steiner, Claudia
Viboud, Cecile
Rohani, Pejman
TI Identifying the Interaction Between Influenza and Pneumococcal Pneumonia
Using Incidence Data
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID TIME-SERIES ANALYSIS; HONG KONG INFLUENZA; STREPTOCOCCUS-PNEUMONIAE;
PANDEMIC INFLUENZA; BACTERIAL PNEUMONIA; RESPIRATORY VIRUSES;
UNITED-STATES; A H1N1; DISEASE; ASSOCIATION
AB The association between influenza virus and the bacterium Streptococcus pneumoniae (pneumococcus) has been proposed as a polymicrobial system, whereby transmission and pathogenicity of one pathogen (the bacterium) are affected by interactions with the other (the virus). However, studies focusing on different scales of resolution have painted an inconsistent picture: Individual-scale animal experiments have unequivocally demonstrated an association, whereas epidemiological support in human populations is, at best, inconclusive. We integrate weekly incidence reports and a mechanistic transmission model within a likelihood-based inference framework to characterize the nature, timing, and magnitude of this interaction. We find support for a strong but short-lived interaction, with influenza infection increasing susceptibility to pneumococcal pneumonia similar to 100-fold. We infer modest population-level impacts arising from strong processes at the level of an individual, thereby resolving the dichotomy in seemingly inconsistent observations across scales. An accurate characterization of the influenza-pneumococcal interaction can form a basis for more effective clinical care and public health measures for pneumococcal pneumonia.
C1 [Shrestha, Sourya; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Shrestha, Sourya; Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Foxman, Betsy] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Weinberger, Daniel M.; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA.
[Weinberger, Daniel M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.
[Steiner, Claudia] US Dept HHS, Healthcare Cost & Utilizat Project, Ctr Delivery Org & Markets, Agcy Healthcare Res & Qual, Rockville, MD 20850 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Shrestha, S (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM sourya@umich.edu
RI Foxman, Betsy/E-1836-2015;
OI Shrestha, Sourya/0000-0002-6106-6834; Foxman, Betsy/0000-0001-6682-238X;
Weinberger, Daniel/0000-0003-1178-8086
FU Vaccine Modeling Initiative of the Bill & Melinda Gates Foundation;
Research and Policy in Infectious Disease Dynamics program of the
Science and Technology Directorate, Department of Homeland Security, the
Fogarty International Center, NIH
FX Funding: S.S. and P. R. were supported by the Vaccine Modeling
Initiative of the Bill & Melinda Gates Foundation. P. R. also received
support from the Research and Policy in Infectious Disease Dynamics
program of the Science and Technology Directorate, Department of
Homeland Security, the Fogarty International Center, NIH.
NR 62
TC 28
Z9 30
U1 2
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUN 26
PY 2013
VL 5
IS 191
AR 191ra84
DI 10.1126/scitranslmed.3005982
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 171KX
UT WOS:000320928000005
PM 23803706
ER
PT J
AU Yewdell, JW
Spiro, DJ
Golding, H
Quill, H
Mittelman, A
Nabel, GJ
AF Yewdell, Jonathan W.
Spiro, David J.
Golding, Hana
Quill, Helen
Mittelman, Abraham
Nabel, Gary J.
TI Getting to the Heart of Influenza
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
C1 [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Mittelman, Abraham; Nabel, Gary J.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Spiro, David J.] NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA.
[Quill, Helen] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM gary.nabel@sanofi.com
FU Intramural NIH HHS [ZIA AI001055-05]
NR 4
TC 0
Z9 0
U1 0
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUN 26
PY 2013
VL 5
IS 191
AR 191ed8
DI 10.1126/scitranslmed.3006735
PG 2
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 171KX
UT WOS:000320928000001
PM 23803701
ER
PT J
AU Amin-ul Mannan, M
Shadrick, WR
Biener, G
Shin, BS
Anshu, A
Raicu, V
Frick, DN
Dey, M
AF Amin-ul Mannan, M.
Shadrick, William R.
Biener, Gabriel
Shin, Byung-Sik
Anshu, Ashish
Raicu, Valerica
Frick, David N.
Dey, Madhusudan
TI An Ire1-Phk1 Chimera Reveals a Dispensable Role of Autokinase Activity
in Endoplasmic Reticulum Stress Response
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE Ire1; RNA splicing; RNase; protein kinase; unfolded protein response
ID UNFOLDED PROTEIN RESPONSE; MESSENGER-RNA; TRANSMEMBRANE PROTEIN;
TRANSCRIPTION FACTOR; FLUORESCENT PROTEIN; CATALYTIC SUBUNIT;
KINASE-ACTIVITY; IRE1 KINASE; MECHANISM; INSIGHTS
AB The endoplasmic reticulunn transmembrane receptor Ire1 senses over-accumulation of unfolded proteins in the endoplasnnic reticulunn and initiates the unfolded protein response (UPR). The cytoplasmic portion of Ire1 has a protein kinase domain (KD) and a kinase extension nuclease (KEN) domain that cleaves an mRNA for encoding the Had transcription factor needed to express UPR genes. During this UPR signaling, Ire1 proteins self-assemble into an oligomer of dimers, which essentially requires autophosphorylation of a constituent activation loop in the KD. However, it is not clear how dimerization, autophosphorylation, and KEN domain function are precisely coordinated. In this study, we uncoupled the KD and KEN domain functions, by removing the activation loop along with an extended region that we called the auto-inhibitory region (AIR), or by swapping the activation loop with a homologous loop from phosphorylase kinase 1 (Ire1(PHK)). Both Ire1(Delta AIR) and Ire1(PHK) activated the UPR even when either protein contained a mutation (D797A) that abolished the ability of Ire1 KD to transfer phosphates to the AIR. Neither protein functioned when containing mutations in key ATP binding residues (E746A and N749A) or in residues that disrupted Ire1 dimer interface (W426A or R697D). We interpret these results as evidence supporting the notion that the primary function of the kinase domain is to autophosphorylate the AIR in order to relieve auto-inhibition and that ADP acts as a switch to activate the KEN domain-catalyzed HAC1 mRNA cleavage. Published by Elsevier Ltd.
C1 [Amin-ul Mannan, M.; Anshu, Ashish; Raicu, Valerica; Dey, Madhusudan] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA.
[Shadrick, William R.; Frick, David N.] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53211 USA.
[Biener, Gabriel; Raicu, Valerica] Univ Wisconsin, Dept Phys, Milwaukee, WI 53211 USA.
[Shin, Byung-Sik] NIH, Bethesda, MD 20892 USA.
RP Dey, M (reprint author), Univ Wisconsin, Dept Biol Sci, Room 460,Lapham Hall,3209 North Maryland Ave, Milwaukee, WI 53211 USA.
EM deym@umw.edu
FU RGI grants (UWM internal funds); National Science Foundation
[IIP-1114305, PHY-1058470, PHY-1126386]
FX We thank Dr. Thomas E. Dever (National Institute of Child Health & Human
Development, National Institutes of Health) for reagents and helpful
discussion throughout the project. We thank Dr. Alan G. Hinnebusch
(National Institute of Child Health & Human Development, National
Institutes of Health) and Prof. Colin Scanes (UW-Milwaukee) for reading
the manuscript and for useful suggestions. This work was partly
supported by RGI grants (UWM internal funds) awarded to M.D. and
National Science Foundation grants (IIP-1114305, PHY-1058470 and
PHY-1126386) awarded to V.R.
NR 43
TC 0
Z9 0
U1 1
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUN 26
PY 2013
VL 425
IS 12
BP 2083
EP 2099
DI 10.1016/j.jmb.2013.02.036
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 164MN
UT WOS:000320414300001
ER
PT J
AU Johnson, BC
Metifiot, M
Ferris, A
Pommier, Y
Hughes, SH
AF Johnson, Barry C.
Metifiot, Mathieu
Ferris, Andrea
Pommier, Yves
Hughes, Stephen H.
TI A Homology Model of HIV-1 Integrase and Analysis of Mutations Designed
to Test the Model
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE HIV; integration; dimerization; infectivity; modeling
ID VIRUS TYPE-1 INTEGRASE; DNA-BINDING DOMAIN; PROTEIN IN-VITRO; TERMINAL
DOMAIN; RETROVIRAL INTEGRATION; MOLECULAR-MECHANISMS; CRYSTAL-STRUCTURE;
STRUCTURAL BASIS; FLEXIBLE LOOP; ACTIVE-SITE
AB Although there are structures of the different domains of human immunodeficiency virus type 1 (HIV-1) integrase (IN), there is no structure of the entire protein. The recently determined crystal structures of the prototype foamy virus (PFV) IN tetramer, in complexes with viral DNA, led to the generation of models of full-length HIV-1 IN. These models were generated, in part, by superimposing the structures of the domains of HIV-1 IN onto the structure of full-length PFV IN. We developed a model for HIV-1 IN-based solely on its sequence alignment with PFV IN-that differs in several ways from the previous models. Specifically, in our model, the junction between the catalytic core domain and C-terminal domain adopts a helix-loop-helix motif that is similar to the corresponding segment of PFV IN and differs from the crystal structures of these two HIV-1 IN domains. The alignment of residues in the C-terminal domain also differs from the previous models. Our model can be used to explain the phenotype of previously published HIV-1 IN mutants. We made additional mutants, and the behavior of these new mutants provides additional support for the model. (c) 2013 Published by Elsevier Ltd.
C1 [Johnson, Barry C.; Ferris, Andrea; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Ctr Canc Res, Ft Detrick, MD 21702 USA.
[Metifiot, Mathieu; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA.
RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, Ctr Canc Res, POB B, Ft Detrick, MD 21702 USA.
EM hughesst@mail.nih.gov
FU National Institutes of Health Intramural Program; Center for Cancer
Research; National Cancer Institute; National Institutes of Health
grants from the AIDS Intramural AIDS Targeted Antiviral Program
FX Our studies were supported by the National Institutes of Health
Intramural Program, Center for Cancer Research, National Cancer
Institute and by National Institutes of Health grants from the AIDS
Intramural AIDS Targeted Antiviral Program. We thank Ferri Soheilian and
Kunio Nagashima at the Electron Microscopy Laboratory at Frederick
National Laboratory for electron microscopy imaging and Al Kane for
assistance with figures.
NR 51
TC 20
Z9 20
U1 0
U2 16
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUN 26
PY 2013
VL 425
IS 12
BP 2133
EP 2146
DI 10.1016/j.jmb.2013.03.027
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 164MN
UT WOS:000320414300003
PM 23542006
ER
PT J
AU Lu, J
Frerich, JM
Turtzo, LC
Li, SQ
Chiang, J
Yang, CZ
Wang, XP
Zhang, C
Wu, CX
Sun, ZC
Niu, G
Zhuang, ZP
Brady, RO
Chen, XY
AF Lu, Jie
Frerich, Jason M.
Turtzo, L. Christine
Li, Siqi
Chiang, Jeffrey
Yang, Chunzhang
Wang, Xiaoping
Zhang, Chao
Wu, Chenxi
Sun, Zhongchan
Niu, Gang
Zhuang, Zhengping
Brady, Roscoe O.
Chen, Xiaoyuan
TI Histone deacetylase inhibitors are neuroprotective and preserve
NGF-mediated cell survival following traumatic brain injury
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NERVE GROWTH-FACTOR; H3 ACETYLATION; UP-REGULATION; HEAD-INJURY;
EXPRESSION; RATS; MICE; ASTROCYTES; ACTIVATION; MECHANISMS
AB Acute traumatic brain injury (TBI) is associated with long-term cognitive and behavioral dysfunction. In vivo studies have shown histone deacetylase inhibitors (HDACis) to be neuroprotective following TBI in rodent models. HDACis are intriguing candidates because they are capable of provoking widespread genetic changes and modulation of protein function. By using known HDACis and a unique small-molecule pan-HDACi (LB-205), we investigated the effects and mechanisms associated with HDACi-induced neuroprotection following CNS injury in an astrocyte scratch assay in vitro and a rat TBI model in vivo. We demonstrate the preservation of sufficient expression of nerve growth factor (NGF) and activation of the neurotrophic tyrosine kinase receptor type 1 (TrkA) pathway following HDACi treatment to be crucial in stimulating the survival of CNS cells after TBI. HDACi treatment up-regulated the expression of NGF, phospho-TrkA, phospho-protein kinase B (p-AKT), NF-kappa B, and B-cell lymphoma 2 (Bcl-2) cell survival factors while down-regulating the expression of p75 neurotrophin receptor (NTR), phospho-JNK, and Bcl-2-associated X protein apoptosis factors. HDACi treatment also increased the expression of the stem cell biomarker nestin, and decreased the expression of reactive astrocyte biomarker GFAP within damaged tissue following TBI. These findings provide further insight into the mechanisms by which HDACi treatment after TBI is neuroprotective and support the continued study of HDACis following acute TBI.
C1 [Lu, Jie; Turtzo, L. Christine; Wu, Chenxi; Sun, Zhongchan; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, Bethesda, MD 20892 USA.
[Frerich, Jason M.; Li, Siqi; Yang, Chunzhang; Wang, Xiaoping; Zhang, Chao; Zhuang, Zhengping; Brady, Roscoe O.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA.
[Chiang, Jeffrey] NCI, NIH, Bethesda, MD 20892 USA.
[Lu, Jie; Turtzo, L. Christine; Chen, Xiaoyuan] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA.
EM zhuangp@ninds.nih.gov; bradyr@ninds.nih.gov; shawn.chen@nih.gov
FU Department of Defense in the Center for Neuroscience and Regenerative
Medicine; Intramural Research Programs of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), NINDS; Imaging Sciences
Training Program (sponsored by Radiology and Imaging Sciences in the
Clinical Center and Intramural Research Programs of the NIBIB); Howard
Hughes Medical Institute-NIH Medical Research Scholars Program
FX We thank Dr. Paul E. Gallant [National Institute of Neurological
Disorders and Stroke (NINDS) Light Microscopy Facility] for assistance
with confocal microscopy, Dr. Dragan Maric (NINDS Flow Cytometry Core
Facility) for assistance with flow cytometry, and Lixte Biotechnology
Holdings for providing LB-205. This work was supported by the Department
of Defense in the Center for Neuroscience and Regenerative Medicine,
Intramural Research Programs of the National Institute of Biomedical
Imaging and Bioengineering (NIBIB), NINDS, Imaging Sciences Training
Program (sponsored by Radiology and Imaging Sciences in the Clinical
Center and Intramural Research Programs of the NIBIB) (J.L.), and Howard
Hughes Medical Institute-NIH Medical Research Scholars Program (J.M.F.).
NR 39
TC 26
Z9 28
U1 1
U2 10
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 JUN 25
PY 2013
VL 110
IS 26
BP 10747
EP 10752
DI 10.1073/pnas.1308950110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179EY
UT WOS:000321503700067
PM 23754423
ER
PT J
AU Chen, Y
Pasapera, AM
Koretsky, AP
Waterman, CM
AF Chen, Yun
Pasapera, Ana M.
Koretsky, Alan P.
Waterman, Clare M.
TI Orientation-specific responses to sustained uniaxial stretching in focal
adhesion growth and turnover
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE mechanosensing; integrin; tissue mechanics
ID CALPAIN-MEDIATED PROTEOLYSIS; ENDOTHELIAL-CELLS; GENE-EXPRESSION; CYCLIC
STRETCH; CARDIAC MYOCYTES; KINASE INHIBITOR; SKELETAL-MUSCLE; SRC;
ACTIVATION; FAK
AB Cells are mechanosensitive to extracellular matrix (ECM) deformation, which can be caused by muscle contraction or changes in hydrostatic pressure. Focal adhesions (FAs) mediate the linkage between the cell and the ECM and initiate mechanically stimulated signaling events. We developed a stretching apparatus in which cells grown on fibronectin-coated elastic substrates can be stretched and imaged live to study how FAs dynamically respond to ECM deformation. Human bone osteosarcoma epithelial cell line U2OS was transfected with GFP-paxillin as an FA marker and subjected to sustained uniaxial stretching. Two responses at different timescales were observed: rapid FA growth within seconds after stretching, and delayed FA disassembly and loss of cell polarity that occurred over tens of minutes. Rapid FA growth occurred in all cells; however, delayed responses to stretch occurred in an orientation-specificmanner, specifically in cells with their long axes perpendicular to the stretching direction, but not in cells with their long axes parallel to stretch. Pharmacological treatments demonstrated that FA kinase (FAK) promotes but Src inhibits rapid FA growth, whereas FAK, Src, and calpain 2 all contribute to delayed FA disassembly and loss of polarity in cells perpendicular to stretching. Immunostaining for phospho-FAK after stretching revealed that FAK activation was maximal at 5 s after stretching, specifically in FAs oriented perpendicular to stretch. We hypothesize that orientation-specific activation of strain/stress-sensitive proteins in FAs upstream to FAK and Src promote orientation-specific responses in FA growth and disassembly that mediate polarity rearrangement in response to sustained stretch.
C1 [Chen, Yun; Koretsky, Alan P.] NINDS, Lab Funct Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Pasapera, Ana M.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Waterman, CM (reprint author), NINDS, Lab Funct Mol Imaging, NIH, Bethesda, MD 20892 USA.
EM watermancm@nhlbi.nih.gov
RI Koretsky, Alan/C-7940-2015;
OI Koretsky, Alan/0000-0002-8085-4756; Waterman, Clare/0000-0001-6142-6775;
Chen, Yun/0000-0001-6917-7814
FU National Research Council Fellowship; National Heart, Lung, and Blood
Institute; National Institute of Neurological Disorders and Stroke
FX We thank Sergey Plotinikov, Robert Fischer, and Ingo Thievessen for
helpful discussions; Bill Shin for maintaining microscopes in the C.M.W.
laboratory; and Ruperto Villadiego for helping build the cell stretcher.
This work was supported by the National Research Council Fellowship (to
Y.C.) and the intramural programs of the National Heart, Lung, and Blood
Institute (A.M.P. and C.M.W.) and the National Institute of Neurological
Disorders and Stroke (Y.C. and A.P.K.).
NR 55
TC 15
Z9 15
U1 2
U2 19
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 JUN 25
PY 2013
VL 110
IS 26
BP E2352
EP E2361
DI 10.1073/pnas.1221637110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179EY
UT WOS:000321503700007
PM 23754369
ER
PT J
AU Truong, QA
Hayden, D
Woodard, PK
Kirby, R
Chou, ET
Nagurney, JT
Wiviott, SD
Fleg, JL
Schoenfeld, DA
Udelson, JE
Hoffmann, U
AF Truong, Quynh A.
Hayden, Douglas
Woodard, Pamela K.
Kirby, Ruth
Chou, Eric T.
Nagurney, John T.
Wiviott, Stephen D.
Fleg, Jerome L.
Schoenfeld, David A.
Udelson, James E.
Hoffmann, Udo
TI Sex Differences in the Effectiveness of Early Coronary Computed
Tomographic Angiography Compared With Standard Emergency Department
Evaluation for Acute Chest Pain The Rule-Out Myocardial Infarction With
Computer-Assisted Tomography (ROMICAT)-II Trial
SO CIRCULATION
LA English
DT Article
DE acute coronary syndrome; chest pain; emergency service, hospital; sex;
tomography; x-ray computed
ID AMERICAN-HEART-ASSOCIATION; CT ANGIOGRAPHY; ARTERY-DISEASE;
CARDIOVASCULAR-RADIOLOGY; DIAGNOSTIC PERFORMANCE; CLINICAL-CARDIOLOGY;
DOSE REDUCTION; RADIATION; RISK; INTERVENTION
AB Background
We evaluate sex-based differences in the effectiveness of early cardiac computed tomographic angiography (CCTA) and standard emergency department (ED) evaluation in patients with acute chest pain.
Methods and Results
In the Rule-Out Myocardial Infarction With Computer-Assisted Tomography (ROMICAT)-II multicenter, controlled trial, we randomized 1000 patients (47% women) 40 to 74 years of age with symptoms suggestive of acute coronary syndrome to an early CCTA or standard ED evaluation. In this prespecified analysis, women in the CCTA arm had a greater reduction in length of stay, lower hospital admission rates, and lesser increased cumulative radiation dose than men in a comparison of ED strategies (P for interaction 0.02). Although women had lower acute coronary syndrome rates than men (3% versus 12%; P<0.0001), sex differences in length of stay persisted after adjustment for baseline differences, including acute coronary syndrome rate (P for interaction <0.03). Length of stay was similar between sexes with normal CCTA findings (P=0.11). There was no missed acute coronary syndrome for either sex. No difference was observed in major adverse cardiac events between sexes and ED strategies (P for interaction =0.39). Women had more normal CCTA examinations than men (58% versus 37%; P<0.0001), less obstructive coronary disease by CCTA (5% versus 17%; P=0.0001), but similar normalcy rates for functional testing (P=0.65). Men in the CCTA arm had the highest rate of invasive coronary angiography (18%), whereas women had comparable low 5% rates regardless of ED strategy.
Conclusions
This trial provides data supporting an early CCTA strategy as an attractive option in women presenting to the ED with symptoms suggestive of acute coronary syndrome. The findings may be explained by lower CAD prevalence and severity in women than men.
C1 [Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Div Cardiol, Boston, MA 02114 USA.
[Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Nagurney, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Dept, Boston, MA 02114 USA.
[Hayden, Douglas; Schoenfeld, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Woodard, Pamela K.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Kirby, Ruth; Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Chou, Eric T.] Kaiser Permanente Fontana Med Ctr, Fontana, CA USA.
[Wiviott, Stephen D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02114 USA.
[Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA.
[Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA.
RP Truong, QA (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, 165 Cambridge St,Ste 400, Boston, MA 02114 USA.
EM qtruong@partners.org
FU National Institutes of Health/National Heart, Lung, and Blood Institute
[U01HL092040, U01HL092022, K23HL098370, L30HL093896]; Qi Imaging; St.
Jude Medical; American College of Radiology Imaging Network; Duke
Clinical Research Institute
FX The study was supported by the National Institutes of Health/National
Heart, Lung, and Blood Institute (U01HL092040 and U01HL092022). Dr
Truong was supported by the National Institutes of Health/National
Heart, Lung, and Blood Institute (K23HL098370 and L30HL093896).; Dr
Truong receives grant support from Qi Imaging, St. Jude Medical,
American College of Radiology Imaging Network, and Duke Clinical
Research Institute. The other authors report no conflicts.
NR 22
TC 9
Z9 9
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 25
PY 2013
VL 127
IS 25
BP 2494
EP 2502
DI 10.1161/CIRCULATIONAHA.113.001736
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 171HU
UT WOS:000320916900013
PM 23685743
ER
PT J
AU Sommers, CL
Rouquette-Jazdanian, AK
Robles, AI
Kortum, RL
Merrill, RK
Li, WM
Nath, N
Wohlfert, E
Sixt, KM
Belkaid, Y
Samelson, LE
AF Sommers, Connie L.
Rouquette-Jazdanian, Alexandre K.
Robles, Ana I.
Kortum, Robert L.
Merrill, Robert K.
Li, Wenmei
Nath, Nandan
Wohlfert, Elizabeth
Sixt, Katherine M.
Belkaid, Yasmine
Samelson, Lawrence E.
TI miRNA Signature of Mouse Helper T Cell Hyper-Proliferation
SO PLOS ONE
LA English
DT Article
ID LYMPHOPROLIFERATIVE DISEASE; HOMEOSTATIC PROLIFERATION; ERK ACTIVATION;
MUTANT MICE; EXPRESSION; MIR-146A; CANCER; LAT; MICRORNA-21; PATHWAY
AB Helper T cells from a mutant mouse model, LAT Y136F, hyper-proliferate and cause a severe lymphoproliferative disease that kills the mice by six months of age. LAT Y136F mice carry a tyrosine to phenylalanine mutation in the Linker for Activation of T cells (LAT) gene. This mutation leads to a number of changes in T cells that result in altered cytokine production including increased IL-4 production, increased proliferation, and decreased apoptosis. Hyper-proliferation of the mutant T cells contributes to lymphadenopathy, splenomegaly, and multi-organ T cell infiltration. miRNAs are short non-coding RNAs that regulate expression of cohorts of genes. This study investigates which miRNAs are expressed in LAT Y136F T cells and compares these to miRNAs expressed in wild type T cells that are undergoing proliferation in two other settings. The first setting is homeostatic proliferation, which was modeled by adoptive transfer of wild type T cells into T cell-deficient mice. The second setting is proliferation in response to infection, which was modeled by infection of wild type mice with the nematode H. polygyrus. By comparing miRNA expression in these three proliferative states (LAT Y136F hyper-proliferation, homeostatic proliferation and proliferation in response to H. polygyrus infection) to expression in wild type naive CD4(+) T cells, we found miRNAs that were highly regulated in all three proliferative states (miR-21 and miR-146a) and some that were more specific to individual settings of proliferation such as those more specific for LAT Y136F lymphoproliferative disease (miR-669f, miR-155 and miR-466a/b). Future experiments that modulate levels of the miRNAs identified in this study may reveal the roles of these miRNAs in T cell proliferation and/or lymphoproliferative disease.
C1 [Sommers, Connie L.; Rouquette-Jazdanian, Alexandre K.; Kortum, Robert L.; Merrill, Robert K.; Li, Wenmei; Nath, Nandan; Sixt, Katherine M.; Samelson, Lawrence E.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Robles, Ana I.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sommers, Connie L.; Wohlfert, Elizabeth; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Sommers, CL (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM sommersc@helix.nih.gov
FU National Cancer Institute Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Cancer Institute Center for Cancer Research. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 49
TC 3
Z9 3
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 25
PY 2013
VL 8
IS 6
AR e66709
DI 10.1371/journal.pone.0066709
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 175IB
UT WOS:000321223000023
PM 23825558
ER
PT J
AU Krist, AH
Glenn, BA
Glasgow, RE
Balasubramanian, BA
Chambers, DA
Fernandez, ME
Heurtin-Roberts, S
Kessler, R
Ory, MG
Phillips, SM
Ritzwoller, DP
Roby, DH
Rodriguez, HP
Sabo, RT
Gorin, SNS
Stange, KC
AF Krist, Alex H.
Glenn, Beth A.
Glasgow, Russell E.
Balasubramanian, Bijal A.
Chambers, David A.
Fernandez, Maria E.
Heurtin-Roberts, Suzanne
Kessler, Rodger
Ory, Marcia G.
Phillips, Siobhan M.
Ritzwoller, Debra P.
Roby, Dylan H.
Rodriguez, Hector P.
Sabo, Roy T.
Gorin, Sherri N. Sheinfeld
Stange, Kurt C.
CA MOHR Study Grp
TI Designing a valid randomized pragmatic primary care implementation
trial: the my own health report (MOHR) project
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Patient-reported measures; Health behaviors; Mental health; Pragmatic
trial; Electronic health record; Primary care
ID BEHAVIORAL-COUNSELING INTERVENTIONS; DECISION-MAKING; UNDERSERVED
COMMUNITY; EDUCATIONAL OUTREACH; PREVENTIVE-SERVICES; SCREENING-TEST;
SCIENCE; CANCER; PHYSICIANS; CONTEXT
AB Background: There is a pressing need for greater attention to patient-centered health behavior and psychosocial issues in primary care, and for practical tools, study designs and results of clinical and policy relevance. Our goal is to design a scientifically rigorous and valid pragmatic trial to test whether primary care practices can systematically implement the collection of patient-reported information and provide patients needed advice, goal setting, and counseling in response.
Methods: This manuscript reports on the iterative design of the My Own Health Report (MOHR) study, a cluster randomized delayed intervention trial. Nine pairs of diverse primary care practices will be randomized to early or delayed intervention four months later. The intervention consists of fielding the MOHR assessment - addresses 10 domains of health behaviors and psychosocial issues - and subsequent provision of needed counseling and support for patients presenting for wellness or chronic care. As a pragmatic participatory trial, stakeholder groups including practice partners and patients have been engaged throughout the study design to account for local resources and characteristics. Participatory tasks include identifying MOHR assessment content, refining the study design, providing input on outcomes measures, and designing the implementation workflow. Study outcomes include the intervention reach (percent of patients offered and completing the MOHR assessment), effectiveness (patients reporting being asked about topics, setting change goals, and receiving assistance in early versus delayed intervention practices), contextual factors influencing outcomes, and intervention costs.
Discussion: The MOHR study shows how a participatory design can be used to promote the consistent collection and use of patient-reported health behavior and psychosocial assessments in a broad range of primary care settings. While pragmatic in nature, the study design will allow valid comparisons to answer the posed research question, and findings will be broadly generalizable to a range of primary care settings. Per the pragmatic explanatory continuum indicator summary (PRECIS) framework, the study design is substantially more pragmatic than other published trials. The methods and findings should be of interest to researchers, practitioners, and policy makers attempting to make healthcare more patient-centered and relevant.
C1 [Krist, Alex H.] Virginia Commonwealth Univ, Dept Family Med & Populat Hlth, Richmond, VA 23298 USA.
[Glenn, Beth A.; Roby, Dylan H.; Rodriguez, Hector P.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA.
[Glasgow, Russell E.; Heurtin-Roberts, Suzanne; Phillips, Siobhan M.] NCI, Implementat Sci Team, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Balasubramanian, Bijal A.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Dallas, TX 75390 USA.
[Chambers, David A.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Fernandez, Maria E.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA.
[Kessler, Rodger] Vermont Coll Med, Dept Family Med, Burlington, VT 05405 USA.
[Ory, Marcia G.] Texas A&M Hlth Sci Ctr, Sch Rural Publ Hlth, Dept Hlth Promot & Community Hlth Sci, College Stn, TX 77843 USA.
[Ritzwoller, Debra P.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80231 USA.
[Sabo, Roy T.] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23298 USA.
[Gorin, Sherri N. Sheinfeld] NCI, SAIC Frederick, NIH, DCCPS, Bethesda, MD 20892 USA.
[Gorin, Sherri N. Sheinfeld] NYPAC, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
[Stange, Kurt C.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Krist, AH (reprint author), Virginia Commonwealth Univ, Dept Family Med & Populat Hlth, POB 980251, Richmond, VA 23298 USA.
EM ahkrist@vcu.edu
FU National Cancer Institute; Agency for Healthcare Research and Quality;
Office of Behavioral and Social Sciences Research; National Center for
Advancing Translational Sciences (CTSA) [ULTR00058]
FX Funding for the MOHR project was provided by the National Cancer
Institute, Agency for Healthcare Research and Quality, Office of
Behavioral and Social Sciences Research, and National Center for
Advancing Translational Sciences (CTSA Grant Number ULTR00058). Dr.
Stange's time is supported in part by a Clinical Research Professorship
from the American Cancer Society and by the National Cancer Society
through the Intergovernmental Personnel Act. The opinions expressed in
this manuscript are those of the authors and do not necessarily reflect
those of the funders. For their support and guidance of the MOHR project
we would like to thank Janice Genervro PhD MSW, David Meyers MD, Robert
M Kaplan PhD, Holly Jimison PhD, Richard Wood MHA, Kayla Fair RN MPH,
Jennifer Leeman PHD MPH, Catherine L Rohweder DrPH, Alexis Moore MPH,
Maria E Fernandez PhD, John Quillin PhD CGC, Melissa Hayes BS, Paul
Estabrooks PhD, Christine Nelson PhD RN, and John Heintzman MD MPH.
NR 71
TC 19
Z9 19
U1 1
U2 19
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 JUN 25
PY 2013
VL 8
AR 73
DI 10.1186/1748-5908-8-73
PG 13
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 171NB
UT WOS:000320935000001
PM 23799943
ER
PT J
AU Pearson, GD
Kaltman, JR
Lauer, MS
AF Pearson, Gail D.
Kaltman, Jonathan R.
Lauer, Michael S.
TI Evidence-Based Medicine Comes of Age in Pediatric Cardiology
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE congenital heart disease; congenital heart surgery; pediatric
cardiovascular research.
ID NATIONAL HEART; LUNG
AB Outcomes have improved significantly in pediatric cardiovascular disease in recent decades. The challenge now is to sustain these advances through innovative clinical trials, fundamental molecular investigations, genetics and genomics, and outreach to families, emphasizing the importance of participating in research. We describe several such efforts and provide a vision of the future for pediatric cardiovascular research. (J Am Coll Cardiol 2013;61:2565-7) (C) 2013 by the American College of Cardiology Foundation
C1 [Pearson, Gail D.; Kaltman, Jonathan R.; Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Pearson, GD (reprint author), NHLBI, Adult & Pediat Cardiac Res Program, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 8132, Bethesda, MD 20892 USA.
EM pearsong@mail.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 11
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUN 25
PY 2013
VL 61
IS 25
BP 2565
EP 2567
DI 10.1016/j.jacc.2013.03.054
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 167AO
UT WOS:000320602700011
PM 23623909
ER
PT J
AU Emery, AC
Eiden, MV
Mustafa, T
Eiden, LE
AF Emery, Andrew C.
Eiden, Maribeth V.
Mustafa, Tomris
Eiden, Lee E.
TI Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in
Neuronal and Endocrine Cells
SO SCIENCE SIGNALING
LA English
DT Article
ID NUCLEOTIDE-EXCHANGE FACTOR; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; NERVE
GROWTH-FACTOR; DROSOPHILA PDZ-GEF; PROTEIN-KINASE; FACTOR CNRASGEF;
CYCLIC-AMP; SYNAPTIC PLASTICITY; POLYPEPTIDE PACAP; PC12 CELLS
AB G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR)-mediated increases in the second messenger cyclic adenosine monophosphate (cAMP) activate the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK), and in neuroendocrine cells, this pathway leads to cAMP-dependent neuritogenesis mediated through Rap1 and B-Raf. We found that the Rap guanine nucleotide exchange factor Rapgef2 was enriched from primary bovine neuroendocrine cells by cAMP-agarose affinity chromatography and that it was specifically eluted by cAMP. With loss-of-function experiments in the rat neuronal cell line Neuroscreen-1 (NS-1) and gain-of-function experiments in human embryonic kidney 293T cells, we demonstrated that Rapgef2 connected GPCR-dependent activation of adenylate cyclase and increased cAMP concentration with the activation of ERK in neurons and endocrine cells. Furthermore, knockdown of Rapgef2 blocked cAMP-and ERK-dependent neuritogenesis. Our data are consistent with a pathway involving the cAMP-mediated activation of Rapgef2, which then stimulates Rap1, leading to increases in B-Raf, MEK, and ERK activity.
C1 [Emery, Andrew C.; Mustafa, Tomris; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Intramural Res Program, Bethesda, MD 20892 USA.
[Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, Intramural Res Program, Bethesda, MD 20892 USA.
RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Intramural Res Program, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
OI Emery, Andrew/0000-0002-6760-2570; Eiden, Lee/0000-0001-7524-944X
FU NIH [1ZIAMH002386, 1ZIAMH002592]
FX This work was funded by the Intramural Research Program of the NIH
Projects 1ZIAMH002386 (to L.E.E.) and 1ZIAMH002592 (to M.V.E.).
NR 58
TC 14
Z9 20
U1 0
U2 14
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
J9 SCI SIGNAL
JI Sci. Signal.
PD JUN 25
PY 2013
VL 6
IS 281
AR ra51
DI 10.1126/scisignal.2003993
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 170LU
UT WOS:000320853200002
PM 23800469
ER
PT J
AU Harper, MT
Londono, JEC
Quick, K
Londono, JC
Flockerzi, V
Philipp, SE
Birnbaumer, L
Freichel, M
Poole, AW
AF Harper, Matthew T.
Londono, Juan E. Camacho
Quick, Kathryn
Londono, Julia Camacho
Flockerzi, Veit
Philipp, Stephan E.
Birnbaumer, Lutz
Freichel, Marc
Poole, Alastair W.
TI Transient Receptor Potential Channels Function as a Coincidence Signal
Detector Mediating Phosphatidylserine Exposure
SO SCIENCE SIGNALING
LA English
DT Article
ID OPERATED CALCIUM-CHANNELS; SMOOTH-MUSCLE-CELLS; HUMAN-PLATELETS;
NA+/CA2+ EXCHANGER; CA2+ ENTRY; TRPC3 CHANNELS; ACTIVATION; THROMBIN;
MOUSE; ORAI1
AB Blood platelet aggregation must be tightly controlled to promote clotting at injury sites but avoid inappropriate occlusion of blood vessels. Thrombin, which cleaves and activates G(q)-coupled protease-activated receptors, and collagen-related peptide, which activates the receptor glycoprotein VI, stimulate platelets to aggregate and form thrombi. Coincident activation by these two agonists synergizes, causing the exposure of phosphatidylserine on the cell surface, which is a marker of cell death in many cell types. Phosphatidylserine exposure is also essential to produce additional thrombin on platelet surfaces, which contributes to thrombosis. We found that activation of either thrombin receptors or glycoprotein VI alone produced a calcium signal that was largely dependent only on store-operated Ca2+ entry. In contrast, experiments with platelets from knockout mice showed that the presence of both ligands activated nonselective cation channels of the transient receptor potential C(TRPC) family, TRPC3 and TRPC6. These channels principally allowed entry of Na+, which coupled to reverse-mode Na+/Ca2+ exchange to allow calcium influx and thereby contribute to Ca2+ signaling and phosphatidylserine exposure. Thus, TRPC channels act as coincidence detectors to coordinate responses to multiple signals in cells, thereby indirectly mediating in platelets an increase in intracellular calcium concentrations and exposure of prothrombotic phosphatidylserine.
C1 [Harper, Matthew T.; Poole, Alastair W.] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England.
[Londono, Juan E. Camacho; Freichel, Marc] Heidelberg Univ, Inst Pharmacol, D-69120 Heidelberg, Germany.
[Londono, Juan E. Camacho; Londono, Julia Camacho; Flockerzi, Veit; Philipp, Stephan E.; Freichel, Marc] Univ Saarland, Fac Med, Dept Expt & Clin Pharmacol & Toxicol, D-66424 Homburg, Germany.
[Quick, Kathryn] UCL, Wolfson Inst Bioned Res, Mol Nocicept Grp, London WC1E 6BT, England.
[Birnbaumer, Lutz] NIH, Transmembrane Signaling Grp, Res Triangle Pk, NC 27709 USA.
RP Harper, MT (reprint author), Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England.
EM m.harper@bris.ac.uk; a.poole@bris.ac.uk
RI Harper, Matthew/G-5630-2013
OI Harper, Matthew/0000-0002-4740-637X
FU British Heart Foundation [RG/10/006/28299]; Klinische Forschergruppe
[196]; DZHK (German Centre for Cardiovascular Research); BMBF (German
Ministry of Education and Research); "Forschungsausschuss" and "HOMFOR"
program der Universitat des Saarlandes; Deutsche Forschungsgemeinschaft
[GK 1326, SFB 530]; Biotechnology and Biological Sciences Research
Council [BB/F000227/1]; NIH [Z01-ES101684]
FX This work was supported by the British Heart Foundation (program grant
RG/10/006/28299; M.T.H. and A.W.P.), the Klinische Forschergruppe 196,
DZHK (German Centre for Cardiovascular Research), the BMBF (German
Ministry of Education and Research), the "Forschungsausschuss" and
"HOMFOR" program der Universitat des Saarlandes (M.F.), the Deutsche
Forschungsgemeinschaft (GK 1326 and SFB 530; S.E.P.), the Biotechnology
and Biological Sciences Research Council (BB/F000227/1; K.Q.), and the
Intramural Research Program of the NIH (project Z01-ES101684; L.B.).
NR 59
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Z9 26
U1 1
U2 6
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 JUN 25
PY 2013
VL 6
IS 281
AR ra50
DI 10.1126/scisignal.2003701
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 170LU
UT WOS:000320853200001
PM 23800468
ER
PT J
AU Yan, Y
Kong, H
Wu, EJ
Newman, AH
Xu, M
AF Yan, Y.
Kong, H.
Wu, E. J.
Newman, A. H.
Xu, M.
TI DOPAMINE D3 RECEPTORS REGULATE RECONSOLIDATION OF COCAINE MEMORY
SO NEUROSCIENCE
LA English
DT Article
DE dopamine D3 receptor; reconsolidation; reward learning; cocaine; mutant
mice; antagonist PG01037
ID NUCLEUS-ACCUMBENS CORE; DRUG-SEEKING BEHAVIOR; D-3 RECEPTORS;
PROTEIN-SYNTHESIS; INDUCED REINSTATEMENT; BASOLATERAL AMYGDALA;
PROGRESSIVE-RATIO; BRAIN REWARD; ADDICTION; EXTINCTION
AB Memories of learned associations between the rewarding properties of drugs of abuse and environmental cues contribute to craving and relapse in humans. Disruption of reconsolidation dampens or even erases previous memories. Dopamine (DA) mediates the acquisition of reward memory and drugs of abuse can pathologically change related neuronal circuits in the mesolimbic DA system. Previous studies showed that DA D3 receptors are involved in cocaine-conditioned place preference (CPP) and reinstatement of cocaine-seeking behavior. However, the role of D3 receptors in reconsolidation of cocaine-induced reward memory remains unclear. In the present study, we combined genetic and pharmacological approaches to investigate the role of D3 receptors in reconsolidation of cocaine-induced CPP. We found that the mutation of the D3 receptor gene weakened reconsolidation of cocaine-induced CPP in mice triggered by a 3-min (min) retrieval. Furthermore, treatment of a selective D3 receptor antagonist PG01037 immediately following the 3-min retrieval disrupted reconsolidation of cocaine-induced CPP in wild-type mice and such disruption remained at least 1 week after the 3-min retrieval. These results suggest that D3 receptors play a key role in reconsolidation of cocaine-induced CPP in mice, and that pharmacological blockade of these receptors may be therapeutic for the treatment of cocaine craving and relapse in clinical settings. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Yan, Y.; Kong, H.; Xu, M.] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA.
[Wu, E. J.] Univ Colorado, Boulder, CO 80309 USA.
[Newman, A. H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Xu, M (reprint author), Univ Chicago, Dept Anesthesia & Crit Care, Box 428, Chicago, IL 60637 USA.
EM mxu@dacc.uchicago.edu
FU NIDA [DA17323, DA025088]; NIDA Intramural Research Program
FX We greatly appreciate Dr. H. Jiao's assistance for mouse genotyping, Dr.
J. Katz for discussions and suggestions, and J. Cao for synthesizing
PG01037. M.X. was supported by Grants from NIDA (DA17323 and DA025088).
A.H.N was supported by the NIDA Intramural Research Program.
NR 67
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U1 0
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD JUN 25
PY 2013
VL 241
BP 32
EP 40
DI 10.1016/j.neuroscience.2013.03.005
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 146MY
UT WOS:000319096400004
PM 23506736
ER
PT J
AU Keil, MF
Briassoulis, G
Nesterova, M
Miraftab, N
Gokarn, N
Wu, TJ
Stratakis, CA
AF Keil, M. F.
Briassoulis, G.
Nesterova, M.
Miraftab, N.
Gokarn, N.
Wu, T. J.
Stratakis, C. A.
TI THREAT BIAS IN MICE WITH INACTIVATING MUTATIONS OF Prkar1a
SO NEUROSCIENCE
LA English
DT Article
DE protein kinase A; amygdala; orbitofrontal cortex; anxiety; Prkar1a;
threat detection
ID PROTEIN-KINASE-A; LONG-TERM POTENTIATION; PREFRONTAL CORTEX; MEMORY
CONSOLIDATION; BASOLATERAL AMYGDALA; SIGNALING PATHWAYS; REGULATORY
SUBUNIT; CARNEY COMPLEX; DEFENSIVE BEHAVIORS; ANATOMICAL LOCATION
AB Anxiety disorders are associated with abnormalities in the neural processing of threat-related stimuli. However, the neurobiological mechanisms underlying threat bias in anxiety are not well understood. We recently reported that a Prkar1a heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the main regulatory subunit (R1 alpha) of protein kinase A (PKA) exhibits an anxiety-like phenotype associated with increased cAMP signaling in the amygdala. Prkar1a(+/-) mice provide a novel model to test the direct effect of altered PKA expression and subsequent anxiety-like behavioral phenotype on the response to threat. We hypothesized that Prkar1a(+/-) mice would exhibit a bias in threat detection since increased amygdala activity during emotional stimuli is associated with a maladaptive response. We measured behavior and PKA activity in brain areas after exposure to predator or control odor exposure in male Prkar1a(+/-) and wild-type (WT) littermates. Indeed, there were significant differences in the behavioral response to threat detection; WT mice showed the expected response of decrease in exploratory behavior during predator vs. control odor exposure, while Prkar1a(+/-) mice did not alter their behavior between conditions. Basal and total PICA activity was independently associated with genotype, with an interaction between genotype and threat condition. Prkar1a(+/-) mice had higher PICA activity in amygdala and ventromedial hypothalamus in response to predator odor. In contrast, WT mice had higher PKA activity in amygdala and orbitofrontal cortex after exposure to control odor. Dysregulated PKA activity in the amygdala-prefrontal cortex circuitry in Prkar1a(+/-) mice is associated with behavioral phenotype of anxiety and a bias for threat. This is likely related to a failure to inhibit the amydgala response, which is an effect of the genotype. These results suggest that the alteration in PKA signaling in Prkar1a(+/-) mice is not ubiquitous in the brain; tissue-specific effects of the cAMP/PKA pathway are related to threat detection and fear sensitization. Published by Elsevier Ltd. on behalf of IBRO.
C1 [Keil, M. F.; Briassoulis, G.; Nesterova, M.; Miraftab, N.; Gokarn, N.; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Keil, M. F.; Wu, T. J.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Keil, M. F.; Wu, T. J.] Uniformed Serv Univ Hlth Sci, Program Neurosci, Bethesda, MD 20814 USA.
RP Keil, MF (reprint author), NICHD, NIH, PDEGEN, 10 Ctr Dr,Bldg 10 CRC,Room 1 E 3330, Bethesda, MD 20892 USA.
EM keilm@mail.nih.gov
FU NICHD, NIH [Z01-HD-000642-04]; Department of Pediatrics, University of
Crete, Heraklion, Crete, Greece; Uniformed Services University of the
Health Sciences; Department of Defense [CO85DP, DMRDP 061 I-10 J6 125]
FX This work was supported by NICHD, NIH intramural project
Z01-HD-000642-04 to Dr. C. A. Stratakis. It was also supported in part
by the Department of Pediatrics, University of Crete, Heraklion, Crete,
Greece (G. Briassoulis). Finally, part of this work was also supported
by intramural graduate student grant from the Uniformed Services
University of the Health Sciences (MFK) and Department of Defense grants
CO85DP and DMRDP 061 I-10 J6 125 (TJW).
NR 67
TC 3
Z9 4
U1 1
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD JUN 25
PY 2013
VL 241
BP 206
EP 214
DI 10.1016/j.neuroscience.2013.03.027
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 146MY
UT WOS:000319096400020
PM 23531435
ER
PT J
AU Becker, AM
Dao, KH
Han, BK
Kornu, R
Lakhanpal, S
Mobley, AB
Li, QZ
Lian, Y
Wu, TF
Reimold, AM
Olsen, NJ
Karp, DR
Chowdhury, FZ
Farrar, JD
Satterthwaite, AB
Mohan, C
Lipsky, PE
Wakeland, EK
Davis, LS
AF Becker, Amy M.
Dao, Kathryn H.
Han, Bobby Kwanghoon
Kornu, Roger
Lakhanpal, Shuchi
Mobley, Angela B.
Li, Quan-Zhen
Lian, Yun
Wu, Tianfu
Reimold, Andreas M.
Olsen, Nancy J.
Karp, David R.
Chowdhury, Fatema Z.
Farrar, J. David
Satterthwaite, Anne B.
Mohan, Chandra
Lipsky, Peter E.
Wakeland, Edward K.
Davis, Laurie S.
TI SLE Peripheral Blood B Cell, T Cell and Myeloid Cell Transcriptomes
Display Unique Profiles and Each Subset Contributes to the Interferon
Signature
SO PLOS ONE
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DISEASE-ACTIVITY; GENE-EXPRESSION;
AUTOIMMUNE-DISEASE; PROTEIN-INTERACTION; IFN-ALPHA; MEMORY; ACTIVATION;
ANTIBODIES; PATHWAYS
AB Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by defective immune tolerance combined with immune cell hyperactivity resulting in the production of pathogenic autoantibodies. Previous gene expression studies employing whole blood or peripheral blood mononuclear cells (PBMC) have demonstrated that a majority of patients with active disease have increased expression of type I interferon (IFN) inducible transcripts known as the IFN signature. The goal of the current study was to assess the gene expression profiles of isolated leukocyte subsets obtained from SLE patients. Subsets including CD19(+) B lymphocytes, CD3(+) CD4(+) T lymphocytes and CD33(+) myeloid cells were simultaneously sorted from PBMC. The SLE transcriptomes were assessed for differentially expressed genes as compared to healthy controls. SLE CD33(+) myeloid cells exhibited the greatest number of differentially expressed genes at 208 transcripts, SLE B cells expressed 174 transcripts and SLE CD3(+) CD4(+) T cells expressed 92 transcripts. Only 4.4% (21) of the 474 total transcripts, many associated with the IFN signature, were shared by all three subsets. Transcriptional profiles translated into increased protein expression for CD38, CD63, CD107a and CD169. Moreover, these studies demonstrated that both SLE lymphoid and myeloid subsets expressed elevated transcripts for cytosolic RNA and DNA sensors and downstream effectors mediating IFN and cytokine production. Prolonged upregulation of nucleic acid sensing pathways could modulate immune effector functions and initiate or contribute to the systemic inflammation observed in SLE.
C1 [Becker, Amy M.; Mobley, Angela B.; Li, Quan-Zhen; Lian, Yun; Chowdhury, Fatema Z.; Farrar, J. David; Satterthwaite, Anne B.; Mohan, Chandra; Wakeland, Edward K.] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
[Becker, Amy M.; Dao, Kathryn H.; Han, Bobby Kwanghoon; Kornu, Roger; Lakhanpal, Shuchi; Wu, Tianfu; Reimold, Andreas M.; Olsen, Nancy J.; Karp, David R.; Satterthwaite, Anne B.; Mohan, Chandra; Davis, Laurie S.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Lipsky, Peter E.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
RP Davis, LS (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
EM Laurie.Davis@UTSouthwestern.edu
OI Wu, Tianfu/0000-0001-8235-5929
FU National Institutes of Health, National Institute of Arthritis and
Musculoskeletal and Skin Diseases [P50AR055503, R01AR45293]; UT
Southwestern Arthritis Center Flow Cytometry Core; MedImmune; Novo
Nordisk; Novo Nordisk, Genentech/Roche; Human Genome Sciences
FX This work was supported by the National Institutes of Health, National
Institute of Arthritis and Musculoskeletal and Skin Diseases grant
P50AR055503 (Mohan), the UT Southwestern Arthritis Center Flow Cytometry
Core (Davis) and the National Institutes of Health, National Institute
of Arthritis and Musculoskeletal and Skin Diseases grant R01AR45293
(Davis). Dr. Nancy Olsen has equity interest in a company, ArthroChip
LLC, which develops assays for autoimmune diseases and she has also
obtained funding from MedImmune, Novo Nordisk, Genentech/Roche and Human
Genome Sciences. Dr. David Karp has received research funding from Human
Genome Sciences. None of these funds were used for the current study.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 77
TC 33
Z9 33
U1 2
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2013
VL 8
IS 6
AR e67003
DI 10.1371/journal.pone.0067003
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182JP
UT WOS:000321738400092
PM 23826184
ER
PT J
AU Harel, A
Bentin, S
AF Harel, Assaf
Bentin, Shlomo
TI Are All Types of Expertise Created Equal? Car Experts Use Different
Spatial Frequency Scales for Subordinate Categorization of Cars and
Faces
SO PLOS ONE
LA English
DT Article
ID OBJECT RECOGNITION; VISUAL EXPERTISE; BASIC-LEVEL; AREA; PERCEPTION;
INFORMATION; CORTEX; INTERFERENCE; SENSITIVITY; COMPETITION
AB A much-debated question in object recognition is whether expertise for faces and expertise for non-face objects utilize common perceptual information. We investigated this issue by assessing the diagnostic information required for different types of expertise. Specifically, we asked whether face categorization and expert car categorization at the subordinate level relies on the same spatial frequency (SF) scales. Fifteen car experts and fifteen novices performed a category verification task with spatially filtered images of faces, cars, and airplanes. Images were categorized based on their basic (e.g. "car'') and subordinate level (e.g. "Japanese car'') identity. The effect of expertise was not evident when objects were categorized at the basic level. However, when the car experts categorized faces and cars at the subordinate level, the two types of expertise required different kinds of SF information. Subordinate categorization of faces relied on low SFs more than on high SFs, whereas subordinate expert car categorization relied on high SFs more than on low SFs. These findings suggest that expertise in the recognition of objects and faces do not utilize the same type of information. Rather, different types of expertise require different types of diagnostic visual information.
C1 [Harel, Assaf] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Bentin, Shlomo] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel.
[Bentin, Shlomo] Hebrew Univ Jerusalem, Ctr Neural Computat, Jerusalem, Israel.
RP Harel, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM assaf.harel@nih.gov
OI Harel, Assaf/0000-0002-4899-6156
FU NIMH [R01 MH 64458]
FX This study was funded by NIMH grant R01 MH 64458 to Shlomo Bentin. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 54
TC 8
Z9 8
U1 2
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2013
VL 8
IS 6
AR e67024
DI 10.1371/journal.pone.0067024
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182JP
UT WOS:000321738400095
PM 23826188
ER
PT J
AU Hoobler, EK
Rai, G
Warrilow, AGS
Perry, SC
Smyrniotis, CJ
Jadhav, A
Simeonov, A
Parker, JE
Kelly, DE
Maloney, DJ
Kelly, SL
Holman, TR
AF Hoobler, Eric K.
Rai, Ganesha
Warrilow, Andrew G. S.
Perry, Steven C.
Smyrniotis, Christopher J.
Jadhav, Ajit
Simeonov, Anton
Parker, Josie E.
Kelly, Diane E.
Maloney, David J.
Kelly, S. L.
Holman, Theodore R.
TI Discovery of a Novel Dual Fungal CYP51/Human 5-Lipoxygenase Inhibitor:
Implications for Anti-Fungal Therapy
SO PLOS ONE
LA English
DT Article
ID MONOXIDE-BINDING PIGMENT; SELECTIVE INHIBITORS; CANDIDA-ALBICANS;
PHENYLENEDIAMINE DERIVATIVES; NORDIHYDROGUAIARETIC ACID; SEBORRHEIC
DERMATITIS; LIVER MICROSOMES; ACCURATE DOCKING; WHOLE-BLOOD;
LIPOXYGENASE
AB We report the discovery of a novel dual inhibitor targeting fungal sterol 14 alpha-demethylase (CYP51 or Erg11) and human 5-lipoxygenase (5-LOX) with improved potency against 5-LOX due to its reduction of the iron center by its phenylenediamine core. A series of potent 5-LOX inhibitors containing a phenylenediamine core, were synthesized that exhibit nanomolar potency and >30-fold selectivity against the LOX paralogs, platelet-type 12-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity against ovine cyclooxygenase-1 and human cyclooxygnease-2. The phenylenediamine core was then translated into the structure of ketoconazole, a highly effective anti-fungal medication for seborrheic dermatitis, to generate a novel compound, ketaminazole. Ketaminazole was found to be a potent dual inhibitor against human 5-LOX (IC50 = 700 nM) and CYP51 (IC50 = 43 nM) in vitro. It was tested in whole blood and found to down-regulate LTB4 synthesis, displaying 45% inhibition at 10 mu M. In addition, ketaminazole selectively inhibited yeast CYP51 relative to human CYP51 by 17-fold, which is greater selectivity than that of ketoconazole and could confer a therapeutic advantage. This novel dual anti-fungal/anti-inflammatory inhibitor could potentially have therapeutic uses against fungal infections that have an anti-inflammatory component.
C1 [Hoobler, Eric K.; Perry, Steven C.; Smyrniotis, Christopher J.; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
[Rai, Ganesha; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Warrilow, Andrew G. S.; Parker, Josie E.; Kelly, Diane E.; Kelly, S. L.] Swansea Univ, Coll Med, Inst Life Sci, Swansea, W Glam, Wales.
RP Maloney, DJ (reprint author), NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
EM maloneyd@mail.nih.gov; s.l.kelly@swansea.ac.uk; holman@ucsc.edu
OI Warrilow, Andrew/0000-0003-0183-8334; Parker, Josie/0000-0002-3855-4194
FU National Institutes of Health [GM56062, S10-RR20939]; Welsh Government
(SLK); ERDF, via the Beacon project
FX This work was supported by the National Institutes of Health (GM56062
(TRH) S10-RR20939 (UCSC MS Equipment grant), the Welsh Government (SLK)
and the ERDF, via the Beacon project (SLK). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 61
TC 5
Z9 5
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2013
VL 8
IS 6
AR e65928
DI 10.1371/journal.pone.0065928
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182JP
UT WOS:000321738400006
PM 23826084
ER
PT J
AU Perl, S
Perlman, J
Weitzel, RP
Phang, O
Hsieh, MM
Tisdale, J
AF Perl, Shira
Perlman, Jordan
Weitzel, R. P.
Phang, Oswald
Hsieh, Matthew M.
Tisdale, John
TI Addition of Rapamycin to Anti-CD3 Antibody Improves Long-Term Glycaemia
Control in Diabetic NOD Mice
SO PLOS ONE
LA English
DT Article
ID T-CELLS; TYPE-1; TRIAL
AB Aims/Hypothesis: Non-Fc-binding Anti CD3 antibody has proven successful in reverting diabetes in the non-obese diabetes mouse model of type 1 diabetes and limited efficacy has been observed in human clinical trials. We hypothesized that addition of rapamycin, an mTOR inhibitor capable of inducing operational tolerance in allogeneic bone marrow transplantation, would result in improved diabetes reversal rates and overall glycemia.
Methods: Seventy hyperglycemic non-obese diabetic mice were randomized to either a single injection of anti CD3 alone or a single injection of anti CD3 followed by 14 days of intra-peritoneal rapamycin. Mice were monitored for hyperglycemia and metabolic control.
Results: Mice treated with the combination of anti CD3 and rapamycin had similar rates of diabetes reversal compared to anti CD3 alone (25/35 vs. 22/35). Mice treated with anti CD3 plus rapamycin had a significant improvement in glycemia control as exhibited by lower blood glucose levels in response to an intra-peritoneal glucose challenge; average peak blood glucose levels 30 min post intra-peritoneal injection of 2 gr/kg glucose were 6.9 mmol/L in the anti CD3 plus rapamycin group vs. 10 mmo/L in the anti CD3 alone (P<0.05).
Conclusions/Interpretation: The addition of rapamycin to anti CD3 results in significant improvement in glycaemia control in diabetic NOD mice.
C1 [Perl, Shira] NHLBI, Ctr Human Immunol, NIH, Bethesda, MD 20892 USA.
[Perl, Shira; Perlman, Jordan; Weitzel, R. P.; Phang, Oswald; Hsieh, Matthew M.; Tisdale, John] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Perl, S (reprint author), NHLBI, Ctr Human Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM perls@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute at the National Institutes of
Health
FX This work is supported by the intramural research program of the
National Heart, Lung, and Blood Institute at the National Institutes of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 11
TC 4
Z9 4
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2013
VL 8
IS 6
AR e67189
DI 10.1371/journal.pone.0067189
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182JP
UT WOS:000321738400116
PM 23826229
ER
PT J
AU Wang, XJ
Misawa, R
Zielinski, MC
Cowen, P
Jo, JH
Periwal, V
Ricordi, C
Khan, A
Szust, J
Shen, JH
Millis, M
Witkowski, P
Hara, M
AF Wang, Xiaojun
Misawa, Ryosuke
Zielinski, Mark C.
Cowen, Peter
Jo, Junghyo
Periwal, Vipul
Ricordi, Camillo
Khan, Aisha
Szust, Joel
Shen, Junhui
Millis, Michael
Witkowski, Piotr
Hara, Manami
TI Regional Differences in Islet Distribution in the Human Pancreas -
Preferential Beta-Cell Loss in the Head Region in Patients with Type 2
Diabetes
SO PLOS ONE
LA English
DT Article
ID RAT; ARCHITECTURE; POLYPEPTIDE; CANCER; SECRETION; SURVIVAL; INSULIN;
MICE; MASS; QUANTIFICATION
AB While regional heterogeneity in islet distribution has been well studied in rodents, less is known about human pancreatic histology. To fill gaps in our understanding, regional differences in the adult human pancreas were quantitatively analyzed including the pathogenesis of type 2 diabetes (T2D). Cadaveric pancreas specimens were collected from the head, body and tail regions of each donor, including subjects with no history of diabetes or pancreatic diseases (n = 23) as well as patients with T2D (n = 12). The study further included individuals from whom islets were isolated (n = 7) to study islet yield and function in a clinical setting of islet transplantation. The whole pancreatic sections were examined using an innovative large-scale image capture and unbiased detailed quantitative analyses of the characteristics of islets from each individual (architecture, size, shape and distribution). Islet distribution/density is similar between the head and body regions, but is >2-fold higher in the tail region. In contrast to rodents, islet cellular composition and architecture were similar throughout the pancreas and there was no difference in glucose-stimulated insulin secretion in islets isolated from different regions of the pancreas. Further studies revealed preferential loss of large islets in the head region in patients with T2D. The present study has demonstrated distinct characteristics of the human pancreas, which should provide a baseline for the future studies integrating existing research in the field and helping to advance bi-directional research between humans and preclinical models.
C1 [Wang, Xiaojun; Misawa, Ryosuke; Millis, Michael; Witkowski, Piotr] Univ Chicago, Dept Surg, Chicago, IL 60637 USA.
[Wang, Xiaojun] Third Mil Med Univ, Southwest Hosp, Inst Hepatobiliary Surg, Chongqing, Peoples R China.
[Zielinski, Mark C.; Cowen, Peter; Shen, Junhui; Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Jo, Junghyo; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA.
[Ricordi, Camillo; Khan, Aisha; Szust, Joel] Univ Miami, Cell Transplant Ctr, Miami, FL USA.
RP Hara, M (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM mhara@uchicago.edu
RI Jo, Junghyo/D-4889-2011;
OI Zielinski, Mark/0000-0002-6950-6689; Ricordi,
Camillo/0000-0001-8092-7153
FU US Public Health Service Grant [DK-020595, DK-072473, AG-042151];
intramural research program of the NIH, NIDDK
FX The study is supported by US Public Health Service Grant DK-020595 to
the University of Chicago Diabetes Research and Training Center (Animal
Models Core), DK-072473, AG-042151, and a gift from the Kovler Family
Foundation (to MH); and the intramural research program of the NIH,
NIDDK (to JJ and VP). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 25
Z9 25
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2013
VL 8
IS 6
AR e67454
DI 10.1371/journal.pone.0067454
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182JP
UT WOS:000321738400149
PM 23826303
ER
PT J
AU Schwartz, JAT
Pearson, SD
AF Schwartz, Jennifer A. T.
Pearson, Steven D.
TI Cost Consideration in the Clinical Guidance Documents of Physician
Specialty Societies in the United States
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID PRACTICE GUIDELINES; AMERICAN-COLLEGE; TASK-FORCE; HEART-ASSOCIATION;
MEDICINE; ALLOCATION; CARDIOLOGY; ISSUES; CARE
AB Importance: Despite increasing concerns regarding the cost of health care, the consideration of costs in the development of clinical guidance documents by physician specialty societies has received little analysis.
Objective: To evaluate the approach to consideration of cost in publicly available clinical guidance documents and methodological statements produced between 2008 and 2012 by the 30 largest US physician specialty societies.
Design: Qualitative document review.
Main Outcomes and Measures: Whether costs are considered in clinical guidance development, mechanism of cost consideration, and the way that cost issues were used in support of specific clinical practice recommendations.
Results: Methodological statements for clinical guidance documents indicated that 17 of 30 physician societies (57%) explicitly integrated costs, 4 (13%) implicitly considered costs, 3 (10%) intentionally excluded costs, and 6 (20%) made no mention. Of the 17 societies that explicitly integrated costs, 9 (53%) consistently used a formal system in which the strength of recommendation was influenced in part by costs, whereas 8 (47%) were inconsistent in their approach or failed to mention the exact mechanism for considering costs. Among the 138 specific recommendations in these guidance documents that included cost as part of the rationale, the most common form of recommendation (50 [36%]) encouraged the use of a specific medical service because of equal effectiveness and lower cost.
Conclusions and Relevance: Slightly more than half of the largest US physician societies explicitly consider costs in developing their clinical guidance documents; among these, approximately half use an explicit mechanism for integrating costs into the strength of recommendations. Many societies remain vague in their approach. Physician specialty societies should demonstrate greater transparency and rigor in their approach to cost consideration in documents meant to influence care decisions.
C1 [Schwartz, Jennifer A. T.; Pearson, Steven D.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Inst Technol Assessment, Boston, MA 02114 USA.
RP Pearson, SD (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM pearsonsd@cc.nih.gov
NR 39
TC 19
Z9 19
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUN 24
PY 2013
VL 173
IS 12
BP 1091
EP 1097
DI 10.1001/jamainternmed.2013.817
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 170OE
UT WOS:000320861700014
PM 23649494
ER
PT J
AU Weigert, R
Porat-Shliom, N
Amornphimoltham, P
AF Weigert, Roberto
Porat-Shliom, Natalie
Amornphimoltham, Panomwat
TI Imaging cell biology in live animals: Ready for prime time
SO JOURNAL OF CELL BIOLOGY
LA English
DT Review
ID RAMAN SCATTERING MICROSCOPY; INTRAVITAL 2-PHOTON MICROSCOPY; GREEN
FLUORESCENT PROTEIN; CD8(+) T-CELLS; IN-VIVO; SKELETAL-MUSCLE;
DRUG-DELIVERY; LIVING MICE; BLOOD-FLOW; TUMOR MICROENVIRONMENT
AB Time-lapse fluorescence microscopy is one of the main tools used to image subcellular structures in living cells. Yet for decades it has been applied primarily to in vitro model systems. Thanks to the most recent advancements in intravital microscopy, this approach has finally been extended to live rodents. This represents a major breakthrough that will provide unprecedented new opportunities to study mammalian cell biology in vivo and has already provided new insight in the fields of neurobiology, immunology, and cancer biology.
C1 [Weigert, Roberto; Porat-Shliom, Natalie; Amornphimoltham, Panomwat] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
FU National Institutes of Health, National Institute of Dental and
Craniofacial Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Dental and
Craniofacial Research.
NR 128
TC 34
Z9 35
U1 1
U2 43
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JUN 24
PY 2013
VL 201
IS 7
BP 969
EP 979
DI 10.1083/jcb.201212130
PG 11
WC Cell Biology
SC Cell Biology
GA 169IK
UT WOS:000320773500003
PM 23798727
ER
PT J
AU Michailidis, E
Ryan, EM
Hachiya, A
Kirby, KA
Marchand, B
Leslie, MD
Huber, AD
Ong, YT
Jackson, JC
Singh, K
Kodama, EN
Mitsuya, H
Parniak, MA
Sarafianos, SG
AF Michailidis, Eleftherios
Ryan, Emily M.
Hachiya, Atsuko
Kirby, Karen A.
Marchand, Bruno
Leslie, Maxwell D.
Huber, Andrew D.
Ong, Yee T.
Jackson, Jacob C.
Singh, Kamalendra
Kodama, Eiichi N.
Mitsuya, Hiroaki
Parniak, Michael A.
Sarafianos, Stefan G.
TI Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA
SO RETROVIROLOGY
LA English
DT Article
DE HIV-1; RT; EFdA; K65R
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; IN-VITRO
SELECTION; DEPENDENT PRIMER UNBLOCKING; THYMIDINE ANALOG MUTATIONS;
TREATMENT-NAIVE PATIENTS; HIGH-LEVEL RESISTANCE; DRUG-RESISTANCE;
MOLECULAR-MECHANISMS; ANGSTROM RESOLUTION
AB Background: The K65R substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is the major resistance mutation selected in patients treated with first-line antiretroviral tenofovir disoproxil fumarate (TDF). 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), is the most potent nucleoside analog RT inhibitor (NRTI) that unlike all approved NRTIs retains a 3'-hydroxyl group and has remarkable potency against wild-type (WT) and drug-resistant HIVs. EFdA acts primarily as a chain terminator by blocking translocation following its incorporation into the nascent DNA chain. EFdA is in preclinical development and its effect on clinically relevant drug resistant HIV strains is critically important for the design of optimal regimens prior to initiation of clinical trials.
Results: Here we report that the K65R RT mutation causes hypersusceptibility to EFdA. Specifically, in single replication cycle experiments we found that EFdA blocks WT HIV ten times more efficiently than TDF. Under the same conditions K65R HIV was inhibited over 70 times more efficiently by EFdA than TDF. We determined the molecular mechanism of this hypersensitivity using enzymatic studies with WT and K65R RT. This substitution causes minor changes in the efficiency of EFdA incorporation with respect to the natural dATP substrate and also in the efficiency of RT translocation following incorporation of the inhibitor into the nascent DNA. However, a significant decrease in the excision efficiency of EFdA-MP from the 3' primer terminus appears to be the primary cause of increased susceptibility to the inhibitor. Notably, the effects of the mutation are DNA-sequence dependent.
Conclusion: We have elucidated the mechanism of K65R HIV hypersusceptibility to EFdA. Our findings highlight the potential of EFdA to improve combination strategies against TDF-resistant HIV-1 strains.
C1 [Michailidis, Eleftherios; Ryan, Emily M.; Kirby, Karen A.; Marchand, Bruno; Leslie, Maxwell D.; Huber, Andrew D.; Ong, Yee T.; Jackson, Jacob C.; Singh, Kamalendra; Sarafianos, Stefan G.] Univ Missouri, Christopher Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA.
[Hachiya, Atsuko] Natl Hosp Org, Nagoya Med Ctr, Dept Infect Dis & Immunol, Clin Res Ctr, Nagoya, Aichi 4600001, Japan.
[Kodama, Eiichi N.] Tohoku Univ, Div Emerging Infect Dis, Sendai, Miyagi 9808575, Japan.
[Mitsuya, Hiroaki] Kumamoto Univ, Dept Internal Med, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NIH, Expt Retrovirol Sect, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Parniak, Michael A.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA.
[Sarafianos, Stefan G.] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA.
RP Sarafianos, SG (reprint author), Univ Missouri, Christopher Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA.
EM sarafianoss@missouri.edu
RI Kodama, Eiichi /C-4032-2009;
OI Kodama, Eiichi /0000-0002-6622-2752; Sarafianos, Stefan
G/0000-0002-5840-154X; Kirby, Karen A./0000-0003-2468-4796
FU National Institutes of Health [AI076119, AI074389, AI076119-S1,
AI076119-02S1, AI100890, AI099284, GM103368, AI079801]
FX Dr. Tatiana Ilina's contribution in the preparation of the RT plasmids
is acknowledged. This work was supported, in whole or in part, by
National Institutes of Health grants AI076119, AI074389, AI076119-S1,
AI076119-02S1, AI100890, AI099284, and GM103368 (S. G. S.) and AI079801
(M. A. P.).
NR 72
TC 12
Z9 12
U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUN 24
PY 2013
VL 10
AR 65
DI 10.1186/1742-4690-10-65
PG 12
WC Virology
SC Virology
GA 172QC
UT WOS:000321018200001
PM 23800377
ER
PT J
AU Iordanova, MD
Haralambous, T
McNally, GP
Westbrook, RF
AF Iordanova, Mihaela D.
Haralambous, Tatiana
McNally, Gowan P.
Westbrook, R. Frederick
TI Accumbal opioid receptors modulate cue competition in one-trial
overshadowing
SO BRAIN RESEARCH
LA English
DT Article
DE Fear; Rat; Ventral striatum; Attention; Morphine; Learning; Memory
ID STIMULI; BLOCKING; LESIONS; SHELL; MODEL; RATS
AB The contribution of opioid receptors in the nucleus accumbens to contextual and auditory fear conditioning was examined. Impairment in contextual fear conditioning was found when training occurred under accumbal infusions of the opioid receptor agonist morphine in a dose-dependent and receptor specific fashion, only when shock onset coincided with auditory stimulus offset. Contextual fear conditioning was spared, however when the delivery of shock was not signalled by an auditory stimulus, the auditory stimulus was of low intensity (70 dB), or an interval (10 s or 30 s) was interpolated between auditory stimulus offset and shock onset. These results provide evidence that opioid receptors in the nucleus accumbens regulate competition between contextual and discrete auditory stimuli for association formation. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Iordanova, Mihaela D.; Haralambous, Tatiana; McNally, Gowan P.; Westbrook, R. Frederick] Univ New S Wales, Sch Psychol, Sydney, NSW 2031, Australia.
[Iordanova, Mihaela D.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Iordanova, Mihaela D.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Iordanova, MD (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, 20 Penn St,HSF 2, Baltimore, MD 21201 USA.
EM iordanovam@gmail.com
OI Iordanova, Mihaela/0000-0001-6232-448X
FU Australian Research Council [DP110105136]; Australian Commonwealth Post
Graduate Award [K99DA032649]
FX This work was supported by a grant DP110105136 from the Australian
Research Council to RFW, an Australian Commonwealth Post Graduate Award
to TH, and grant K99DA032649 to MDI.
NR 20
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JUN 23
PY 2013
VL 1517
BP 57
EP 67
DI 10.1016/j.brainres.2013.04.019
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 173ME
UT WOS:000321082800006
PM 23603410
ER
PT J
AU Golubeva, YG
Smith, RM
Sternberg, LR
AF Golubeva, Yelena G.
Smith, Roberta M.
Sternberg, Lawrence R.
TI Optimizing Frozen Sample Preparation for Laser Microdissection:
Assessment of CryoJane Tape-Transfer System (R)
SO PLOS ONE
LA English
DT Article
ID CAPTURE MICRODISSECTION; TISSUE SAMPLES; EXPRESSION; SECTIONS; CANCER;
BONE; RNA; DNA
AB Laser microdissection is an invaluable tool in medical research that facilitates collecting specific cell populations for molecular analysis. Diversity of research targets (e.g., cancerous and precancerous lesions in clinical and animal research, cell pellets, rodent embryos, etc.) and varied scientific objectives, however, present challenges toward establishing standard laser microdissection protocols. Sample preparation is crucial for quality RNA, DNA and protein retrieval, where it often determines the feasibility of a laser microdissection project. The majority of microdissection studies in clinical and animal model research are conducted on frozen tissues containing native nucleic acids, unmodified by fixation. However, the variable morphological quality of frozen sections from tissues containing fat, collagen or delicate cell structures can limit or prevent successful harvest of the desired cell population via laser dissection. The CryoJane Tape-Transfer System (R), a commercial device that improves cryosectioning outcomes on glass slides has been reported superior for slide preparation and isolation of high quality osteocyte RNA (frozen bone) during laser dissection. Considering the reported advantages of CryoJane for laser dissection on glass slides, we asked whether the system could also work with the plastic membrane slides used by UV laser based microdissection instruments, as these are better suited for collection of larger target areas. In an attempt to optimize laser microdissection slide preparation for tissues of different RNA stability and cryosectioning difficulty, we evaluated the CryoJane system for use with both glass (laser capture microdissection) and membrane (laser cutting microdissection) slides. We have established a sample preparation protocol for glass and membrane slides including manual coating of membrane slides with CryoJane solutions, cryosectioning, slide staining and dissection procedure, lysis and RNA extraction that facilitated efficient dissection and high quality RNA retrieval from CryoJane preparations. CryoJane technology therefore has the potential to facilitate standardization of laser microdissection slide preparation from frozen tissues.
C1 [Golubeva, Yelena G.; Smith, Roberta M.; Sternberg, Lawrence R.] Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Golubeva, YG (reprint author), Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
EM golubevay@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX The project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. No
additional external funding received for this study. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 20
TC 2
Z9 2
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2013
VL 8
IS 6
AR e66854
DI 10.1371/journal.pone.0066854
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 170JP
UT WOS:000320846500109
PM 23805281
ER
PT J
AU Parra, GI
Azure, J
Fischer, R
Bok, K
Sandoval-Jaime, C
Sosnovtsev, SV
Sander, P
Green, KY
AF Parra, Gabriel I.
Azure, JoLynn
Fischer, Renate
Bok, Karin
Sandoval-Jaime, Carlos
Sosnovtsev, Stanislav V.
Sander, Peter
Green, Kim Y.
TI Identification of a Broadly Cross-Reactive Epitope in the Inner Shell of
the Norovirus Capsid
SO PLOS ONE
LA English
DT Article
ID VIRUS-LIKE PARTICLES; BLOOD GROUP ANTIGENS; MONOCLONAL-ANTIBODIES;
GENOGROUP-II; PROTEIN; GASTROENTERITIS; EXPRESSION; INFECTION; VACCINE;
DETERMINANTS
AB Noroviruses are major pathogens associated with acute gastroenteritis. They are diverse viruses, with at least six genogroups (GI-GVI) and multiple genotypes defined by differences in the major capsid protein, VP1. This diversity has challenged the development of broadly cross-reactive vaccines as well as efficient detection methods. Here, we report the characterization of a broadly cross-reactive monoclonal antibody (MAb) raised against the capsid protein of a GII. 3 norovirus strain. The MAb reacted with VLPs and denatured VP1 protein from GI, GII, GIV and GV noroviruses, and mapped to a linear epitope located in the inner shell domain. An alignment of all available VP1 sequences showed that the putative epitope (residues 52-56) is highly conserved across the genus Norovirus. This broadly cross-reactive MAb thus constitutes a valuable reagent for the diagnosis and study of these diverse viruses.
C1 [Parra, Gabriel I.; Azure, JoLynn; Bok, Karin; Sandoval-Jaime, Carlos; Sosnovtsev, Stanislav V.; Green, Kim Y.] NIAID, Caliciviruses Sect, Infect Dis Lab, DHHS,NIH, Bethesda, MD 20892 USA.
[Fischer, Renate; Sander, Peter] R Biopharm AG, Clin Diagnost, Darmstadt, Germany.
RP Parra, GI (reprint author), NIAID, Caliciviruses Sect, Infect Dis Lab, DHHS,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM parrag@niaid.nih.gov; kgreen@niaid.nih.gov
OI Parra, Gabriel/0000-0002-1102-4740
FU NIH, NIAID
FX This research was partially supported by the Intramural Research Program
of the NIH, NIAID. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. No additional external funding received for this study.
NR 43
TC 14
Z9 14
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2013
VL 8
IS 6
AR e67592
DI 10.1371/journal.pone.0067592
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 170JP
UT WOS:000320846500147
PM 23805319
ER
PT J
AU Yin, J
Wang, C
Mody, A
Bao, L
Hung, SH
Svoronos, SA
Tseng, Y
AF Yin, Jun
Wang, Chengyuan
Mody, Aaron
Bao, Lin
Hung, Shen-Hsiu
Svoronos, Spyros A.
Tseng, Yiider
TI The Effect of Z-Ligustilide on the Mobility of Human Glioblastoma T98G
Cells
SO PLOS ONE
LA English
DT Article
ID PC12 CELLS; IN-VITRO; RHO
AB Z-ligustilide (LIG), an essential oil extract from Radix Angelica sinensis, has broad pharmaceutical applications in treating cardio-vascular diseases and ischemic brain injury. Recently, LIG has been connected to Glioblastoma multiforme (GBM) because of its structural similarity to 3-n-alkyphthalide (NBP), which is specifically cytotoxic to GBM cells. Hence, we investigated LIG's effect on GBM T98G cells. The study shows that LIG can significantly reduce T98G cells' migration in a dose-dependent manner. Furthermore, the attenuation of cellular mobility can be linked to the activity of the Rho GTPases (RhoA, Rac1 and Cdc42), the three critical molecular switches governing cytoskeleton remodeling; thus, regulating cell migration. LIG significantly reduces the expression of RhoA and affects in a milder manner the expression of Cdc42 and Rac1.
C1 [Yin, Jun; Mody, Aaron; Bao, Lin; Hung, Shen-Hsiu; Svoronos, Spyros A.; Tseng, Yiider] Univ Florida, Dept Chem Engn, Gainesville, FL 32611 USA.
[Wang, Chengyuan] Chongqing Technol & Business Univ, Res Ctr Med Chem & Chem Biol, Chongqing, Peoples R China.
[Yin, Jun; Hung, Shen-Hsiu; Tseng, Yiider] NCI, Phys Sci Oncol Ctr, Gainesville, FL USA.
[Tseng, Yiider] Inst Cell Engn & Regenerat Med, Gainesville, FL USA.
RP Tseng, Y (reprint author), Univ Florida, Dept Chem Engn, Gainesville, FL 32611 USA.
EM ytseng@che.ufl.edu
FU NIH/NCI [U54CA143868]
FX This study was supported in part by grants from NIH/NCI U54CA143868. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. No additional
external funding received for this study.
NR 17
TC 7
Z9 8
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2013
VL 8
IS 6
AR e66598
DI 10.1371/journal.pone.0066598
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 170JP
UT WOS:000320846500073
PM 23805245
ER
PT J
AU Johnson, TP
Tyagi, R
Patel, K
Schiess, N
Calabresi, PA
Nath, A
AF Johnson, Tory P.
Tyagi, Richa
Patel, Karan
Schiess, Nicoline
Calabresi, Peter A.
Nath, Avindra
TI Impaired toll-like receptor 8 signaling in multiple sclerosis
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Toll-like receptor; Multiple sclerosis; Gene expression; Interleukin 12;
TLR8
ID T-CELLS; ACTIVATION; DISEASE; ALPHA
AB Background: The etiology and immunopathology of multiple sclerosis (MS) is not well understood. It is recognized that although autoreactive T cells are the main early mediators of disease, other cell types, including cells of the innate immune system contribute to MS pathogenesis. The objective of this study was to determine if Toll-like receptor (TLR) signaling is functionally altered in patients with MS.
Findings: Peripheral blood mononuclear cells from healthy donors and patients with relapsing remitting MS were stimulated with specific agonists of TLRs 3, 7, 8 and 9. Using quantitative polymerase chain reaction transcript levels of tumor necrosis factor-a, interferon-a and interleukin (IL)-12 beta were quantified from patients with MS and healthy donors. TLR8-induced production of IL12B transcripts and protein was functionally impaired in patients with MS as compared to healthy controls (P < 0.05 and P < 0.005, respectively). Patients with MS also expressed lower baseline levels of TLR8 as compared to healthy controls (P < 0.05).
Conclusions: TLR8 expression and signaling is impaired in peripheral blood mononuclear cells from patients with MS. This finding suggests that loss of TLR8 signaling may be contributing to autoimmune processes in MS.
C1 [Johnson, Tory P.; Tyagi, Richa; Patel, Karan; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Schiess, Nicoline; Calabresi, Peter A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bldg 10,7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM avindra.nath@nih.gov
FU National Multiple Sclerosis Society [TR 3760-A-3]; Stegg family; NINDS
FX The authors would like to acknowledge Dr. Steve Jacobson for providing
the clinical samples. This work was supported by the National Multiple
Sclerosis Society (grant number TR 3760-A-3); a generous grant from the
Stegg family; and NINDS intramural funds.
NR 18
TC 7
Z9 8
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD JUN 21
PY 2013
VL 10
AR 74
DI 10.1186/1742-2094-10-74
PG 4
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 171IS
UT WOS:000320920000001
PM 23787171
ER
PT J
AU Xu, Y
Liu, YF
Lee, JG
Ye, YH
AF Xu, Yue
Liu, Yanfen
Lee, Jin-Gu
Ye, Yihong
TI A Ubiquitin-like Domain Recruits an Oligomeric Chaperone to a
Retrotranslocation Complex in Endoplasmic Reticulum-associated
Degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID QUALITY-CONTROL; MEMBRANE-PROTEINS; LIGASE; HRD1P; GP78; BAT3;
DIMETHYLATION; POLYPEPTIDES; ELIMINATION; INTEGRATION
AB The Bag6-Ubl4A-Trc35 complex is a multifunctional chaperone that regulates various cellular processes. The diverse functions of Bag6 are supported by its ubiquitous localization to the cytoplasm, the nucleus, and membranes of the endoplasmic reticulum (ER) in cells. In ER-associated degradation (ERAD) pathways, Bag6 can interact with the membrane-associated ubiquitin ligase gp78 via its ubiquitin-like (UBL) domain, but the relative low affinity of this interaction does not reconcile with the fact that a fraction of Bag6 is tightly bound to the membranes. Here, we demonstrate that the UBL domain of Bag6 is required for interaction with the ER membranes. We find that in addition to gp78, the Bag6 UBL domain also binds a UBL-binding motif in UbxD8, an essential component of the gp78 ubiquitinating machinery. Importantly, Bag6 contains a proline-rich (PR) domain termed PDP (Proline rich-DUF3587-Proline rich) that forms homo-oligomer, allowing the UBL domain to form multivalent interactions with gp78 and UbxD8, which are essential for recruitment of Bag6 to the ER membrane. Furthermore, the PR domain comprises largely intrinsically disordered segments, which are sufficient for interaction with an unfolded substrate. We propose that simultaneous association with multiple ERAD factors helps to anchor a disordered chaperone oligomer to the site of retrotranslocation to prevent protein aggregation in ERAD.
C1 [Xu, Yue; Liu, Yanfen; Lee, Jin-Gu; Ye, Yihong] NIH, NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Ye, YH (reprint author), NIH, NIDDK, Mol Biol Lab, 5 Ctr Dr, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
RI Xu, Yue/F-8188-2015
FU NIDDK at the National Institutes of Health
FX This work was supported by the Intramural Research Program of the NIDDK
at the National Institutes of Health.
NR 35
TC 24
Z9 24
U1 0
U2 15
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 21
PY 2013
VL 288
IS 25
BP 18068
EP 18076
DI 10.1074/jbc.M112.449199
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 168QZ
UT WOS:000320721900013
PM 23665563
ER
PT J
AU Chertova, E
Bergamaschi, C
Chertov, O
Sowder, R
Bear, J
Roser, JD
Beach, RK
Lifson, JD
Felber, BK
Pavlakis, GN
AF Chertova, Elena
Bergamaschi, Cristina
Chertov, Oleg
Sowder, Raymond
Bear, Jenifer
Roser, James D.
Beach, Rachel K.
Lifson, Jeffrey D.
Felber, Barbara K.
Pavlakis, George N.
TI Characterization and Favorable in Vivo Properties of Heterodimeric
Soluble IL-15 center dot IL-15R alpha Cytokine Compared to IL-15 Monomer
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CD8(+) T-CELLS; RECEPTOR-ALPHA-CHAIN; NATURAL-KILLER-CELLS; SIGNAL
PEPTIDE; INTERLEUKIN (IL)-15; ESTABLISHED TUMORS; TRANS PRESENTATION;
NONHUMAN-PRIMATES; RHESUS MACAQUES; CD4(+) CELLS
AB Interleukin-15 (IL-15), a 114-amino acid cytokine related to IL-2, regulates immune homeostasis and the fate of many lymphocyte subsets. We reported that, in the blood of mice and humans, IL-15 is present as a heterodimer associated with soluble IL-15 receptor alpha (sIL-15R alpha). Here, we show efficient production of this noncovalently linked but stable heterodimer in clonal human HEK293 cells and release of the processed IL-15 center dot sIL-15R alpha heterodimer in the medium. Purification of the IL-15 and sIL-15R alpha polypeptides allowed identification of the proteolytic cleavage site of IL-15R alpha and characterization of multiple glycosylation sites. Administration of the IL-15 center dot sIL-15R alpha heterodimer reconstituted from purified subunits resulted in sustained plasma IL-15 levels and in robust expansion of NK and T cells in mice, demonstrating pharmacokinetics and in vivo bioactivity superior to single chain IL-15. These identified properties of heterodimeric IL-15 provide a strong rationale for the evaluation of this molecule for clinical applications.
C1 [Chertova, Elena; Sowder, Raymond; Roser, James D.; Lifson, Jeffrey D.] Frederick Natl Lab, AIDS & Canc Virus Program, Ft Detrick, MD 21702 USA.
[Chertov, Oleg] Frederick Natl Lab, Prot Chem Lab, Adv Technol Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
[Bergamaschi, Cristina; Beach, Rachel K.; Pavlakis, George N.] NCI, Ctr Canc Res, Vaccine Branch, Human Retrovirus Sect, Frederick, MD 21702 USA.
[Bear, Jenifer; Beach, Rachel K.; Felber, Barbara K.] NCI, Ctr Canc Res, Vaccine Branch, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA.
RP Pavlakis, GN (reprint author), NCI, Ctr Canc Res, Vaccine Branch, Human Retrovirus Sect, Frederick, MD 21702 USA.
EM pavlakig@mail.nih.gov
FU Intramural Research Program, National Cancer Institute, National
Institutes of Health (NCI/National Institutes of Health); National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX This work was supported by the Intramural Research Program, National
Cancer Institute, National Institutes of Health (NCI/National Institutes
of Health) and federal funds from the National Cancer Institute,
National Institutes of Health, under contract number HHSN261200800001E.
NR 60
TC 22
Z9 22
U1 1
U2 12
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 21
PY 2013
VL 288
IS 25
BP 18093
EP 18103
DI 10.1074/jbc.M113.461756
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 168QZ
UT WOS:000320721900015
PM 23649624
ER
PT J
AU Zhang, SF
Schones, DE
Malicet, C
Rochman, M
Zhou, M
Foisner, R
Bustin, M
AF Zhang, Shaofei
Schones, Dustin E.
Malicet, Cedric
Rochman, Mark
Zhou, Ming
Foisner, Roland
Bustin, Michael
TI High Mobility Group Protein N5 (HMGN5) and Lamina-associated Polypeptide
2 alpha (LAP2 alpha) Interact and Reciprocally Affect Their Genome-wide
Chromatin Organization
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CHROMOSOMAL-PROTEINS; LINKER HISTONE; RNA-SEQ; DIFFERENTIATION; H1;
NUCLEOSOMES; COMPLEXES
AB The interactions of nuclear lamins with the chromatin fiber play an important role in regulating nuclear architecture and chromatin function; however, the full spectrum of these interactions is not known. We report that the N-terminal domain of the nucleosome-binding protein HMGN5 interacts with the C-terminal domain of the lamin-binding protein LAP2 alpha and that these proteins reciprocally alter their interaction with chromatin. Chromatin immunoprecipitation analysis of cells lacking either HMGN5 or LAP2 alpha reveals that loss of either protein affects the genome-wide distribution of the remaining partner. Our study identifies a new functional link between chromatin-binding and lamin-binding proteins.
C1 [Zhang, Shaofei; Malicet, Cedric; Rochman, Mark; Bustin, Michael] NCI, NIH, Prot Sect, Lab Metab,Ctr Canc Res, Bethesda, MD 20892 USA.
[Schones, Dustin E.] Beckman Res Inst City Hope, Dept Canc Biol, Duarte, CA 91010 USA.
[Zhou, Ming] NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD 21702 USA.
[Foisner, Roland] Med Univ Vienna, Max Perutz Labs, A-1030 Vienna, Austria.
RP Bustin, M (reprint author), NCI, NIH, Prot Sect, Lab Metab,Ctr Canc Res, Bethesda, MD 20892 USA.
EM Bustin@helix.nih.gov
RI Bustin, Michael/G-6155-2015
FU Center for Cancer Research, Intramural Program of the NCI, National
Institutes of Health; United States-Israel Binational Science Foundation
(BSF) [2009236]; NCI [K22 HL101950]; Austrian Research Fund (FWF)
[P22043-B12]
FX This work was supported, in whole or in part, by the Center for Cancer
Research, Intramural Program of the NCI, National Institutes of Health
(to M. B.). This work was also supported by United States-Israel
Binational Science Foundation (BSF) Grants 2009236 (to M. B.) and NCI
Grant K22 HL101950 (to D. E. S.) and by Grant P22043-B12 of the Austrian
Research Fund (FWF) (to R. F.).
NR 27
TC 10
Z9 10
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 JUN 21
PY 2013
VL 288
IS 25
BP 18104
EP 18109
DI 10.1074/jbc.C113.469544
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 168QZ
UT WOS:000320721900016
PM 23673662
ER
PT J
AU Allende, ML
Sipe, LM
Tuymetova, G
Wilson-Henjum, KL
Chen, WP
Proia, RL
AF Allende, Maria L.
Sipe, Laura M.
Tuymetova, Galina
Wilson-Henjum, Kelsey L.
Chen, Weiping
Proia, Richard L.
TI Sphingosine-1-phosphate Phosphatase 1 Regulates Keratinocyte
Differentiation and Epidermal Homeostasis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PERMEABILITY BARRIER; CELL-DEATH; IN-VITRO; SKIN; PHOSPHOHYDROLASE;
SPHINGOLIPIDS; CERAMIDE; METABOLISM; EXPRESSION; RECEPTOR
AB Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphorylated by the actions of two S1P-specific phosphatases, sphingosine-1-phosphate phosphatases 1 and 2. To identify the physiological functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1(-/-) mice appeared normal at birth, but during the 1st week of life they exhibited stunted growth and suffered desquamation, with most dying before weaning. Both Sgpp1(-/-) pups and surviving adults exhibited multiple epidermal abnormalities. Interestingly, the epidermal permeability barrier developed normally during embryogenesis in Sgpp1(-/-) mice. Keratinocytes isolated from the skin of Sgpp1(-/-) pups had increased intracellular S1P levels and displayed a gene expression profile that indicated overexpression of genes associated with keratinocyte differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.
C1 [Allende, Maria L.; Sipe, Laura M.; Tuymetova, Galina; Wilson-Henjum, Kelsey L.; Chen, Weiping; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, Bldg 10,Rm 9D-06,10 Ctr Dr MSC 1821, Bethesda, MD 20892 USA.
EM rp36y@nih.gov
FU National Institutes of Health from NIDDK [P30 CA138313, P20 RR017677]
FX This work was supported, in whole or in part, by National Institutes of
Health grants from NIDDK, Grant P30 CA138313 (to Lipidomics Shared
Resource, Hollings Cancer Center, Medical University of South Carolina),
and Grant P20 RR017677 (to Lipidomics Core in the South Carolina
Lipidomics and Pathobiology COBRE).
NR 63
TC 10
Z9 10
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
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 21
PY 2013
VL 288
IS 25
BP 18381
EP 18391
DI 10.1074/jbc.M113.478420
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 168QZ
UT WOS:000320721900041
PM 23637227
ER
PT J
AU Jorgensen, NW
Sibley, CT
McClelland, RL
AF Jorgensen, Neal W.
Sibley, Christopher T.
McClelland, Robyn L.
TI Using imputed pre-treatment cholesterol in a propensity score model to
reduce confounding by indication: results from the multi-ethnic study of
atherosclerosis
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Multiple imputation; Confounding by indication; Propensity score;
Inverse probability of treatment weights; Statins
ID RANDOMIZED CONTROLLED-TRIALS; MULTIPLE IMPUTATION; MISSING-DATA;
METAANALYSIS; ASSOCIATIONS; SURVIVAL; THERAPY; WEIGHTS; STATINS; RISK
AB Background: Studying the effects of medications on endpoints in an observational setting is an important yet challenging problem due to confounding by indication. The purpose of this study is to describe methodology for estimating such effects while including prevalent medication users. These techniques are illustrated in models relating statin use to cardiovascular disease (CVD) in a large multi-ethnic cohort study.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) includes 6814 participants aged 45-84 years free of CVD. Confounding by indication was mitigated using a two step approach: First, the untreated values of cholesterol were treated as missing data and the values imputed as a function of the observed treated value, dose and type of medication, and participant characteristics. Second, we construct a propensity-score modeling the probability of medication initiation as a function of measured covariates and estimated pre-treatment cholesterol value. The effect of statins on CVD endpoints were assessed using weighted Cox proportional hazard models using inverse probability weights based on the propensity score.
Results: Based on a meta-analysis of randomized controlled trials (RCT) statins are associated with a reduced risk of CVD (relative risk ratio = 0.73, 95% CI: 0.70, 0.77). In an unweighted Cox model adjusting for traditional risk factors we observed little association of statins with CVD (hazard ratio (HR) = 0.97, 95% CI: 0.60, 1.59). Using weights based on a propensity model for statins that did not include the estimated pre-treatment cholesterol we observed a slight protective association (HR = 0.92, 95% CI: 0.54-1.57). Results were similar using a new-user design where prevalent users of statins are excluded (HR = 0.91, 95% CI: 0.45-1.80). Using weights based on a propensity model with estimated pre-treatment cholesterol the effects of statins (HR = 0.74, 95% CI: 0.38, 1.42) were consistent with the RCT literature.
Conclusions: The imputation of pre-treated cholesterol levels for participants on medication at baseline in conjunction with a propensity score yielded estimates that were consistent with the RCT literature. These techniques could be useful in any example where inclusion of participants exposed at baseline in the analysis is desirable, and reasonable estimates of pre-exposure biomarker values can be estimated.
C1 [Jorgensen, Neal W.; McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Sibley, Christopher T.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Jorgensen, NW (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
EM njorgens@u.washington.edu
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169];
[R01 HL 103729-01A1]
FX Analysis for this project was supported by R01 HL 103729-01A1. The MESA
study was supported by contracts N01-HC-95159 through N01-HC-95169 from
the National Heart, Lung, and Blood Institute.
NR 25
TC 0
Z9 0
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD JUN 21
PY 2013
VL 13
AR 81
DI 10.1186/1471-2288-13-81
PG 10
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 171LU
UT WOS:000320931200001
PM 23800038
ER
PT J
AU Kellman, P
Arai, AE
Xue, H
AF Kellman, Peter
Arai, Andrew E.
Xue, Hui
TI T1 and extracellular volume mapping in the heart: estimation of error
maps and the influence of noise on precision
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE T1 Map; Error; Precision; MOLLI; Extracellular; Diffuse Fibrosis;
Cardiovascular Magnetic Resonance
ID DIFFUSE MYOCARDIAL FIBROSIS; INVERSION-RECOVERY MOLLI;
MAGNETIC-RESONANCE; QUANTIFICATION; INFARCTION; VALIDATION; REGRESSION
AB Background: Quantitative measurements in the myocardium may be used to detect both focal and diffuse disease processes that result in an elevation of T1 and/or extracellular volume (ECV) fraction. Detection of abnormal myocardial tissue by these methods is affected by both the accuracy and precision. The sensitivity for detecting abnormal elevation of T1 and ECV is limited by the precision of T1 estimates which is a function of the number and timing of measurements along the T1-inversion recovery curve, the signal-to-noise ratio (SNR), the tissue T1, and the method of fitting.
Methods: The standard deviation (SD) of T1 and ECV estimates are formulated and SD maps are calculated on a pixel-wise basis using the Modified Look-Locker Inversion recovery (MOLLI) method. SD estimates are validated by numerical simulation using Monte-Carlo analysis and with phantoms using repeated trials. SD estimates are provided for pre- and post-contrast optimized protocols for a range of T1s and SNRs. In-vivo examples are provide for normal, myocarditis, and HCM in human subjects. The formulation of SD maps was extended to R1 and ECV.
Results: The measured myocardial SNR ranged from 23 to 43 across the heart using the specific T1-mapping protocol in this study. In this range of SNRs, the estimated SD for T1 was approximately 20-45 ms for pre-contrast myocardial T1 around 1000 ms, and was approximately 10-20 ms for post contrast T1 around 400 ms. The proposed estimate of SD was an unbiased estimate of the standard deviation of T1 validated by numerical simulation and had > 99% correlation with phantom measurements. The measured SD maps exhibited variation across the heart due to drop off in surface coil sensitivity as expected for the variation in SNR. Focal elevation in T1 and ECV was shown to have statistical significance on a pixel-wise basis for in-vivo examples.
Conclusions: Pixel-wise estimates of T1 mapping errors have been formulated and validated, and the formulation has been extended to ECV. The ability to quantify the measurement error has potential to determine the statistical significance of subtle abnormalities that arise due to diffuse disease processes involving fibrosis and/or edema and is useful both as a confidence metric for overall quality, and in optimization and comparison of imaging protocols.
C1 [Kellman, Peter; Arai, Andrew E.; Xue, Hui] Natl Heart Lung & Blood Inst, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA.
RP Kellman, P (reprint author), Natl Heart Lung & Blood Inst, Natl Inst Hlth, DHHS, 10 Ctr Dr MSC 1061, Bethesda, MD 20892 USA.
EM kellman@nih.gov
FU National Heart, Lung and Blood Institute, National Institutes of Health
by the Division of Intramural Research, NHLBI, NIH, DHHS
[HL004607-14CPB]
FX Supported by the National Heart, Lung and Blood Institute, National
Institutes of Health by the Division of Intramural Research, NHLBI, NIH,
DHHS (HL004607-14CPB).
NR 29
TC 37
Z9 37
U1 0
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD JUN 21
PY 2013
VL 15
AR 56
DI 10.1186/1532-429X-15-56
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 177KP
UT WOS:000321374200001
PM 23800276
ER
PT J
AU Rietveld, CA
Medland, SE
Derringer, J
Yang, J
Esko, T
Martin, NW
Westra, HJ
Shakhbazov, K
Abdellaoui, A
Agrawal, A
Albrecht, E
Alizadeh, BZ
Amin, N
Bamard, J
Baumeister, SE
Benke, KS
Bielak, LF
Boatman, JA
Boyle, PA
Davies, G
De Leeuw, C
Eklund, N
Evans, DS
Ferhmann, R
Fischer, K
Gieger, C
Gjessing, HK
Hagg, S
Harris, JR
Hayward, C
Holzapfel, C
Ibrahim-Verbaas, CA
Ingelsson, E
Jacobsson, B
Joshi, PK
Jugessur, A
Kaakinen, M
Kanoni, S
Karjalainen, J
Kolcic, I
Kristiansson, K
Kutalik, Z
Lahti, J
Lee, SH
Lin, P
Lind, PA
Liu, YM
Lohman, K
Loitfelder, M
McMahon, G
Vidal, PM
Meirelles, O
Milani, L
Myhre, R
Nuotio, ML
Oldmeadow, CJ
Petrovic, KE
Peyrot, WJ
Polasek, O
Quaye, L
Reinmaa, E
Rice, JP
Rizzi, TS
Schmidt, H
Schmidt, R
Smith, AV
Smith, JA
Tanaka, T
Terracciano, A
van der Loos, MJHM
Vitart, V
Volzke, H
Wellmann, J
Yu, L
Zhao, W
Allik, J
Attia, JR
Bandinelli, S
Bastardot, F
Beauchamp, J
Bennett, DA
Berger, K
Bierut, LJ
Boomsma, DI
Bultmann, U
Campbell, H
Chabris, CF
Cherkas, L
Chung, MK
Cucca, F
de Andrade, M
De Jager, PL
De Neve, JE
Deary, IJ
Dedoussis, GV
Deloukas, P
Dimitriou, M
Eiriksdottir, G
Elderson, MF
Eriksson, JG
Evans, DM
Faul, JD
Ferrucci, L
Garcia, ME
Gronberg, H
Guonason, V
Hall, P
Harris, JM
Harris, TB
Hastie, ND
Heath, AC
Hernandez, DG
Hoffmann, W
Hofman, A
Holle, R
Holliday, EG
Hottenga, JJ
Iacono, WG
Illig, T
Jarvelin, MR
Kahonen, M
Kaprio, J
Kirkpatrick, RM
Kowgier, M
Latvala, A
Launer, LJ
Lawlor, DA
Lehtimaki, T
Li, JM
Lichtenstein, P
Lichtner, P
Liewald, DC
Madden, PA
Magnusson, PKE
Makinen, TE
Masala, M
McGue, M
Metspalu, A
Mielck, A
Miller, MB
Montgomery, GW
Mukherjee, S
Nyholt, DR
Oostra, BA
Palmer, LJ
Palotie, A
Penninx, BWJH
Perola, M
Peyser, PA
Preisig, M
Raikkonen, K
Raitakari, OT
Realo, A
Ring, SM
Ripatti, S
Rivadeneira, F
Rudan, I
Rustichini, A
Salomaa, V
Sarin, AP
Schlessinger, D
Scott, RJ
Snieder, H
St Pourcain, B
Starr, JM
Sul, JH
Surakka, I
Svento, R
Teumer, A
Tiemeier, H
van Rooij, FJA
Van Wagoner, DR
Vartiainen, E
Viikari, J
Vollenweider, P
Vonk, JM
Waeber, G
Weir, DR
Wichmann, HE
Widen, E
Willemsen, G
Wilson, JF
Wright, AF
Conley, D
Davey-Smith, G
Franke, L
Groenen, PJF
Hofman, A
Johannesson, M
Kardia, SLR
Krueger, RF
Laibson, D
Martin, NG
Meyer, MN
Posthuma, D
Thurik, AR
Timpson, NJ
Uitterlinden, AG
van Duijn, CM
Visscher, PM
Benjamin, DJ
Cesarini, D
Koellinger, PD
AF Rietveld, Cornelius A.
Medland, Sarah E.
Derringer, Jaime
Yang, Jian
Esko, Tonu
Martin, Nicolas W.
Westra, Harm-Jan
Shakhbazov, Konstantin
Abdellaoui, Abdel
Agrawal, Arpana
Albrecht, Eva
Alizadeh, Behrooz Z.
Amin, Najaf
Bamard, John
Baumeister, Sebastian E.
Benke, Kelly S.
Bielak, Lawrence F.
Boatman, Jeffrey A.
Boyle, Patricia A.
Davies, Gail
De Leeuw, Christiaan
Eklund, Niina
Evans, Daniel S.
Ferhmann, Rudolf
Fischer, Krista
Gieger, Christian
Gjessing, Hakon K.
Haegg, Sara
Harris, Jennifer R.
Hayward, Caroline
Holzapfel, Christina
Ibrahim-Verbaas, Carla A.
Ingelsson, Erik
Jacobsson, Bo
Joshi, Peter K.
Jugessur, Astanand
Kaakinen, Marika
Kanoni, Stavroula
Karjalainen, Juha
Kolcic, Ivana
Kristiansson, Kati
Kutalik, Zoltan
Lahti, Jari
Lee, Sang H.
Lin, Peng
Lind, Penelope A.
Liu, Yongmei
Lohman, Kurt
Loitfelder, Marisa
McMahon, George
Vidal, Pedro Marques
Meirelles, Osorio
Milani, Lili
Myhre, Ronny
Nuotio, Marja-Liisa
Oldmeadow, Christopher J.
Petrovic, Katja E.
Peyrot, Wouter J.
Polasek, Ozren
Quaye, Lydia
Reinmaa, Eva
Rice, John P.
Rizzi, Thais S.
Schmidt, Helena
Schmidt, Reinhold
Smith, Albert V.
Smith, Jennifer A.
Tanaka, Toshiko
Terracciano, Antonio
van der Loos, Matthijs J. H. M.
Vitart, Veronique
Voelzke, Henry
Wellmann, Juergen
Yu, Lei
Zhao, Wei
Allik, Jueri
Attia, John R.
Bandinelli, Stefania
Bastardot, Franois
Beauchamp, Jonathan
Bennett, David A.
Berger, Klaus
Bierut, Laura J.
Boomsma, Dorret I.
Bueltmann, Ute
Campbell, Harry
Chabris, Christopher F.
Cherkas, Lynn
Chung, Mina K.
Cucca, Francesco
de Andrade, Mariza
De Jager, Philip L.
De Neve, Jan-Emmanuel
Deary, Ian J.
Dedoussis, George V.
Deloukas, Panos
Dimitriou, Maria
Eiriksdottir, Guony
Elderson, Martin F.
Eriksson, Johan G.
Evans, David M.
Faul, Jessica D.
Ferrucci, Luigi
Garcia, Melissa E.
Groenberg, Henrik
Guonason, Vilmundur
Hall, Per
Harris, Juliette M.
Harris, Tamara B.
Hastie, Nicholas D.
Heath, Andrew C.
Hernandez, Dena G.
Hoffmann, Wolfgang
Hofman, Adriaan
Holle, Rolf
Holliday, Elizabeth G.
Hottenga, Jouke-Jan
Iacono, William G.
Illig, Thomas
Jaervelin, Marjo-Riitta
Kaehoenen, Mika
Kaprio, Jaakko
Kirkpatrick, Robert M.
Kowgier, Matthew
Latvala, Antti
Launer, Lenore J.
Lawlor, Debbie A.
Lehtimaeki, Terho
Li, Jingmei
Lichtenstein, Paul
Lichtner, Peter
Liewald, David C.
Madden, Pamela A.
Magnusson, Patrik K. E.
Maekinen, Tomi E.
Masala, Marco
McGue, Matt
Metspalu, Andres
Mielck, Andreas
Miller, Michael B.
Montgomery, Grant W.
Mukherjee, Sutapa
Nyholt, Dale R.
Oostra, Ben A.
Palmer, Lyle J.
Palotie, Aarno
Penninx, Brenda W. J. H.
Perola, Markus
Peyser, Patricia A.
Preisig, Martin
Raeikkoenen, Katri
Raitakari, Olli T.
Realo, Anu
Ring, Susan M.
Ripatti, Samuli
Rivadeneira, Fernando
Rudan, Igor
Rustichini, Aldo
Salomaa, Veikko
Sarin, Antti-Pekka
Schlessinger, David
Scott, Rodney J.
Snieder, Harold
St Pourcain, Beate
Starr, John M.
Sul, Jae Hoon
Surakka, Ida
Svento, Rauli
Teumer, Alexander
Tiemeier, Henning
van Rooij, Frank J. A.
Van Wagoner, David R.
Vartiainen, Erkki
Viikari, Jorma
Vollenweider, Peter
Vonk, Judith M.
Waeber, Gerard
Weir, David R.
Wichmann, H. -Erich
Widen, Elisabeth
Willemsen, Gonneke
Wilson, James F.
Wright, Alan F.
Conley, Dalton
Davey-Smith, George
Franke, Lude
Groenen, Patrick J. F.
Hofman, Albert
Johannesson, Magnus
Kardia, Sharon L. R.
Krueger, Robert F.
Laibson, David
Martin, Nicholas G.
Meyer, Michelle N.
Posthuma, Danielle
Thurik, A. Roy
Timpson, Nicholas J.
Uitterlinden, Andre G.
van Duijn, Cornelia M.
Visscher, Peter M.
Benjamin, Daniel J.
Cesarini, David
Koellinger, Philipp D.
CA LifeLines Cohort Study
TI GWAS of 126,559 Individuals Identifies Genetic Variants Associated with
Educational Attainment
SO SCIENCE
LA English
DT Article
ID ENVIRONMENT; PREFERENCES; LOCI
AB A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R-2 approximate to 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximate to 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.
C1 [Rietveld, Cornelius A.; van der Loos, Matthijs J. H. M.; Thurik, A. Roy; Koellinger, Philipp D.] Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, NL-3000 DR Rotterdam, Netherlands.
[Rietveld, Cornelius A.; van der Loos, Matthijs J. H. M.; Rivadeneira, Fernando; Tiemeier, Henning; van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Koellinger, Philipp D.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Medland, Sarah E.; Martin, Nicolas W.; Lee, Sang H.; Lind, Penelope A.; Montgomery, Grant W.; Nyholt, Dale R.; Martin, Nicholas G.; Visscher, Peter M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Derringer, Jaime] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
[Yang, Jian; Shakhbazov, Konstantin; Visscher, Peter M.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4102, Australia.
[Esko, Tonu; Fischer, Krista; Milani, Lili; Reinmaa, Eva; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[Martin, Nicolas W.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia.
[Westra, Harm-Jan; Ferhmann, Rudolf; Karjalainen, Juha; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 GZ Groningen, Netherlands.
[Shakhbazov, Konstantin; Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
[Abdellaoui, Abdel; Boomsma, Dorret I.; Hottenga, Jouke-Jan; Willemsen, Gonneke] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
[Agrawal, Arpana; Lin, Peng; Rice, John P.; Bierut, Laura J.; Madden, Pamela A.] Washington Univ, Dept Psychiat, Sch Med, St Louis, MO 63110 USA.
[Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
[Alizadeh, Behrooz Z.; Snieder, Harold; Vonk, Judith M.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands.
[Amin, Najaf; Ibrahim-Verbaas, Carla A.; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands.
[Bamard, John; Chung, Mina K.; Van Wagoner, David R.] Cleveland Clin, Heart & Vasc & Lerner Res Inst, Cleveland, OH 44195 USA.
[Baumeister, Sebastian E.; Voelzke, Henry; Hoffmann, Wolfgang] Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany.
[Benke, Kelly S.] Univ Toronto, Samuel Lunenfeld Res Inst, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Bielak, Lawrence F.; Smith, Jennifer A.; Zhao, Wei; Peyser, Patricia A.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Boatman, Jeffrey A.] Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA.
[Boyle, Patricia A.; Yu, Lei; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Davies, Gail; Deary, Ian J.; Liewald, David C.; Starr, John M.] Univ Edinburgh, Ctr Cognit Aging & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[De Leeuw, Christiaan; Rizzi, Thais S.; Posthuma, Danielle] Vrije Univ Amsterdam, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands.
[De Leeuw, Christiaan; Rizzi, Thais S.; Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, NL-1081 HV Amsterdam, Netherlands.
Radboud Univ Nijmegen, Machine Learning Grp, Inst Comp & Informat Sci, Fac Sci, NL-6500 GL Nijmegen, Netherlands.
[Eklund, Niina; Kristiansson, Kati; Nuotio, Marja-Liisa; Kaprio, Jaakko; Palotie, Aarno; Perola, Markus; Ripatti, Samuli; Sarin, Antti-Pekka; Surakka, Ida; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland.
[Eklund, Niina; Kristiansson, Kati; Nuotio, Marja-Liisa; Perola, Markus; Ripatti, Samuli; Surakka, Ida] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki 00014, Finland.
[Evans, Daniel S.; Perola, Markus] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA.
[Gjessing, Hakon K.; Harris, Jennifer R.; Jacobsson, Bo; Jugessur, Astanand; Myhre, Ronny] Norwegian Inst Publ Hlth, Div Epidemiol, Dept Genes & Environm, N-0403 Oslo, Norway.
[Haegg, Sara; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden.
[Haegg, Sara; Ingelsson, Erik] Uppsala Univ, Sci Life Lab, S-75123 Uppsala, Sweden.
[Haegg, Sara; Ingelsson, Erik; Groenberg, Henrik; Hall, Per; Lichtenstein, Paul; Magnusson, Patrik K. E.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Hayward, Caroline; Vitart, Veronique; Hastie, Nicholas D.; Wright, Alan F.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Holzapfel, Christina] Tech Univ Munich, Univ Hosp, Klinikum Rechts Isar, Else Kroener Fresenius Ctr Nutr Med, D-81675 Munich, Germany.
[Holzapfel, Christina; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
[Ibrahim-Verbaas, Carla A.] Erasmus MC, Dept Neurol, NL-3000 CA Rotterdam, Netherlands.
[Jacobsson, Bo] Sahgrenska Univ Hosp, Sahlgrenska Acad, Inst Publ Hlth, Dept Obstet & Gynecol, S-41345 Gothenburg, Sweden.
[Joshi, Peter K.; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Kaakinen, Marika; Jaervelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu 90014, Finland.
[Kaakinen, Marika; Jaervelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland.
[Kanoni, Stavroula; Deloukas, Panos; Palotie, Aarno; Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
[Kolcic, Ivana; Polasek, Ozren] Univ Split, Fac Med, Split 21000, Croatia.
[Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
[Kutalik, Zoltan] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
[Lahti, Jari; Raeikkoenen, Katri] Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland.
[Liu, Yongmei] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27157 USA.
[Lohman, Kurt] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Loitfelder, Marisa; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Div Neurogeriatr, A-8036 Graz, Austria.
[McMahon, George; Ring, Susan M.] Univ Bristol, Sch Social & Community Med, Bristol BS8 2PR, Avon, England.
[Vidal, Pedro Marques] Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1005 Lausanne, Switzerland.
[Meirelles, Osorio; Tanaka, Toshiko; Terracciano, Antonio; Ferrucci, Luigi; Garcia, Melissa E.; Harris, Tamara B.; Hernandez, Dena G.; Launer, Lenore J.; Schlessinger, David] NIA, NIH, Baltimore, MD 20892 USA.
[Oldmeadow, Christopher J.; Attia, John R.; Holliday, Elizabeth G.; Scott, Rodney J.] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2308, Australia.
[Oldmeadow, Christopher J.; Attia, John R.; Holliday, Elizabeth G.; Scott, Rodney J.] Univ Newcastle, Fac Hlth, Newcastle, NSW 2308, Australia.
[Petrovic, Katja E.] Gen Hosp, Div Gen Neurol, Dept Neurol, A-8036 Graz, Austria.
[Petrovic, Katja E.] Med Univ Graz, A-8036 Graz, Austria.
[Peyrot, Wouter J.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands.
[Quaye, Lydia; Cherkas, Lynn; Harris, Juliette M.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
[Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, A-8036 Graz, Austria.
[Smith, Albert V.; Eiriksdottir, Guony; Guonason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Smith, Albert V.; Guonason, Vilmundur] Univ Iceland, Dept Med, IS-101 Reykjavik, Iceland.
[Terracciano, Antonio] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Wellmann, Juergen; Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, D-48129 Munster, Germany.
[Allik, Jueri; Realo, Anu] Univ Tartu, Dept Psychol, EE-50410 Tartu, Estonia.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, I-50125 Florence, Italy.
[Bastardot, Franois; Preisig, Martin; Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Beauchamp, Jonathan] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA.
[Bueltmann, Ute] Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci Community & Occupat Med, NL-9700 AD Groningen, Netherlands.
[Chabris, Christopher F.] Union Coll, Dept Psychol, Schenectady, NY 12308 USA.
[Cucca, Francesco; Masala, Marco] Consejo Invest Nacl Italiano CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy.
[Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Ss, Italy.
[de Andrade, Mariza] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat Neuropsychiat Genom, Boston, MA 02115 USA.
[De Neve, Jan-Emmanuel] UCL, Sch Publ Policy, London WC1H 9QU, England.
[De Neve, Jan-Emmanuel] London Sch Econ, Ctr Econ Performance, London WC2A 2AE, England.
[Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Dedoussis, George V.; Dimitriou, Maria] Harokopio Univ Athens, Dept Nutr & Dietet, Athens 17671, Greece.
[Elderson, Martin F.; LifeLines Cohort Study] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, NL-9700 RB Groningen, Netherlands.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki 00280, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki 00250, Finland.
[Eriksson, Johan G.] Vaasa Cent Hosp, Vaasa 65130, Finland.
[Evans, David M.; Lawlor, Debbie A.; St Pourcain, Beate; Davey-Smith, George; Timpson, Nicholas J.] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2PR, Avon, England.
[Faul, Jessica D.; Weir, David R.] Univ Michigan, Survey Res Ctr, Inst Social Res, Ann Arbor, MI 48106 USA.
[Heath, Andrew C.] Washington Univ, Div Biol & Biomed Sci, St Louis, MO 63110 USA.
[Hofman, Adriaan] Univ Groningen, Fac Behav & Social Sci, NL-9747 AD Groningen, Netherlands.
[Iacono, William G.; Kirkpatrick, Robert M.; McGue, Matt; Miller, Michael B.; Krueger, Robert F.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Holle, Rolf; Mielck, Andreas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Hlth Econ & Hlth Care Management, D-85764 Neuherberg, Germany.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany.
[Jaervelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
[Jaervelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu 90220, Finland.
[Jaervelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children & Young People & Families, Oulu 90101, Finland.
[Kaehoenen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33520, Finland.
[Kaehoenen, Mika] Univ Tampere, Sch Med, Tampere 33520, Finland.
[Kaprio, Jaakko; Latvala, Antti] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland.
[Kaprio, Jaakko; Latvala, Antti] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki 00300, Finland.
[Kowgier, Matthew; Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Lehtimaeki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, Tampere 33520, Finland.
[Li, Jingmei] Genome Inst Singapore, Singapore 138672, Singapore.
[Lichtner, Peter] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Human Genet, D-85764 Neuherberg, Germany.
[Maekinen, Tomi E.] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Helsinki 00271, Finland.
[Mukherjee, Sutapa] Sir Charles Gairdner Hosp, Western Australia Sleep Disorders Res Inst, Perth, WA 6009, Australia.
[Mukherjee, Sutapa] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada.
[Mukherjee, Sutapa] Univ Toronto, Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada.
[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki 00014, Finland.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
[Rustichini, Aldo] Univ Minnesota, Dept Econ, Minneapolis, MN 55455 USA.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol Unit, Helsinki 00271, Finland.
[St Pourcain, Beate] Univ Bristol, Sch Oral & Dent Sci, Bristol BS1 2LY, Avon, England.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Sul, Jae Hoon] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA.
[Svento, Rauli] Univ Oulu, Oulu Business Sch, Dept Econ, Oulu 90014, Finland.
[Teumer, Alexander] Univ Med Greifswald, Dept Funct Genom, Interfac Inst Genet & Funct Genom, D-17487 Greifswald, Germany.
[Tiemeier, Henning; Posthuma, Danielle] Erasmus MC, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands.
[Vartiainen, Erkki] Natl Inst Hlth & Welf, Div Welf & Hlth Promot, Helsinki 00271, Finland.
[Viikari, Jorma] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany.
[Wichmann, H. -Erich] Klinikum Grosshadern, D-81377 Munich, Germany.
[Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, D-85764 Neuherberg, Germany.
[Conley, Dalton] NYU, Dept Sociol, New York, NY 10012 USA.
[Laibson, David] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA.
[Meyer, Michelle N.] Harvard Univ, Sch Law, Petrie Flom Ctr Hlth Law Policy Biotechnol & Bioe, Cambridge, MA 02138 USA.
[Meyer, Michelle N.] SUNY Albany, Nelson A Rockefeller Inst Govt, Albany, NY 12203 USA.
[Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands.
[Groenen, Patrick J. F.] Erasmus Univ, Econometr Inst, Erasmus Sch Econ, NL-3000 DR Rotterdam, Netherlands.
[Johannesson, Magnus] Stockholm Sch Econ, Dept Econ, S-11383 Stockholm, Sweden.
[Thurik, A. Roy] Panteia, NL-2701 AA Zoetermeer, Netherlands.
[Thurik, A. Roy] GSCM Montpellier Business Sch, F-34185 Montpellier, France.
[van Duijn, Cornelia M.] Leiden Univ, Med Ctr, Ctr Med Syst Biol, NL-2300 RC Leiden, Netherlands.
[Cesarini, David] Cornell Univ, Dept Econ, Ithaca, NY 14853 USA.
[Cesarini, David] NYU, Ctr Expt Social Sci, Dept Econ, New York, NY 10012 USA.
[Cesarini, David] New York Univ Abu Dhabi, Div Social Sci, Abu Dhabi, U Arab Emirates.
[Cesarini, David] Res Inst Ind Econ, S-10215 Stockholm, Sweden.
RP Benjamin, DJ (reprint author), Cornell Univ, Dept Econ, Ithaca, NY 14853 USA.
EM visscher@uq.edu.au; db468@cornell.edu; dac12@nyu.edu;
koellinger@ese.eur.nl
RI Attia, John/F-5376-2013; Lin, P/G-7702-2014; Nyholt, Dale/C-8384-2013;
Palmer, Lyle/K-3196-2014; Lee, Sang Hong/A-2569-2011; Evans,
David/H-6325-2013; Li, Jingmei/I-2904-2012; Johannesson,
Magnus/E-9680-2011; terracciano, antonio/B-1884-2008; Lind,
Penelope/B-2553-2009; Van Wagoner, David/C-6783-2008; Colaus,
PsyColaus/K-6607-2013; Deloukas, Panos/B-2922-2013; Rudan,
Igor/I-1467-2012; Smith, Albert/K-5150-2015; Yang, Jian/A-5852-2010;
Holle, Rolf/D-9333-2013; Hayward, Caroline/M-8818-2016; Realo,
Anu/M-9524-2016; Franke, Lude/P-7036-2016; Fox, Laura /C-6249-2016;
Karjalainen, Juha/P-8624-2016; Davey Smith, George/A-7407-2013;
Magnusson, Patrik/C-4458-2017; Kolcic, Ivana/E-2713-2017; Thurik,
Roy/A-9386-2012; Medland, Sarah/C-7630-2013; Fehrmann,
Rudolf/E-2551-2011; Marques-Vidal, Pedro/C-9449-2009; Allik,
Juri/D-5609-2009; Milani, Lili/C-8759-2011; Gudnason,
Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery,
Grant/B-7148-2008; Rivadeneira, Fernando/O-5385-2015
OI Visscher, Peter/0000-0002-2143-8760; Eriksson,
Johan/0000-0002-2516-2060; Evans, David/0000-0003-0663-4621; Smith,
Jennifer/0000-0002-3575-5468; Kaprio, Jaakko/0000-0002-3716-2455;
Timpson, Nicholas/0000-0002-7141-9189; Lawlor, Debbie
A/0000-0002-6793-2262; Lahti, Jari/0000-0002-4310-5297; Attia,
John/0000-0001-9800-1308; Palmer, Lyle/0000-0002-1628-3055; Lee, Sang
Hong/0000-0001-9701-2718; Li, Jingmei/0000-0001-8587-7511; Johannesson,
Magnus/0000-0001-8759-6393; Van Wagoner, David/0000-0001-8250-9828;
Deloukas, Panos/0000-0001-9251-070X; Tiemeier,
Henning/0000-0002-4395-1397; Esko, Tonu/0000-0003-1982-6569;
lichtenstein, paul/0000-0003-3037-5287; Kristiansson,
Kati/0000-0003-4688-107X; Maki-Opas, Tomi/0000-0002-0472-719X; Gieger,
Christian/0000-0001-6986-9554; Rudan, Igor/0000-0001-6993-6884; Smith,
Albert/0000-0003-1942-5845; Yang, Jian/0000-0003-2001-2474; Holle,
Rolf/0000-0001-5395-2695; Hayward, Caroline/0000-0002-9405-9550; Franke,
Lude/0000-0002-5159-8802; Davey Smith, George/0000-0002-1407-8314;
Kolcic, Ivana/0000-0001-7918-6052; Peyrot, Wouter/0000-0001-7954-8383;
St Pourcain, Beate/0000-0002-4680-3517; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Groenen, Patrick/0000-0001-6683-8971;
Nuotio, Marja-Liisa/0000-0002-6688-027X; Latvala,
Antti/0000-0001-5695-117X; Joshi, Peter/0000-0002-6361-5059; Kaakinen,
Marika/0000-0002-9228-0462; Koellinger, Philipp/0000-0001-7413-0412;
Cesarini, David/0000-0002-0043-009X; Ziad Alizadeh,
Behrooz/0000-0002-1415-8007; Lind, Penelope/0000-0002-3887-2598;
Raikkonen, Katri/0000-0003-3124-3470; Martin,
Nicholas/0000-0003-4069-8020; Thurik, Roy/0000-0002-0242-6908; Medland,
Sarah/0000-0003-1382-380X; Fehrmann, Rudolf/0000-0002-7516-315X;
Marques-Vidal, Pedro/0000-0002-4548-8500; Allik,
Juri/0000-0002-8358-4747; Milani, Lili/0000-0002-5323-3102; Gudnason,
Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862;
Montgomery, Grant/0000-0002-4140-8139; Rivadeneira,
Fernando/0000-0001-9435-9441
FU Social Science Genetic Association Consortium (SSGAC); EAGER grant from
the NSF; NIH Office of Behavioral and Social Sciences Research
[SES-1064089]; Ragnar Soderberg Foundation [E9/11]; National Institute
on Aging (NIA)/NIH [P01-AG005842, P01-AG005842-20S2, P30-AG012810,
T32-AG000186-23]
FX This research was carried out under the auspices of the Social Science
Genetic Association Consortium (SSGAC), a cooperative enterprise among
medical researchers and social scientists that coordinates
genetic-association studies for social-science variables. Data for our
analyses come from many studies and organizations, some of which are
subject to a materials transfer agreement (5). Results from the
meta-analysis are available at the Web site of the consortium,
www.ssgac.org. The formation of the SSGAC was made possible by an EAGER
grant from the NSF and a supplemental grant from the NIH Office of
Behavioral and Social Sciences Research (SES-1064089). This research was
also funded in part by the Ragnar Soderberg Foundation (E9/11); the
National Institute on Aging (NIA)/NIH through grants P01-AG005842,
P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23; and the Intramural
Research Program of the NIA/NIH. For a full list of acknowledgments, see
(5).
NR 21
TC 186
Z9 186
U1 6
U2 135
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 21
PY 2013
VL 340
IS 6139
BP 1467
EP 1471
DI 10.1126/science.1235488
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 167QL
UT WOS:000320647000046
PM 23722424
ER
PT J
AU Gilbert, MR
Dignam, J
Won, M
Blumenthal, DT
Vogelbaum, MA
Aldape, KD
Colman, H
Chakravarti, A
Jeraj, R
Armstrong, TS
Wefel, JS
Brown, PD
Jaeckle, KA
Schiff, D
Atkins, JN
Brachman, D
Werner-Wasik, M
Komaki, R
Sulman, EP
Mehta, MP
AF Gilbert, Mark R.
Dignam, James
Won, Minhee
Blumenthal, Deborah T.
Vogelbaum, Michael A.
Aldape, Kenneth D.
Colman, Howard
Chakravarti, Arnab
Jeraj, Robert
Armstrong, Terri S.
Wefel, Jeffrey Scott
Brown, Paul D.
Jaeckle, Kurt A.
Schiff, David
Atkins, James Norman
Brachman, David
Werner-Wasik, Maria
Komaki, Ritsuko
Sulman, Erik P.
Mehta, Minesh P.
TI RTOG 0825: Phase III double-blind placebo-controlled trial evaluating
bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma
(GBM).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 31-JUN 04, 2013
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
Radiat Therapy Oncol Grp, Philadelphia, PA USA.
Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel.
Cleveland Clin Fdn, Cleveland, OH 44195 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
Ohio State Univ, Arthur G James Canc Ctr, Columbus, OH 43210 USA.
Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA.
Univ Texas Hlth Sci Ctr Houston, Sch Nursing, Houston, TX 77030 USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Univ Virginia, Med Ctr, Charlottesville, VA USA.
Natl Surg Adjuvant Breast & Bowel Project, Goldboro, NC USA.
SCCC CCOP, Goldboro, NC USA.
Arizona Oncol Serv Fdn, Phoenix, AZ USA.
Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
Univ Maryland, Baltimore, MD 21201 USA.
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2013
VL 31
IS 18
SU S
MA 1
PG 1
WC Oncology
SC Oncology
GA AG6YC
UT WOS:000335564000002
ER
PT J
AU Sulman, EP
Won, M
Blumenthal, DT
Vogelbaum, MA
Colman, H
Jenkins, RB
Chakravarti, A
Jeraj, R
Brown, PD
Jaeckle, KA
Schiff, D
Dignam, J
Atkins, JN
Brachman, D
Werner-Wasik, M
Komaki, R
Gilbert, MR
Mehta, MP
Aldape, KD
AF Sulman, Erik P.
Won, Minhee
Blumenthal, Deborah T.
Vogelbaum, Michael A.
Colman, Howard
Jenkins, Robert B.
Chakravarti, Arnab
Jeraj, Robert
Brown, Paul D.
Jaeckle, Kurt A.
Schiff, David
Dignam, James
Atkins, James Norman
Brachman, David
Werner-Wasik, Maria
Komaki, Ritsuko
Gilbert, Mark R.
Mehta, Minesh P.
Aldape, Kenneth D.
TI Molecular predictors of outcome and response to bevacizumab (BEV) based
on analysis of RTOG 0825, a phase III trial comparing chemoradiation
(CRT) with and without BEV in patients with newly diagnosed glioblastoma
(GBM).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 31-JUN 04, 2013
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Radiat Therapy Oncol Grp, Philadelphia, PA USA.
Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel.
Cleveland Clin Fdn, Cleveland, OH 44195 USA.
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
Mayo Clin, Rochester, MN USA.
Ohio State Univ, Arthur G James Canc Ctr, Columbus, OH 43210 USA.
Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Univ Virginia, Med Ctr, Charlottesville, VA USA.
Natl Surg Adjuvant Breast & Bowel Project, Goldboro, NC USA.
SCCC CCOP, Goldboro, NC USA.
Arizona Oncol Serv Fdn, Phoenix, AZ USA.
Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
Univ Maryland, Baltimore, MD 21201 USA.
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2013
VL 31
IS 18
SU S
MA LBA2010
PG 2
WC Oncology
SC Oncology
GA AG6YC
UT WOS:000335564000020
ER
PT J
AU Bellon, M
Ko, NL
Lee, MJ
Yao, Y
Waldmann, TA
Trepel, JB
Nicot, C
AF Bellon, Marcia
Ko, Nga Ling
Lee, Min-Jung
Yao, Yuan
Waldmann, Thomas A.
Trepel, Jane B.
Nicot, Christophe
TI Adult T-cell leukemia cells overexpress Wnt5a and promote osteoclast
differentiation
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; BETA-CATENIN; SIGNALING PATHWAY; CONSTITUTIVE
ACTIVATION; IN-VIVO; HYPERCALCEMIA; CANCER; PROLIFERATION; EXPRESSION;
TARGET
AB Adult T-cell leukemia/lymphoma (ATL) is etiologically linked to infection with the human T-cell leukemia/lymphoma virus type 1 (HTLV-I). ATL is classified into 4 distinct clinical diseases: acute, lymphoma, chronic, and smoldering. Acute ATL is the most aggressive form, representing 60% of cases and has a 4-year survival of <5%. A frequent complication and cause of death in acute ATL patients is the presence of lytic bone lesions and hypercalcemia. We analyzed the Wnt/beta-catenin pathway because of its common role in cancer and bone remodeling. Our study demonstrated that ATL cells do not express high levels of beta-catenin but displayed high levels of LEF-1/TCF genes along with elevated levels of beta-catenin (LEF-1/TCF target genes) responsive genes. By profiling Wnt gene expression, we discovered that ATL patient leukemia cells shifted expression toward the noncanonical Wnt pathway. Interestingly, ATL cells overexpressed the osteolytic-associated genes-Wnt5a, PTHLH, and RANKL. We further show that Wnt5a secreted by ATL cells favors osteoclast differentiation and expression of RANK. Our results suggest that Wnt5a is a major contributing factor to the increase in osteolytic bone lesions and hypercalcemia found in ATL patients. Anti-Wnt5a therapy may prevent or reduce osteolytic lesions found in ATL patients and improve therapy outcome.
C1 [Bellon, Marcia; Ko, Nga Ling; Yao, Yuan; Nicot, Christophe] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Ctr Viral Oncol, Kansas City, KS 66103 USA.
[Lee, Min-Jung; Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Waldmann, Thomas A.] NIH, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Nicot, C (reprint author), Ctr Viral Oncol, 3901 Rainbow Blvd,3025 Wahl Hall West, Kansas City, KS 66160 USA.
EM cnicot@kumc.edu
FU National Institutes of Health [AI 058944, CA106258]; National Cancer
Institute; Biomedical Research Training Program
FX This work was supported by the National Institutes of Health (AI 058944,
CA106258) (C.N.), the Intramural Research Program of the National Cancer
Institute (T.A.W., J.B.T.), and the Biomedical Research Training Program
(M.B.).
NR 42
TC 9
Z9 9
U1 0
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 20
PY 2013
VL 121
IS 25
BP 5045
EP 5054
DI 10.1182/blood-2012-07-439109
PG 10
WC Hematology
SC Hematology
GA 184NR
UT WOS:000321898500013
PM 23660959
ER
PT J
AU Niesen, MJM
Bhattacharya, S
Grisshammer, R
Tate, CG
Vaidehi, N
AF Niesen, Michiel J. M.
Bhattacharya, Supriyo
Grisshammer, Reinhard
Tate, Christopher G.
Vaidehi, Nagarajan
TI Thermostabilization of the beta(1)-Adrenergic Receptor Correlates with
Increased Entropy of the Inactive State
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; MOLECULAR-DYNAMICS SIMULATIONS; ADENOSINE
A(2A) RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; CONFORMATIONAL ENSEMBLES;
STRUCTURAL INSIGHTS; CRYSTAL-STRUCTURE; AGONIST; ACTIVATION; STABILITY
AB The dynamic nature of GPCRs is a major hurdle in their purification and crystallization. Thermostabilization can facilitate GPCR structure determination, as has been shown by the structure of the thermostabilized beta(1)-adrenergic receptor (beta(1)AR) mutant, m23-beta(1)AR, which has been thermostabilized in the inactive state. However, it is undear from the structure how the six thermostabilizing mutations in m23-beta(1)AR affect receptor dynamics. We have used molecular dynamics simulations in explicit solvent to compare the conformational ensembles for both wild type beta(1)AR (wt-beta(1)AR) and m23-beta(1)AR. Thermostabilization results in an increase in the number of accessible microscopic conformational states within the inactive state ensemble, effectively increasing the side chain entropy of the inactive state at room temperature, while suppressing large-scale main chain conformational changes that lead to activation. We identified several diverse mechanisms of thermostabilization upon mutation. These include decrease of long-range correlated movement between residues in the G-protein coupling site to the extracellular region (Y227A(5.58), F338M(7.48)), formation of new hydrogen bonds (R68S), and reduction of local stress (Y227(5.58), F327(7.37), and F338(7.48)). This study provides insights into microscopic mechanisms underlying thermostability that leads to an understanding of the effect of these mutations on the structure of the receptor.
C1 [Niesen, Michiel J. M.; Bhattacharya, Supriyo; Vaidehi, Nagarajan] City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA.
[Grisshammer, Reinhard] NINDS, Membrane Prot Struct Funct Unit, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Tate, Christopher G.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
RP Vaidehi, N (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM NVaidehi@coh.org
RI Niesen, Michiel/L-8985-2013; Grisshammer, Reinhard/C-3089-2015
FU NIH [RO1-GM097261]
FX The authors thank Mr. Jeffrey Wagner for help with some of the scripts
used for analysis. This work was supported by NIH RO1-GM097261.
NR 56
TC 8
Z9 8
U1 0
U2 17
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 JUN 20
PY 2013
VL 117
IS 24
BP 7283
EP 7291
DI 10.1021/jp403207c
PG 9
WC Chemistry, Physical
SC Chemistry
GA 171FQ
UT WOS:000320910900016
PM 23697892
ER
PT J
AU Morens, DM
Taubenberger, JK
Fauci, AS
AF Morens, David M.
Taubenberger, Jeffery K.
Fauci, Anthony S.
TI Pandemic Influenza Viruses - Hoping for the Road Not Taken
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Morens, David M.; Fauci, Anthony S.] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Off Director, Bethesda, MD USA.
[Taubenberger, Jeffery K.] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Viral Pathogenesis & Evolut Sect, Lab Infect Dis, Bethesda, MD USA.
RP Morens, DM (reprint author), Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Off Director, Bethesda, MD USA.
FU Intramural NIH HHS [ZIA AI000986-06]
NR 5
TC 31
Z9 34
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 20
PY 2013
VL 368
IS 25
BP 2345
EP 2348
DI 10.1056/NEJMp1307009
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 167AE
UT WOS:000320601700001
PM 23738514
ER
PT J
AU Hudson, KL
Guttmacher, AE
Collins, FS
AF Hudson, Kathy L.
Guttmacher, Alan E.
Collins, Francis S.
TI In Support of SUPPORT - A View from the NIH
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID SEVERE RETINOPATHY; INFANTS
C1 [Hudson, Kathy L.; Guttmacher, Alan E.; Collins, Francis S.] Natl Inst Hlth, Bethesda, MD USA.
RP Hudson, KL (reprint author), Natl Inst Hlth, Bethesda, MD USA.
NR 4
TC 27
Z9 27
U1 1
U2 7
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 20
PY 2013
VL 368
IS 25
BP 2349
EP 2351
DI 10.1056/NEJMp1306986
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 167AE
UT WOS:000320601700003
PM 23738511
ER
PT J
AU Wang, P
Dong, Q
Zhang, C
Kuan, PF
Liu, Y
Jeck, WR
Andersen, JB
Jiang, W
Savich, GL
Tan, TX
Auman, JT
Hoskins, JM
Misher, AD
Moser, CD
Yourstone, SM
Kim, JW
Cibulskis, K
Getz, G
Hunt, HV
Thorgeirsson, SS
Roberts, LR
Ye, D
Guan, KL
Xiong, Y
Qin, LX
Chiang, DY
AF Wang, P.
Dong, Q.
Zhang, C.
Kuan, P-F
Liu, Y.
Jeck, W. R.
Andersen, J. B.
Jiang, W.
Savich, G. L.
Tan, T-X
Auman, J. T.
Hoskins, J. M.
Misher, A. D.
Moser, C. D.
Yourstone, S. M.
Kim, J. W.
Cibulskis, K.
Getz, G.
Hunt, H. V.
Thorgeirsson, S. S.
Roberts, L. R.
Ye, D.
Guan, K-L
Xiong, Y.
Qin, L-X
Chiang, D. Y.
TI Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in
intrahepatic cholangiocarcinomas and share hypermethylation targets with
glioblastomas
SO ONCOGENE
LA English
DT Article
DE DNA methylation; epigenetics; tumor metabolism
ID CELL SELF-RENEWAL; IDH2 MUTATIONS; COLORECTAL-CANCER; MAFFUCCI SYNDROME;
OLLIER DISEASE; MAMMALIAN DNA; TET PROTEINS; STEM-CELLS; PHENOTYPE;
5-CARBOXYLCYTOSINE
AB Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79). Mutations in IDH1 or IDH2 were associated with longer overall survival (P = 0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (P = 0.021). IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors.
C1 [Wang, P.; Jiang, W.; Guan, K-L; Xiong, Y.] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200032, Peoples R China.
[Wang, P.; Jiang, W.; Ye, D.; Guan, K-L; Xiong, Y.] Fudan Univ, Inst Biomed Sci, Mol & Cell Biol Lab, Shanghai 200032, Peoples R China.
[Dong, Q.; Qin, L-X] Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China.
[Dong, Q.; Qin, L-X] Fudan Univ, Zhongshan Hosp, Inst Biomed Sci, Shanghai 200032, Peoples R China.
[Zhang, C.; Liu, Y.] Univ N Carolina, Carolina Ctr Genome Sci, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA.
[Kuan, P-F] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Kuan, P-F; Jeck, W. R.; Savich, G. L.; Tan, T-X; Auman, J. T.; Hoskins, J. M.; Misher, A. D.; Yourstone, S. M.; Xiong, Y.; Chiang, D. Y.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Jeck, W. R.; Savich, G. L.; Tan, T-X; Yourstone, S. M.; Chiang, D. Y.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Andersen, J. B.; Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Auman, J. T.; Hoskins, J. M.; Misher, A. D.] Univ N Carolina, Inst Pharmacogen & Individualized Med, Chapel Hill, NC 27599 USA.
[Moser, C. D.; Roberts, L. R.] Mayo Clin, Ctr Canc, Ctr Cell Signaling Gastroenterol, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Kim, J. W.] Wake Forest Univ, Baptist Med Ctr, Ctr Canc Genom, Winston Salem, NC 27109 USA.
[Cibulskis, K.; Getz, G.] 7 Cambridge Ctr, Broad Inst, Genome Sequencing Anal Program & Platform, Cambridge, MA USA.
[Hunt, H. V.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Guan, K-L] Fudan Univ, Shanghai Med Coll, Dept Biochem, Shanghai 200032, Peoples R China.
[Guan, K-L] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Guan, K-L] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Xiong, Y.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
RP Xiong, Y (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295,450 West Dr, Chapel Hill, NC 27599 USA.
EM yxiong@email.unc.edu; qin.lunxiu@zs-hospital.sh.cn; chiang@med.unc.edu
OI Chiang, Derek/0000-0002-1131-6065; Roberts, Lewis/0000-0001-7885-8574;
Andersen , Jesper B/0000-0003-1760-5244
FU 985 Program from the Chinese Ministry of Education; MOST 973
[2009CB918401, 2011CB910600, 2012CB910300, 2012CB910101]; NSFC Program
of International Cooperation and Exchanges [81120108016]; China National
Key Projects for Infectious Disease [2008ZX10002-021, 2012ZX10002-012];
National Institutes of Health; James S McDonnell Foundation; Samuel
Waxman Cancer Research Foundation; American Gastroenterological
Association Foundation for Digestive Health and Nutrition; Alfred P
Sloan Foundation; Nancy Stegman Cancer Research Fund; University Cancer
Research Fund
FX The UNC Biospecimen Core Facility, Mammalian Genotyping Core Facility
and Translational Pathology Laboratory provided technical assistance for
this study. Funding for this research was provided by: the 985 Program
from the Chinese Ministry of Education (KLG, YX), MOST 973 (No.
2009CB918401, No. 2011CB910600, No. 2012CB910300, No. 2012CB910101; DY,
YX and KLG); the NSFC Program of International Cooperation and Exchanges
(No. 81120108016; LXQ, YX) and the China National Key Projects for
Infectious Disease (2008ZX10002-021, 2012ZX10002-012; LZQ), the National
Institutes of Health (KLG, YX, SST, LRR), the James S McDonnell
Foundation (YX), the Samuel Waxman Cancer Research Foundation (YX), the
American Gastroenterological Association Foundation for Digestive Health
and Nutrition (LRR), the Alfred P Sloan Foundation fellowship (DYC), the
Nancy Stegman Cancer Research Fund (DYC) and the University Cancer
Research Fund (DYC, YX).
NR 46
TC 86
Z9 89
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 20
PY 2013
VL 32
IS 25
BP 3091
EP 3100
DI 10.1038/onc.2012.315
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 168KX
UT WOS:000320705700009
PM 22824796
ER
PT J
AU Findley, K
Oh, J
Yang, J
Conlan, S
Deming, C
Meyer, JA
Schoenfeld, D
Nomicos, E
Park, M
Kong, HH
Segre, JA
AF Findley, Keisha
Oh, Julia
Yang, Joy
Conlan, Sean
Deming, Clayton
Meyer, Jennifer A.
Schoenfeld, Deborah
Nomicos, Effie
Park, Morgan
Kong, Heidi H.
Segre, Julia A.
CA NIH Intramural Sequencing Ctr Comp
TI Topographic diversity of fungal and bacterial communities in human skin
SO NATURE
LA English
DT Article
ID RIBOSOMAL-RNA SEQUENCES; HUMAN MICROBIOME; RISK-FACTORS; TINEA-PEDIS;
PREVALENCE; ALIGNMENT; ACCURACY; DISEASES; PROJECT; SAMPLES
AB Traditional culture-based methods have incompletely defined the microbial landscape of common recalcitrant human fungal skin diseases, including athlete's foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms and provides a home for diverse commensal microbiota(1). Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders(2-4). However, microbial diversity is not limited to bacteria; microorganisms such as fungi also have major roles in microbial community stability, human health and disease(5). Genomic methodologies to identify fungal species and communities have been limited compared with those that are available for bacteria(6). Fungal evolution can be reconstructed with phylogenetic markers, including ribosomal RNA gene regions and other highly conserved genes(7). Here we sequenced and analysed fungal communities of 14 skin sites in 10 healthy adults. Eleven core-body and arm sites were dominated by fungi of the genus Malassezia, with only species-level classifications revealing fungal-community composition differences between sites. By contrast, three foot sites-plantar heel, toenail and toe web-showed high fungal diversity. Concurrent analysis of bacterial and fungal communities demonstrated that physiologic attributes and topography of skin differentially shape these two microbial communities. These results provide a framework for future investigation of the contribution of interactions between pathogenic and commensal fungal and bacterial communities to the maintainenace of human health and to disease pathogenesis.
C1 [Findley, Keisha; Oh, Julia; Yang, Joy; Conlan, Sean; Deming, Clayton; Meyer, Jennifer A.; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Schoenfeld, Deborah; Nomicos, Effie; Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Park, Morgan] NHGRI, NIH Intramural Sequencing Ctr, NIH, Rockville, MD 20852 USA.
RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; jsegre@nhgri.nih.gov
RI Conlan, Sean/B-4401-2008;
OI Conlan, Sean/0000-0001-6848-3465; Kong, Heidi/0000-0003-4424-064X
FU US National Institutes of Health (NIH) NHGRI and NCI Intramural Research
Programs; NIH [1K99AR059222, 1UH2AR057504-01, 4UH3AR057504-02]
FX We thank J. Heitman, A. Amend, Y. Shea, M. Turner, I. Brownell and M.
Udey for helpful discussions. We thank J. Fekecs for assistance with the
figures. This work was supported by the US National Institutes of Health
(NIH) NHGRI and NCI Intramural Research Programs, and in part by NIH
grant no. 1K99AR059222 (to H. H. K.). Sequencing was funded by grants
from the NIH (1UH2AR057504-01 and 4UH3AR057504-02).
NR 41
TC 198
Z9 206
U1 23
U2 218
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 JUN 20
PY 2013
VL 498
IS 7454
BP 367
EP +
DI 10.1038/nature12171
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900041
PM 23698366
ER
PT J
AU Lammermann, T
Afonso, PV
Angermann, BR
Wang, JM
Kastenmuller, W
Parent, CA
Germain, RN
AF Laemmermann, Tim
Afonso, Philippe V.
Angermann, Bastian R.
Wang, Ji Ming
Kastenmueller, Wolfgang
Parent, Carole A.
Germain, Ronald N.
TI Neutrophil swarms require LTB4 and integrins at sites of cell death in
vivo
SO NATURE
LA English
DT Article
ID INNATE IMMUNE-RESPONSE; STERILE INFLAMMATION; AMMATORY ARTHRITIS;
IMAGING REVEALS; HOST-DEFENSE; MICE LACKING; LYMPH-NODES; BONE-MARROW;
MIGRATION; RECEPTOR
AB Neutrophil recruitment from blood to extravascular sites of sterile or infectious tissue damage is a hallmark of early innate immune responses, and the molecular events leading to cell exit from the bloodstream have been well defined(1,2). Once outside the vessel, individual neutrophils often show extremely coordinated chemotaxis and cluster formation reminiscent of the swarming behaviour of insects(3-11). The molecular players that direct this response at the single-cell and population levels within the complexity of an inflamed tissue are unknown. Using two-photon intravital microscopy in mouse models of sterile injury and infection, we show a critical role for intercellular signal relay among neutrophils mediated by the lipid leukotriene B4, which acutely amplifies local cell death signals to enhance the radius of highly directed interstitial neutrophil recruitment. Integrin receptors are dispensable for long-distance migration(12), but have a previously unappreciated role in maintaining dense cellular clusters when congregating neutrophils rearrange the collagenous fibre network of the dermis to form a collagen-free zone at the wound centre. In this newly formed environment, integrins, in concert with neutrophil-derived leukotriene B4 and other chemoattractants, promote local neutrophil interaction while forming a tight wound seal. This wound seal has borders that cease to grow in kinetic concert with late recruitment of monocytes and macrophages at the edge of the displaced collagen fibres. Together, these data provide an initial molecular map of the factors that contribute to neutrophil swarming in the extravascular space of a damaged tissue. They reveal how local events are propagated over large-range distances, and how auto-signalling produces coordinated, self-organized neutrophil-swarming behaviour that isolates the wound or infectious site from surrounding viable tissue.
C1 [Laemmermann, Tim; Angermann, Bastian R.; Kastenmueller, Wolfgang; Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Afonso, Philippe V.; Parent, Carole A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wang, Ji Ming] NCI, Lab Mol Immunoregulat, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Kastenmueller, Wolfgang] Univ Bonn, Inst Mol Med, D-53105 Bonn, Germany.
[Kastenmueller, Wolfgang] Univ Bonn, Inst Expt Immunol, D-53105 Bonn, Germany.
RP Lammermann, T (reprint author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM laemmermannt@niaid.nih.gov; rgermain@niaid.nih.gov
RI Afonso, Philippe/D-2234-2014
OI Afonso, Philippe/0000-0002-4828-3797
FU Human Frontiers Science Program Long-Term Fellowship; Deutsche
Forschungsgemeinschaft (DFG); National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Cancer
Institute, National Institutes of Health
FX We thank L. Birnbaumer, R. Fassler, E. Tuomanen, P. M. Murphy, S. Akira,
S. Monkley, D. Critchley, R. Wedlich-Soldner and M. Sixt for providing
mice for this study, J.G. Egen and J. Tang for assistance with imaging,
M. Parsek for providing P. aeruginosa-GFP, J. H. Kehrl, P. M. Murphy, R.
Varma and members of the Germain laboratory for discussions. This work
was supported by the Intramural Research Program of National Institute
of Allergy and Infectious Diseases and National Cancer Institute,
National Institutes of Health. T. L. was supported by a Human Frontiers
Science Program Long-Term Fellowship. W. K. is presently a member of the
Deutsche Forschungsgemeinschaft (DFG)-funded excellence cluster
ImmunoSensation, Bonn, Germany.
NR 49
TC 170
Z9 172
U1 9
U2 71
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 371
EP +
DI 10.1038/nature12175
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900042
PM 23708969
ER
PT J
AU Cooper, A
Garcia, M
Petrovas, C
Yamamoto, T
Koup, RA
Nabel, GJ
AF Cooper, Arik
Garcia, Mayra
Petrovas, Constantinos
Yamamoto, Takuya
Koup, Richard A.
Nabel, Gary J.
TI HIV-1 causes CD4 cell death through DNA-dependent protein kinase during
viral integration
SO NATURE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS MOLECULAR CLONE; T-CELLS;
IN-VIVO; RETROVIRAL INFECTION; QUANTITATIVE ASSAY; LYMPHOCYTES;
INHIBITOR; DEPLETION; DYNAMICS
AB Human immunodeficiency virus-1 (HIV-1) has infected more than 60 million people and caused nearly 30 million deaths worldwide(1), ultimately the consequence of cytolytic infection of CD4(+) T cells. In humans and in macaque models, most of these cells contain viral DNA and are rapidly eliminated at the peak of viraemia(2-4), yet the mechanism by which HIV-1 induces helper T-cell death has not been defined. Here we show that virus-induced cell killing is triggered by viral integration. Infection by wild-type HIV-1, but not an integrase-deficient mutant, induced the death of activated primary CD4 lymphocytes. Similarly, raltegravir, a pharmacologic integrase inhibitor, abolished HIV-1-induced cell killing both in cell culture and in CD4(+) T cells from acutely infected subjects. The mechanism of killing during viral integration involved the activation of DNA-dependent protein kinase (DNA-PK), a central integrator of the DNA damage response, which caused phosphorylation of p53 and histone H2AX. Pharmacological inhibition of DNA-PK abolished cell death during HIV-1 infection in vitro, suggesting that processes which reduce DNA-PK activation in CD4 cells could facilitate the formation of latently infected cells that give rise to reservoirs in vivo. We propose that activation of DNA-PK during viral integration has a central role in CD4(+) T-cell depletion, raising the possibility that integrase inhibitors and interventions directed towards DNA-PK may improve T-cell survival and immune function in infected individuals.
C1 [Cooper, Arik; Garcia, Mayra; Nabel, Gary J.] NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Petrovas, Constantinos; Yamamoto, Takuya; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Nabel, GJ (reprint author), NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA.
EM Gary.Nabel@sanofi.com
RI Yamamoto, Takuya/L-2642-2013
OI Yamamoto, Takuya/0000-0003-3753-1211
FU Intramural Research Program of the Vaccine Research Center, NIAID,
National Institutes of Health
FX We thank D. Ambrozak, R. Nguyen, and S. Perfetto for help with cell
sorting, U. Olshevsky, J. Casazza, D. Bolton, A. Pegu and M. Louder for
discussions and technical help, and A. Tislerics and B. Hartman for
manuscript preparation. This research was supported by the Intramural
Research Program of the Vaccine Research Center, NIAID, National
Institutes of Health. The findings and conclusions in this report are
those of the authors and do not necessarily reflect the views of the
funding agency.
NR 39
TC 90
Z9 92
U1 5
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 376
EP +
DI 10.1038/nature12274
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900043
PM 23739328
ER
PT J
AU Prater, SN
Patel, TT
Buckley, AF
Mandel, H
Vlodavski, E
Banugaria, SG
Feeney, EJ
Raben, N
Kishnani, PS
AF Prater, Sean N.
Patel, Trusha T.
Buckley, Anne F.
Mandel, Hanna
Vlodavski, Eugene
Banugaria, Suhrad G.
Feeney, Erin J.
Raben, Nina
Kishnani, Priya S.
TI Skeletal muscle pathology of infantile Pompe disease during long-term
enzyme replacement therapy
SO ORPHANET JOURNAL OF RARE DISEASES
LA English
DT Article
DE Pompe disease; Glycogen storage disease type II; Enzyme replacement
therapy; rhGAA; Alglucosidase alfa; Myozyme; Skeletal muscle; Pathology;
Autophagy; Genetic diseases
ID ACID ALPHA-GLUCOSIDASE; STORAGE-DISEASE; ALGLUCOSIDASE ALPHA;
CLINICAL-OUTCOMES; DISORDERS; TETRASACCHARIDE; ULTRASTRUCTURE; BIOMARKER
AB Background: Pompe disease is an autosomal recessive metabolic neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). It has long been believed that the underlying pathology leading to tissue damage is caused by the enlargement and rupture of glycogen-filled lysosomes. Recent studies have also implicated autophagy, an intracellular lysosome-dependent degradation system, in the disease pathogenesis. In this study, we characterize the long-term impact of enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) on lysosomal glycogen accumulation and autophagy in some of the oldest survivors with classic infantile Pompe disease (IPD).
Methods: Muscle biopsies from 8 [4 female, 4 male; 6 cross-reactive immunologic material (CRIM)-positive, 2 CRIM-negative] patients with a confirmed diagnosis of classic IPD were examined using standard histopathological approaches. In addition, muscle biopsies were evaluated by immunostaining for lysosomal marker (lysosomal-associated membrane protein-2; LAMP2), autophagosomal marker (microtubule-associated protein 1 light chain 3; LC3), and acid and alkaline ATPases. All patients received rhGAA by infusion at cumulative biweekly doses of 20-40 mg/kg.
Results: Median age at diagnosis of classic IPD was 3.4 months (range: 0 to 6.5 months; n = 8). At the time of muscle biopsy, the patients' ages ranged from 1 to 103 months and ERT duration ranged from 0 (i.e., baseline, pre-ERT) to 96 months. The response to therapy varied considerably among the patients: some patients demonstrated motor gains while others experienced deterioration of motor function, either with or without a period of initial clinical benefit. Skeletal muscle pathology included fiber destruction, lysosomal vacuolation, and autophagic abnormalities (i.e., buildup), particularly in fibers with minimal lysosomal enlargement. Overall, the pathology reflected clinical status.
Conclusions: This is the first study to investigate the impact of rhGAA ERT on lysosomal glycogen accumulation and autophagic buildup in patients with classic IPD beyond 18 months of treatment. Our findings indicate that ERT does not fully halt or reverse the underlying skeletal muscle pathology in IPD. The best outcomes were observed in the two patients who began therapy early, namely at 0.5 and 1.1 months of age.
C1 [Prater, Sean N.; Patel, Trusha T.; Banugaria, Suhrad G.; Kishnani, Priya S.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA.
[Buckley, Anne F.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Mandel, Hanna] Technion Israel Inst Technol, Rambam Med Ctr, Fac Med, Metab Unit,Meyer Childrens Hosp, Haifa, Israel.
[Vlodavski, Eugene] Technion Israel Inst Technol, Rambam Med Ctr, Fac Med, Dept Pathol, Haifa, Israel.
[Feeney, Erin J.; Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
RP Raben, N (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
EM rabenn@mail.nih.gov; priya.kishnani@dm.duke.edu
FU Lysosomal Disease Network, a part of National Institutes of Health Rare
Diseases Clinical Research Network (RDCRN); National Institute of
Arthritis and Musculoskeletal and Skin Diseases of the National
Institutes of Health
FX We thank the patients, their families and the health-care providers who
participated in and contributed to this study. This project was funded
in part by the Lysosomal Disease Network, a part of National Institutes
of Health Rare Diseases Clinical Research Network (RDCRN). This research
was also supported in part by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health.
NR 34
TC 14
Z9 14
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1172
J9 ORPHANET J RARE DIS
JI Orphanet J. Rare Dis.
PD JUN 20
PY 2013
VL 8
AR 90
DI 10.1186/1750-1172-8-90
PG 12
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 171WC
UT WOS:000320959800001
PM 23787031
ER
PT J
AU Kummar, S
Allen, D
Monks, A
Polley, EC
Hose, CD
Ivy, SP
Turkbey, IB
Lawrence, S
Kinders, RJ
Choyke, P
Simon, R
Steinberg, SM
Doroshow, JH
Helman, L
AF Kummar, Shivaani
Allen, Deborah
Monks, Anne
Polley, Eric C.
Hose, Curtis D.
Ivy, S. Percy
Turkbey, Ismail B.
Lawrence, Scott
Kinders, Robert J.
Choyke, Peter
Simon, Richard
Steinberg, Seth M.
Doroshow, James H.
Helman, Lee
TI Cediranib for Metastatic Alveolar Soft Part Sarcoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID FACTOR SIGNALING INHIBITOR; SOLID TUMORS; GENE; MET; AZD2171; CANCER;
ADOLESCENTS; PATTERNS; CHILDREN
AB Purpose
Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs).
Patients and Methods
We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging.
Results
Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis.
Conclusion
In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. (C) 2013 by American Society of Clinical Oncology
C1 [Kummar, Shivaani; Allen, Deborah; Polley, Eric C.; Ivy, S. Percy; Turkbey, Ismail B.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee] NCI, Bethesda, MD 20892 USA.
[Monks, Anne; Hose, Curtis D.; Lawrence, Scott; Kinders, Robert J.] Frederick Natl Lab Canc Res, SAIC Frederick, Frederick, MD USA.
RP Kummar, S (reprint author), NCI, NIH, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM kummars@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX Supported in whole or in part with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract No.
HHSN261200800001E.
NR 25
TC 59
Z9 59
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2013
VL 31
IS 18
BP 2296
EP U106
DI 10.1200/JCO.2012.47.4288
PG 8
WC Oncology
SC Oncology
GA 164XV
UT WOS:000320446700015
PM 23630200
ER
PT J
AU Virgo, KS
Lerro, CC
Klabunde, CN
Earle, C
Ganz, PA
AF Virgo, Katherine S.
Lerro, Catherine C.
Klabunde, Carrie N.
Earle, Craig
Ganz, Patricia A.
TI Barriers to Breast and Colorectal Cancer Survivorship Care: Perceptions
of Primary Care Physicians and Medical Oncologists in the United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID FOLLOW-UP; SOCIETY; EXPERIENCE; PROVIDERS; QUALITY; UPDATE; ACCESS
AB Purpose
High-quality, well-coordinated cancer survivorship care is needed yet barriers remain owing to fragmentation in the United States health care system. This article is a nationwide survey of barriers perceived by primary care physicians (PCPs) and medical oncologists (MOs) regarding breast and colorectal cancer survivorship care beyond 5 years after treatment.
Methods
The Survey of Physician Attitudes Regarding the Care of Cancer Survivors was mailed out in 2009 to a nationally-representative sample (n = 3,596) of US PCPs and MOs. Ten physician-perceived cancer survivorship care barriers/concerns were compared between the two provider types. Using weighted multinomial logistic regression, we modeled each barrier, adjusting for physician demographics, reimbursement, training, and practice characteristics.
Results
We received responses from 2,202 physicians (1,072 PCPs; 1,130 MOs; 65.1% cooperation rate). In adjusted patient-related barriers models, MOs were more likely than PCPs to report patient language barriers (odds ratio, [OR], 1.72; 95% CI, 1.22 to 2.42), insurance restrictions impeding test/treatment use (OR, 1.42; 95% CI, 1.03 to 1.96), and patients requesting more aggressive testing (OR, 4.08; 95% CI, 2.73 to 6.10). In adjusted physician-related barriers models, PCPs were more likely to report inadequate training (OR, 3.06; 95% CI, 2.03 to 4.61) and ordering additional tests/treatments because of malpractice concerns (OR, 1.87; 95% CI, 1.20 to 2.93). MOs were more likely to report uncertainty regarding general preventive care responsibility (often/always: OR, 1.97; 95% CI, 1.13 to 3.43; sometimes: OR, 2.16; 95% CI, 1.60 to 2.93).
Conclusion
MOs and PCPs perceive different cancer follow-up care barriers/concerns to be problematic. Resolving inadequate training, malpractice-driven test ordering, and preventive-care responsibility concerns may require continuing education, explicit guidelines, and survivorship care plans. Reviewing care plans with survivors may also reduce patients' requests for unnecessary testing. (C) 2013 by American Society of Clinical Oncology
C1 [Virgo, Katherine S.] Emory Univ, Atlanta, GA 30329 USA.
[Lerro, Catherine C.] Yale Univ, New Haven, CT USA.
[Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Earle, Craig] Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Earle, Craig] Univ Toronto, Toronto, ON, Canada.
RP Virgo, KS (reprint author), Emory Univ, Dept Hlth Policy & Management, RSPH, 1360 Stephens Dr NE, Atlanta, GA 30329 USA.
EM kvirgo@emory.edu
FU National Cancer Institute [HHSN261201000316C]; American Cancer Society
National Home Office Intramural Research Department
FX Supported by Grant No. HHSN261201000316C from the National Cancer
Institute and American Cancer Society National Home Office Intramural
Research Department.
NR 34
TC 26
Z9 26
U1 4
U2 12
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2013
VL 31
IS 18
BP 2322
EP 2336
DI 10.1200/JCO.2012.45.6954
PG 15
WC Oncology
SC Oncology
GA 164XV
UT WOS:000320446700018
PM 23690429
ER
PT J
AU Wang, LN
Yin, QY
He, GM
Rossiter, SJ
Holmes, EC
Cui, J
AF Wang, Lina
Yin, Qiuyuan
He, Guimei
Rossiter, Stephen J.
Holmes, Edward C.
Cui, Jie
TI Ancient invasion of an extinct gammaretrovirus in cetaceans
SO VIROLOGY
LA English
DT Article
DE Endogenous gammaretrovirus; Cetaceans; Molecular dating; Phylogeny
ID ENDOGENOUS RETROVIRUSES; EVOLUTION; DISCOVERY; SEQUENCES
AB Endogenous gammaretroviruses (EGVs) have been widely studied in terrestrial mammals but seldom so in marine species. A genomic mining of the bottlenose dolphin (Tursiops truncatus) genome revealed a new EGV, termed Tursiops truncatus endogenous retrovirus (TTEV), which is divergent from extant mammalian EGVs. Molecular clock dating estimated the invasion time of TTEV into the host genome to be approximately 10-19 million years ago (MYA), while a previously identified killer whale endogenous gammaretrovirus (KWERV) was estimated to have invaded the host genome approximately 3-5 MYA. Using a PCR-based technique, we then verified that similar endogenous viruses exist in nine cetacean genomes. Phylogenetic analysis revealed that these cetacean EGVs are highly divergent from their counterparts in other mammals, including KWERV from the killer whale. In sum, we conclude that there have been at least two invasion episodes of EGVs into cetaceans during their evolutionary history. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Wang, Lina; Yin, Qiuyuan; He, Guimei] E China Normal Univ, Inst Mol Ecol & Evolut, Inst Adv Interdisciplinary Res, Shanghai 200062, Peoples R China.
[Rossiter, Stephen J.] Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
[Holmes, Edward C.; Cui, Jie] Univ Sydney, Sydney Emerging Infect & Biosecur Inst, Sch Biol Sci, Sydney, NSW 2006, Australia.
[Holmes, Edward C.; Cui, Jie] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Cui, J (reprint author), Univ Sydney, Sydney Emerging Infect & Biosecur Inst, Sch Biol Sci, Sydney, NSW 2006, Australia.
EM jiecui@yahoo.com
RI Rossiter, Stephen/E-2111-2011;
OI Cui, Jie/0000-0001-8176-9951; Holmes, Edward/0000-0001-9596-3552
NR 15
TC 3
Z9 3
U1 0
U2 16
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 JUN 20
PY 2013
VL 441
IS 1
BP 66
EP 69
DI 10.1016/j.viro1.2013.03.006
PG 4
WC Virology
SC Virology
GA 147PU
UT WOS:000319180300009
PM 23545142
ER
PT J
AU Cournil, A
De Vincenzi, I
Gaillard, P
Cames, C
Fao, P
Luchters, S
Rollins, N
Newell, ML
Bork, K
Read, JS
AF Cournil, Amandine
De Vincenzi, Isabelle
Gaillard, Philippe
Cames, Cecile
Fao, Paulin
Luchters, Stanley
Rollins, Nigel
Newell, Marie-Louise
Bork, Kirsten
Read, Jennifer S.
CA Kesho Bora Study Grp
TI Relationship between mortality and feeding modality among children born
to HIV-infected mothers in a research setting: the Kesho Bora Study
SO AIDS
LA English
DT Article
DE Africa; breastfeeding; HIV-exposed children; marginal structural models;
mortality; replacement feeding
ID UNINFECTED CHILDREN; POOLED ANALYSIS; INFANTS BORN; POSTNATAL
TRANSMISSION; ANTIRETROVIRAL THERAPY; PROSPECTIVE COHORT; POSITIVE
MOTHERS; FREE SURVIVAL; SOUTH-AFRICA; WOMEN
AB Objective:To assess the relationship between infant feeding practices and mortality by 18 months of age among children born to HIV-infected mothers in the Kesho Bora trial (Burkina-Faso, Kenya and South Africa).Methods:Enrolled HIV-infected women were counseled to choose between breastfeeding up to 6 months or replacement feeding from delivery. Multivariable Cox models were used to compare the infant mortality risks according to feeding practices over time defined as never breastfed, weaned or still breastfed. The category still breastfed' was disaggregated as exclusively, predominantly or partially breastfed to compare modes of breastfeeding. The relationship between weaning and mortality was also assessed using marginal structural models to control for time-dependent confounders, such as maternal or infant morbidity (reverse causality).Results:Among 795 mothers, 618 (77.7%) initiated breastfeeding. Mortality rates by 18 months among uninfected and infected children were 6 and 38%, respectively. Never breastfed and weaned children were at greater risk of death compared with those still breastfed. Adjusted hazard ratios were 6.7 [95% confidence interval (CI)=2.5-17.9; P<0.001] and 6.9 (CI=2.8-17.2; P<0.001) for never breastfed and weaned children, respectively. Estimation of the effect of weaning using marginal structural models led to similar results. No statistically significant differences were observed according to mode of breastfeeding (exclusive, predominant or partial).Conclusion:Within 6 months after birth, weaned or never breastfed children were at about seven-fold higher risk of dying compared with children who were still breastfed despite a context in which interventions were provided to reduce risks associated with replacement feeding.
C1 [Cournil, Amandine; Cames, Cecile; Bork, Kirsten] Univ Montpellier, Inst Rech Dev, F-34059 Montpellier, France.
[De Vincenzi, Isabelle; Gaillard, Philippe] WHO, CH-1211 Geneva, Switzerland.
[Fao, Paulin] Ctr Muraz, Bobo Dioulasso, Burkina Faso.
[Luchters, Stanley] Int Ctr Reprod Hlth, Mombasa, Kenya.
[Luchters, Stanley] Univ Ghent, Int Ctr Reprod Hlth, B-9000 Ghent, Belgium.
[Luchters, Stanley] Burnet Inst, Ctr Int Hlth, Melbourne, Vic, Australia.
[Rollins, Nigel] Univ KwaZulu Natal, Durban, South Africa.
[Rollins, Nigel] WHO, Dept Maternal Newborn Child & Adolescent Hlth, CH-1211 Geneva, Switzerland.
[Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Somkhele, South Africa.
[Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Bethesda, MD USA.
[Read, Jennifer S.] NVPO OASH OS DHHS, Washington, DC USA.
RP Cournil, A (reprint author), Inst Rech Dev, BP 64501, F-34394 Montpellier 5, France.
EM amandine.cournil@ird.fr
RI Van de Perre, Philippe/B-9692-2008;
OI Van de Perre, Philippe/0000-0002-3912-0427; Bork,
Kirsten/0000-0002-5909-7332; Newell, Marie-Louise/0000-0002-1074-7699;
Njagi, Ephantus/0000-0002-1484-0241
FU l'Agence Nationale de Recherches sur le Sida et les Hepatites Virales
(ANRS); UNDP/UNFPA/World Bank/WHO Special Programme of Research,
Development and Research Training in Human Reproduction (WHO/HRP); ANRS;
WHO/HRP; European and Developing Countries Clinical Trials Partnership
(EDCTP); Thrasher Research Fund; Belgian Directorate General for
International Cooperation
FX The Bobo-Dioulasso site was funded by l'Agence Nationale de Recherches
sur le Sida et les Hepatites Virales (ANRS) and UNDP/UNFPA/World
Bank/WHO Special Programme of Research, Development and Research
Training in Human Reproduction (WHO/HRP).; The Mombasa site was funded
by ANRS, WHO/HRP, European and Developing Countries Clinical Trials
Partnership (EDCTP), Thrasher Research Fund, Belgian Directorate General
for International Cooperation.
NR 45
TC 8
Z9 8
U1 1
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 JUN 19
PY 2013
VL 27
IS 10
BP 1621
EP 1630
DI 10.1097/QAD.0b013e32835d5226
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 250HG
UT WOS:000326840700011
PM 23262499
ER
PT J
AU Hobbs, CV
De La Vega, P
Penzak, SR
Van Vliet, J
Krzych, U
Sinnis, P
Borkowsky, W
Duffy, PE
AF Hobbs, Charlotte V.
De La Vega, Patricia
Penzak, Scott R.
Van Vliet, Jillian
Krzych, Urszula
Sinnis, Photini
Borkowsky, William
Duffy, Patrick E.
TI The effect of antiretrovirals on Plasmodium falciparum liver stages
SO AIDS
LA English
DT Article
ID TYPE-1 PROTEASE INHIBITORS; HUMAN HEPATOCYTE LINE; MALARIA PARASITES;
IN-VITRO; SPOROZOITES; AGENTS
C1 [Hobbs, Charlotte V.; Van Vliet, Jillian; Duffy, Patrick E.] NIAID, NIH, Lab Malaria Immunol & Vaccinol, Rockville, MD 20852 USA.
[De La Vega, Patricia; Krzych, Urszula] Walter Reed Army Inst Res, Malaria Vaccine Branch, Dept Cellular Immunol, Silver Spring, MD USA.
[Penzak, Scott R.] NIH, Dept Pharm, Ctr Clin, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA.
[Sinnis, Photini] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Borkowsky, William] NYU, Sch Med, Dept Pediat, Div Infect Dis & Immunol, New York, NY USA.
RP Hobbs, CV (reprint author), NIAID, NIH, Rockville, MD 20852 USA.
EM charlotte.hobbs@nih.gov
FU NIH, NIAID, Division of Intramural Research; US Army and Materiel
Command
FX This work was funded by the NIH, NIAID, Division of Intramural Research
and by the by the US Army and Materiel Command.
NR 21
TC 8
Z9 8
U1 0
U2 1
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 JUN 19
PY 2013
VL 27
IS 10
BP 1674
EP 1677
DI 10.1097/QAD.0b013e3283621dd4
PG 4
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 250HG
UT WOS:000326840700017
PM 23907270
ER
PT J
AU Liu, R
Guo, XG
Park, Y
Wang, J
Huang, XM
Hollenbeck, A
Blair, A
Chen, HL
AF Liu, Rui
Guo, Xuguang
Park, Yikyung
Wang, Jian
Huang, Xuemei
Hollenbeck, Albert
Blair, Aaron
Chen, Honglei
TI Alcohol Consumption, Types of Alcohol, and Parkinson's Disease
SO PLOS ONE
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION;
RETIRED-PERSONS DIET; NATIONAL-INSTITUTES; PLASMA URATE; RISK;
RESVERATROL; PREDICTOR; DEMENTIA; DECLINE
AB Background: The epidemiologic evidence on alcohol consumption and Parkinson's disease (PD) is equivocal. We prospectively examined total alcohol consumption and consumption of specific types of alcoholic beverage in relation to future risk of PD.
Methods: The study comprised 306,895 participants (180,235 male and 126,660 female) ages 50-71 years in 1995-1996 from the NIH-AARP Diet and Health Study. Consumption of alcoholic beverages in the past 12 months was assessed in 1995-1996. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models.
Results: A total of 1,113 PD cases diagnosed between 2000 and 2006 were included in the analysis. Total alcohol consumption was not associated with PD. However, the association differed by types of alcoholic beverages. Compared with non-beer drinkers, the multivariate ORs for beer drinkers were 0.79 (95% CI: 0.68, 0.92) for <1 drink/day, 0.73 (95% CI: 0.50, 1.07) for 1-1.99 drinks/day, and 0.86 (95% CI: 0.60, 1.21) for >= 2 drinks/day. For liquor consumption, a monotonic increase in PD risk was suggested: ORs (95% CI) were 1.06 (0.91, 1.23), 1.22 (0.94, 1.58), and 1.35 (1.02, 1.80) for<1, 1-1.99, and >= 2 drinks/day, respectively (P for trend <0.03). Additional analyses among exclusive drinkers of one specific type of alcoholic beverage supported the robustness of these findings. The results for wine consumption were less clear, although a borderline lower PD risk was observed when comparing wine drinkers of 1-1.99 drinks/day with none drinkers (OR = 0.74, 95% CI: 0.53, 1.02).
Conclusions: Our results suggest that beer and liquor consumption may have opposite associations with PD: low to moderate beer consumption with lower PD risk and greater liquor consumption with higher risk. These findings and potential underlying mechanisms warrant further investigations.
C1 [Liu, Rui; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Guo, Xuguang] Westat Corp, Res Triangle Pk, NC USA.
[Park, Yikyung; Blair, Aaron] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Wang, Jian] Fudan Univ, Dept Neurol, Huashan Hosp, Shanghai 200433, Peoples R China.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Liu, R (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
EM liur2@niehs.nih.gov
OI Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X
FU National Institute of Health; National Institute of Environmental Health
Sciences [Z01-ES-101986]; National Cancer Institute [Z01 CP010196-02]
FX This study was supported by the intramural research program of the
National Institute of Health, the National Institute of Environmental
Health Sciences (Z01-ES-101986) and the National Cancer Institute (Z01
CP010196-02). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 24
TC 5
Z9 5
U1 1
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 19
PY 2013
VL 8
IS 6
AR e66452
DI 10.1371/journal.pone.0066452
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 190ST
UT WOS:000322361200081
PM 23840473
ER
PT J
AU Manchia, M
Adli, M
Akula, N
Ardau, R
Aubry, JM
Backlund, L
Banzato, CEM
Baune, BT
Bellivier, F
Bengesser, S
Biernacka, JM
Brichant-Petitjean, C
Bui, E
Calkin, CV
Cheng, ATA
Chillotti, C
Cichon, S
Clark, S
Czerski, PM
Dantas, C
Del Zompo, M
DePaulo, JR
Detera-Wadleigh, SD
Etain, B
Falkai, P
Frisen, L
Frye, MA
Fullerton, J
Gard, S
Garnham, J
Goes, FS
Grof, P
Gruber, O
Hashimoto, R
Hauser, J
Heilbronner, U
Hoban, R
Hou, LP
Jamain, S
Kahn, JP
Kassem, L
Kato, T
Kelsoe, JR
Kittel-Schneider, S
Kliwicki, S
Kuo, PH
Kusumi, I
Laje, G
Lavebratt, C
Leboyer, M
Leckband, SG
Jaramillo, CAL
Maj, M
Malafosse, A
Martinsson, L
Masui, T
Mitchell, PB
Mondimore, F
Monteleone, P
Nallet, A
Neuner, M
Novak, T
O'Donovan, C
Osby, U
Ozaki, N
Perlis, RH
Pfennig, A
Potash, JB
Reich-Erkelenz, D
Reif, A
Reininghaus, E
Richardson, S
Rouleau, GA
Rybakowski, JK
Schalling, M
Schofield, PR
Schubert, OK
Schweizer, B
Seemuller, F
Grigoroiu-Serbanescu, M
Severino, G
Seymour, LR
Slaney, C
Smoller, JW
Squassina, A
Stamm, T
Steele, J
Stopkova, P
Tighe, SK
Tortorella, A
Turecki, G
Wray, NR
Wright, A
Zandi, PP
Zilles, D
Bauer, M
Rietschel, M
McMahon, FJ
Schulze, TG
Alda, M
AF Manchia, Mirko
Adli, Mazda
Akula, Nirmala
Ardau, Raffaella
Aubry, Jean-Michel
Backlund, Lena
Banzato, Claudio E. M.
Baune, Bernhard T.
Bellivier, Frank
Bengesser, Susanne
Biernacka, Joanna M.
Brichant-Petitjean, Clara
Bui, Elise
Calkin, Cynthia V.
Cheng, Andrew Tai Ann
Chillotti, Caterina
Cichon, Sven
Clark, Scott
Czerski, Piotr M.
Dantas, Clarissa
Del Zompo, Maria
DePaulo, J. Raymond
Detera-Wadleigh, Sevilla D.
Etain, Bruno
Falkai, Peter
Frisen, Louise
Frye, Mark A.
Fullerton, Jan
Gard, Sebastien
Garnham, Julie
Goes, Fernando S.
Grof, Paul
Gruber, Oliver
Hashimoto, Ryota
Hauser, Joanna
Heilbronner, Urs
Hoban, Rebecca
Hou, Liping
Jamain, Stephane
Kahn, Jean-Pierre
Kassem, Layla
Kato, Tadafumi
Kelsoe, John R.
Kittel-Schneider, Sarah
Kliwicki, Sebastian
Kuo, Po-Hsiu
Kusumi, Ichiro
Laje, Gonzalo
Lavebratt, Catharina
Leboyer, Marion
Leckband, Susan G.
Lopez Jaramillo, Carlos A.
Maj, Mario
Malafosse, Alain
Martinsson, Lina
Masui, Takuya
Mitchell, Philip B.
Mondimore, Frank
Monteleone, Palmiero
Nallet, Audrey
Neuner, Maria
Novak, Tomas
O'Donovan, Claire
Osby, Urban
Ozaki, Norio
Perlis, Roy H.
Pfennig, Andrea
Potash, James B.
Reich-Erkelenz, Daniela
Reif, Andreas
Reininghaus, Eva
Richardson, Sara
Rouleau, Guy A.
Rybakowski, Janusz K.
Schalling, Martin
Schofield, Peter R.
Schubert, Oliver K.
Schweizer, Barbara
Seemueller, Florian
Grigoroiu-Serbanescu, Maria
Severino, Giovanni
Seymour, Lisa R.
Slaney, Claire
Smoller, Jordan W.
Squassina, Alessio
Stamm, Thomas
Steele, Jo
Stopkova, Pavla
Tighe, Sarah K.
Tortorella, Alfonso
Turecki, Gustavo
Wray, Naomi R.
Wright, Adam
Zandi, Peter P.
Zilles, David
Bauer, Michael
Rietschel, Marcella
McMahon, Francis J.
Schulze, Thomas G.
Alda, Martin
TI Assessment of Response to Lithium Maintenance Treatment in Bipolar
Disorder: A Consortium on Lithium Genetics (ConLiGen) Report
SO PLOS ONE
LA English
DT Article
ID MAPPING SUSCEPTIBILITY GENES; PROPHYLACTIC LITHIUM; OBSERVER AGREEMENT;
MOOD DISORDERS; ONSET; ASSOCIATION; RELIABILITY; MORTALITY; ILLNESS; AGE
AB Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study.
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (kappa)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (kappa = 0.66 and kappa = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders).
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
C1 [Manchia, Mirko; Calkin, Cynthia V.; Garnham, Julie; O'Donovan, Claire; Slaney, Claire; Alda, Martin] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada.
[Adli, Mazda; Stamm, Thomas] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany.
[Akula, Nirmala; Bui, Elise; Detera-Wadleigh, Sevilla D.; Hou, Liping; Kassem, Layla; Laje, Gonzalo; Richardson, Sara; Steele, Jo; McMahon, Francis J.; Schulze, Thomas G.] NIMH, Human Genet Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[Ardau, Raffaella; Chillotti, Caterina; Del Zompo, Maria] Univ Hosp Cagliari, Clin Pharmacol Unit, Cagliari, Italy.
[Aubry, Jean-Michel; Malafosse, Alain; Nallet, Audrey] Hop Univ Geneve, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
[Backlund, Lena; Frisen, Louise; Martinsson, Lina] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Banzato, Claudio E. M.; Dantas, Clarissa] Univ Estadual Campinas, Dept Psychiat, Campinas, Brazil.
[Baune, Bernhard T.; Clark, Scott; Schubert, Oliver K.] Univ Adelaide, Dept Psychiat, Adelaide, SA, Australia.
[Bellivier, Frank; Brichant-Petitjean, Clara] Grp Hosp Lariboisiere F Widal, AP HP, Paris, France.
[Bengesser, Susanne; Reininghaus, Eva] Med Univ Graz, Dept Psychiat, Graz, Austria.
[Biernacka, Joanna M.; Frye, Mark A.; Seymour, Lisa R.] Mayo Clin, Dept Psychiat, Rochester, MN USA.
[Cheng, Andrew Tai Ann] Acad Sinica, Inst Biomed Sci, Div Epidemiol & Genet, Taipei, Taiwan.
[Cichon, Sven] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Cichon, Sven] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Czerski, Piotr M.] Poznan Univ Med Sci, Psychiat Genet Unit, Poznan, Poland.
[Del Zompo, Maria; Severino, Giovanni; Squassina, Alessio] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cagliari, Italy.
[DePaulo, J. Raymond; Goes, Fernando S.; Mondimore, Frank; Potash, James B.; Schweizer, Barbara; Tighe, Sarah K.; Schulze, Thomas G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Fac Med, Equipe 15, Inst Mondor Rech Biomed, INSERM,Unite 955, Creteil, France.
[Falkai, Peter; Seemueller, Florian] Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany.
[Fullerton, Jan; Schofield, Peter R.] Neurosci Res Australia Genet Mental Illness & Bra, Sydney, NSW, Australia.
[Gard, Sebastien] Hop Charles Perrens, Psychiat Serv, Bordeaux, France.
[Grof, Paul] Mood Disorders Ctr Ottawa, Ottawa, ON, Canada.
[Grof, Paul] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Gruber, Oliver; Heilbronner, Urs; Reich-Erkelenz, Daniela; Zilles, David; Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany.
[Hashimoto, Ryota] Osaka Univ, Grad Sch Med, Osaka, Japan.
[Hauser, Joanna] Poznan Univ Med Sci, Psychiat Genet Unit, Poznan, Poland.
[Hoban, Rebecca; Kelsoe, John R.; Leckband, Susan G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Hoban, Rebecca; Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, Dept Psychiat, San Diego, CA USA.
[Kahn, Jean-Pierre] Ctr Hosp Univ Nancy, Serv Psychiat & Psychol Clin, Nancy, France.
[Kato, Tadafumi; Kusumi, Ichiro] RIKEN, Brain Sci Inst, Lab Mol Dynam Mental Disorders, Saitama, Japan.
[Kittel-Schneider, Sarah; Neuner, Maria; Reif, Andreas] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, D-97070 Wurzburg, Germany.
[Kliwicki, Sebastian; Rybakowski, Janusz K.] Poznan Univ Med Sci, Dept Adult Psychiat, Poznan, Poland.
[Kuo, Po-Hsiu] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
[Kusumi, Ichiro; Masui, Takuya] Hokkaido Univ, Grad Sch Med, Dept Psychiat, Sapporo, Hokkaido, Japan.
[Lavebratt, Catharina; Osby, Urban; Schalling, Martin] Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Lavebratt, Catharina; Osby, Urban; Schalling, Martin] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden.
[Leckband, Susan G.] Vet Affairs San Diego Healthcare Syst, Dept Pharm, San Diego, CA USA.
[Leckband, Susan G.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA.
[Lopez Jaramillo, Carlos A.] Univ Antioquia, Dept Psychiat, Medellin, Colombia.
[Maj, Mario; Monteleone, Palmiero; Tortorella, Alfonso] Univ Naples Federico II, Dept Psychiat, Naples, Italy.
[Mitchell, Philip B.; Wright, Adam] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia.
[Mitchell, Philip B.; Wright, Adam] Black Dog Inst, Sydney, NSW, Australia.
[Novak, Tomas; Stopkova, Pavla] Univ Prague, Prague Psychiat Ctr, Prague, Czech Republic.
[Ozaki, Norio] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan.
[Ozaki, Norio] Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi 4648601, Japan.
[Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Perlis, Roy H.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA.
[Pfennig, Andrea; Bauer, Michael] Tech Univ Dresden, Dept Psychiat & Psychotherapy, Dresden, Germany.
[Potash, James B.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Rouleau, Guy A.] Univ Montreal, Ctr Hosp Univ Montreal, Ctr Excellence Neurosci, Montreal, PQ, Canada.
[Rouleau, Guy A.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Grigoroiu-Serbanescu, Maria] Alexandru Obregia Psychiat Hosp, Biometr Psychiat Genet Res Unit, Bucharest, Romania.
[Turecki, Gustavo] Douglas Mental Hlth Univ Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada.
[Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Rietschel, Marcella; Schulze, Thomas G.] Heidelberg Univ, Univ Med Ctr Mannheim, Cent Inst Mental Hlth Mannheim, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
RP Schulze, TG (reprint author), NIMH, Human Genet Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
EM thomas.schulze@med.uni-goettingen.de; malda@dal.ca
RI Banzato, Claudio/B-2517-2008; Cichon, Sven/H-8803-2013; Cichon,
Sven/B-9618-2014; Ozaki, Norio/M-8908-2014; Hou, Liping/G-1648-2011;
BELLIVIER, FRANK/H-5197-2012; Novak, Tomas/B-8008-2017; Kato,
Tadafumi/J-3583-2014; Serbanescu, Maria/D-4306-2011; Hashimoto,
Ryota/P-8572-2014; Wray, Naomi/C-8639-2015
OI Kuo, Po-Hsiu/0000-0003-0365-3587; Jamain, Stephane/0000-0002-4321-4100;
McMahon, Francis/0000-0002-9469-305X; Backlund,
Lena/0000-0001-9399-5024; Banzato, Claudio/0000-0002-8556-3982; Manchia,
Mirko/0000-0003-4175-6413; Lavebratt, Catharina/0000-0003-4987-2718;
Reininghaus, Eva/0000-0001-5964-4087; Kittel-Schneider,
Sarah/0000-0003-3057-6150; Mitchell, Philip/0000-0002-7954-5235; Lopez,
Carlos/0000-0002-1875-1369; Cichon, Sven/0000-0002-9475-086X; Cichon,
Sven/0000-0002-9475-086X; Ozaki, Norio/0000-0002-7360-4898; Hou,
Liping/0000-0003-3972-245X; Novak, Tomas/0000-0001-9156-9654; Kato,
Tadafumi/0000-0001-7856-3952; Serbanescu, Maria/0000-0002-1304-6687;
Hashimoto, Ryota/0000-0002-5941-4238; Wray, Naomi/0000-0001-7421-3357
FU Canadian Institutes of Health Research [64410]; Unitatea Executiva
pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si
Inovarii (UEFISCDI), Bucharest, Romania [89/2012]; Swiss National
Foundation [32003B_125469/1]; National Institute of Mental Health (NIMH)
at the National Institutes of Health (NIH), Department of Health and
Human Services, United States Government; Deutsche
Forschungsgemeinschaft [RI 908/7-1]
FX The work on assessment of lithium response has been supported by a grant
from Canadian Institutes of Health Research #64410 to MA. MG-S was
supported by Unitatea Executiva pentru Finantarea Invatamantului
Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI), Bucharest,
Romania (grant no. 89/2012). JMA and AN were supported by a grant from
the Swiss National Foundation (#32003B_125469/1 to JM Aubry). ConLiGen
is in part supported by funds from the Intramural Research Program of
the National Institute of Mental Health (NIMH) at the National
Institutes of Health (NIH), Department of Health and Human Services,
United States Government. It is further supported by a grant from the
Deutsche Forschungsgemeinschaft to MR, MB, and TGS (RI 908/7-1). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 44
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U2 32
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 JUN 19
PY 2013
VL 8
IS 6
AR e65636
DI 10.1371/journal.pone.0065636
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 190ST
UT WOS:000322361200028
PM 23840348
ER
PT J
AU Guo, ZY
Li, CZ
Li, XJ
Wang, YL
Mattson, MP
Lu, CB
AF Guo, Zhi Y.
Li, Cheng Z.
Li, Xiao J.
Wang, Ya L.
Mattson, Mark P.
Lu, Cheng B.
TI The developmental regulation of glutamate receptor-mediated calcium
signaling in primary cultured rat hippocampal neurons
SO NEUROREPORT
LA English
DT Article
DE -amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor; calcium; cell
culture; N-methyl-D-aspartate receptor; voltage-dependent calcium
channels
ID LONG-TERM POTENTIATION; NMDA RECEPTORS; AMPA RECEPTORS; CELL-DEATH
AB We have studied the developmental changes of glutamate-induced calcium (Ca2+) response in primary cultured hippocampal neurons at three different stages of cultures, 3, 7-8, and 14-16 days in vitro (DIV), using fura-2 single-cell digital micro-fluorimetry. We found that glutamate-induced Ca2+ signaling was altered during development, and that two different ionotropic glutamate receptors, -amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs), were differently involved in the modulation of calcium response at different stages of neuronal culture. In the stages of culture at 3 and 8 DIV, glutamate-induced Ca2+ influx was mostly because of AMPAR activation and subsequent opening of voltage-dependent calcium channels, as Ca2+ response can be largely reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by nifedipine. In the advanced culture (14-17 DIV), glutamate-induced Ca2+ response was less sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione and nifedipine. Furthermore, AMPA-induced Ca2+ response increased in a time-dependent manner during the cultures of 3-8 DIV and then reduced in the advanced culture of 14-17 DIV. NMDA-induced Ca2+ influx increased in a time-dependent manner, with a marked increase in the advanced culture (14-17 DIV). These results suggest that glutamate-induced Ca2+ signaling switched from AMPA-voltage-dependent calcium channel to NMDA-calcium signaling during development.
C1 [Guo, Zhi Y.; Li, Cheng Z.; Li, Xiao J.; Wang, Ya L.; Lu, Cheng B.] Xinxiang Med Univ, Dept Physiol & Neurobiol, Xinxiang 453003, Peoples R China.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Lu, CB (reprint author), Xinxiang Med Univ, Dept Physiol & Neurobiol, Key Lab Brain Res Henan Prov, Xinxiang 453003, Peoples R China.
EM johnlu9001@hotmail.com
FU National Science Foundation [31070938, 81271422]; Intramural Research
Program of the National Institute on Aging, NIH
FX This research was supported by the National Science Foundation
(31070938; 81271422) and the Intramural Research Program of the National
Institute on Aging, NIH.
NR 21
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U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD JUN 19
PY 2013
VL 24
IS 9
BP 492
EP 497
DI 10.1097/WNR.0b013e32836206b5
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 202KH
UT WOS:000323213800009
PM 23660635
ER
PT J
AU Poland, GA
Quill, H
Togias, A
AF Poland, Gregory A.
Quill, Helen
Togias, Alkis
TI Understanding the human immune system in the 21st century: The Human
Immunology Project Consortium
SO VACCINE
LA English
DT Editorial Material
C1 [Poland, Gregory A.] Mayo Clin & Mayo Fdn, Mayo Vaccine Res Grp, Rochester, MN 55905 USA.
[Quill, Helen] NIAID, Basic Immunol Branch, Bethesda, MD 20817 USA.
[Togias, Alkis] NIAID, Allergy Asthma & Airway Biol Branch, Bethesda, MD 20817 USA.
RP Poland, GA (reprint author), Mayo Clin & Mayo Fdn, Mayo Vaccine Res Grp, Rochester, MN 55905 USA.
EM poland.gregory@mayo.edu; helen.quill@nih.gov; alkis.togias@nih.gov
NR 0
TC 5
Z9 5
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUN 19
PY 2013
VL 31
IS 28
BP 2911
EP 2912
DI 10.1016/j.vaccine.2013.04.043
PG 2
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 175KW
UT WOS:000321230600001
PM 23648045
ER
PT J
AU Shimp, RL
Rowe, C
Reiter, K
Chen, B
Nguyen, V
Aebig, J
Rausch, KM
Kumar, K
Wu, YM
Jin, AJ
Jones, DS
Narum, DL
AF Shimp, Richard L., Jr.
Rowe, Christopher
Reiter, Karine
Chen, Beth
Vu Nguyen
Aebig, Joan
Rausch, Kelly M.
Kumar, Krishan
Wu, Yimin
Jin, Albert J.
Jones, David S.
Narum, David L.
TI Development of a Pfs25-EPA malaria transmission blocking vaccine as a
chemically conjugated nanoparticle
SO VACCINE
LA English
DT Article
DE Pfs25; Malaria; Transmission blocking vaccine; Nanoparticle;
Chemical-conjugate; Recombinant protein
ID SECONDARY STRUCTURE ANALYSES; PLASMODIUM-FALCIPARUM; MEMBRANE-PROTEIN;
SURFACE-PROTEINS; CANDIDATE; ANTIBODY; CRYSTALLIZATION; IMMUNOGENICITY;
RESPONSES; PEPTIDES
AB Successful efforts to control infectious diseases have often required the use of effective vaccines. The current global strategy for control of malaria, including elimination and eradication will also benefit from the development of an effective vaccine that interrupts malaria transmission. To this end, a vaccine that disrupts malaria transmission within the mosquito host has been investigated for several decades targeting a 25 kDa ookinete specific surface protein, identified as Pfs25. Phase 1 human trial results using a recombinant Pfs25H/Montanide ISA51 formulation demonstrated that human Pfs25 specific antibodies block parasite infectivity to mosquitoes; however, the extent of blocking was likely insufficient for an effective transmission blocking vaccine. To overcome the poor immunogenicity, processes to produce and characterize recombinant Pfs25H conjugated to a detoxified form of Pseudomonas aeruginosa exoprotein A (EPA) have been developed and used to manufacture a cGMP pilot lot for use in human clinical trials. The Pfs25-EPA conjugate appears as a nanoparticle with an average molar mass in solution of approximately 600 kDa by static light scattering with an average diameter 20 nm (range 10-40 nm) by dynamic light scattering. The molar ratio of Pfs25H to EPA is about 3 to 1 by amino acid analysis, respectively. Outbred mice immunized with the Pfs25-EPA conjugated nanoparticle formulated on Alhydrogel(R) had a 75-110 fold increase in Pfs25H specific antibodies when compared to an unconjugated Pfs25H/Alhydrogel(R) formulation. A phase 1 human trial using the Pfs25-EPA/Alhydrogel(R) formulation is ongoing in the United States. Published by Elsevier Ltd.
C1 [Shimp, Richard L., Jr.; Rowe, Christopher; Reiter, Karine; Chen, Beth; Vu Nguyen; Aebig, Joan; Rausch, Kelly M.; Kumar, Krishan; Wu, Yimin; Jones, David S.; Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
[Jin, Albert J.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Narum, DL (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Room 1115, Rockville, MD 20852 USA.
EM dnarum@niaid.nih.gov
OI Jin, Albert/0000-0003-3826-1081
FU Intramural Research Program of the NIH, including NIAID and NIBIB
FX We acknowledge the support of those within the units of the LMIV core,
especially Emma Barnafo for formulation, Lynn Lambert for excellent
animal husbandry, Dominique Jones for analytical support and Olga
Muratova for performing the membrane feeding assays. Dr. Svetlana Kotova
provided excellent technical support for the AFM studies. We thank Drs.
Michael Nold (Waters Corp.) and L. Renee Olano (Research Technology
Branch, NIAID, NIH) for their critical evaluation of the quantitative
peptide mapping analysis. We appreciate the work of Brian Bell and Jay
Wood for the successful technology transfer to the WRAIR Biopilot
Production facility. This research was supported by the Intramural
Research Program of the NIH, including NIAID and NIBIB.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUN 19
PY 2013
VL 31
IS 28
BP 2954
EP 2962
DI 10.1016/j.vaccine.2013.04.034
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 175KW
UT WOS:000321230600007
PM 23623858
ER
PT J
AU Guo, J
Xu, XH
Rasheed, TK
Yoder, A
Yu, DY
Liang, HZ
Yi, F
Hawley, T
Jin, T
Ling, BH
Wu, YT
AF Guo, Jia
Xu, Xuehua
Rasheed, Taban K.
Yoder, Alyson
Yu, Dongyang
Liang, Huizhi
Yi, Fei
Hawley, Todd
Jin, Tian
Ling, Binhua
Wu, Yuntao
TI Genistein interferes with SDF-1-and HIV-mediated actin dynamics and
inhibits HIV infection of resting CD4 T cells
SO RETROVIROLOGY
LA English
DT Article
DE HIV-1; Actin; SDF-1; Genistein; Sunitinib; Cofilin; LIMK1
ID MATRIX-METALLOPROTEINASE TYPE-2; TYROSINE PHOSPHORYLATION;
PROSTATE-CANCER; CORTICAL ACTIN; COFILIN PHOSPHORYLATION; CHEMOKINE
RECEPTOR; HUMAN MACROPHAGES; BINDING PROTEINS; NEF PROTEIN; LIM-KINASE
AB Background: Binding of HIV to the chemokine coreceptor CXCR4 mediates viral fusion and signal transduction that promotes actin dynamics critical for HIV infection of blood resting CD4 T cells. It has been suggested that this gp 120-mediated actin activity resembles the chemotactic actin dynamics mediated by chemokines such as SDF-1. To determine whether inhibiting SDF-1-mediated chemotactic activity can also inhibit HIV infection, we screened several inhibitors known to reduce SDF-1-mediated chemotaxis of T cells.
Results: We found that a tyrosine kinase inhibitor, genistein, inhibited both SDF-1-mediated chemotaxis and HIV infection of resting CD4 T cells. Genistein was also found to interfere with SDF-1- and HIV-mediated actin dynamics in CD4 T cells. This reduction in actin activity correlates with genistein-mediated inhibition of viral DNA accumulation in resting CD4 T cells. In addition, we also tested two other tyrosine kinase inhibitors, sunitinib and AG1478. Sunitinib, but not AG1478, inhibited HIV infection of resting CD4 T cells. We further tested the safety of genistein in 3 Chinese rhesus macaques (Macaca mulatta), and each animal was given a monotherapy of genistein at 10 mg/kg orally for 12 weeks. No adverse drug effects were observed in these animals.
Conclusions: Our results suggest that novel therapeutic strategies can be developed based on targeting cellular proteins involved in HIV-dependent signaling. This approach can interfere with HIV-mediated actin dynamics and inhibit HIV infection.
C1 [Guo, Jia; Rasheed, Taban K.; Yoder, Alyson; Yu, Dongyang; Liang, Huizhi; Yi, Fei; Hawley, Todd; Wu, Yuntao] George Mason Univ, Natl Ctr Biodef & Infect Dis, Dept Mol & Microbiol, Manassas, VA 20110 USA.
[Xu, Xuehua; Jin, Tian] NIAID, NIH, Twinbrook Facil, Immunogenet Lab,Chemotaxis Signal Sect, Rockville, MD 20852 USA.
[Ling, Binhua] Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA.
RP Wu, YT (reprint author), George Mason Univ, Natl Ctr Biodef & Infect Dis, Dept Mol & Microbiol, Manassas, VA 20110 USA.
EM ywu8@gmu.edu
RI Guo, Jia/L-2102-2013; Guo, Jia/C-8678-2014;
OI xu, xuehua/0000-0002-3863-9593
FU NIH Public Health Service Grant from NIAID [1R01AI081568]; NIAID [R01
AI093307-01A1]; National Center for Research Resources; Office of
Research Infrastructure Programs (ORIP) of NIH [OD011104-51]; NYCDC AIDS
Ride
FX We thank the George Mason University (GMU) Student Health Center for
blood donations; the NIH AIDS Research and Reference Reagent Program,
NIAID, NIH for reagents; Ann-Marie Johnson for technical support; the
veterinary staff at the Tulane National Primate Research Center; M.
Rosen and the donors and riders from the 2010 NYCDC AIDS Ride. This work
was supported by NIH Public Health Service Grant grants 1R01AI081568
from NIAID to YW; R01 AI093307-01A1 from NIAID to BL; the National
Center for Research Resources, and the Office of Research Infrastructure
Programs (ORIP) of NIH (through grant OD011104-51). The study was
supported in part by the 2010 NYCDC AIDS Ride organized by M. Rosen.
NR 83
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U1 2
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUN 19
PY 2013
VL 10
AR 62
DI 10.1186/1742-4690-10-62
PG 15
WC Virology
SC Virology
GA 171SL
UT WOS:000320949300001
PM 23782904
ER
PT J
AU Spong, CY
AF Spong, Catherine Y.
TI Defining "Term" Pregnancy Recommendations From the Defining "Term"
Pregnancy Workgroup
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID HEALTH; CARE
C1 [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Spong, CY (reprint author), NICHHD, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA.
EM spongc@mail.nih.gov
NR 8
TC 95
Z9 99
U1 0
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 19
PY 2013
VL 309
IS 23
BP 2445
EP 2446
DI 10.1001/jama.2013.6235
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 165SW
UT WOS:000320505100023
PM 23645117
ER
PT J
AU Hsu, CH
Ovcharenko, I
AF Hsu, Chih-Hao
Ovcharenko, Ivan
TI Effects of gene regulatory reprogramming on gene expression in human and
mouse developing hearts
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE gene regulation; lineage-specific heart enhancers; cis-regulatory
evolution
ID UCSC GENOME BROWSER; ELEMENTS; ENHANCERS; CHIP; TRANSCRIPTION;
CHROMATIN; IDENTIFICATION; PROMOTERS; DYNAMICS; DATABASE
AB Lineage-specific regulatory elements underlie adaptation of species and play a role in disease susceptibility. We compared functionally conserved and lineage-specific enhancers by cross-mapping 5042 human and 6564 mouse heart enhancers. Of these, 79 per cent are lineage-specific, lacking a functional orthologue. Heart enhancers tend to cluster and, commonly, there are multiple heart enhancers in a heart locus providing a regulatory stability to the locus. We observed little cross-clustering, however, between lineage-specific and functionally conserved heart enhancers suggesting regulatory function acquisition and development in loci previously lacking heart activity. We also identified 862 human-specific heart enhancers: 417 featuring sequence conservation with mouse (class II) and 445 with neither sequence nor function conservation (class III). Ninety-eight per cent of class III enhancers were deleted from the mouse genome, and we estimated a similar-sized enhancer gain in the human lineage. Human-specific enhancers display no detectable decrease in the negative selection pressure and are strongly associated with genes partaking in the heart regulatory programmes. The loss of a heart enhancer could be compensated by activity of a redundant heart enhancer; however, we observed redundancy in only 15 per cent of class II and III enhancer loci indicating a large-scale reprogramming of the heart regulatory programme in mammals.
C1 [Hsu, Chih-Hao; Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Ovcharenko, I (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM ovcharen@nih.gov
FU Intramural Research Program of the NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
NIH, National Library of Medicine. We are also grateful to the reviewers
of the manuscript for their input and suggestions, which have been
invaluable in improving the manuscript.
NR 35
TC 3
Z9 3
U1 0
U2 9
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD JUN 19
PY 2013
VL 368
IS 1620
AR 20120366
DI 10.1098/rstb.2012.0366
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 139WD
UT WOS:000318614800008
PM 23650638
ER
PT J
AU Khadra, A
Tomic, M
Yan, ZH
Zemkova, H
Sherman, A
Stojilkovic, SS
AF Khadra, Anmar
Tomic, Melanija
Yan, Zonghe
Zemkova, Hana
Sherman, Arthur
Stojilkovic, Stanko S.
TI Dual Gating Mechanism and Function of P2X7 Receptor Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID P2X(7) RECEPTOR; AGONIST BINDING; ACTIVATION; CALCIUM; INTERNALIZATION;
PERMEATION; KINETICS; CURRENTS; CELLS; DYES
AB The ATP-gated P2X7 receptor channel (P2X7R) operates as a cytolytic and apoptotic receptor but also controls sustained cellular responses, including cell growth and proliferation. However, it has not been clarified how the same receptor mediates such opposing effects. To address this question, we have combined electrophysiological, imaging, and mathematical studies using wild-type and mutant rat P2X7Rs. Activation of naive (not previously stimulated) receptors by low agonist concentrations caused monophasic slow desensitizing currents and internalization of receptors without other changes in the cellular morphology, much like other P2XRs. In contrast, saturating agonist concentrations induced high-amplitude biphasic currents, reflecting pore dilation and causing rapid cell swelling and lysis. The existence of these two signaling patterns was accounted for using a revised Markov-state model that included, in addition to naive and sensitized states, desensitized states. Occupancy of one or two ATP-binding sites of naive receptors favored a slow transition to desensitized states, whereas occupancy of the third binding site favored a transition to sensitized/dilated states. Consistent with model predictions, nondilating P2X7R mutants always generated desensitizing currents. These results suggest that the level of saturation of the ligand binding sites determines the nature of the P2X7R gating and cellular actions.
C1 [Khadra, Anmar] McGill Univ, Dept Physiol, Montreal, PQ, Canada.
[Tomic, Melanija; Yan, Zonghe; Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Zemkova, Hana] Acad Sci Czech Republic, Inst Phys, Dept Cellular & Mol Neuroendocrinol, Prague, Czech Republic.
[Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA.
RP Khadra, A (reprint author), McGill Univ, Dept Physiol, Montreal, PQ, Canada.
EM anmar.khadra@mcgill.ca
RI Zemkova, Hana/C-1844-2012; Tomic, Melanija/C-3371-2016
FU National Institute of Child Health and Human Development; National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health; Grant Agency of the Czech Republic [P304/12/G069];
McGill University
FX This work was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development and National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, the Grant Agency of the Czech Republic
(P304/12/G069), and the McGill University.
NR 31
TC 17
Z9 17
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUN 18
PY 2013
VL 104
IS 12
BP 2612
EP 2621
DI 10.1016/j.bpj.2013.05.006
PG 10
WC Biophysics
SC Biophysics
GA 169DI
UT WOS:000320757100006
PM 23790369
ER
PT J
AU Zheng, XH
Mueller, GA
DeRose, EF
London, RE
AF Zheng, Xunhai
Mueller, Geoffrey A.
DeRose, Eugene F.
London, Robert E.
TI Protein-Mediated Antagonism between HIV Reverse Transcriptase Ligands
Nevirapine and MgATP
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID HIGH-RESOLUTION STRUCTURES; NONNUCLEOSIDE INHIBITOR; RESISTANCE
MUTATIONS; CONFORMATIONAL FLEXIBILITY; CRYSTAL-STRUCTURES;
DRUG-RESISTANCE; SLOW DYNAMICS; TROSY NMR; MECHANISM; COMPLEXES
AB Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, but their mechanisms of action are incompletely understood. The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase (RT) is characterized by a preference for the open conformation of the fingers/thumb subdomains, and a reported variation of three orders of magnitude between the binding affinity of NVP for RT in the presence or absence of primer/template DNA. To investigate the relationship between conformation and ligand binding, we evaluated the use of methionine NMR probes positioned near the tip of the fingers or thumb subdomains. Such probes would be expected to be sensitive to changes in the local environment depending on the fractions of open and closed RT. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. The exchange kinetics of the M63 resonance are fast on the chemical shift timescale, but become slow in the presence of NVP due to the slow binding of RT with the inhibitor. The simplest model consistent with this behavior involves a rapid open/closed equilibrium coupled with a slow interaction of the inhibitor with the open conformation. Studies of RT in the presence of both NVP and MgATP indicate a strong negative cooperativity. Binding of MgATP reduces the fraction of RT bound to NVP, as indicated by the intensity of the NVP-perturbed M230 resonance, and enhances the dissociation rate constant of the NVP, resulting in an increase of the open/closed interconversion rate, so that the M63 resonance moves into the fast/intermediate-exchange regime. Protein-mediated interactions appear to explain most of the affinity variation of NVP for RT.
C1 [Zheng, Xunhai; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM london@niehs.nih.gov
RI Zheng, Xunhai/G-1187-2015
OI Zheng, Xunhai/0000-0003-0390-2491
FU Intramural National Institutes of Health (NIH) Research Program of the
National Institute of Environmental Health Sciences (NIEHS)
[Z01-ES050147]; NIEHS; NIH [HHSN273200700046U]
FX This research was supported by the Intramural National Institutes of
Health (NIH) Research Program of the National Institute of Environmental
Health Sciences (NIEHS; grant Z01-ES050147 to R.E.L.). E.F.D. is
supported by the NIEHS, NIH, under Delivery Order HHSN273200700046U. NVP
was obtained from the NIH AIDS Research and Reference Reagent Program.
NR 48
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Z9 5
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUN 18
PY 2013
VL 104
IS 12
BP 2695
EP 2705
DI 10.1016/j.bpj.2013.04.015
PG 11
WC Biophysics
SC Biophysics
GA 169DI
UT WOS:000320757100015
PM 23790378
ER
PT J
AU Xu, BY
Zhi, N
Hu, GQ
Wan, ZH
Zheng, XB
Liu, XH
Wong, SS
Kajigaya, S
Zhao, KJ
Mao, Q
Young, NS
AF Xu, Baoyan
Zhi, Ning
Hu, Gangqing
Wan, Zhihong
Zheng, Xiaobin
Liu, Xiaohong
Wong, Susan
Kajigaya, Sachiko
Zhao, Keji
Mao, Qing
Young, Neal S.
TI Hybrid DNA virus in Chinese patients with seronegative hepatitis
discovered by deep sequencing
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hepatitis-associated aplastic anemia; liver failure; Solexa sequencing;
virological diagnosis
ID NON-A; NON-B; TRANSPLANT PATIENTS; B19 PARVOVIRUS; UNITED-STATES; NON-C;
DISEASE; EVOLUTION; LIVER; ETIOLOGY
AB Seronegative hepatitis-non-A, non-B, non-C, non-D, non-E hepatitis-is poorly characterized but strongly associated with serious complications. We collected 92 sera specimens from patients with non-A-E hepatitis in Chongqing, China between 1999 and 2007. Ten sera pools were screened by Solexa deep sequencing. We discovered a 3,780-bp contig present in all 10 pools that yielded BLASTx E scores of 7e-05-0.008 against parvoviruses. The complete sequence of the in silico-assembled 3,780-bp contig was confirmed by gene amplification of overlapping regions over almost the entire genome, and the virus was provisionally designated NIH-CQV. Further analysis revealed that the contig was composed of two major ORFs. By protein BLAST, ORF1 and ORF2 were most homologous to the replication-associated protein of bat circovirus and the capsid protein of porcine parvovirus, respectively. Phylogenetic analysis indicated that NIH-CQV is located at the interface of Parvoviridae and Circoviridae. Prevalence of NIH-CQV in patients was determined by quantitative PCR. Sixty-three of 90 patient samples (70%) were positive, but all those from 45 healthy controls were negative. Average virus titer in the patient specimens was 1.05 e4 copies/mu L. Specific antibodies against NIH-CQV were sought by immunoblotting. Eighty-four percent of patients were positive for IgG, and 31% were positive for IgM; in contrast, 78% of healthy controls were positive for IgG, but all were negative for IgM. Although more work is needed to determine the etiologic role of NIH-CQV in human disease, our data indicate that a parvovirus-like virus is highly prevalent in a cohort of patients with non-A-E hepatitis.
C1 [Xu, Baoyan; Zhi, Ning; Wan, Zhihong; Liu, Xiaohong; Wong, Susan; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Xu, Baoyan; Mao, Qing] Third Mil Med Univ, Southwest Hosp, Inst Infect Dis, Chongqing 400038, Peoples R China.
[Zheng, Xiaobin] Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
RP Zhi, N (reprint author), NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
EM zhin@nhlbi.nih.gov; qingmao@yahoo.com
RI HU, GANGQING/K-5849-2012
FU National Institutes of Health Intramural Research Program
FX We thank Dr. Jun Zhu at the DNA Sequencing and Genomics Core of the
National Heart, Lung, and Blood Institute (NHLBI) for assistance in
deep-sequencing and data analysis; Dr. Amit Kapoor of Columbia
University for technical advice; and Genoveffa Franchini of the National
Cancer Institute, Leonid Margolis of the National Institute of Child
Health and Development, Cynthia Dunbar of the NHLBI, and Mike Fang in
our laboratory for their careful reading of the manuscript. This work
was supported by the National Institutes of Health Intramural Research
Program.
NR 42
TC 24
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U1 1
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 18
PY 2013
VL 110
IS 25
BP 10264
EP 10269
DI 10.1073/pnas.1303744110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179DU
UT WOS:000321500200056
PM 23716702
ER
PT J
AU Chow, HM
Horovitz, SG
Carr, WS
Picchioni, D
Coddington, N
Fukunaga, M
Xu, YS
Balkin, TJ
Duyn, JH
Braun, AR
AF Chow, Ho Ming
Horovitz, Silvina G.
Carr, Walter S.
Picchioni, Dante
Coddington, Nate
Fukunaga, Masaki
Xu, Yisheng
Balkin, Thomas J.
Duyn, Jeff H.
Braun, Allen R.
TI Rhythmic alternating patterns of brain activity distinguish rapid eye
movement sleep from other states of consciousness
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE EEG; fMRI; thalamus; slow-wave sleep; brain dynamics
ID DEFAULT MODE NETWORK; FUNCTIONAL CONNECTIVITY; HZ OSCILLATIONS;
LOW-FREQUENCY; REM-SLEEP; MEMORY; FLUCTUATIONS; WAKEFULNESS; CORTICES;
CORTEX
AB Rapid eye movement (REM) sleep constitutes a distinct "third state" of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects "level of consciousness," we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.
C1 [Chow, Ho Ming; Xu, Yisheng; Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA.
[Horovitz, Silvina G.] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Horovitz, Silvina G.; Fukunaga, Masaki; Duyn, Jeff H.] NINDS, Sect Adv MRI, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Carr, Walter S.; Picchioni, Dante; Balkin, Thomas J.] Walter Reed Army Inst Res, Behav Biol Branch, Ctr Psychiat & Neurosci, Silver Spring, MD 20910 USA.
[Coddington, Nate] Univ Virginia, Dept Neurosci, Charlottesville, VA 22903 USA.
[Fukunaga, Masaki] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Osaka 5650871, Japan.
RP Chow, HM (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA.
EM chowh@nidcd.nih.gov
RI Fukunaga, Masaki/F-6441-2013
OI Fukunaga, Masaki/0000-0003-1010-2644
FU National Institute on Deafness and Other Communication Disorders,
National Institute of Neurological Disorders and Stroke; Walter Reed
Army Institute of Research
FX The authors thank Carmen Brewer, Christopher Zalewski, Teresa Kessinger,
and Jim Paterson for key collaboration and support; and Alex Martin and
Kelly Barnes for insightful and critical reviews of this manuscript.
This work was supported by the Intramural Research Programs of the
National Institute on Deafness and Other Communication Disorders,
National Institute of Neurological Disorders and Stroke, and the Walter
Reed Army Institute of Research.
NR 39
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Z9 35
U1 5
U2 38
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 JUN 18
PY 2013
VL 110
IS 25
BP 10300
EP 10305
DI 10.1073/pnas.1217691110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179DU
UT WOS:000321500200062
PM 23733938
ER
PT J
AU Kristensen, U
Epanchintsev, A
Rauschendorf, MA
Laugel, V
Stevnsner, T
Bohr, VA
Coin, F
Egly, JM
AF Kristensen, Ulrik
Epanchintsev, Alexey
Rauschendorf, Marc-Alexander
Laugel, Vincent
Stevnsner, Tinna
Bohr, Vilhelm A.
Coin, Frederic
Egly, Jean-Marc
TI Regulatory interplay of Cockayne syndrome B ATPase and stress-response
gene ATF3 following genotoxic stress
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID RNA-POLYMERASE-II; PURKINJE-CELL DEGENERATION; PLURIPOTENT STEM-CELLS;
COUPLING FACTOR CSB/ERCC6; DE-LANGE-SYNDROME; DNA-REPAIR;
ALPHA-AMANITIN; UV-IRRADIATION; NIPPED-B; IN-VIVO
AB Cockayne syndrome type B ATPase (CSB) belongs to the SwItch/Sucrose nonfermentable family. Its mutations are linked to Cockayne syndrome phenotypes and classically are thought to be caused by defects in transcription-coupled repair, a subtype of DNA repair. Here we show that after UV-C irradiation, immediate early genes such as activating transcription factor 3 (ATF3) are overexpressed. Although the ATF3 target genes, including dihydrofolate reductase (DHFR), were unable to recover RNA synthesis in CSB-deficient cells, transcription was restored rapidly in normal cells. There the synthesis of DHFR mRNA restarts on the arrival of RNA polymerase II and CSB and the subsequent release of ATF3 from its cAMP response element/ATF target site. In CSB-deficient cells ATF3 remains bound to the promoter, thereby preventing the arrival of polymerase II and the restart of transcription. Silencing of ATF3, as well as stable introduction of wild-type CSB, restores RNA synthesis in UV-irradiated CSB cells, suggesting that, in addition to its role in DNA repair, CSB activity likely is involved in the reversal of inhibitory properties on a gene-promoter region. We present strong experimental data supporting our view that the transcriptional defects observed in UV-irradiated CSB cells are largely the result of a permanent transcriptional repression of a certain set of genes in addition to some defect in DNA repair.
C1 [Kristensen, Ulrik; Epanchintsev, Alexey; Rauschendorf, Marc-Alexander; Coin, Frederic; Egly, Jean-Marc] Univ Strasbourg, CNRS, INSERM, Inst Genet & Mol & Cellular Biol,Dept Funct Genom, F-67404 Illkirch Graffenstaden, France.
[Laugel, Vincent] Univ Strasbourg, Lab Med Genet, F-67404 Illkirch Graffenstaden, France.
[Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol, CDK-8000 Aarhus C, Denmark.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Coin, F (reprint author), Univ Strasbourg, CNRS, INSERM, Inst Genet & Mol & Cellular Biol,Dept Funct Genom, F-67404 Illkirch Graffenstaden, France.
EM fredr@igbmc.fr; egly@igbmc.fr
RI Coin, Frederic/F-5925-2013
FU European Research Council Advanced Scientists; Institut National du
Cancer Grant [INCA-2008-041]; l'Association de la Recherche contre le
Cancer (ARC) [3153]; Advanced European Research Council; ARC; French
Ministere des Affaires Etrangeres
FX We thank R. Velez Cruz, A. Zadorin, and E. Compe for fruitful
discussions; Charlotte Saint-Andre for helping with antibody production
and protein expression; and the Institute of Genetics and Molecular and
Cellular Biology Cell Culture Facility. This study was supported by
grants from the European Research Council Advanced Scientists (to
J.-M.E.), the Institut National du Cancer Grant INCA-2008-041 (to F.
C.), and l'Association de la Recherche contre le Cancer (ARC) Grant
3153. U. K, was supported by a JME (Jean-Marc Egly) Advanced European
Research Council grant and by an ARC fellowship for young scientists.
M.-A. R. was supported by the French Ministere des Affaires Etrangeres
(Sejour Scientifique de Haut Niveau).
NR 64
TC 5
Z9 5
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 18
PY 2013
VL 110
IS 25
BP E2261
EP E2270
DI 10.1073/pnas.1220071110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179DU
UT WOS:000321500200007
PM 23733932
ER
PT J
AU Chukoskie, L
Snider, J
Mozer, MC
Krauzlis, RJ
Sejnowski, TJ
AF Chukoskie, Leanne
Snider, Joseph
Mozer, Michael C.
Krauzlis, Richard J.
Sejnowski, Terrence J.
TI Learning where to look for a hidden target
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ideal observer; oculomotor; reinforcement learning; saccades
ID EYE-MOVEMENTS; VISUAL-SEARCH; PARIETAL CORTEX; SCENE CONTEXT; MATCHING
BEHAVIOR; DECISION-MAKING; REINFORCEMENT; ATTENTION; SELECTION; FEATURES
AB Survival depends on successfully foraging for food, for which evolution has selected diverse behaviors in different species. Humans forage not only for food, but also for information. We decide where to look over 170,000 times per day, approximately three times per wakeful second. The frequency of these saccadic eye movements belies the complexity underlying each individual choice. Experience factors into the choice of where to look and can be invoked to rapidly redirect gaze in a context and task-appropriate manner. However, remarkably little is known about how individuals learn to direct their gaze given the current context and task. We designed a task in which participants search a novel scene for a target whose location was drawn stochastically on each trial from a fixed prior distribution. The target was invisible on a blank screen, and the participants were rewarded when they fixated the hidden target location. In just a few trials, participants rapidly found the hidden targets by looking near previously rewarded locations and avoiding previously unrewarded locations. Learning trajectories were well characterized by a simple reinforcement-learning (RL) model that maintained and continually updated a reward map of locations. The RL model made further predictions concerning sensitivity to recent experience that were confirmed by the data. The asymptotic performance of both the participants and the RL model approached optimal performance characterized by an ideal-observer theory. These two complementary levels of explanation show how experience in a novel environment drives visual search in humans and may extend to other forms of search such as animal foraging.
C1 [Chukoskie, Leanne; Snider, Joseph; Mozer, Michael C.; Sejnowski, Terrence J.] Univ Calif San Diego, Inst Neural Computat, La Jolla, CA 92093 USA.
[Sejnowski, Terrence J.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Mozer, Michael C.] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA.
[Mozer, Michael C.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA.
[Krauzlis, Richard J.] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
[Sejnowski, Terrence J.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
[Sejnowski, Terrence J.] Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA 92037 USA.
RP Sejnowski, TJ (reprint author), Univ Calif San Diego, Inst Neural Computat, La Jolla, CA 92093 USA.
EM terry@salk.edu
FU National Science Foundation (NSF) [SBE 0542013]; NSF Science of Learning
Center; San Diego Foundation; Office of Naval Research Multidisciplinary
University Research Initiative [N00014-10-1-0072]; Howard Hughes Medical
Institute
FX We thank Krista Kornylo and Natalie Dill for technical assistance. This
work was supported in part by National Science Foundation (NSF) Grant
SBE 0542013 to the Temporal Dynamics of Learning Center, an NSF Science
of Learning Center grant (to L. C., J.S., M. C. M., and T.J.S.), a
Blasker Rose-Miah grant from the San Diego Foundation (to L. C.), Office
of Naval Research Multidisciplinary University Research Initiative Award
N00014-10-1-0072 (to J.S. and T.J.S.), and Howard Hughes Medical
Institute (T.J.S.).
NR 66
TC 15
Z9 15
U1 2
U2 27
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 JUN 18
PY 2013
VL 110
SU 2
BP 10438
EP 10445
DI 10.1073/pnas.1301216110
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179DZ
UT WOS:000321500900015
PM 23754404
ER
PT J
AU El-Haibi, CP
Sharma, P
Singh, R
Gupta, P
Taub, DD
Singh, S
Lillard, JW
AF El-Haibi, Christelle P.
Sharma, Praveen
Singh, Rajesh
Gupta, Pranav
Taub, Dennis D.
Singh, Shailesh
Lillard, James W., Jr.
TI Differential G protein subunit expression by prostate cancer cells and
their interaction with CXCR5
SO MOLECULAR CANCER
LA English
DT Article
DE Prostate cancer; Chemokine; G proteins; G protein-coupled receptor
ID HETEROTRIMERIC G-PROTEINS; CHEMOKINE RECEPTOR; SIGNAL-TRANSDUCTION;
ALPHA-SUBUNIT; GAMMA-SUBUNIT; MEDIATED PHOSPHORYLATION; COUPLED
RECEPTORS; BONE METASTASIS; BETA; GROWTH
AB with PCa progression, and mediate PCa cell migration and invasion following interaction with CXCL13. However, the differential expression of G protein alpha,beta, and. subunits by PCa cell lines and the precise combination of these proteins with CXCR5 has not been elucidated.
Methods: We examined differences in G protein expression of normal prostate (RWPE-1) and PCa cell lines (LNCaP, C4-2B, and PC3) by western blot analysis. Further, we immunoprecipitated CXCR5 with different G protein subunits, and CXCR4, following CXCL13 stimulation. To investigate constitutive coupling of CXCR5 with CXCR4 and PAR-1 we performed invasion assay in PCa cells transfected with G(aq/i2) or G(a13) siRNA, following CXCL13 treatment. We also investigated Rac and RhoA activity by G-LISA activation assay in PCa cells following CXCL13/thrombin stimulation.
Result: Of the 22 G proteins studied, G(ai1-3), G(beta 1-4), G(Y5), G(Y7), and G.10 were expressed by both normal and PCa cell lines. Gas was moderately expressed in C4-2B and PC3 cell lines, G(aq/11) was only present in RWPE-1 and LNCaP cell lines, while G(a12) and Ga-13 were expressed in C4-2B and PC3 cell lines. G.9 was expressed only in PCa cell lines. G(a16), G(beta 5), G(Y1-4), and G(Y13) were not detected in any of the cell lines studied. Surprisingly, CXCR4 co-immunoprecipitated with CXCR5 in PCa cell lines irrespective of CXCL13 treatment. We also identified specific G protein isoforms coupled to CXCR5 in its resting and active states. G(aq/11/)G(beta 3)/G(Y9) in LNCaP and G(ai2)/G(beta 3)/G(Y9) in C4-2B and PC3 cell lines, were coupled to CXCR5 and disassociated following CXCL13 stimulation. Interestingly, G(a13) co-immunoprecipitated with CXCR5 in CXCL13-treated, but not in untreated PCa cell lines. Inhibition of G(aq/i2) significantly decreased the ability of cells to invade, whereas silencing Ga13 did not affect CXCL13-dependent cell invasion. Finally, CXCL13 treatment significantly increased Rac activity in G(aq/i2) dependent manner, but not RhoA activity, in PCa cell lines.
Conclusions: These findings offer insight into molecular mechanisms of PCa progression and can help to design some therapeutic strategies involving CXCR5 and/or CXCL13 blockade and specific G protein inhibition to abrogate PCa metastasis.
C1 [El-Haibi, Christelle P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Sharma, Praveen] Cent Univ Jharkhand, Ctr Life Sci, Sch Nat Sci, Ranchi, Bihar, India.
[Singh, Rajesh; Gupta, Pranav; Singh, Shailesh; Lillard, James W., Jr.] Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA.
[Taub, Dennis D.] NIA, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Lillard, JW (reprint author), Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA.
EM jlillard@msm.edu
RI Sharma, Praveen/M-2810-2014
OI Sharma, Praveen/0000-0002-7020-3570
FU National Institute of Health [S21MD000101, G12RR03034, G12MD007602,
U54CA118638]; Department of Defense (DoD); Prostate Cancer Research
Program Award [W81XWH-06-1-0562, W81XWH-11-1-0109]
FX The content of this manuscript benefited from many fruitful
conversations with members of the Morehouse School of Medicine. This
work benefited from the cooperation between investigators from the
Morehouse School of Medicine and the Wallace Tumor Institute at the
University of Alabama at Birmingham via the National Cancer Institute
sponsored "Comprehensive Minority Institution / Cancer Center
Partnership". This study was supported by funds from National Institute
of Health Grants S21MD000101, G12RR03034, G12MD007602, U54CA118638, and
Department of Defense (DoD) Prostate Cancer Research Program Award
W81XWH-06-1-0562, and W81XWH-11-1-0109.
NR 50
TC 9
Z9 9
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD JUN 18
PY 2013
VL 12
AR 64
DI 10.1186/1476-4598-12-64
PG 11
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 187SJ
UT WOS:000322139200001
PM 23773523
ER
PT J
AU Ferreira, RD
Zhou, DW
Ferreira, JG
Silva, MCC
Silva-Lucca, RA
Mentele, R
Paredes-Gamero, EJ
Bertolin, TC
Correia, MTD
Paiva, PMG
Gustchina, A
Wlodawer, A
Oliva, MLV
AF Ferreira, Rodrigo da Silva
Zhou, Dongwen
Ferreira, Joana Gasperazzo
Cabral Silva, Mariana Cristina
Silva-Lucca, Rosemeire Aparecida
Mentele, Reinhard
Paredes-Gamero, Edgar Julian
Bertolin, Thiago Carlos
dos Santos Correia, Maria Tereza
Guedes Paiva, Patricia Maria
Gustchina, Alla
Wlodawer, Alexander
Vilela Oliva, Maria Luiza
TI Crystal Structure of Crataeva tapia Bark Protein (CrataBL) and Its
Effect in Human Prostate Cancer Cell Lines
SO PLOS ONE
LA English
DT Article
ID TRYPSIN-INHIBITOR; SERINE RESIDUE; REACTIVE SITE; BINDING; LECTIN;
APOPTOSIS; MECHANISM; SEEDS; DU145; GLYCOSAMINOGLYCANS
AB A protein isolated from the bark of Crataeva tapia (CrataBL) is both a Kunitz-type plant protease inhibitor and a lectin. We have determined the amino acid sequence and three-dimensional structure of CrataBL, as well as characterized its selected biochemical and biological properties. We found two different isoforms of CrataBL isolated from the original source, differing in positions 31 (Pro/Leu); 92 (Ser/Leu); 93 (Ile/Thr); 95 (Arg/Gly) and 97 (Leu/Ser). CrataBL showed relatively weak inhibitory activity against trypsin (K-iapp = 43 mu M) and was more potent against Factor Xa (K-iapp = 8.6 mu M), but was not active against a number of other proteases. We have confirmed that CrataBL contains two glycosylation sites and forms a dimer at high concentration. The high-resolution crystal structures of two different crystal forms of isoform II verified the beta-trefoil fold of CrataBL and have shown the presence of dimers consisting of two almost identical molecules making extensive contacts (similar to 645 angstrom(2)). The structure differs from those of the most closely related proteins by the lack of the N-terminal beta-hairpin. In experiments aimed at investigating the biological properties of CrataBL, we have shown that addition of 40 mM of the protein for 48 h caused maximum growth inhibition in MTT assay (47% of DU145 cells and 43% of PC3 cells). The apoptosis of DU145 and PC3 cell lines was confirmed by flow cytometry using Annexin V/FITC and propidium iodide staining. Treatment with CrataBL resulted in the release of mitochondrial cytochrome c and in the activation of caspase-3 in DU145 and PC3 cells.
C1 [Ferreira, Rodrigo da Silva; Ferreira, Joana Gasperazzo; Cabral Silva, Mariana Cristina; Paredes-Gamero, Edgar Julian; Vilela Oliva, Maria Luiza] Univ Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil.
[Zhou, Dongwen; Gustchina, Alla; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Silva-Lucca, Rosemeire Aparecida] Univ Estadual Oeste Parana, Ctr Engn & Ciencias Exatas, Toledo, Parana, Brazil.
[Mentele, Reinhard] Max Planck Inst Biochem, Inst Clin Neuroimmunol LMU, Munich, Germany.
[Mentele, Reinhard] Max Planck Inst Biochem, Dept Prot Analyt, Munich, Germany.
[Bertolin, Thiago Carlos] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil.
[dos Santos Correia, Maria Tereza; Guedes Paiva, Patricia Maria] Univ Fed Pernambuco, Dept Bioquim, Recife, PE, Brazil.
RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA.
EM wlodawer@nih.gov; olivaml.bioq@epm.br
RI Silva, Mariana/B-9530-2012; Ferreira, Rodrigo/C-1763-2013; Oliva, Maria
Luiza/B-9537-2012; Paredes-Gamero, Edgar/C-4791-2012;
OI Ferreira, Rodrigo/0000-0003-4103-6870; Paredes-Gamero,
Edgar/0000-0003-3686-8402; Paiva, Patricia/0000-0003-3467-708X
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; CAPES; Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq); Sao Paulo Research Foundation (FAPESP)
[09/53766-5]; Intramural Research Program of the National Institutes of
Health (NIH), National Cancer Institute, Center for Cancer Research
FX Use of the APS was supported by the U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences under Contract No.
W-31-109-Eng-38. The authors are grateful to CAPES, Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq) and Sao Paulo Research
Foundation (FAPESP) (Process 09/53766-5) for providing financial
support. This project was also supported in part by the Intramural
Research Program of the National Institutes of Health (NIH), National
Cancer Institute, Center for Cancer Research. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 69
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U1 0
U2 14
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 JUN 18
PY 2013
VL 8
IS 6
AR e64426
DI 10.1371/journal.pone.0064426
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166SA
UT WOS:000320576400001
ER
PT J
AU Foltz, JL
Makumbi, I
Sejvar, JJ
Malimbo, M
Ndyomugyenyi, R
Atai-Omoruto, AD
Alexander, LN
Abang, B
Melstrom, P
Kakooza, AM
Olara, D
Downing, RG
Nutman, TB
Dowell, SF
Lwamafa, DKW
AF Foltz, Jennifer L.
Makumbi, Issa
Sejvar, James J.
Malimbo, Mugagga
Ndyomugyenyi, Richard
Atai-Omoruto, Anne Deborah
Alexander, Lorraine N.
Abang, Betty
Melstrom, Paul
Kakooza, Angelina M.
Olara, Dennis
Downing, Robert G.
Nutman, Thomas B.
Dowell, Scott F.
Lwamafa, D. K. W.
TI An Epidemiologic Investigation of Potential Risk Factors for Nodding
Syndrome in Kitgum District, Uganda
SO PLOS ONE
LA English
DT Article
ID CLINICAL CLASSIFICATION; ONCHOCERCA-VOLVULUS; SOUTHERN SUDAN; EPILEPSY;
TANZANIA; SEIZURES
AB Introduction: Nodding Syndrome (NS), an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda.
Methods: In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations.
Results: Surveillance identified 224 cases; most (95%) were 5-15-years-old (range = 2-27). Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0.6-46). The case-control investigation (n = 49 case/village control pairs) showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR(1)) = 14.4 (2.7, 78.3)], exposure to munitions [AOR(1)= 13.9 (1.4, 135.3)], and consumption of crushed roots [AOR(1)= 5.4 (1.3, 22.1)] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84%) and controls (75%).
Conclusion: NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5 to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies.
C1 [Foltz, Jennifer L.] Ctr Dis Control & Prevent, Div Nutr Phys Activ & Obes, Atlanta, GA 30333 USA.
[Makumbi, Issa; Malimbo, Mugagga; Ndyomugyenyi, Richard; Atai-Omoruto, Anne Deborah; Lwamafa, D. K. W.] Uganda Minist Hlth, Kampala, Uganda.
[Sejvar, James J.] Ctr Dis Control & Prevent, Div High Consequence Pathogens & Pathol, Atlanta, GA USA.
[Alexander, Lorraine N.; Abang, Betty; Olara, Dennis; Downing, Robert G.] Centers Dis Control & Prevent Uganda, Div Global HIV AIDS, Entebbe, Uganda.
[Melstrom, Paul] Ctr Dis Control & Prevent, Div Environm Hazards & Hlth Effects, Atlanta, GA USA.
[Kakooza, Angelina M.] Makerere Univ, Coll Hlth Sci, Sch Med, Kampala, Uganda.
[Nutman, Thomas B.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Dowell, Scott F.] Ctr Dis Control & Prevent, Div Global Dis Detect & Emergency Response, Atlanta, GA USA.
RP Foltz, JL (reprint author), Ctr Dis Control & Prevent, Div Nutr Phys Activ & Obes, Atlanta, GA 30333 USA.
EM jfoltz@cdc.gov
FU CDC; WHO; MoH Uganda for public health investigations
FX The investigation was supported with resources available from CDC, WHO,
and MoH Uganda for public health investigations. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 27
TC 31
Z9 31
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 18
PY 2013
VL 8
IS 6
AR e66419
DI 10.1371/journal.pone.0066419
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166SA
UT WOS:000320576400106
PM 23823012
ER
PT J
AU Liu, HX
Fang, YP
Hu, Y
Gonzalez, FJ
Fang, JW
Wan, YJY
AF Liu, Hui-Xin
Fang, Yaping
Hu, Ying
Gonzalez, Frank J.
Fang, Jianwen
Wan, Yu-Jui Yvonne
TI PPAR beta Regulates Liver Regeneration by Modulating Akt and E2f
Signaling
SO PLOS ONE
LA English
DT Article
ID ACTIVATED RECEPTOR-DELTA; CANCER CELL-LINES; ALPHA-NULL MICE; LIGAND
ACTIVATION; PARTIAL-HEPATECTOMY; GENE-EXPRESSION; GROWTH-FACTOR;
PEROXISOME; PROLIFERATION; METABOLISM
AB The current study tests the hypothesis that peroxisome proliferator-activated receptor beta (PPAR beta) has a role in liver regeneration due to its effect in regulating energy homeostasis and cell proliferation. The role of PPARb in liver regeneration was studied using two-third partial hepatectomy (PH) in Wild-type (WT) and PPARb-null (KO) mice. In KO mice, liver regeneration was delayed and the number of Ki-67 positive cells reached the peak at 60 hr rather than at 36-48 hr after PH shown in WT mice. RNA-sequencing uncovered 1344 transcriptomes that were differentially expressed in regenerating WT and KO livers. About 70% of those differentially expressed genes involved in glycolysis and fatty acid synthesis pathways failed to induce during liver regeneration due to PPAR beta deficiency. The delayed liver regeneration in KO mice was accompanied by lack of activation of phosphoinositide-dependent kinase 1 (PDK1)/Akt. In addition, cell proliferation-associated increase of genes encoding E2f transcription factor (E2f) 1-2 and E2f7-8 as well as their downstream target genes were not noted in KO livers 36-48 hr after PH. E2fs have dual roles in regulating metabolism and proliferation. Moreover, transient steatosis was only found in WT, but not in KO mice 36 hr after PH. These data suggested that PPAR beta-regulated PDK1/Akt and E2f signaling that controls metabolism and proliferation is involved in the normal progression of liver regeneration.
C1 [Liu, Hui-Xin; Hu, Ying; Wan, Yu-Jui Yvonne] Calif State Univ Sacramento, Dept Med Pathol & Lab Med, Sacramento, CA 95819 USA.
[Fang, Yaping; Fang, Jianwen] Univ Kansas, Appl Bioinformat Lab, Lawrence, KS 66045 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Wan, YJY (reprint author), Calif State Univ Sacramento, Dept Med Pathol & Lab Med, Sacramento, CA 95819 USA.
EM yjywan@ucdavis.edu
OI Fang, Yaping/0000-0001-6075-0768
FU National Institutes of Health [CA53596, DK092100]
FX This study is supported by grants funded by National Institutes of
Health CA53596 and DK092100. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 14
Z9 14
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 18
PY 2013
VL 8
IS 6
AR e65644
DI 10.1371/journal.pone.0065644
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166SA
UT WOS:000320576400016
PM 23823620
ER
PT J
AU Nguyen, HD
Becker, J
Thu, YM
Costanzo, M
Koch, EN
Smith, S
Myung, K
Myers, CL
Boone, C
Bielinsky, AK
AF Nguyen, Hai Dang
Becker, Jordan
Thu, Yee Mon
Costanzo, Michael
Koch, Elizabeth N.
Smith, Stephanie
Myung, Kyungjae
Myers, Chad L.
Boone, Charles
Bielinsky, Anja-Katrin
TI Unligated Okazaki Fragments Induce PCNA Ubiquitination and a Requirement
for Rad59-Dependent Replication Fork Progression
SO PLOS ONE
LA English
DT Article
ID DNA-LIGASE-I; YEAST SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE
EXCISION-REPAIR; NEARBY INVERTED REPEATS; CELL NUCLEAR ANTIGEN; BUDDING
YEAST; HOMOLOGOUS RECOMBINATION; MITOTIC RECOMBINATION;
COMPLEX-FORMATION; ESSENTIAL GENES
AB Deficiency in DNA ligase I, encoded by CDC9 in budding yeast, leads to the accumulation of unligated Okazaki fragments and triggers PCNA ubiquitination at a non-canonical lysine residue. This signal is crucial to activate the S phase checkpoint, which promotes cell cycle delay. We report here that a pol30-K107 mutation alleviated cell cycle delay in cdc9 mutants, consistent with the idea that the modification of PCNA at K107 affects the rate of DNA synthesis at replication forks. To determine whether PCNA ubiquitination occurred in response to nicks or was triggered by the lack of PCNA-DNA ligase interaction, we complemented cdc9 cells with either wild-type DNA ligase I or a mutant form, which fails to interact with PCNA. Both enzymes reversed PCNA ubiquitination, arguing that the modification is likely an integral part of a novel nick-sensory mechanism and not due to non-specific secondary mutations that could have occurred spontaneously in cdc9 mutants. To further understand how cells cope with the accumulation of nicks during DNA replication, we utilized cdc9-1 in a genome-wide synthetic lethality screen, which identified RAD59 as a strong negative interactor. In comparison to cdc9 single mutants, cdc9 rad59D double mutants did not alter PCNA ubiquitination but enhanced phosphorylation of the mediator of the replication checkpoint, Mrc1. Since Mrc1 resides at the replication fork and is phosphorylated in response to fork stalling, these results indicate that Rad59 alleviates nick-induced replication fork slowdown. Thus, we propose that Rad59 promotes fork progression when Okazaki fragment processing is compromised and counteracts PCNA-K107 mediated cell cycle arrest.
C1 [Nguyen, Hai Dang; Becker, Jordan; Thu, Yee Mon; Bielinsky, Anja-Katrin] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
[Costanzo, Michael; Boone, Charles] Univ Toronto, Donnelly Ctr, Banting & Best Dept Med Res, Toronto, ON, Canada.
[Boone, Charles] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Koch, Elizabeth N.; Myers, Chad L.] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN USA.
[Smith, Stephanie; Myung, Kyungjae] Natl Inst Hlth, Natl Human Genome Res Inst, Genet & Mol Biol Branch, Genome Instabil Sect, Bethesda, MD USA.
RP Bielinsky, AK (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
EM bieli003@umn.edu
OI Bielinsky, Anja/0000-0003-1783-619X
FU National Institutes of Health (NIH) [GM074917]; National Human Genome
Research Institute; NIH [HG005084, HG005853]; NSF [DBI0953881]; Canadian
Institutes of Health Research [MOP-102629, MOP-97939]; Ontario Research
Fund [GL2-0122]
FX This work was supported by National Institutes of Health (NIH) grant
GM074917 to AKB, who is a Scholar of the Leukemia and Lymphoma Society.
The intramural Research Programs of the National Human Genome Research
Institute supported KM. EK is a National Science Foundation (NSF)
Graduate Research Fellow. EK and CLM were supported by a grant from the
NIH (HG005084), and the NSF (DBI0953881). CB and CLM are supported by a
grant from the NIH (HG005853). CB is supported by grants from the
Canadian Institutes of Health Research (MOP-102629 and MOP-97939) and
the Ontario Research Fund (GL2-0122). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 64
TC 7
Z9 7
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 18
PY 2013
VL 8
IS 6
AR UNSP e66379
DI 10.1371/journal.pone.0066379
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166SA
UT WOS:000320576400098
PM 23824283
ER
PT J
AU Einhorn, PT
Cushman, WC
Whelton, PK
AF Einhorn, Paula T.
Cushman, William C.
Whelton, Paul K.
CA ALLHAT Collaborative Res Grp
TI Chlorthalidone Versus Hydrochlorothiazide
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID LIPID-LOWERING TREATMENT; HEART-ATTACK TRIAL; HYPERTENSIVE PATIENTS
C1 [Einhorn, Paula T.] NHLBI, Bethesda, MD 20892 USA.
[Cushman, William C.] Vet Affairs Med Ctr, Memphis, TN USA.
[Whelton, Paul K.] Tulane Univ, New Orleans, LA 70118 USA.
RP Einhorn, PT (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
FU NHLBI NIH HHS [N01-HC-35130]; PHS HHS [HHSN268201100036C]
NR 5
TC 1
Z9 1
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 18
PY 2013
VL 158
IS 12
BP 922
EP 923
DI 10.7326/0003-4819-158-12-201306180-00018
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 167PW
UT WOS:000320645000027
PM 23778917
ER
PT J
AU Nandhikonda, P
Yasgar, A
Baranowski, AM
Sidhu, PS
McCallum, MM
Pawlak, AJ
Teske, K
Feleke, B
Yuan, NY
Kevin, C
Bikle, DD
Ayers, SD
Webb, P
Rai, G
Simeonov, A
Jadhav, A
Maloney, D
Arnold, LA
AF Nandhikonda, Premchendar
Yasgar, Adam
Baranowski, Athena M.
Sidhu, Preetpal S.
McCallum, Megan M.
Pawlak, Alan J.
Teske, Kelly
Feleke, Belaynesh
Yuan, Nina Y.
Kevin, Chinedum
Bikle, Daniel D.
Ayers, Steven D.
Webb, Paul
Rai, Ganesha
Simeonov, Anton
Jadhav, Ajit
Maloney, David
Arnold, Leggy A.
TI Peroxisome Proliferation-Activated Receptor delta Agonist GW0742
Interacts Weakly with Multiple Nuclear Receptors, Including the Vitamin
D Receptor
SO BIOCHEMISTRY
LA English
DT Article
ID CANCER-CELL-LINES; HUMAN PROSTATIC-CARCINOMA; THYROID-HORMONE RECEPTOR;
FACTOR BINDING PROTEIN-3; LIGAND ACTIVATION; 1-ALPHA,25-DIHYDROXYVITAMIN
D-3; 1,25-DIHYDROXYVITAMIN D-3; CRYSTAL-STRUCTURES; ESTROGEN-RECEPTOR;
LEUKEMIA-CELLS
AB A high-throughput screening campaign was conducted to identify small molecules with the ability to inhibit the interaction between the vitamin D receptor (VDR) and steroid receptor coactivator 2. These inhibitors represent novel molecular probes for modulating gene regulation mediated by VDR. Peroxisome proliferator-activated receptor (PPAR) delta agonist GW0742 was among the identified VDR-coactivator inhibitors and has been characterized herein as a pan nuclear receptor antagonist at concentrations of >12.1 mu M. The highest antagonist activity for GW0742 was found for VDR and the androgen receptor. Surprisingly, GW0742 behaved as a PPAR agonist and antagonist, activating transcription at lower concentrations and inhibiting this effect at higher concentrations. A unique spectroscopic property of GW0742 was identified as well. In the presence of rhodamine-derived molecules, GW0742 increased the fluorescence intensity and level of fluorescence polarization at an excitation wavelength of 595 nm and an emission wavelength of 615 nm in a dose-dependent manner. The GW0742-inhibited NR-coactivator binding resulted in a reduced level of expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3, and TRPV6 were negatively regulated by GW0742. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D-3.
C1 [Nandhikonda, Premchendar; Baranowski, Athena M.; Sidhu, Preetpal S.; McCallum, Megan M.; Pawlak, Alan J.; Teske, Kelly; Feleke, Belaynesh; Yuan, Nina Y.; Kevin, Chinedum; Arnold, Leggy A.] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53211 USA.
[Bikle, Daniel D.] Vet Affairs Med Ctr, Dept Med, Endocrine Res Unit, San Francisco, CA 94121 USA.
[Ayers, Steven D.; Webb, Paul] Methodist Hosp, Res Inst, Houston, TX 77030 USA.
[Yasgar, Adam; Rai, Ganesha; Simeonov, Anton; Jadhav, Ajit; Maloney, David] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Arnold, LA (reprint author), Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53211 USA.
EM arnold2@uwm.edu
RI Sidhu, Preetpal/L-5727-2013; Nandhikonda, Premchendar/K-1473-2014;
Ayers, Stephen/O-4535-2014
OI Ayers, Stephen/0000-0003-1390-8969
FU University of Wisconsin-Milwaukee (UWM); UWM Research Growth Initiative
(RGI Grant) [2012]; National Institutes of Health Grant [R03DA031090];
UWM Research Foundation (Catalyst grant); Lynde and Harry Bradley
Foundation; Richard and Ethel Herzfeld Foundation; Molecular Libraries
Initiative of the National Institutes of Health Roadmap for Medical
Research [U54MH084681]
FX This work was supported by the University of Wisconsin-Milwaukee (UWM)
(L.A.A.), the UWM Research Growth Initiative (RGI Grant 2012) (L.A.A.),
National Institutes of Health Grant R03DA031090 (L.A.A.), the UWM
Research Foundation (Catalyst grant), the Lynde and Harry Bradley
Foundation (L.A.A.), the Richard and Ethel Herzfeld Foundation (L.A.A.),
and the Molecular Libraries Initiative of the National Institutes of
Health Roadmap for Medical Research (Grant U54MH084681) (G.R., A.S.,
A.J., A.Y., and D.M.).
NR 71
TC 8
Z9 8
U1 0
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 18
PY 2013
VL 52
IS 24
BP 4193
EP 4203
DI 10.1021/bi400321p
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 169AC
UT WOS:000320748300008
PM 23713684
ER
PT J
AU Ambroggio, XI
Dommer, J
Gopalan, V
Dunham, EJ
Taubenberger, JK
Hurt, DE
AF Ambroggio, Xavier I.
Dommer, Jennifer
Gopalan, Vivek
Dunham, Eleca J.
Taubenberger, Jeffery K.
Hurt, Darrell E.
TI HASP server: a database and structural visualization platform for
comparative models of influenza A hemagglutinin proteins
SO BMC BIOINFORMATICS
LA English
DT Article
DE Influenza A; HASP; Hemagglutinin; Receptor binding; Membrane fusion;
ROSETTA; Sialic acid; Flu; Homology modeling; Molecular visualization
ID VIRUS HEMAGGLUTININ; SUBTYPES
AB Background: Influenza A viruses possess RNA genomes that mutate frequently in response to immune pressures. The mutations in the hemagglutinin genes are particularly significant, as the hemagglutinin proteins mediate attachment and fusion to host cells, thereby influencing viral pathogenicity and species specificity. Large-scale influenza A genome sequencing efforts have been ongoing to understand past epidemics and pandemics and anticipate future outbreaks. Sequencing efforts thus far have generated nearly 9,000 distinct hemagglutinin amino acid sequences.
Description: Comparative models for all publicly available influenza A hemagglutinin protein sequences (8,769 to date) were generated using the Rosetta modeling suite. The C-alpha root mean square deviations between a randomly chosen test set of models and their crystallographic templates were less than 2 angstrom, suggesting that the modeling protocols yielded high-quality results. The models were compiled into an online resource, the Hemagglutinin Structure Prediction (HASP) server. The HASP server was designed as a scientific tool for researchers to visualize hemagglutinin protein sequences of interest in a three-dimensional context. With a built-in molecular viewer, hemagglutinin models can be compared side-by-side and navigated by a corresponding sequence alignment. The models and alignments can be downloaded for offline use and further analysis.
Conclusions: The modeling protocols used in the HASP server scale well for large amounts of sequences and will keep pace with expanded sequencing efforts. The conservative approach to modeling and the intuitive search and visualization interfaces allow researchers to quickly analyze hemagglutinin sequences of interest in the context of the most highly related experimental structures, and allow them to directly compare hemagglutinin sequences to each other simultaneously in their two- and three-dimensional contexts. The models and methodology have shown utility in current research efforts and the ongoing aim of the HASP server is to continue to accelerate influenza A research and have a positive impact on global public health.
C1 [Ambroggio, Xavier I.; Dommer, Jennifer; Gopalan, Vivek; Hurt, Darrell E.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Dunham, Eleca J.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Hurt, DE (reprint author), NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM darrellh@niaid.nih.gov
FU Office of Science Management and Operations of the National Institute of
Allergy and Infectious Diseases
FX We are grateful to Dr. Yentram Huyen and Mike Tartakovsky for their
support of the project. We also thank Dr. Michael Dolan for helpful
comments on HASP, and Dr. Meghan Coakley for assistance in writing this
manuscript. This research was supported in part by the Office of Science
Management and Operations of the National Institute of Allergy and
Infectious Diseases. This study utilized the high-performance
computational capabilities of the Biowulf Linux cluster at the National
Institutes of Health, Bethesda, Maryland. (http://biowulf.nih.gov).
NR 17
TC 0
Z9 0
U1 0
U2 3
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 JUN 18
PY 2013
VL 14
AR 197
DI 10.1186/1471-2105-14-197
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 171PM
UT WOS:000320941500001
PM 23777206
ER
PT J
AU Mofenson, LM
Cotton, MF
AF Mofenson, Lynne M.
Cotton, Mark F.
TI The challenges of success: adolescents with perinatal HIV infection
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Editorial Material
DE perinatal HIV infection; adolescents; HIV care
ID CHILDREN; YOUTH; DISCLOSURE; DIAGNOSIS; BARRIERS
AB The great success in the prevention and treatment of pediatric HIV in high resource countries, and now in low resource countries, has changed the face of the HIV epidemic in children from one of near certain mortality to that of a chronic disease. However, these successes pose new challenges as perinatally HIV-infected youth survive into adulthood. Increased survival of HIV-infected children is associated with challenges in maintaining adherence to what is likely life-long therapy, and in selecting successive antiretroviral drug regimens, given the limited availability of pediatric formulations, limitations in pharmacokinetic and safety data of drugs in children, and the development of extensive drug resistance in multi-drug-experienced children. Pediatric HIV care must now focus on morbidity related to long-term HIV infection and its treatment. Survival into adulthood of perinatally HIV-infected youth in high resource countries provides important lessons about how the epidemic will change with increasing access to antiretroviral therapy for children in low resource countries. This series of papers will focus on issues related to management of perinatally infected youth and young adults.
C1 [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Rockville, MD 20852 USA.
[Cotton, Mark F.] Univ Stellenbosch, Tygerberg Childrens Hosp, Div Infect Dis, Cape Town, South Africa.
RP Mofenson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, 6100 Execut Blvd,Room 4B11, Rockville, MD 20852 USA.
OI Mofenson, Lynne/0000-0002-2818-9808
NR 24
TC 22
Z9 22
U1 0
U2 8
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUN 18
PY 2013
VL 16
AR 18650
DI 10.7448/IAS.16.1.18650
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 167CO
UT WOS:000320608300001
PM 23782484
ER
PT J
AU Puthanakit, T
Siberry, GK
AF Puthanakit, Thanyawee
Siberry, George K.
TI Bone health in children and adolescents with perinatal HIV infection
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Review
DE perinatal HIV infection; bone mineral density (BMD); fracture;
dual-energy X-ray absorptiometry (DXA); peak bone mass (PBM)
ID TENOFOVIR DISOPROXIL FUMARATE; B LIGAND RANKL; MINERAL DENSITY;
ANTIRETROVIRAL THERAPY; ABACAVIR-LAMIVUDINE; FRACTURE RISK; MASS;
CHILDHOOD; CALCIUM; COHORT
AB The long-term impact on bone health of lifelong HIV infection and prolonged ART in growing and developing children is not yet known. Measures of bone health in youth must be interpreted in the context of expected developmental and physiologic changes in bone mass, size, density and strength that occur from fetal through adult life. Low bone mineral density (BMD) appears to be common in perinatally HIV-infected youth, especially outside of high-income settings, but data are limited and interpretation complicated by the need for better pediatric norms. The potential negative effects of tenofovir on BMD and bone mass accrual are of particular concern as this drug may be used more widely in younger children. Emphasizing good nutrition, calcium and vitamin D sufficiency, weight-bearing exercise and avoidance of alcohol and smoking are effective and available approaches to maintain and improve bone health in all settings. More data are needed to inform therapies and monitoring for HIV-infected youth with proven bone fragility. While very limited data suggest lack of marked increase in fracture risk for youth with perinatal HIV infection, the looming concern for these children is that they may fail to attain their expected peak bone mass in early adulthood which could increase their risk for fractures and osteoporosis later in adulthood.
C1 [Puthanakit, Thanyawee] Chulalongkorn Univ, Fac Med, Dept Pediat, Bangkok 10330, Thailand.
[Puthanakit, Thanyawee] Thai Red Cross AIDS Res Ctr, HIVNAT, Bangkok, Thailand.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis MPID Branch, NIH, Bethesda, MD 20892 USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis MPID Branch, NIH, 6100 Executive Blvd,Room 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
FU National Research University Project of Commission of Higher Education;
Ratchadapiseksomphot Endowment Fund [HR 1161A-55]; Senior Researcher
Scholar, Thai Research Fund (TRF)
FX Dr. Puthanakit is funded in part by the National Research University
Project of Commission of Higher Education and the Ratchadapiseksomphot
Endowment Fund (HR 1161A-55) and the Senior Researcher Scholar, Thai
Research Fund (TRF).
NR 71
TC 11
Z9 11
U1 0
U2 9
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUN 18
PY 2013
VL 16
AR 18575
DI 10.7448/IAS.16.1.18575
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 167CG
UT WOS:000320607500001
PM 23782476
ER
PT J
AU Sohn, AH
Hazra, R
AF Sohn, Annette H.
Hazra, Rohan
TI The changing epidemiology of the global paediatric HIV epidemic: keeping
track of perinatally HIV-infected adolescents
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Review
DE adolescent; HIV; outcomes; perinatal; surveillance
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS;
REVERSE-TRANSCRIPTASE INHIBITOR; BONE-MINERAL DENSITY; ACQUIRED HIV;
DRUG-RESISTANCE; OBSERVATIONAL DATABASE; PSYCHIATRIC-DISORDERS;
VIROLOGICAL FAILURE; METABOLIC-CHANGES
AB The global paediatric HIV epidemic is shifting into a new phase as children on antiretroviral therapy (ART) move into adolescence and adulthood, and face new challenges of living with HIV. UNAIDS reports that 3.4 million children aged below 15 years and 2 million adolescents aged between 10 and 19 years have HIV. Although the vast majority of children were perinatally infected, older children are combined with behaviourally infected adolescents and youth in global reporting, making it difficult to keep track of their outcomes. Perinatally HIV-infected adolescents (PHIVA) are a highly unique patient sub-population, having been infected before development of their immune systems, been subject to suboptimal ART options and formulations, and now face transition from complete dependence on adult caregivers to becoming their own caregivers. As we are unable to track long-term complications and survival of PHIVA through national and global reporting systems, local and regional cohorts are the main sources for surveillance and research among PHIVA. This global review will utilize those data to highlight the epidemiology of PHIVA infection, treatment challenges and chronic disease risks. Unless mechanisms are created to count and separate out PHIVA outcomes, we will have few opportunities to characterize the negative consequences of life-long HIV infection in order to find ways to prevent them.
C1 [Sohn, Annette H.] TREAT Asia AmfAR Fdn AIDS Res, Bangkok, Thailand.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA.
RP Sohn, AH (reprint author), TREAT Asia AmfAR Fdn AIDS Res, 388 Sukhumvit Rd,Suite 2104, Bangkok, Thailand.
EM annette.sohn@treatasia.org
NR 85
TC 24
Z9 24
U1 1
U2 14
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUN 18
PY 2013
VL 16
AR 18555
DI 10.7448/IAS.16.1.18555
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 167CB
UT WOS:000320606800001
PM 23782474
ER
PT J
AU Torchia, MLG
Conze, DB
Ashwell, JD
AF Giardino Torchia, Maria Letizia
Conze, Dietrich B.
Ashwell, Jonathan D.
TI c-IAP1 and c-IAP2 Redundancy Differs between T and B Cells
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; ALPHA-DEPENDENT APOPTOSIS; MULTIPLE-MYELOMA; ACTIVATION;
CIAP2; TRAF2; UBIQUITINATION; RECEPTOR; IAPS; INHIBITOR
AB Cellular Inhibitors of Apoptosis 1 and 2 (c-IAP1 and c-IAP2) are ubiquitin protein ligases (E3s) that constitutively ubiquitinate and induce proteasomal-mediated degradation of NF-kappa B Inducing Kinase (NIK) and repress non-canonical NF-kappa B activation. Mice expressing an E3-inactive c-IAP2 mutant (c-IAP2(H570A)) have constitutive activation of non-canonical NF-kappa B, resulting in B cell hyperplasia and T cell costimulation-independence. If, and if so to what extent, c-IAP1 and c-IAP2 are redundant in NF-kappa B regulation in these mice is not known. Here we have generated mice expressing a mutant c-IAP1 that lacks E3 activity (c-IAP1(H582A)). These mice were phenotypically normal and did not have constitutive NF-kappa B activation in B cells or MEFs. siRNA-mediated knockdown of c-IAP2 showed that accumulated c-IAP2, resulting from lack of c-IAP1-dependent degradation, compensated for absent c-IAP1 E3 activity. Surprisingly, c-IAP1(H582A) T cells had a lower p100/p52 ratio than wild type T cells, and in the absence of costimulation proliferated to a degree intermediate between wild type and c-IAP2(H570A) T cells. Therefore, although c-IAP1 and c-IAP2 both can repress constitutive NF-kappa B activation, the relative importance of each varies according to cell type.
C1 [Giardino Torchia, Maria Letizia; Conze, Dietrich B.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
EM jda@pop.nci.nih.gov
FU National Institutes of Health, Center for Cancer Research, National
Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Center for Cancer Research, National
Cancer Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 2
Z9 2
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 17
PY 2013
VL 8
IS 6
AR e66161
DI 10.1371/journal.pone.0066161
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 177TH
UT WOS:000321397800026
ER
PT J
AU Liu, W
Chen, Z
Ma, YS
Wu, XC
Jin, YP
Hou, S
AF Liu, Wei
Chen, Zhi
Ma, Yansen
Wu, Xiaochun
Jin, Yaping
Hou, Steven
TI Genetic Characterization of the Drosophila Birt-Hogg-Dube Syndrome Gene
SO PLOS ONE
LA English
DT Article
ID MTOR ACTIVATION; AMINO-ACIDS; GROWTH; TUMORIGENESIS; REQUIREMENTS;
MELANOGASTER; MECHANISMS; FOLLICULIN; INTERACTS; RAPAMYCIN
AB Folliculin (FLCN) is a conserved tumor suppressor gene whose loss is associated with the human Birt-Hogg-Dube (BHD) syndrome. However, its molecular functions remain largely unknown. In this work, we generated a Drosophila BHD model through genomic deletion of the FLCN gene (DBHD-). The DBHD mutant larvae grew slowly and stopped development before pupation, displaying various characteristics of malnutrition. We found the growth delay was sensitive to the nutrient supplies. It became more severe upon restrictions of the dietary yeast; while high levels of yeast significantly restored the normal growth, but not viability. We further demonstrated that leucine was able to substitute for yeast to provide similar rescues. Moreover, the human FLCN could partially rescue the DBHD- phenotypes, indicating the two genes are involved in certain common mechanisms. Our work provides a new animal model of the BHD syndrome and suggests that modulation of the local nutrient condition might be a potential treatment of the BHD lesions.
C1 [Liu, Wei; Chen, Zhi; Ma, Yansen; Wu, Xiaochun; Jin, Yaping] Northwest A&F Univ, Coll Vet Med, Minist Agr, Key Lab Anim Biotechnol, Yangling, Shaanxi, Peoples R China.
[Liu, Wei; Hou, Steven] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA.
RP Jin, YP (reprint author), Northwest A&F Univ, Coll Vet Med, Minist Agr, Key Lab Anim Biotechnol, Yangling, Shaanxi, Peoples R China.
EM yapingjin@163.com; hous@mail.nih.gov
FU NSAF Foundation; Doctoral Programs Foundation of Ministry of Education
of China; Intramural Research Program of the National Institutes of
Health, National Cancer Institute
FX This work was supported by NSAF Foundation (W.L.), Doctoral Programs
Foundation of Ministry of Education of China (Y.J.) and the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute (S.H). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 27
TC 9
Z9 9
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 17
PY 2013
VL 8
IS 6
AR e65869
DI 10.1371/journal.pone.0065869
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 177TH
UT WOS:000321397800018
PM 23799055
ER
PT J
AU Xu, X
Mackem, S
AF Xu, Xing
Mackem, Susan
TI Tracing the Evolution of Avian Wing Digits
SO CURRENT BIOLOGY
LA English
DT Review
ID HOX GENES; SONIC HEDGEHOG; FRAME-SHIFT; LIMB BUD; BIRDS; ORIGIN;
HOMOLOGY; IDENTITY; EXPRESSION; DINOSAURS
AB It is widely accepted that birds are a subgroup of dinosaurs, but there is an apparent conflict: modern birds have been thought to possess only the middle three fingers (digits II-III-IV) of an idealized five-digit tetrapod hand based on embryological data, but their Mesozoic tetanuran dinosaur ancestors are considered to have the first three digits (I-II-III) based on fossil evidence. How could such an evolutionary quirk arise? Various hypotheses have been proposed to resolve this paradox. Adding to the confusion, some recent developmental studies support a designation for avian wing digits whereas some recent paleontological data are consistent with a identification of the Mesozoic tetanuran digits. A comprehensive analysis of both paleontological and developmental data suggests that the evolution of the avian wing digits may have been driven by homeotic transformations of digit identity, which are more likely to have occurred in a partial and piecemeal manner. Additionally, recent genetic studies in mouse models showing plausible mechanisms for central digit loss invite consideration of new alternative possibilities (I-II-IV or I-III-IV) for the homologies of avian wing digits. While much progress has been made, some advances point to the complexity of the problem and a final resolution to this ongoing debate demands additional work from both paleontological and developmental perspectives, which will surely yield new insights on mechanisms of evolutionary adaptation.
C1 [Xu, Xing] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origin, Beijing 100044, Peoples R China.
[Mackem, Susan] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Xu, X (reprint author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origin, Beijing 100044, Peoples R China.
EM xu.xing@ivpp.ac.cn; mackems@mail.nih.gov
FU National Natural Science Foundation of China [41120124002]; 973 program
[2012CB821900]
FX The author thanks James Clark, Jonah Choiniere, Corwin Sullivan, David
W.E. Hone, and Mikio Tanaka for discussions, and James Clark and Corwin
Sullivan for constructive comments on the manuscript. This project was
supported by the National Natural Science Foundation of China (grant
number: 41120124002) and 973 program (2012CB821900).
NR 80
TC 4
Z9 5
U1 5
U2 58
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD JUN 17
PY 2013
VL 23
IS 12
BP R538
EP R544
DI 10.1016/j.cub.2013.04.071
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 168CH
UT WOS:000320682800015
PM 23787052
ER
PT J
AU Saleh, AD
Simone, BA
Palazzo, J
Savage, JE
Sano, Y
Dan, T
Jin, LJ
Champ, CE
Zhao, SP
Lim, M
Sotgia, F
Camphausen, K
Pestell, RG
Mitchell, JB
Lisanti, MP
Simone, NL
AF Saleh, Anthony D.
Simone, Brittany A.
Palazzo, Juan
Savage, Jason E.
Sano, Yuri
Dan, Tu
Jin, Lianjin
Champ, Colin E.
Zhao, Shuping
Lim, Meng
Sotgia, Frederica
Camphausen, Kevin
Pestell, Richard G.
Mitchell, James B.
Lisanti, Michael P.
Simone, Nicole L.
TI Caloric restriction augments radiation efficacy in breast cancer
SO CELL CYCLE
LA English
DT Article
DE caloric restriction; breast cancer; radiation; IGF; tumor regression;
cytotoxic therapy
ID GROWTH-FACTOR-I; RANDOMIZED CONTROLLED-TRIAL; ACTIVATED PROTEIN-KINASE;
DIETARY RESTRICTION; GENE-EXPRESSION; FACTOR RECEPTOR;
CELL-PROLIFERATION; OXIDATIVE STRESS; MAMMARY-TUMORS; OPEN-LABEL
AB Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories provided more significant tumor regression than alternate day feeding. At the molecular level, tumors treated with CR and IR showed less proliferation and more apoptosis. cDNA array analysis demonstrated the IGF-1R pathway plays a key role in achieving this physiologic response, and multiple members of the IGF-1R pathway including IGF-1R, IRS, PIK3ca and mTOR were found to be downregulated. The innovative use of CR as a novel therapeutic option has the potential to change the biology of tumors and enhance the opportunity for clinical benefit in the treatment of patients with TNBC.
C1 [Saleh, Anthony D.; Savage, Jason E.; Zhao, Shuping; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Simone, Brittany A.; Sano, Yuri; Dan, Tu; Jin, Lianjin; Champ, Colin E.; Lim, Meng; Simone, Nicole L.] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19107 USA.
[Palazzo, Juan] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Pathol, Philadelphia, PA 19107 USA.
[Sotgia, Frederica; Pestell, Richard G.; Lisanti, Michael P.] Thomas Jefferson Univ, Dept Canc Biol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Mitchell, James B.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Simone, NL (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19107 USA.
EM nicole.simone@jeffersonhospital.org
OI Champ, Colin/0000-0002-1879-7463; Dan, Tu/0000-0003-1154-0507
FU American Society for Radiation Oncology; Intramural Research Program of
the NIH; Kimmel Cancer Center Radiation Oncology Facility; NCI Cancer
Center [P30 CA56036]; Thomas Jefferson University; Manchester Cancer
Research Centre (MCRC); Breakthrough Breast Cancer (BBC); European
Research Council (ERC)
FX This research was supported in part by the American Society for
Radiation Oncology, the Intramural Research Program of the NIH and the
Kimmel Cancer Center Radiation Oncology Facility, which is supported
partly by NCI Cancer Center Grant P30 CA56036. During the course of this
work, Drs Lisanti and Sotgia were funded by the resources of Thomas
Jefferson University. Also, Dr Lisanti's and Dr Sotgia's current
affiliation is the University of Manchester, where they receive funding
from the Manchester Cancer Research Centre (MCRC), Breakthrough Breast
Cancer (BBC) and The European Research Council (ERC).
NR 61
TC 16
Z9 21
U1 0
U2 11
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUN 15
PY 2013
VL 12
IS 12
BP 1955
EP 1963
DI 10.4161/cc.25016
PG 9
WC Cell Biology
SC Cell Biology
GA 201VD
UT WOS:000323170200027
PM 23708519
ER
PT J
AU Jinnah, HA
DeLong, MR
Hallett, M
AF Jinnah, H. A.
DeLong, Mahlon R.
Hallett, Mark
TI The dystonias: Past, present, and future
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
C1 [Jinnah, H. A.; DeLong, Mahlon R.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[DeLong, Mahlon R.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Jinnah, HA (reprint author), Emory Univ, Sch Med, Dept Neurol, 6300 Woodruff Mem Bldg, Atlanta, GA 30322 USA.
EM hjinnah@emory.edu
FU NCATS NIH HHS [U54 TR001456]; NINDS NIH HHS [R01 NS040470, U54 NS065701]
NR 15
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUN 15
PY 2013
VL 28
IS 7
BP 849
EP 850
DI 10.1002/mds.25564
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 188ZH
UT WOS:000322235700001
PM 23893441
ER
PT J
AU Albanese, A
Bhatia, K
Bressman, SB
DeLong, MR
Fahn, S
Fung, VSC
Hallett, M
Jankovic, J
Jinnah, HA
Klein, C
Lang, AE
Mink, JW
Teller, JK
AF Albanese, Alberto
Bhatia, Kailash
Bressman, Susan B.
DeLong, Mahlon R.
Fahn, Stanley
Fung, Victor S. C.
Hallett, Mark
Jankovic, Joseph
Jinnah, Hyder A.
Klein, Christine
Lang, Anthony E.
Mink, Jonathan W.
Teller, Jan K.
TI Phenomenology and classification of dystonia: A consensus update
SO MOVEMENT DISORDERS
LA English
DT Review
DE dystonia; classification; definition
ID PRIMARY TORSION DYSTONIA; CLINICAL CHARACTERISTICS; DYT1 PHENOTYPE;
FOCAL DYSTONIA; PATHOGENESIS; DIAGNOSIS; BLEPHAROSPASM; PARKINSONISM;
GUIDELINES; DISEASE
AB This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. (C) 2013 Movement Disorder Society
C1 [Albanese, Alberto] Univ Cattolica Sacro Cuore, Dept Neurol, I-20123 Milan, Italy.
[Albanese, Alberto] Ist Nazl Neurol Carlo Besta, Dept Neurol, Milan, Italy.
[Bhatia, Kailash] UCL, Sobell Dept Motor Neurosci & Movement Disorders, Inst Neurol, London, England.
[Bressman, Susan B.] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA.
[Bressman, Susan B.] Albert Einstein Coll Med, Dept Neurol, New York, NY USA.
[Bressman, Susan B.] Beth Israel Deaconess Med Ctr, Dept Neurol, Bronx, NY USA.
[Bressman, Susan B.] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA.
[DeLong, Mahlon R.; Jinnah, Hyder A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Fahn, Stanley] Columbia Univ, Dept Neurol, New York, NY USA.
[Fung, Victor S. C.] Univ Sydney, Movement Disorders Unit, Dept Neurol, Westmead Hosp, Sydney, NSW 2006, Australia.
[Fung, Victor S. C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Houston, TX 77030 USA.
[Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA.
[Jinnah, Hyder A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
[Jinnah, Hyder A.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Klein, Christine] Med Univ Lubeck, Sect Clin & Mol Neurogenet, Dept Neurol, D-23538 Lubeck, Germany.
[Lang, Anthony E.] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Clin, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.] Univ Toronto, Toronto, ON, Canada.
[Mink, Jonathan W.] Univ Rochester, Dept Neurol, Rochester, NY USA.
[Mink, Jonathan W.] Univ Rochester, Dept Neurobiol & Anat, Rochester, NY USA.
[Mink, Jonathan W.] Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY USA.
[Mink, Jonathan W.] Univ Rochester, Dept Pediat, Rochester, NY USA.
[Teller, Jan K.] Dystonia Med Res Fdn, Chicago, IL USA.
RP Albanese, A (reprint author), Fdn Ist Neurol Carlo Besta, Via G Celoria 11, I-20133 Milan, Italy.
EM alberto.albanese@unicatt.it
OI Bhatia, Kailash/0000-0001-8185-286X
FU Dystonia Medical Research Foundation; Dystonia Coalition; European
Dystonia COST Action; Merz GmbH; Ipsen Pharma
FX The efforts of the consensus committee were supported by the Dystonia
Medical Research Foundation, The Dystonia Coalition, the European
Dystonia COST Action, and unrestricted educational grants from Merz GmbH
and Ipsen Pharma.
NR 46
TC 298
Z9 302
U1 7
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUN 15
PY 2013
VL 28
IS 7
BP 863
EP 873
DI 10.1002/mds.25475
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 188ZH
UT WOS:000322235700003
PM 23649720
ER
PT J
AU Jinnah, HA
Berardelli, A
Comella, C
DeFazio, G
DeLong, MR
Factor, S
Galpern, WR
Hallett, M
Ludlow, CL
Perlmutter, JS
Rosen, AR
AF Jinnah, H. A.
Berardelli, Alfredo
Comella, Cynthia
DeFazio, Giovanni
DeLong, Mahlon R.
Factor, Stewart
Galpern, Wendy R.
Hallett, Mark
Ludlow, Christy L.
Perlmutter, Joel S.
Rosen, Ami R.
CA Dystonia Coalition Investigators
TI The focal dystonias: Current views and challenges for future research
SO MOVEMENT DISORDERS
LA English
DT Review
DE focal dystonia; cervical dystonia; blepharospasm; spasmodic dysphonia;
focal hand dystonia
ID DEEP-BRAIN-STIMULATION; IDIOPATHIC CERVICAL DYSTONIA; BENIGN ESSENTIAL
BLEPHAROSPASM; PRIMARY TORSION DYSTONIA; BOTULINUM TOXIN TREATMENT;